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Патент США №

6583411

Автор(ы)

Altmann и др.

Дата выдачи

24 июня 2003 г.


Multiple local probe measuring device and method



РЕФЕРАТ

The invention provides a local probe measuring device for effecting local measurements refering to a sample, comprising a plurality of local probes for local measurements with respect to a sample or a reference surface, a measurement condition adjustment arrangement adapted to commonly adjust measurement conditions of said local probes with respect to the sample or the reference surface, a plurality of detection arrangements, each being associated or adapted to be associated to one particular of said local probes and adapted to independently detect measurement data refering to local measurements effected by said particular local probe. Further, methods for effecting local measurements and local manipulations by means of multiple local probes are provided.


Авторы:

Stephan Maximilian Altmann (Grafenwohr, DE), Johann Karl Heinrich Horber (Weiltingen, DE)

Заявитель:

Europaisches Laboratorium fur Molekularbiologie (EMBL) (Heidelberg, DE)

ID семейства патентов

24651352

Номер заявки:

09/660,885

Дата регистрации:

13 сентября 2000 г.

Класс патентной классификации США:

850/4; 250/307; 250/309; 250/310; 250/311; 850/33; 850/55; 977/874

Класс совместной патентной классификации:

G01Q 70/06 (20130101); G01Q 40/00 (20130101); B82Y 35/00 (20130101); Y10S 977/874 (20130101)

Класс международной патентной классификации (МПК):

G01N 27/00 (20060101); G01B 7/34 (20060101); G12B 21/00 (20060101); G12B 21/24 (20060101); G12B 21/20 (20060101); H01J 37/00 (20060101); H01J 037/00 ()

Область поиска:

;250/306,307,310,311,309

Использованные источники

[Referenced By]

Патентные документы США

RE33387October 1990Binnig
5220555June 1993Yanagisawa et al.
5262643November 1993Hammond et al.
5304924April 1994Yamano et al.
5508527April 1996Kuroda et al.
5600137February 1997Saito et al.
5929643July 1999Sakai et al.
6028305February 2000Minne et al.

Зарубежные патентные документы

WO 00 19166Apr 2000WO

Другие источники


Aime, J.P. Elkaakour, Z., Odin, C., Bouhacina, T., Michel, D., Curely, J., and Dautant, A. Comments on the Use of the Force Mode in Atomic Force Microscopy for Polymer Films. Journal of Applied Physics, 76:754-762, 1994. .
Albrecht, T., Akamine, S., Carver, T., und Quate, C. Microfabrication of Cantilever Styli for the Atomic Force Microscope. Journal of Vacuum Science Technology A, 8:3386-3396, 1990. .
Arai, T. and Masamichi, F. Effect of Tip Shape on Force-Distance Curves for AFM in Aqueous Electrolytes. Journal of Electroanalytical Chemistry 374, pp. 269-273, 1994. .
Binnig, G. and Smith, D.P. Single-Tube Three-Dimensional Scanner for Scanning Tunneling Microscopy. Review of Scientific Instruments, 57:1688-1689, 1986. .
Binnig, G., Rohrer, H., Gerber, C., and Weibel, E. Tunneling Through a Controlable Vacuum Gap. Applied Physics Letters, 40:178-180, 1982. .
Burnham, N.A, Dominguez, D.D., Mowery, R.L., and Colton, R.J. Probing the Surface Forces of Monolayer Films with an Atomic Force Microscope. Physical Review Letters, 64:1931-1934, 1990. .
Butt, H.J. Measuring Electrostatic, van der Waals, and Hydration Forces in Electrolyte Solutions with an Atomic Force Microscope. Biophysical Journal 60, pp. 1438-1444, 1991. .
Butt, H.J. and Jaschke, M. Calculation of Thermal Noise in Atomic Force Microscopy. Nanotechnology, 6:1-7, 1995. .
Butt, H.J., Muller, T. and Gross, H. Immobilizing Biomolecules for Scanning Force Microscopy by Embedding in Carbon. Journal of Structural Biology, 110:127-132, 1993. .
Butt, H.J., Siedle, P., Seifert, K., Fendler, K., Seger, T., Bamberg, E., Weisenhorn, A.L., Goldie, K., and Engel, A. Scan Speed Limit in Atomic Force Microscopy. Journal of Microscopy, 169:75-84, 1993. .
Firtel, M. and Beveridge, T.J. Scanning Probe Microscopy in Microbiology. Micron, 26:347-362, 1995. .
Florin, E., Moy, V., and Gaub, H. Adhesion Forces Between Individual Ligand-Receptor Pairs. Science 264, pp. 415-417, 1994. .
Grant, M.L., and Saville, D.A. Electrostatic Interactions Between a Nonuniformly Charged Sphere and a Charged Surface. Journal of Colloidal Interface Science, 171:35-45, 1995. .
Guethner, P., Fischer, and U.C., Dransfeld, K. Scanning Near-Field Acoustic Microscopy. Applied Physics B, 48:89-92, 1989. .
Hinterdorfer, P., Baumgartner, W., Gruber, H.J., Schilcher, K., and Schindler, H. Detection and Localization of Individual Antibody-Antigen Recognition Events by Atomic Force Microscopy. Proceedings of the National Academy of Sciences, U.S.A., 93:3477-3481, 1996. .
Hoh, J., et al. Quantized Adhesion Detection with the Atomic Force Microscope. Journal of the American Chemical Society, 114, 1992. .
Hutter, J. and Bechhofer, J. Measurement and Manipulation of van der Waals Forces in Atomic Force Microscopy. Journal of Vacuum Science Technology B 12 (3), pp. 2251-2253, 1994. .
Lee, G., Chrisey, L., and Colton, R. Direct Measurement of the Forces Between Complementary Strands of DNA. Science 266, pp. 771-773, 1994. .
Lee, G., Kidwell, D., and Colton, R. Sensing Discrete Streptavidin-Biotin Interactions with Atomic Force Microscopy. Langmuir 10, pp. 354-357, 1994. .
Meyer, G. and Amer, N.M. Novel Optical Approch to Atomic Force Microscopy. Applied Physics Letters, 53:1045-1047, 1988. .
Mueller, D., Amrein, M., and Engel, A. Adsorption of Biological Molecules to a Solid Support for Scanning Probe Microscopy. Journal of Structural Bilogy, 119:172-188, 1997. .
Mueller, D., Schoenenberger, C.-A., Schabert, F., and Engel, A. Structural Changes in Native Membrane Proteins Monitored at Subnanometer Resolution with the Atomic Force Microscope: A Review. Journal of Structural Biology, 119:149-157, 1997. .
Rief, M., Gautel, M., Oesterhelt, F., Fernandez, J., and Gaub, H. Reversible Unforlding of Indivdual Titin Immunoglobin Domains by AFM. Science 276, pp. 1109-1112, 1997. .
Rief, M., Oesterhelt, F., Heymann, B., and Gaub, H. Single Molecule Force Spectroscopy on Polysaccharides by Atomic force Microscopy. Science 275, pp. 1295-1297, 1997. .
Roth, C. and Lenhoff, A. Electrostatic and van der Waals Contributions to Protein Adsorbtion: Computation of Equilibrium Constants. Langmuir 9, pp. 962-972, 1993. .
Roth, C.M., and Lenhoff, A.M. Electrostatic and van der Waals Contributions to Protein Adsorption: Comparison of Theory and Experiment. Langmuir, 11:3500-3509, 1995. .
Salapka, M.V., Bergh, H.S., Lai, J., Majumdar, A., and McFarland, E. Multi-Mode Noise Analysis of Cantilevers for Scanning Probe Microscopy. Journal of Applied Physics, 81(6):2480-2487, 1997. .
Van Cleef, M., Holt, S.A., Watson, G.S., and Myhra, S. Polysterene Sheres on Mica Substrates: AFM Calibration, Tip parameters and Scan Artefacts. Journal of Microscopy, 181:2-9, 1996. .
Wong, T. and Descouts, P. Atomic Force Microscopy under Liquid: A Comparative Study of Three Different AC Mode Operations. Journal of Microscopy 178, pp. 7-13, 1994. .
Xu, W., Blackford, B.L., Cordes, J.G., Jericho, M.H., Pink, D.A., Levadny, V.G., and Beveridge, T. Atomic Force microscope Measurements of Long-Range forces Near Lipid-Coated Surfaces in Electrolytes. Biophysical Journal, 72:1404-1413, 1997. .
Yip, C.M., Yip, C.C., and Ward, M.D. Direct Force Measurements of Insulin Monomer-Monomer Interactions. Biochemistry, 37:5439-5449, 1998. .
G. Binning and C. F. Quate and Ch. Gerber, Atomic Force Microscope, Physical Review Letters, vol. 56, No. 9, pp. 930-933, Mar. 3, 1986. .
Philippe Cluzel, Anne Lebrun, Christoph Heller, Richard Lavery, Jean-Louis Viovy, Didier Chatenay, Francois Caron, DNA: An Extensible Molecule, Science, vol. 271, pp. 792-794, Feb. 9, 1996. .
D. E. Leckband, J. N. Israelachvili, F. J. Schmitt, W. Knoll, Long-Range Attraction and Molecular Rearrangements in Receptor-Ligand Interactions, Science, vol. 255, pp. 1419-1421, Mar. 13, 1992. .
Jurgen Fritz, Dario Anselmetti and Janina Jarchow and Xavier Fernandez-Busquets, Probing Single Biomolecules with Atomic Force Microscopy, Journal of Structural Biology 119, pp. 165-171 (1997) Article No. SB973887. .
Roters A. and Johannsmann, D. distance Dependent Noise Measurements in Scanning Force Microscopy. Journal of Physics: Condensed Matter, 8:7561 ff., 1996. .
Lutwyche M. et al.: "Microfabrication and Parallel Operation of 5X5 2D AFM Cantilever Arrays for Data Storage and Imaging," MEMS 98. Proceedings IEEE of the 11th Annual International Workshop on Micro Electro Mechanical Systems, An Investigation of Micro Structures, Sensors, Actuators, Machines and Systems. Heidelberg, Jan. 25-29, 1998, IEEE Workshop on Micro Electro ME, Jan. 25, 1998, pp. 8-11. .
Hideki Kawakatsu et al.: "Crystalline Lattice for Metrological Applications and Positioning Control by a Dual Tunneling-Unit Scanning Tunneling Microscope," Journal of Vacuum Science and Technology: Part B, American Institute of Physics, New York, US, vol. 9, No. 2 Part 2, Mar. 1, 1991, pp. 651-654. .
Chui B. W. et al.: "Sidewall-Implanted Dual-Axis Piezoresistive Cantilever for AFM Data Storage Readback and Tracking," MEMS 98. Proceedings IEEE of the 11th Annual International Workshop on Micro Electro Mechanical Systems. An Investigation of Micro Structures, Sensors, Actuators, Machines and Systems. Heidelberg, Jan. 25-29, 1998, IEEE Workshop on Micro Electro ME, Jan. 25, 1998, pp. 12-17. .
Diploma Thesis of Stephan M. Altmann, University of Heidelberg on or after Sep. 22, 1998. .
Albrecht T., "Microfabrication of cantilever styli for the atomic force microscope", J. Vac. Sc. Technol. A8(4), Jul./Aug. 1990, pp. 3385-3396..

Главный эксперт: Lee; John R.
Assistant Examiner: Vanore; David A.
Уполномоченный, доверенный или фирма: Rothwell, Figg, Ernst & Manbeck


ФОРМУЛА ИЗОБРЕТЕНИЯ



What is claimed is:

1. A local probe measuring device for effecting local measurements referring to a sample, the device comprising: a plurality of local probes for local measurements with respect to a sample or a reference surface; a rigid mechanical coupling between said local probes; a position adjusting means for commonly adjusting distance and lateral position relations of said local probes with respect to the sample or the reference surface; a plurality of detection means, each being associated to a particular one of said local probes to independently detect measurement data from local measurements effected by said particular local probe; and a controller that controls or stabilizes via said position adjusting means said distance and lateral position relations on the basis of certain measurement data which refer to local measurements effected by at least one of said local probes and which reflect said distance relations.

2. The device according to claim 1, wherein said controller controls or stabilizes via said position adjusting means a distance relation and a lateral positioning relation of at least one of said local probes on the basis of local measurements effected by at least one other local probe.

3. A local probe measuring device for measuring local interactions between a local probe arrangement and a sample, the device comprising: a plurality of local probes adapted to interact locally with a sample or a reference surface; a rigid mechanical coupling between the local probes; a position adjusting means for commonly adjusting for all of said local probes at least one of a distance of the respective local probe with respect to the sample or the reference surface, and a local interaction of the respective local probe with the sample or the reference surfaces, and for commonly adjusting for all of said local probes at least one of a first lateral coordinate of the respective local probe with respect to the sample or the reference surface, and a second lateral coordinate of the respective local probe with respect to the sample or the reference surface; and a plurality of detection arrangements, each being associated to a particular one of said local probes and each independently detects a local interaction of said particular local probe with the sample or the reference surface; and a controller that controls or stabilizes via said position adjusting means for at least one of said local probes at least one of said distance and said local interaction on the basis of detection results obtained for at least one of said local probes via the respective detection arrangement, and said controller controls or stabilizes via said position adjusting means for at least one of said local probes at least one of said first lateral coordinate and said second lateral coordinate on the basis of detection results obtained for at least one of said local probes via the respective detection arrangement.

4. The device according to claim 3, wherein said controller controls or stabilizes via said position adjusting means for at least one of said local probes at least one of said distance and said local interaction on basis of detection results obtained for at least one other of said local probes via the respective detection arrangement.

5. The device according to claim 3, wherein said controller controls or stabilizes via said position adjusting means for at least one of said local probes at least one of said distance, said first lateral coordinate, said second lateral coordinate and said local interaction on basis of detection results obtained for at least one other of said local probes via the respective detection arrangement.

6. The device according to claim 5, wherein said controller controls or stabilizes via said position adjusting means for at least one of said local probes said distance and at least one of said first lateral coordinate and said second lateral coordinate of basis of detection results obtained for at least one other of said local probes via the respective detection arrangement.

7. The device according to claim 5, wherein said controller controls or stabilizes via said position adjusting means for said at least one of said local probes said distance, said first lateral coordinate and said second lateral coordinate on basis of detection results obtained for at least one other of said local probes via the respective detection arrangement.

8. The device according to claim 3, wherein under local interaction conditions with the sample or the reference surface at least one of said local probe and the respective detection arrangement associated therewith are sensitive to at least one of a change of its distance, a change of its first lateral coordinate and a change of its second lateral coordinate with respect to the sample or the reference surface.

9. The device according to claim 8, wherein at least one local probe and the respective detection arrangement associated therewith are sensitive substantially only to a change of the distance of said local probe with respect to the sample or the reference surface or have a substantially higher sensitivity to a change of the distance of said local probe with respect to the sample or the reference surface than to a change of one or both of said lateral coordinates with respect to the sample or the reference surface.

10. The device according to claim 8, wherein at least one local probe and the respective detection arrangement associated therewith are sensitive substantially only to a change of the first lateral coordinate of said local probe with respect to the sample or the reference surface or have a substantially higher sensitivity to a change of the first lateral coordinate of said local probe with respect to the sample or the reference surface than to a change of one or both of said distance and said second lateral coordinate with respect to the sample or the reference surface.

11. The device according to claim 8, wherein at least one local probe and the respective detection arrangement associated therewith are substantially sensitive only to a change of the second lateral coordinate of said local probe with respect to the sample or the reference surface or have a substantially higher sensitivity to a change of the second lateral coordinate of said local probe with respect to the sample or the reference surface than to a change of one or both of said distance and said first lateral coordinate with respect to the sample or the reference surface.

12. The device according to claim 8, wherein at least one local probe and the respective detection arrangement associated therewith are substantially sensitive only to a change of the distance and the first lateral coordinate of said local probe with respect to the sample or the reference surface or have a substantially higher sensitivity to a change of the distance and the first lateral coordinate of said local probe with respect to the sample or the reference surface than to a change of said second lateral coordinate with respect to the sample or the reference surface.

13. The device according to claim 8, wherein at least one local probe and the respective detection arrangement associated therewith are sensitive substantially only to a change of the distance and the second lateral coordinate of said local probe with respect to the sample or the reference surface or have a substantially higher sensitivity to a change of the distance and the second lateral coordinate of said local probe with to the sample or the reference surface than to a change of said first lateral coordinate with respect to the sample or the reference surface.

14. The device according to claim 8, wherein at least one local probe and the respective detection arrangement associated therewith are substantially sensitive to a change of the first lateral coordinate and the second lateral coordinate of said local probe with respect to the sample or the reference surface.

15. A local probe measuring device for measuring local interactions between a cantilever probe arrangement and a sample, comprising: a plurality of cantilever probes that interact locally with a sample or a reference surface; a rigid mechanical coupling between respective base sections of said cantilever probes; a position adjusting means for commonly adjusting for all of said cantilever probes: a distance of the base section of the respective cantilever probe with respect to the sample or the reference surface, a first lateral coordinate of the base section of the respective cantilever probe with respect to the sample or the reference surface, and a second lateral coordinate of the base section of the respective cantilever probe with respect to the sample or the reference surface, said first and second lateral coordinates defining the lateral position of the base section of the cantilever probe with respect to the sample or the reference surface; a plurality of detection arrangements, each being associated to a particular one of said cantilever probes and each independently detects at least one of a deflection of said particular cantilever probe, a torsion of said particular cantilever probe and a local interaction of said particular cantilever probe with said sample or reference surface; and a controller that controls or stabilizes via said position adjusting means for at least one of said cantilever probes at least one of said first and second lateral coordinates on the basis of detection results -obtained for at least one of said cantilever probes via the respective detection arrangement.

16. The device according to claim 15, wherein said controller controls or stabilizes via said positioning arrangement for at least one of said cantilever probes at least one of said distance, said first lateral coordinate, said second lateral coordinate and said local interaction on basis of detection results obtained for at least one other of said cantilever probes via the respective detection arrangement.

17. The device according to claim 15, wherein said controller controls or stabilizes via said position adjusting means for at least one of said cantilever probes said distance and at least one of said first lateral coordinate and said second lateral coordinate on basis of detection results obtained for at least one other of said cantilever probes via the respective detection arrangement.

18. The device according to claim 15, wherein said controller controls or stabilizes via said position adjusting means for at least one of said cantilever probes said distance, said first lateral coordinate and said second lateral coordinate on basis of detection results obtained for at least one other of said cantilever probes via the respective detection arrangement.

19. The device according to claim 15, wherein at least one of said cantilever probes is a triangular cantilever probe and wherein the particular detection arrangement provided measures a deflection of said triangular cantilever probe.

20. The device according to claim 15, wherein at least one of said cantilever probes is a beam-shaped cantilever probe and wherein in the particular detection arrangement provided measures at least one of a deflection and a torsion of said beam-shaped cantilever probe.

21. The device according to claim 20, wherein said detection arrangement measures a torsion of said beam-shaped cantilever probe.

22. The device according to claim 20, wherein said detection arrangement measures both a deflection and a torsion of said beam-shaped cantilever probe substantially independently of each other.

23. The device according to claim 15, wherein a first beam-shaped cantilever probe and a second beam-shaped cantilever probe of said cantilever probes extend at an angle of about 90 degrees with respect to each other and that a first and a second detection arrangement are provided, the first detection arrangement measures at least a torsion of the first beam-shaped cantilever probe and the second detection arrangement measures at least a torsion of the second beam-shaped cantilever probe.

24. The device according to claim 23, wherein said detection arrangements additionally measure a deflection of the respective beam-shaped cantilever probes substantially independently of the torsion of said beam-shaped cantilever probe.

25. The device according to claim 15, wherein a first of said cantilever probes is a cantilever probe, which is substantially softer with respect to torsion and bending as a second of said cantilever probes, and wherein a first and a second detection arrangement are provided, the first detection arrangement independently measures a torsion and a deflection of the first cantilever probe and the second detection arrangement measures at least a deflection of the second cantilever probe.

26. The device according to claim 25, wherein said second cantilever probe is a triangular cantilever probe.

27. The device according to claim 15, wherein said detection arrangements are based on at least one of an optical detection, a thermal detection, a capacitive detection, a piezo-electric detection and a detection of electronic tunneling.

28. The device according to claim 27, wherein at least one of said detection arrangements comprises an optical detection arrangement.

29. The device according to claim 27, characterized in that at least one of said detection arrangements comprises a position sensitive detector that receives a laser beam reflected by a tip portion of the respective cantilever probe.

30. The device according to claim 29, characterized in that the laser beam directed to the tip portion of one of the cantilever probes and the resulting reflected laser beam substantially extend in a longitudinal direction of the respective cantilever probe, if seen in a projection on a surface of said sample or on said reference surface or in a projection on a support surface for supporting said sample.

31. The device according to claim 29, wherein the laser beam directed to the tip portion of one of the cantilever probes and the resulting reflected laser beam substantially extend in a direction orthogonal to the longitudinal direction of the respective cantilever probe, if seen in a projection on a surface of said sample or on said reference surface or in a projection on a support surface for supporting said sample.

32. The device according to claim 29, wherein for at least one of said cantilever probes the respective position sensitive detector resolves an incidence position of the reflected laser beam on the detector only within one dimension.

33. The device according to claim 29, wherein for at least one of said cantilever probes the respective position sensitive detector resolves an incidence position of the reflected laser beam on the detector within two dimensions.

34. A method of effecting local measurements referring to a sample, the method comprising: providing at least two local probes in a positional relation with respect to a sample or a reference surface; adjusting a distance relation and a lateral positioning relation of the respective local probe for at least one of said local probes with respect to the sample or the reference surface, on the basis of measurements effected with respect to at least one other of said local probes; and effecting a measurement with respect said at least one local probe with reference to said measurements effected with respect to said at least one other local probe.

35. The method according to claim 34, wherein said lateral positioning relation is adjusted with respect to only one lateral coordinate on the basis of measurements effected with respect to at least one other of said local probes.

36. The method according to claim 34, wherein said lateral positioning relation is adjusted with respect to two lateral coordinates on the basis of measurements effected with respect to at least one other of said local probes, wherein said two lateral coordinates define the lateral position of the local probe with respect to the sample or reference surface.

37. A method of effecting local manipulations referring to a sample, the method comprising: providing at least two local probes in a positional relation with respect to a sample or a reference surface; adjusting a distance relation and a lateral positioning relation of the respective local probe with respect to the sample or the reference surface, said distance relation and said lateral positioning relation being adjusted on the basis of measurements effected with respect to at least one other of said local probes; and manipulating said sample by means of said at least one local probe with reference to said measurements effected with respect to said at least one other local probe.

38. The method according to claim 37, wherein said lateral positioning relation is adjusted with respect to only one lateral coordinate on the basis of measurements effected with respect to at least one other of said local probes.

39. The method according to claim 37, wherein said lateral positioning relation is adjusted with respect to two lateral coordinates on the basis of measurements effected with respect to at least one other of said local probes, and wherein said two lateral coordinates define the lateral position of the local probe with respect to the sample or reference surface.


ОПИСАНИЕ



The present invention concerns a multiple local probe measuring device for effecting local measurements referring to a sample, a multiple local probe measuring method and a multiple local probe manipulation method. One application field of the novel device and the novel methods is the scanning force microscopy (SFM), also known as atomic force microscopy (AFM). However, the invention is not restricted to such an application. The basic concept is applicable to the whole range of local probe techniques developed so far, especially all other scanning probe microscopy (SPM) techniques which require stabilization of measurement conditions, e.g. distance relations, for microscope probes, possibly cantilevers, for high-resolution measurements. Since it is hardly possible to give a complete list of scanning probe microscope techniques to which the invention can be applied, only some important techniques are given: scanning tunneling microscopy (STM), magnetic force microscopy (MFM), scanning near-field. optical microscopy (SNOM), lateral force microscopy (LFM), electrical field/force microscopy (EFM), magneto-tunneling microscopy and spin sensitive tunneling microscopy.

An object of the invention is to allow measurements with well defined measurement conditions. To this end, the invention provides for at least one of a stabilization of measurement conditions and a calibration and detection of measurement conditions.

In many local probe microscopy techniques, a distance of a local probe with respect to a sample or a reference surface is an essential parameter defining the measurement conditions. Accordingly, at least one of a stabilization, calibration, and detection of a distance associated with a local probe with respect to a sample or a reference surface is a central field to which the invention can be applied. As will be explained in more detail, the invention proposes providing a plurality of local probes to allow at least one of a calibration, detection, and stabilization of measurement conditions for at least one local probe on the basis of measurement effected with respect to at least one other local probe. For many applications, it will be sufficient to provide two local probes, one of the local probes being used for at least one of calibration, detection, and stabilization of the measurement conditions of the other local probe.

In the following the background and concept of the present invention will be exemplified with reference to the scanning force microscopy technique on the basis of two local probes in the form of cantilevers, as commonly used for scanning force/atomic force microscopy. According to the invention, there is provided a detector arrangement allowing independent detection of first measurement data referring to local measurements effected by first local probe and independent detection of second measurement data referring to local measurements effected by a second local probe. In the following, it will be assumed that this detection arrangement is realized by a double sensor system.

The concept of the invention can easily be extended to multiple local probe measurement devices having more than two local probes by providing a corresponding detection arrangement adapted to independently detect measurement data for each local probe with respect to the sample or the reference surface. Such a detection arrangement may be realized by a multiple independent sensor system. The provision of more local probes than a first probe and a second local probe allows a further increase of the stability and well defined measurement conditions possibly comprising a well defined orientation of a local probe in three-dimensional space.


ПРЕДПОСЫЛКИ СОЗДАНИЯ ИЗОБРЕТЕНИЯ



Scanning force microscopes (SFM) were in developed in 1986 by Binnig et al. (compare: Binnig, G. et al., PhysRev Letters, 1986, Vol. 56(9), p. 930-933) for imaging non-conducting surface with atomic resolution. They have since become a widely used tool in the semi-conductor industry, biological research and surface science. The first SFM was basically a thin metal foil acting as a cantilever, which was jammed between an STM-tip and the sample surface. Since the cantilever was a conducting metal, it become possible to measure the surface corrugation of non-conducting samples by monitoring how the foremost tip of the cantilever pointing towards the sample was deflected while moving across the sample surface on the basis of a tunneling current between the cantilever and a probing tip according to the scanning tunneling microscopy principle. Today, the registration of a laser's deflection from the back of the cantilever on a segmented photodiode is commonly used for this task (compare: Meyer, G. et al., Physics Letters, 1988, Vol. 53, p. 1045-1047).

Just as Binnig and Rohrer were originally interested in doing local spectroscopy on superconductors while developing the scanning tunneling microscope (STM) in 1981 (compare: Binnig, G. et al., ApplPhys Letters, 1982, Vol. 40, p. 178-180), the SFM was soon applied to local measurements of forces between different materials in vacuum, gaseous atmospheres, and in liquid. For many researches in different fields, the SFM has become an instrument for measuring local force-distance profiles on the atomic and molecular scale. Measurements that have been performed recently were concerned with ligand-receptor binding forces (compare: Florin et al., Science 1994, Vol. 264, p. 415-417), the unfolding and refolding of proteins (compare: Rief et al., Science, 1997, Vol. 276, p. 1109-1112), stretching of DNA as well as monitoring charge migration on semiconductors and conductor/insulator surfaces (compare: Yoo, M. J., et al., Science, 1997, Vol. 276, p. 579-582).

In the context of e.g. atomic force microscopy it is known, that the optical beam deflection detection method allows simultaneous measurement of height displacements and torsion (induced by lateral forces) of the cantilever used as local probe (compare: Kees. O. van der Werf, Constant A. J. Putman, Bart G. de Grooth, Frans B. Segerink, Eric H. Schipper, Niek F. van Hulst, and Jan Greve, Review of Scientific Instruments, October 1993, Volume 64, Issue 10, p. 2892-2897, "Compact stand-alone atomic force microscope").

Local measurements of forces between tip and surface suffer from the following problems: 1) drift of the positioning arrangement, generally a piezo (immediately after the piezo has been extended or compressed); 2) hysteresis of the positioning arrangement or piezo; 3) mechanical drift; 4) thermal drift between sensor and sample on time scales ranging from seconds to hours; and 5) general mechanical instability resulting from the fact that the sensors' mechanical "feedback" on the sample is typically realized via a mechanical arm of much larger dimensions and mass than the sensor itself.

These problems can be alleviated to some degree if the force between tip and surface and, therefore, the distance between substrate and sample surface is kept constant, for instance, by keeping the deflectionangle of the cantilever constant (constant force mode). This is restricted to cases, though, where the lever (cantilever) is actually in contact with the sample surface and the normal force on the tip is large enough so as to be well distinguishable from any background noise.

A minimal force-level in the range of a hundred pN is generally required to provide a stable feedback control. Many interactions, especially of biological molecules under physiological conditions, are in the range well below 100 pN down to the level of thermally induced fluctuation forces of the cantilever. Presently available instruments are not capable of locally stabilized measurements at well-defined distances from the sample in this important force range of thermally fluctuating sensors (few pN).

Furthermore, data often need to be sampled locally over time periods of seconds to hours. Stability problems (as enumerated above) of instruments available to date ultimately render such measurements impossible.

OVERVIEW OF THE INVENTION

One object of the invention is to provide a fast, independent, active, and in itself stable control of measurement conditions for local probe measurements, possibly the distance between a sensor tip and a sample surface.

Another object of the invention is to provide a way to detect the distance between the sensor tip and the sample surface.

Another object of the invention is to provide a way to calibrate the distance between the sensor tip and the sample surface.

Another object of the invention is to provide for a lateral positional stabilization for the sensor tip with respect to the sample.

According to one aspect, the invention provides a control system to achieve at least one of said objects. The basic concept behind this control system is based on the fundamental idea of appropriate mechanical and geometric scaling of feedback components for spacial stabilization of sensors used in local probe techniques.

Development on local probes in general and scanning probe instruments in particular has lately been focussed largely on the miniaturization of probes for measurements of very small distances, forces and energies. Problems with the stability of such instruments result from overlooking the fact that mechanical stability of such systems is still controlled by feedback components of relatively large mass which are linked by more or less rigid connections over long distances and which are usually made of different materials as well. Especially scanning probe instruments are characterized by such connections which reach from the sensor holder via some more.or less rigid coupling to the instrument body to the scanning stage and finally the sample holder.

The basic idea behind faster and more stable feedback controls proposed here rests on the concept of reducing the distance as well the mass of the mechanical coupling between the sample and sensor as much as possible. This can be done by short-distance-low-mass closing of the "mechanical feedback loop" through rigidly coupling two or more independent miniature sensors for generating at least one independent force-distance-control feedback signal. By reducing mass and length of the mechanical coupling in the feedback loop to the dimensions of the sensory-system intended for measurements one increases substantially stability and with an independent distance measurement the experimental freedom.

One example for a multi-sensor system according to the invention exemplifying the concept of the invention is a system having one additional cantilever/sensor in a scanning probe microscope (SPM), according to a preferred embodiment in a scanning force microscope (SFM) for achieving higher stability and gaining access to a new applications. The most important advantage of such a double sensor SPM (DS-SPM) is its unique stability over unrestricted time scales, supplying a new and sound basis for measuring forces and potentials with Angstroem spatial and pN force resolution.

The multi-sensor system will be exemplified in the following on the basis of a double-sensor system for scanning force microscopy. The principles of the invention can easily be extended to multi-sensor system of any scanning probe microscopy technique having two or more local probes.

Commercial SFM exclusively use one and the same lever/sensor for two tasks: 1) to acquire sensory-data about the interactions between tip and sample surface, and 2) to control the force-distance between tip and surface. The double-sensor system for SFM is based on a concept allowing a stabilization and optimization of local SFM measurements, according to which the tasks 1) and 2) are split up onto two or more sensors sitting next to each other, e.g., on the same substrate. As sample and substrate approach each other, the first sensor to reach the surface will be called the distance sensor. The second sensor to reach the surface will then be called the interaction sensor. The sequence according to which the sensors approach the surface can be determined in advance.

Which of the two tips reaches the sample surface first and how much further the distance between sample and surface must be reduced for the second lever to come into contact with the surface depends on the size of and the distance between the levers employed, especially if commercially available cantilevers are used. A typical height difference between cantilevers of commercially available substrates is about 5 to 10 micrometers, and a typical lateral distance between the cantilevers is about 100 micrometers. The heigth difference may be changed by tilting the short face of the substrate against the sample surface, for example to obtain a height difference of 1 to 50, preferably 10 to 20 micrometers.

The distance sensor can always be kept in contact with the surface and will therefore continuously supply a clear force signal for the distance feedback with Angstrom resolution. The second interaction sensor can now be used for independently detecting force distance profiles on, close to and also at well defined distances from the sample surface. Splitting the tasks of distance and interaction detection between two separate sensors sitting side by side (possibly on the same substrate) thus provides a new level of stability to scanning probe microscopes and adds important additional freedom for the design of measurements.

The cantilever deflection needs to be detected independently for each of the two levers. This can be done by two independent optical beam deflection setups, for example. Other options would be to use any combination of optical, interference or electrical lever detection schemes. Especially cantilevers with integrated piezo-crystal detectors are very promising for this task.

Conventional SFM are based on just one sensor and become locally stable only when a feedback signal with a sufficient signal-to-noise ratio is available. This is only the case after the single sensor tip has contacted the surface and a certain deflection amplitude is reached. The latter must at least be greater than the combined thermal and detection-noise-amplitude of the free lever and, therefore, easily leads to normal forces on the scale of 100 or more pN which compromise the sensitivity, the design and the general freedom of the experiment considerably. A well-defined distance control before the tip of the single lever has reached or after it has left the surface is impossible in these conventional setups.

The double-sensor system solves these problems by means of the interaction sensor and the distance sensor. The distance between the interaction sensor and the sample surface can actively be controlled with Angstrom resolution as soon as the distance sensor has made contact with the surface. At this point, the interaction sensor is still typically 1 to 50 micrometers above the sample surface. The sensory signal coming from this lever can now be used to do measurements at any distance from the surface and in contact with the surface at normal forces determined only by the sensitivity of the detection system and the spring constant of the cantilever used.

The interaction sensor may approach and retract from the surface while the distance between substrate and sample is actively controlled by the distance sensor feedback. Any creep or drift of the piezo in height direction can be corrected on long as well as on short time scales, i.e. from milliseconds to hours, possibly even days. This means especially that it is possible to stop the approach or retract of the interaction sensor at any desired distance from the surface for any duration of time. The lever will stay at exactly this position, i.e. the distance between substrate and surface will be kept at exactly this value by the distance sensor feedback. Depending on the nature of the sample surface it is also possible to scan the interaction sensor in parallel to the surface at well defined distances.

The approach according to the invention differs substantially from approaches of the prior art aiming to determine the distance of the lever from the sample by additional detection means based on fiber-optical interference (compare: Martin, Y., et al., J. ApplPhys. 1987, Vol. 61, p. 4723 et seq) or simultaneous capacitance measurements (compare: Barret, R. C. and Quate, C. F., J. Appl.Phys., 1991, Vol. 70, p. 2725 et seq). Both known approaches immediately set specific requirements on the sample surface or the constancy of ionic strength of solutions used in fluid-cell experiments. Experimental requirements must therefore be compromised without the attainment of true distance and thus force control.

A crucial and highly important but in no way critical point of the double-sensor system (or multi-sensor system) according to the invention for atomic force microscopy and the like is a high mechanical stability with respect to the sensors, which can be reached by introducing a rigid mechanical coupling between the distance feedback sensor(s) and interaction sensor(s) on the scale of only a few hundred micrometers, generally on a scale in the order of dimensions of the local probes themselves. As has already been indicated, in conventional SFM a mechanical coupling between the sample and the sensor is realized via more or less rigid connections between the sample, piezo, piezo-holder, instrument base and sample holder. The coupling is thus relayed over a distance of several centimeters instead of a few hundred micrometers.

Commercially available cantilever designs for SFM already typically offer several levers of different lengths and spring constants. Therefore, existing supplies of cantilever substrates can be used together with a proper design of a multiple detection system, preferably a multiple optical detection system. Such optical detection systems can be integrated rather easily in nearly all commercial instruments and thus may provide a new generation of scanning probe instruments with unprecedented stability and tip/sample approach control.

The principle of the invention can be extended to any local probe measuring device and any local probe measuring method allowing local measurements referring to a sample. Accordingly, the invention provides a local probe measuring device for effecting local measurements refering to a sample, comprising a first local probe for local measurements with respect to a sample or a reference surface, a second local probe for local measurements with respect to the sample or the reference surface, a measurement condition adjustment arrangement adapted to commonly adjust a first measurement condition of the first local probe with respect to the sample or the reference surface and a second measurement condition of the second local probe with respect to the sample or the reference surface, a detection arrangement comprising a first detection arrangement associated with the first local probe adapted to independently detect first measurement data refering to local measurements effected by said first local probe and a second detection arrangement associated with the second local probe adapted to independently detect second measurement data refering to local measurements effected by said second local probe.

The local probe measuring device according to the invention may comprise a controller adapted to control via said measurement condition adjustment arrangement said first and second measurement conditions on the basis of one of said first and second measurement data.

It is to advantage if the controller and the detection arrangement are adapted to adjust via said measurement condition adjustment arrangement at least one of said first and second measurement conditions on the basis of one of said first and second measurement data and then to obtain the respective other said first and second measurement data for the adjusted measurement condition.

It is proposed that said controller, said positioning arrangement and said detection arrangement are adapted to adjust said first measurement condition on the basis of said first measurement data and then to obtain said second measurement data for the resulting second measurement condition or to adjust said second measurement condition on the basis of said second measurement data and then to obtain said first measurement data for the resulting first measurement condition.

At least one of said first and second measurement conditions may roughly be adjusted on the basis of one of said first and second measurement data and may finely be adjusted on the basis of the other of said first and second measurement data.

It is suggested, that at least one of said first and second measurement conditions is adjusted on the basis of one of said first and second measurement data according to a time constant and is adjusted on the basis of the other of said first and second measurement data according to another time constant.

Said first and second measurement conditions may comprise distance relations of the local probes with respect to the sample or the reference surface. In this case, the measurement condition adjustment arrangement may comprise a positioning arrangement adapted to commonly adjust said distance relations. The positioning arrangement may comprise at least one piezo-crystal.

The local probe measuring device may comprise more than two local probes adapted to effect local measurements with respect to the sample or the reference surface. The measurement conditions of this plurality of local probes may be commonly adjusted by said measurement condition adjustment arrangement (possibly the positioning arrangement). In the case of more than two local probes, it is preferred that the detection arrangement be adapted to independently detect measurement data referring to local measurements effected by each local probe.

Preferably, there are provisions to control measurement conditions of at least one of said local probes (two local probes or more) via said measurement condition adjustment arrangement (possibly the positioning arrangement) on the basis of local measurements effected by at least one other local probe of said local probes. According to a preferred embodiment there are provisions to control measurement conditions of one of said local probes on the basis of local measurements effected by at least three other local probes of said local probes. Preferably, the at least three other local probes are arranged around said one local probe.

At least one of said local probes may be one of an atomic force microscopy probe, a lateral force microscopy probe, a tunneling microscopy probe, a magnetic force microscopy probe, an electric force microscopy probe, a near-field optical microscopy probe and an other local probe microscopy probe. It is possible that all the local probes used during one measurement are of the same probe type. For certain measurements, however, it may be useful if at least two of the local probes used during one measurement are of different probe types.

One may characterize the invention according to this aspect alternatively also as follows: Provided is a local probe measuring device for effecting local measurements refering to a sample, which comprises: a plurality of local probes for local measurements with respect to a sample or a reference surface, a measurement condition adjustment arrangement adapted to commonly adjust measurement conditions of said local probes with respect to the sample or the reference surface, a plurality of detection arrangements, each being associated or adapted to be associated to one particular of said local probes and adapted to independently detect measurement data refering to local measurements effected by said particular local probe. One of these local probes may be identified as the first local probe and another of these local probes may be identified as the second local probe mentioned above.

Said measurement conditions may comprise distance relations of the local probes with respect to the sample or the reference surface. Accordingly, it is to advantage, if said measurement condition adjustment arrangement comprises a positioning arrangement adapted to commonly adjust said distance relations.

Said measurement conditions may comprise distance relations and lateral positioning relations of the local probes with respect to the sample or the reference surface. In this case it is prefered, that said measurement condition adjustment arrangement comprises a positioning arrangement adapted to commonly adjust said distance relations and said lateral positioning relations.

According to one aspect of the invention, a local probe measuring device for effecting local measurements referring to a sample is provided which comprises: a first local probe for local measurements with respect to a sample or a reference surface, a second local probe for local measurements with respect to the sample or the reference surface, a rigid mechanical coupling between the first local probe and the second local probe, a positioning arrangement adapted to commonly adjust distance relations of the probes with respect to the sample or the reference surface to commonly adjust a first measurement condition of the first local probe with respect to the sample or the reference surface and a second measurement condition of the second local probe with respect to the sample or the reference surface, a detection arrangement comprising a first detection arrangement associated with the first local probe adapted to independently detect first measurement data refering to local measurements effected by said first local probe and a second detection arrangement associated with the second local probe adapted to independently detect second measurement data refering to local measurements effected by said second local probe.

It is suggested, that said rigid mechanical coupling extends over a coupling path between said local probes having a path length in the order of magnitude as dimensions of the local probes itself.

It is further suggested, that said rigid mechanical coupling has associated a resonance frequency well above at least one of a resonance frequency or resonance frequencies associated with said local probes and a limiting frequency associated with said detection arrangement.

At least one of said first and second probes may be adapted to interact locally with the sample or the reference surface.

It is suggested, that said adjustment of said first measurement condition comprises at least one of an adjustment of a first distance of the first local probe with respect to the sample or the reference surface and an adjustment of a first local interaction of the first local probe with the sample or the reference surface.

Said adjustment of said second measurement condition may comprise at least one of an adjustment of a second distance of the second local probe with respect to the sample or the reference surface and an adjustment of a second local interaction of the first local probe with the sample or the reference surface.

Said first detection arrangement may be adapted to detect a first interaction of said first local probe with the sample or the reference surface independently of any interaction of said second local probe with the sample or the reference surface to obtain said first measurement data.

It is suggested, that said second detection arrangement is adapted to detect a second interaction of said second local probe with the sample or the reference surface independently of any interaction of said first local probe with the sample or the reference surface to obtain said second measurement data.

Preferably, a controller is provided which is adapted to control via said positioning arrangement said distance relations on the basis of at least one of said first and second measurement data.

Said controller and said detection arrangement may be adapted to adjust via said positioning arrangement at least one of said first and second measurement conditions on the basis of one of said first and second measurement data and then to obtain the respective other of said first and second measurement data for the adjusted measurement condition.

In particular, it is suggested, that said controller, said positioning arrangement and said detection arrangement are adapted i) to adjust said first measurement condition on the basis of said first measurement data and then to obtain said second measurement data for the resulting second measurement condition or ii) to adjust said second measurement condition on the basis of said second measurement data and then to obtain said first measurement data for the resulting first measurement condition.

At least one of said first and second measurement conditions may roughly be adjusted on the basis of one of said first and second measurement data and may finely be adjusted on the basis of the other of said first and second measurement data.

Preferably, at least one of said first and second measurement conditions is adjusted on the basis of one of said first and second measurement data according to a time constant and is adjusted on the basis of the other of said first and second measurement data according to another time constant.

It is suggested, that said controller and said detection arrangement are adapted to obtain first measurement data as a function of second measurement data or vice versa.

Said controller and said detection arrangement may be adapted to manipulate said sample via said positioning arrangement and one of said first and second local probes with reference to measurement data refering to local measurements effected by the respective other local probe.

It is useful to provide a feedback control loop comprising said positioning arrangement and one of said first and second detection arrangements to stabilize at least on of said first and second measurement conditions. Said feedback control loop may be adapted to stabilize a distance or interaction relation for at least on of said first and second local probes with respect to said sample or said reference surface.

Said feedback control loop may comprise two feedback control sub-loops, one comprising one of said first and second detection arrangements and the other comprising the other of said first and second detection arrangements, said feedback control loops having different time constants.

It is useful to provide more than two local probes for local local measurements with respect to the sample or the reference surface, which are rigidly mechanically coupled with each other and are commonly adjustable by the positioning arrangement.

Preferably, said rigid mechanical coupling extends over a coupling path between said local probes having a path length in the order of magnitude as dimensions of the local probes itself.

Said detection arrangement may be adapted to independently detect measurement data refering to local measurements effected by each local probe.

Provisions to control measurement conditions of at least one of said local probes via said positioning arrangement on the basis of local measurements effected by at least one other local probe of said local probes are very useful.

Further, provisions to control measurement conditions of one of said local probes on the basis of local measurements effected by at least three other local probes of said local probes, which are arranged around said one local probe, are useful as well.

At least on of said local probes may be functionalized with respect to the sample.

Said positioning arrangement may be adapted to effect a lateral scanning of said sample or said reference surface by said local probes.

Preferably, a distance between interaction or measurement sections of said local probes in a height direction associated with said sample or said reference surface is adjustable. The distance may be adjustable by tilting at least on of a mounting arrangement of said local probes and a probe substrate integral with said local probes.

It is suggested, that a distance in the order of a typical interaction length associated with the interaction of one of said local probes with said sample or reference surface is provided or is adjustable between interaction or measurement sections of said local probes in a height direction associated with said sample or said reference surface.

Preferably, a distance of about 1 to 50 .mu.m between interaction or measurement sections of said local probes in a height direction associated with said sample or said reference surface is provided or is adjustable.

Said detection arrangement may comprise an optical detection arrangement. In particular, said detection arrangement may comprise at least one laser source and for at least one of said local probes a respective position sensitive detector adapted to receive a laser beam reflected by the respective local probe. In this context it is suggested, that a laser beam directed to said first local probe and the resulting reflected laser beam extend in a first plane and a laser beam directed to said second local probe and the resulting reflected laser beam extend in a second plane, said planes are arranged at an angle with respect to each other. Said angle may amount to about 90.degree..

An other possiblitiy is, that said detection arrangement comprises an piezo-electrical detection arrangement, wherein at least one of said local probes comprises piezo-electrical material sensitive to movements of the respective local probe.

At least on of said local probes may be one of an atomic force microscopy probe, a lateral force microscopy probe, a tunneling microscopy probe, a magnetic force microscopy probe, an electric force microscopy probe, a near-field optical microscopy probe and an other local probe microscopy probe. Said local probes may be of the same probe type. An other possibility is, that at least two of said local probes are of different probe type.

At least one of said local probes may have associated an interaction field generator generating an interaction field to bring about or to influence an local interaction of the respective local probe with the sample or the reference surface. Said interaction field may be an electromagnetic or optical field interacting with the sample or the reference surface. Said local interaction of the respective local probe with said sample or said reference surface may be a detection of a response of the sample or the reference surface to the interaction field.

Said detection of said response may comprise a detection of an optical near-field resulting from an illumination of said sample or reference surface by an optical field serving as said interaction field, the respective local probe having associated an aperture to serve as near-field optical microscopy probe.

It is suggested, that at least one of said local probes has associated an interaction medium supply or an interaction medium receptacle for bringing or holding interaction medium in a region around at least an interaction portion of the respective local probe and at least a portion of said sample or said reference surface near said interaction portion or the respective local probe, said interaction medium bringing about or influencing a local interaction of the respective local probe with the sample or the reference surface.

One may characterize the invention according to this aspect alternatively also as follows: It is provided a local probe measuring device for effecting local measurements referring to a sample, which comprises: a plurality of local probes for local measurements with respect to a sample or a reference surface, a rigid mechanical coupling between said local probes, a positioning arrangement adapted to commonly adjust distance relations of said local probes with respect to the sample or the reference surface, a plurality of detection arrangements, each being associated or adapted to be associated to one particular of said local probes and adapted to independently detect measurement data refering to local measurements effected by said particular local probe. One of these local probes may be identified as the first local probe and another of these local probes may be identified as the second local probe mentioned above.

Preferably a controller is provided, which is adapted to control or stabilize via said positioning arrangement said distance relations on the basis of certain measurement data which refer to local measurements effected by at least one of said local probes and which reflect said distance relations.

It is suggested, that said positioning arrangement is adapted further to commonly adjust lateral positioning relations of the local probes with respect to the sample or the reference surface, and that said controller is further adapted to control or stabilize via said positioning arrangement said lateral positioning relations on the basis of measurement data which refer to local measurements effected by at least one of said local probes and which reflect said lateral positioning relations. In particular, said controller may be adapted to control or stabilize via said positioning arrangement a distance relation of at least one of said local probes on the basis of local measurements effected by at least one other local probe of said local probes. Preferably, said controller is adapted to control or stabilize via said positioning arrangement a distance relation and a lateral positioning relation of at least one of said local probes on the basis of local measurements effected by at least one other local probe of said local probes.

According to a further aspect, the invention provides a local probe measuring device for measuring local interactions between a local probe arrangement and a sample, comprising: a first local probe adapted to interact locally with a sample or a reference surface, a second local probe adapted to interact locally with the sample or a reference surface, a rigid mechanical coupling between the first local probe and the second local probe, a positioning arrangement adapted to commonly adjust at least one of a first distance of the first local probe with respect to the sample or the reference surface and a first local interaction of the first probe with the sample or the reference surface and at least one of a second distance of the second local probe with respect to the sample or the reference surface and a second local interaction of the second local probe with the sample or the reference surface, a detection arrangement comprising a first detection arrangement associated with the first local probe adapted to detect at least one of the first distance and the first local interaction independently of the second distance and the second local interaction and a second detection arrangement associated with the second local probe adapted to detect at least one of the second distance and the second local interaction independently of the first distance and the first interaction.

Preferably, said rigid mechanical coupling extends over a coupling path between said local probes having a path length in the order of magnitude as dimensions of the local probes itself.

It is further prefered, that said rigid mechanical coupling has associated a resonance frequency well above at least one of a resonance frequency or resonance frequencies associated with said local probes and a limiting frequency associated with said detection arrangement.

A controller may be provided which is adapted to control via said positioning arrangement said first distance or said first local interaction on the one hand and said second distance or said second local interaction on the other hand on the basis of at least one of said detected first and second distances or on the basis of at least one of said detected first and said detected second interactions.

Preferably, said controller and said detection arrangement are adapted to adjust via said positioning arrangement at least one of said first and second distances or one of said first and second interactions on the basis of said one detected distance or interaction and then to measure the other of said first and second distances or the other of said first and second interactions. Said controller, said positioning arrangement and said detection arrangement may be adapted i) to adjust said first distance or said first interaction on the basis of said detected first distance or interaction and then to measure said second distance or interaction for the resulting adjustment of the second local probe or ii) to adjust said second distance or said second interaction on the basis of said detected second distance or interaction and then to measure said first distance or interaction for the resulting adjustment of the first local probe.

It is suggested, that the respective distance or the respective interaction is roughly adjusted on the basis of one of said first and second distance or interaction and is finely adjusted on the basis of the other of said first and second distance or interaction.

The respective distance or interaction may be adjusted on the basis of one of said first and second distance or interaction according to a time constant and is adjusted on the basis of the other of said first and second distance or interaction according to another time constant.

Preferably, said controller and said detection arrangement are adapted to measure said first distance or interaction as a function of said second distance or interaction or vice versa.

Said controller and said detection arrangement may be adapted to manipulate said sample via said positioning arrrangement and one of said first and second local probes with reference to the respective distance or interaction of the other local probe.

A feedback control loop comprising said positioning arrangement and one of said first and second detection arrangements to stabilize a distance or interaction relation for at least on of said first and second local probes with respect to said sample or said reference surface is very useful.

Said feedback control loop may comprise two feedback control sub-loops, one comprising one of said first and second detection arrangements and the other comprising the other of said first and second detection arrangements, said feedback control loops having different time constants.

It is useful to provide more than two local probes adapted to interact locally with the sample or the reference surface, which are rigidly mechanically coupled with each other and are commonly adjustable by the positioning arrangement. Preferably, said rigid mechanical coupling extends over a coupling path between said local probes having a path length in the order of magnitude as dimensions of the local probes itself.

Said detection arrangement may be adapted to independently detect the distance of each local probe with respect to the sample or the reference surface or the interaction of each local probe with the sample or the reference surface.

Provisions to control measurement conditions of at least one of said local probes via said positioning arrangement on the basis of detection results obtained for of at least one other local probe of said local probes are very useful.

Provisions to control measurement conditions of one of said local probes via said positioning arrangement on the basis of detection results obtained for at least three other local probes of said local probes, which are arranged around said one local probe, are useful as well.

At least one of said local probes may be functionalized with respect to the sample.

Said positioning arrangement may be adapted to effect a lateral scanning of said sample or said reference surface by said local probes.

It is suggested, that a distance between interaction or measurement sections of said local probes in a height direction associated with said sample or said reference surface is adjustable. The distance may be adjustable by tilting at least on of a mounting arrangement of said local probes and a probe substrate integral with said local probes.

Preferably, a distance in the order of a typical interaction length associated with the interaction of one of said local probes with said sample or reference surface is provided or is adjustable between interaction or measurement sections of said local probes in a height direction associated with said sample or said reference surface. A distance of about 1 to 50 .mu.m between interaction or measurement sections of said local probes in a height direction associated with said sample or said reference surface may be provided or may be adjustable.

Said detection arrangement may comprise an optical detection arrangement. Said detection arrangement may comprise at least one laser source and for at least one of said local probes a respective position sensitive detector adapted to receive a laser beam reflected by the respective local probe. In this context it is suggested, that a laser beam directed to said first local probe and the resulting reflected laser beam extend in a first plane and a laser beam directed to said second local probe and the resulting reflected laser beam extend in a second plane, said planes are arranged at an angle with respect to each other. Said angle may amount to about 90.degree..

An other possiblitiy is, that said detection arrangement comprises an piezo-electrical detection arrangement, wherein at least one of said local probes comprises piezo-electrical material sensitive to movements of the respective local probe.

At least on of said local probes may be one of an atomic force microscopy probe, a lateral force microscopy probe, a tunneling microscopy probe, a magnetic force microscopy probe, an electric force microscopy probe, a near-field optical microscopy probe and an other local probe microscopy probe. Said local probes may be of the same probe type. An other possiblity is, that at least two of said local probes are of different probe type.

At least one of said local probes may have associated an interaction field generator generating an interaction field to bring about or to influence said local interaction of the respective local probe with the sample or the reference surface. Said interaction field may be an electromagnetic or optical field interacting with the sample or the reference surface. Said local interaction of the respective local probe with said sample or said reference surface may be a detection of a response of the sample or the reference surface to the interaction field. Said detection of said response may comprise a detection of an optical near-field resulting from an illumination of said sample or reference surface by an optical field serving as interaction field, the respective local probe having associated an aperture to serve as near-field optical microscopy probe.

At least one of said local probes may have associated an interaction medium supply or an interaction medium receptacle for bringing or holding interaction medium in a region around at least an interaction portion of the respective local probe and at least a portion of said sample or said reference surface near said interaction portion or the respective local probe, said interaction medium bringing about or influencing said local interaction of the respective local probe with the sample or the reference surface.

One may characterize the invention according to this aspect alternatively also as follows: Provided is a local probe measuring device for measuring local interactions between a local probe arrangement and a sample, which comprises: a plurality of local probes adapted to interact locally with a sample or a reference surface, a rigid mechanical coupling between the local probes, a positioning arrangement adapted to commonly adjust for all of said local probes at least one of i) a distance of the respective local probe with respect to the sample or the reference surface, and ii) a local interaction of the respective local probe with the sample or the reference surface, and a plurality of detection arrangements, each being associated or adapted to be associated to a particular of said local probes and adapted to independently detect a local interaction of said particular local probe with the sample or the reference surface. One of these local probes may be identified as the first local probe and another of these local probes may be identified as the second local probe mentioned above.

Preferably, a controller is provided, which is adapted to control or stabilize via said positioning arrangement for at least one of said local probes at least one of said distance, said first lateral coordinate, said second lateral coordinate and said local interaction on the basis of detection results obtained for at least one of said local probes via the respective detection arrangement.

It is to advantage, if said positioning arrangement is further adapted to commonly adjust for all of said local probes at least one of i) a first lateral coordinate of the respective local probe with respect to the sample or the reference surface, and ii) a second lateral coordinate of the respective local probe with respect to the sample or the reference surface, said first and second lateral coordinates defining the lateral position of the local probe with respect to the sample or the reference surface, and if said controller is further adapted to control or stabilize via said positioning arrangement for at least one of said local probes at least one of said first lateral coordinate and said second lateral coordinate on the basis of detection results obtained for at least one of said local probes via the respective detection arrangement.

Preferably, said controller is adapted to control or stabilize via said positioning arrangement for at least one of said local probes at least one of said distance and said local interaction on basis of detection results obtained for at least one other of said local probes via the respective detection arrangement. In particular, said controller may be adapted to control or stabilize via said positioning arrangement for at least one of said local probes at least one of said distance, said first lateral coordinate, said second lateral coordinate and said local interaction on basis of detection results obtained for at least one other of said local probes via the respective detection arrangement.

Preferably, said controller is adapted to control or stabilize via said positioning arrangement for said at least one of said local probes said distance and at least one of said first lateral coordinate and said second lateral coordinate on basis of detection results obtained for at least one other of said local probes via the respective detection arrangement. It is even more prefered, if said controller is adapted to control or stabilize via said positioning arrangement for said at least one of said local probes said distance, said first lateral coordinate and said second lateral coordinate on basis of detection results obtained for at least one other of said local probes via the respective detection arrangement.

Under local interaction conditions with the sample or the reference surface at least one of said local probe and the respective detection arrangement associated therewith may be sensitive to at least one of a change of its distance, a change of its first lateral coordinate and a change of its second lateral coordinate with respect to the sample or the reference surface.

At least one local probe and the respective detection arrangement associated therewith may be sensitive substantially only to a change of the distance of said local probe with respect to the sample or the reference surface or may be substantially higher sensitive to a change of the distance of said local probe with respect to the sample or the reference surface than to a change of one or both of said lateral coordinates with respect to the sample or the reference surface.

An other possibility is, that at least one local probe and the respective detection arrangement associated therewith are sensitive substantially only to a change of the first lateral coordinate of said local probe with respect to the sample or the reference surface or are substantially higher sensitive to a change of the first lateral coordinate of said local probe with respect to the sample or the reference surface than to a change of one or both of said distance and said second lateral coordinate with respect to the sample or the reference surface.

A further possibility is, that at least one local probe and the respective detection arrangement associated therewith are substantially sensitive only to a change of the second lateral coordinate of said local probe with respect to the sample or the reference surface or are substantially higher sensitive to a change of the second lateral coordinate of said local probe with respect to the sample or the reference surface than to a change of one or both of said distance and said first lateral coordinate with respect to the sample or the reference surface.

Further, it is proposed, that at least one local probe and the respective detection arrangement associated therewith are substantially sensitive only to a change of the distance and the first lateral coordinate of said local probe with respect to the sample or the reference surface or are substantially higher sensitive to a change of the distance and the first lateral coordinate of said local probe with respect to the sample or the reference surface than to a change of said second lateral coordinate with respect to the sample or the reference surface.

At least one local probe and the respective detection arrangement associated therewith may be sensitive substantially only to a change of the distance and the second lateral coordinate of said local probe with respect to the sample or the reference surface or may be substantially higher sensitive to a change of the distance and the second lateral coordinate of said local probe with respect to the sample or the reference surface than to a change of said first lateral coordinate with respect to the sample or the reference surface.

At least one local probe and the respective detection arrangement associated therewith may be substantially sensitive to a change of the first lateral coordinate and the second lateral coordinate of said local probe with respect to the sample or the reference surface.

Further, according to still another aspect the invention provides a local probe measuring device for measuring local interactions between a cantilever probe arrangement and a sample, comprising: a first cantilever probe adapted to interact locally with a sample or a reference surface, a second cantilever probe adapted to interact locally with the sample or a reference surface, a rigid mechanical coupling between a base section of the first cantilever probe and a base section of the second cantilever probe, a positioning arrangement adapted to commonly adjust a first distance of the base section of the first cantilever probe with respect to the sample or the reference surface and a second distance of the base section of the second local probe with respect to the sample or the reference surface, a detection arrangement comprising a first detection arrangement associated with the first cantilever probe adapted to independently detect at least one of a first deflection of the first cantilever probe and a first local interaction of the first cantilever probe with said sample or reference surface and a second detection arrangement associated with the second cantilever probe adapted to independently detect at least one of a second deflection of the second cantilever probe and a second local interaction of the second cantilever probe with said sample or reference surface.

Preferably, said rigid mechanical coupling extends over a coupling path between said cantilever probes having a path length in the order of magnitude as dimensions of the cantilever probes itself.

It is to advantage, if said rigid mechanical coupling has associated a resonance frequency well above at least one of a resonance frequency or resonance frequencies associated with said cantilever probes and a limiting frequency associated with said detection arrangement.

A controller may be provided, which is adapted to control via said positioning arrangement said first distance on the one hand and said second distance on the other hand on the basis of at least one of said detected first and second deflections or on the basis of at least one of said detected first and second local interactions. Said controller and said detection arrangement may be adapted to adjust via said positioning arrangement at least one of said first and second deflections or one of said first and second local interactions on the basis of said one detected deflection or interaction and then to measure the other of said first and second deflections or the other of said first and second interactions. Preferably, said controller, said positioning arrangement and said detection arrangement are adapted i) to adjust said first deflection or interaction on the basis of said detected first deflection or interaction and then to measure said second deflection or interaction for the resulting second distance or ii) to adjust said second deflection or interaction on the basis of said detected second deflection or interaction and then to measure said first deflection or interaction for the resulting first distance.

It is suggested, that the respective deflection or the respective interaction is roughly adjusted on the basis of one of said first and second deflection or interaction and is finely adjusted on the basis of the other of said first and second deflection or interaction.

The respective deflection or interaction may be adjusted on the basis of one of said first and second deflection or interaction according to a time constant and may be adjusted on the basis of the other of said first and second deflection or interaction according to another time constant.

Said controller and said detection arrangement may be adapted to measure said first deflection or interaction as a function of said second deflection or interaction or vice versa. Further, said controller and said detection arrangement may be adapted to manipulate said sample via said positioning arrrangement and one of said first and second cantlilever probes with reference to the respective deflection or interaction of the other cantilever probe.

A feedback control loop comprising said positioning arrangement and one of said first and second detection arrangements to stabilize at least one of said first and second distances with respect to said sample or said reference surface is very useful. Said feedback control loop may comprise two feedback control sub-loops, one comprising one of said first and second deflection arrangements and the other comprising the other of said first and second detection arrangements and the other comprising the other of said first and second detection arrangements, said feedback control loops having different time constants.

It is useful, to provide more than two cantilever probes adapted to interact locally with the sample or the reference surface are provided, which are rigidly mechanically coupled with each other at a respective cantilever base portion and are commonly adjustable by the positioning arrangement. In this case it is prefered, if said rigid mechanical coupling extends over a coupling path between said cantilever probes having a path length in the order of magnitude as dimensions of the cantilever probes itself. Said detection arrangement may be adapted to independently detect a respective deflection or interaction of each cantilever probe.

Provisions to control a distance of the base section of at least one of said cantilever probes with respect to the sample or the reference surface via said positioning arrangement on the basis of deflection or interaction results obtained for of at least one other cantilever probe of said cantilever probes are very useful.

Provisions to control a distance of the base section of one of said cantilever probes with respect to the sample or the reference surface via said positioning arrangement on the basis of deflection or interaction results obtained for of at least three other cantilever probe of said cantilever probes, which are arranged around said one cantilever probe, are useful as well.

It is suggested, that at least one of said cantilever probes is functionalized with respect to the sample.

Said positioning arrangement may be adapted to effect a lateral scanning of said sample or said reference surface by said cantilever probes.

Prefereably, a distance between tip sections of said cantilever probes in a height direction associated with said sample or said reference surface is adjustable. The distance may be adjustable by tilting at least on of a mounting arrangement of said cantilever probes and a cantilever substrate integral with said cantilever probes.

A distance in the order of a typical interaction length associated with the interaction of one of said cantilever probes with said sample or reference surface may be provided or may be adjustable between interaction or measurement sections of said local probes in a height direction associated with said sample or said reference surface. Preferably, a distance of about 1 to 50 .mu.m between tip sections of said cantilever probes in a height direction associated with said sample or said reference surface is provided or is adjustable.

Said detection arrangement may comprise an optical detection arrangement. Said detection arrangement may comprise at least one laser source and for at least one of said cantilever probes a respective position sensitive detector adapted to receive a laser beam reflected by a tip portion of the respective cantilever probe. A laser beam directed to the tip portion of said first cantilever probe and the resulting reflected laser beam may extend in a first plane and a laser beam directed to the tip portion of said second cantilever probe and the resulting reflected laser beam may extend in a second plane, said planes are arranged at an angle with respect to each other. Said angle may amount to about 90.degree..

An other possiblity is, that said detection arrangement comprises an piezo-electrical detection arrangement, wherein at least one of said cantilever probes comprises piezo-electrical material sensitive to the deflection of the respective cantilever probe.

At least on of said cantilever probes may be one of an atomic force microscopy probe, lateral force microscopy probe, a tunneling microscopy probe, a magnetic force microscopy probe, an electric force microscopy probe, a near-field optical microscopy probe and an other local probe microscopy probe. Said cantilever probes may be of the same probe type. An other possiblity is, that at least two of said cantilever probes are of different probe type.

At least one of said cantilever probes may have associated an interaction field generator generating an interaction field to bring about or to influence said local interaction of the respective cantilever probe with the sample or the reference surface. Said interaction field may be an electromagnetic or optical field interacting with the sample or the reference surface. Said local interaction of the respective cantilever probe with said sample or said reference surface may be a detection of a response of the sample or the reference surface to the interaction field. Said detection of said response may comprise a detection of an optical near-field resulting from an illumination of said sample or reference surface by an optical field serving as interaction field, the respective cantilever probe having associated an aperture to serve as near-field optical microscopy probe.

At least one of said cantilever probes may have associated an interaction medium supply or an interaction medium receptacle for bringing or holding interaction medium in a region around at least an interaction portion of the respective cantilever probe and at least a portion of said sample or said reference surface near said interaction portion or the respective cantilever probe, said interaction medium bringing about or influencing said local interaction of the respective cantilever probe with the sample or the reference surface.

One may characterize the invention according to this aspect alternatively also as follows: It is provided a local probe measuring device for measuring local interactions between a cantilever probe arrangement and a sample, which comprises: a plurality of cantilever probes adapted to interact locally with a sample or a reference surface, a rigid mechanical coupling between respective base sections of said cantilever probes, a positioning arrangement adapted to commonly adjust for all of said cantilever probes a distance of the base section of the respective cantilever probe with respect to the sample or the reference surface, and a plurality of detection arrangements, each being associated or adapted to be associated to one particular of said cantilever probes and adapted to independently detect at least one of a deflection of said particular cantilever probe and a local interaction of said particular cantilever probe with said sample or reference surface. One of these cantilever probes may be identified as the first cantilever probe and another of these cantilever probes may be identified as the second cantilever probe mentioned above.

In particular, it is provided a local probe measuring device for measuring local interactions between a cantilever probe arrangement and a sample, which comprises: a plurality of cantilever probes adapted to interact locally with a sample or a reference surface, a rigid mechanical coupling between respective base sections of said cantilever probes, a positioning arrangement adapted to commonly adjust for all of said cantilever probes i) a distance of the base section of the respective cantilever probe with respect to the sample or the reference surface, ii) a first lateral coordinate of the base section of the respective cantilever probe with respect to the sample or the reference surface, and iii) a second lateral coordinate of the base section of the respective cantilever probe with respect to the sample or the reference surface, said first and second lateral coordinates defining the lateral position of the base section of the cantilever probe with respect to the sample or the reference surface, a plurality of detection arrangements, each being associated or adapted to be associated to one particular of said cantilever probes and adapted to independently detect at least one of a deflection of said particular cantilever probe, a torsion of said particular cantilever probe and a local interaction of said particular cantilever probe with said sample or reference surface, and a controller adapted to control or stabilize via said positioning arrangement for at least one of said cantilever probes at least one of said first and second lateral coordinates on the basis of detection results obtained for at least one of said cantilever probes via the respective detection arrangement.

Said controller may be adapted to control or stabilize via said positioning arrangement for at least one of said cantilever probes at least one of said distance, said first lateral coordinate, said second lateral coordinate and said local interaction on basis of detection results obtained for at least one other of said cantilever probes via the respective detection arrangement. Preferably, said controller is adapted to control or stabilize via said positioning arrangement for at least one of said cantilever probes said distance and at least one of said first lateral coordinate and said second lateral coordinate on basis of detection results obtained for at least one other of said cantilever probes via the respective detection arrangement. According to a highly prefered embodiment, said controller is adapted to control or stabilize via said positioning arrangement for at least one of said cantilever probes said distance, said first lateral coordinate and said second lateral coordinate on basis of detection results obtained for at least one other of said cantilever probes via the respective detection arrangement.

At least one of said cantilever probes may be a triangular cantilever probe. The triangular cantilever may have associated a detection arrangement is provided, which is adapted to measure a deflection of said triangular cantilever probe.

At least one of said cantilever probes may be a beam-shaped cantilever probe. The beam-shaped cantilever probe may have associated a detection arrangement which is adapted to measure at least one of a deflection and a torsion of said beam-shaped cantilever probe. Said detection arrangement may be adapted to measure a torsion of said beam-shaped cantilever probe. Preferably, said detection arrangement is adapted to measure both a deflection and a torsion of said beam-shaped cantilever probe substantially independently of each other.

According to one embodiment, a first beam-shaped cantilever probe and a second beam-shaped cantilever probe of said cantilever probes extend at an angle of about 90 degrees with respect to each other. A first and a second detection arrangement are provided, the first detection arrangement being adapted to measure at least a torsion of the first beam-shaped cantilever probe and the second detection arrangement being adapted to measure at least a torsion of the second beam-shaped cantilever probe. Preferably, said detection arrangements are adapted to additionally measure a deflection of the respective beam-shaped cantilever probes substantially independently of the torsion of said beam-shaped cantilever probe.

It is proposed, that a first of said cantilever probes is a beam-shaped cantilever probe, which is substantially softer with respect to torsion and bending as a second of said cantilever probes, and that a first and a second detection arrangement are provided, the first detection arrangement being adapted to independently measure a torsion and a deflection of the first cantilever probe and the second detection arrangement being adapted to measure at least a deflection of the second beam-shaped cantilever probe. Said second cantilever probe may be a triangular cantilever probe.

Preferably, said detection arrangements are based on at least one of an optical detection, a thermal detection, a capacitive detection, a piezo-electric detection and a detection of electronic tunneling. In particular, at least one of said detection arrangements may comprise an optical detection arrangement. In this respect it is suggested, that at least one of said detection arrangements comprises a position sensitive detector adapted to receive a laser beam reflected by a tip portion of the respective cantilever probe, the laser beam being emitted by an associated laser source.

According to one approach, a laser beam directed to the tip portion of one of the cantilever probes and the resulting reflected laser beam substanially extend in a longitudinal direction of the respective cantilever probe, if seen in a projection on a surface of said sample or on said reference surface or in a projection on a support surface for supporting said sample.

According to an other approach, a laser beam directed to the tip portion of one of the cantilever probes and the resulting reflected laser beam substanially extend in a direction orthogonal to the longitudinal direction of the respective cantilever probe, if seen in a projection on a surface of said sample or on said reference surface or in a projection on a support surface for supporting said sample.

For at least one of said cantilever probes the respective position sensitive detector may resolve an incidence position of the reflected laser beam on the detector only within one dimension. Preferably, for at least one of said cantilever probes the respective position sensitive detector resolves an incidence position of the reflected laser beam on the detector within two dimensions.

According to another aspect of the invention, a method of effecting local measurements referring to a sample is provided, which comprises: providing at least two local probes in a positional relation with respect to a sample or a reference surface, adjusting a respective measurement condition for at least one of said local probes on the basis of measurements effected with respect to at least one other of said local probes, and effecting a measurement with respect said at least one local probe with reference to said measurements effected with respect to said at least one other local probe. Preferably, said local probes are rigidly mechanically coupled with each other. It is to advantage, if said rigid mechanical coupling extends over a coupling path between said local probes having a path length in the order of magnitude as dimensions of the local probes itself. A local probe measuring device as defined above may be used.

It is suggested, that local measurement data are obtained comprising interaction data indicating a local interaction with said sample or reference surface sensed by at least one of said local probes and associated distance data indicating a distance relation of said at least one local probe with respect to said sample or said reference surface, said distance data being obtained or calibrated on the basis of measurements concomitantly effected with respect to at least one other of said local probes.

The method may comprise the step of scanning said local probes in a height direction associated with said sample or said reference surface.

Sensing interaction-distance-profiles indicating a dependency of a local interaction sensed by a respective local probe of a distance of said respective local probe with respect to said sample or said reference surface may give interesting information. Said interaction-distance profiles may comprise force-distance-profiles. Said interaction-distance profiles may comprise current-distance-profiles.

Thermal position fluctuations of at least one of said local probes may be detected. Said position fluctations may be detected for distance relations of said at least one local probe with respect to said sample or said reference surface, which are defined by measurements concomitantly effected with respect to at least one other of said local probes.

Said sample may be one of an atomic, molecular and macromolecular sample. Further, said sample may be a biological sample. An other possibility is, that said sample is a semiconductor sample. Further, said sample may be a magnetic storage disc type sample.

The method may comprise the step to functionalize at least one of said local probes with respect to the sample or the reference surface. Said functionalization may involve at least on of an attachment of functionalization material on the respective local probe, an chemical modification of at least a surface part of the respective local probe and an impressing an electric or magnetic field on the respective local probe. Said functionalization material may be molecular material. Further, said molecular material may be biological material.

It is suggested, that said molecular material comprises at least one protein. Said protein may be adapted to interact with at least one associated protein of the sample.

Further, it is suggested, that said molecular material comprises one of receptor molecules and ligand molecules.

Further, it is suggested, that said functionalization material is at least one of at least one single atom and at least one cluster of atoms.

At least one of an interaction field and an interaction medium may be provided in interaction relation with at least one of said local probes and with said sample or said reference surface. Said interaction field may be one of an electromagnetic field, an optical field, a static magnetic field and a static electric field. Said interaction medium may be one of a liquid and a gas or one of a mixture of liquids and a mixture of gases.

Said local probes and said sample or reference surface may be held under vacuum during said local measurements.

Said measurement condition may comprise a distance relation of the respective local probe with respect to the sample or the reference surface, said distance relation being adjusted on the basis of measurements effected with respect to at least one other of said local probes.

Preferably, said measurement condition comprises a distance relation and a lateral positioning relation of the respective local probe with respect to the sample or the reference surface, said distance relation and said lateral positioning relation being adjusted on the basis of measurements effected with respect to at least one other of said local probes.

Often it is sufficient, if said lateral positioning relation is adjusted with respect to only one lateral coordinate on the basis of measurements effected with respect to at least one other of said local probes. However, it is prefered, that said lateral positioning relation is adjusted with respect to two lateral coordinates on the basis of measurements effected with respect to at least one other of said local probes, wherein said two lateral coordinates define the lateral position of the local probe with respect to the sample or reference surface.

According to still another aspect of the invention, a method of effecting local manipulations referring to a sample is provided, which comprises: providing at least two local probes in a positional relation with respect to a sample or a reference surface, adjusting a respective manipulation condition for at least one of said local probes on the basis of measurements effected with respect to at least one other of said local probes, and manipulating said sample by means of said at least one local probe with reference to said measurements effected with respect to said at least one other local probe. Preferably,said local probes are rigidly mechanically coupled with each other. Said rigid mechanical coupling may extend over a coupling path between said local probes which has a path length in the order of magnitude as dimensions of the local probes itself. A local probe measuring device as defined above may be used.

Said sample may be one of an atomic, molecular and macromolecular sample. Further, said sample may be a chemical or biological sample.

Said manipulation may involve at least on of an streching, an unfolding and unbinding of molecular bonds of proteins or polymers or other biological or chemical molecules.

The method may comprise the step to functionalize at least one of said local probes with respect to the sample or the reference surface. Said functionalization may involve at least on of an attachment of functionalization material on the respective local probe, an chemical modification of at least a surface part of the respective local probe and an impressing an electric or magnetic field on the respective local probe.

Said functionalization material may be molecular material. Further, said molecular material may be biological material.

Said molecular material may comprise at least one protein. Said protein may be adapted to interact with at least one associated protein of the sample.

An other possiblity is, that said molecular material comprises one of receptor molecules and ligand molecules.

Said functionalization material may be at least one of at least one single atom and at least one cluster of atoms.

At least one of an interaction field and an interaction medium may be provided in interaction relation with at least one of said local probes and with said sample or said reference surface. Said interaction field may be one of an electromagnetic field, an optical field, a static magnetic field and a static electric field. Said interaction medium may be one of a liquid and a gas or one of a mixture of liquids and a mixture of gases.

Said local probes and said sample or reference surface may be held under vacuum during said local manipulations.

Said manipulation condition may comprise a distance relation of the respective local probe with respect to the sample or the reference surface, said distance relation being adjusted on the basis of measurements effected with respect to at least one other of said local probes.

Preferably, said manipulation condition comprises a distance relation and a lateral positioning relation of the respective local probe with respect to the sample or the reference surface, said distance relation and said lateral positioning relation being adjusted on the basis of measurements effected with respect to at least one other of said local probes.

Often it is sufficient, if said lateral positioning relation is adjusted with respect to only one lateral coordinate on the basis of measurements effected with respect to at least one other of said local probes. However, it is prefered, that said lateral positioning relation is adjusted with respect to two lateral coordinates on the basis of measurements effected with respect to at least one other of said local probes, wherein said two lateral coordinates define the lateral position of the local probe with respect to the sample or reference surface.

A local probe measuring device according to the invention, a local probe measuring method according to the invention and a local probe manipulation method according to the invention each open up options for many new applications which can hardly be foreseen at present. In the context of atomic force microscopy or scanning force microscopy and the like, some new applications are the following:

1) Samples, e.g. in biological applications, can locally be measured at effectively vanishing normal-forces between tip and sample. This is especially interesting for measuring specific protein interactions, e.g. ligand/receptor interactions, in a controlled way. This is an important feature for the application of SFM in drug screening applications.

2) The invention also allows for force-spectroscopy on proteins and polymers where contact between tip and sample can be reached at almost zero-force and thus minimal mechanical interaction between sample and sensor. The active control of the interaction sensor and sample surface distance opens up the possibility of measuring e.g. unfolding potentials of proteins with very soft levers or the unbinding of molecular adhesion bonds under constant force in liquid environments (compare: Evans, E. and Ritchie, K., BioPhys J., 1997, Vol 72, p. 1541-1555).

3) By employing levers for the interaction sensor with different and especially with very soft or hard spring constants it is now possible to measure interactions close as well as further away from the sample surface at Angstroem- und pN-resolution. For these measurements it is necessary to keep the interaction sensor at well defined distances from the sample surface for times which increase as the spring constant of the lever decreases. These times can reach up to seconds for the recording of time-series of the thermal position fluctuations of the sensor-tip in local potentials, which can be analyzed by correlation and spectral transforms. Using only the thermally excited amplitudes of the cantilever, one decreases the influence of the sensor on the sample and the danger of dissipating energy into the sample to a minimum and thereby reduces the danger of locally altering or even destroying the sample.

4) One option for implementing lateral scanning at well defined distances from the surfaces may be based on e.g. Si/SiN.sub.3 sample carriers, which would allow for atomically flat reference surfaces over which the distance sensor may be scanned laterally at constant normal force without changing the distance between interaction sensor and any locally decorated sample surface.

5) A multi-sensor system according to the invention allows a stabilisation at minimal interaction forces for attractive mode measurements in scanning force microscopy (atomic force microscopy).

6) A multi-sensor setup according to the invention can easily be adapted to flow chamber experiments, since thermal or mechanical disturbances can be compensated by the multi-sensor system. Since additional optical interference sensors are not necessary, the exchange of fluids in liquid cells becomes easier.

7) Instruments equipped with a multi-sensor system according to the invention are well suited for product control or general measurements under mechanically unstable conditions. The only limitation results from the speed of the feedback which compensates for these disturbances through the distance sensor force-distance feedback.

In the following, some embodiments of local probe measuring devices will be explained solely as examples and with reference to the figures. Further, some examples of applications of local probe measuring devices according to the invention will be given.

FIG. 1 is a schematic diagram of a local probe measuring device according to a first embodiment of the invention having two local probes.

FIG. 2 shows a plurality of cantilever probes to be used as local probes which are integral parts of a cantilever substrate, two of those cantilever probes being illuminated by laser radiation to detect displacements of the respective cantilever probe.

FIG. 3 shows schematically a near-field optical microscopy probe of the cantilever type, which can be used for effecting scanning near-field optical microscopy (SNOM) measurements.

FIG. 4 shows three schematic diagrams illustrating examples of measurements which can be effected with a local probe measuring device according to the invention of the scanning force microscopy (SFM) or atomic force microscopy (AFM) type.

FIG. 5 shows measurement results obtained with a cantilever probe measuring device according to the invention which refer to thermal position fluctuations of a cantilever probe for twominute distances of the respective cantilever probe with respect to a surface.

FIG. 6 shows further measurement results obtained with the cantilever probe measuring device referring to thermal position fluctuations of the respective cantilever probe for so-called "soft contact" and so-called "hard contact" of the cantilever probe with the surface.

FIG. 7 shows schematically a multiple local probe device with two sensors in an enlarged front view (FIG. 7a) and in a side-view (FIG. 7b).

FIG. 8 is a schematic diagram of a local probe measuring device according to an other embodiment of the invention having two local probes.

FIG. 9 shows schematically a multiple local probe device with three sensors, which are used simultaneously. Two of the sensors serve to stabilize and control the measurement conditions of the third sensor.

FIG. 10 shows schematically a multiple local probe device with two sensors, which are used simultaneously. One of the sensors serves to provide the same control and stabilization as the two sensors of the arrangement according to FIG. 9.

FIG. 11 shows schematically a multiple local probe device with three sensors, which are used simultaneously. Two of the sensors serve to stabilize and control the measurement conditions of the third sensor.

FIG. 12 shows schematically a multiple local probe device with four sensors. Three of the sensors or all four sensor are used simultaneously. Two or three of the sensors serve to stabilize and control the measurement condtions of one other of the sensors.

FIG. 13 shows schematically two cantilever sensors in a front view (FIG. 13a) and in a view from above (FIG. 13b). On basis of an optical detection of a bending and torsion of the cantilever sensors by means of laser beams reflected therefrom, the sensors serve to stabilize and control the measurement condtions of at least one other sensor not shown.

FIG. 14 shows the two cantilever sensors of FIG. 13 in a front view (FIG. 14a) and in a view from above (FIG. 14b) for a different detection situation.

FIG. 1 shows a multiple local probe measuring device according to one embodiment of the present invention. The local probe measuring device 10 has a first local probe 12 and a second local probe 14, which are rigidly connected with each other by means of a connection part 16, possibly a substrate which is integral with the local probes 12 and 14. The local probes may be of the cantilever type. In this case, the respective local probe may comprise a beam cantilever (cf. cantilever 18 in FIG. 2) or a triangular cantilever (cf. cantilever 20 in FIG. 2) having, at a free end, a tip serving to probe a sample 22. In case of cantilever probes, the local probe measuring device may also be denoted as cantilever probe measuring device.

FIG. 1 shows schematically the general structure of a multiple local probe measuring device according to an example independently of any particular local probe measuring technique. For example, the local probe measuring device may be used for effecting atomic force microscopy (AFM) or scanning force microscopy (SFM) measurements. Other examples are lateral force microscopy (LFM) measurements, scanning tunneling microscopy (STM) measurements, and scanning near-field optical microscopy (SNOM) measurements, to name but a few local probe techniques. However, the local probe measuring device 10 shown in FIG. 1 may as well be adapted to effect any other local probe microscopy measurements, such as electric field/force microscopy (EFM) measurements, magnetic field/force microscopy (MFM) measurements, scanning near-field acoustic microscopy (SNAM) measurements, magneto-tunneling microscopy measurements, and the like, which require a local probe held mechanically in the vicinity of a sample.

Referring again to FIG. 1, the device 10 comprises a bracket 24 holding the connecting part 16 together with the local probes 12 and 14 over the sample 22, which is arranged on a sample stage 26. The sample stage 26 and, accordingly, the sample may be finely positioned with respect to the two local probes 12 and 14 by means of a piezo transducer 28, which is adapted to move the sample stage 26 with the sample 22 in X-, Y-, and Z-directions.

A coarse approach and positioning of the sample 22 with respect to the local probes 12 and 14 may be effected by means of a coarse positioning arrangement 30, possibly comprising a support plate mounted on a tripot adjustable by means of slow-motion tangent screws or/and an electrical motor (e.g., a DC motor) coupled by means of a gear (possibly a slow-motion tangent screw or the like) with the tripot.

If one considers one of the two local probes 12 and 14, the respective local probe, on the one hand, and the sample 22, on the other, are located at opposite ends of a mechanical linkage loop comprising the connecting part 16, the bracket 24, the coarse positioning arrangement 30, the piezo transducer 28, the sample stage 26, and any further mechanical connection components between the mentioned parts, such as intermediate members 34, 36 between the course positioning arrangement 30, the piezo transducer 28, and the sample stage 26. If a distance between one of the local probes and the sample is adjusted by means of the piezo transducer 28 and the coarse positioning arrangement 30, any mechanical instability of the mentioned mechanical loop and any piezo drift of the piezo transducer will cause variations of the adjusted distance between the respective local probe and the sample.

According to a prior-art approach, one could use detection results obtained for the respective probe by means of a detector (detector 40 for probe 12, and detector 42 for probe 14) to stabilize the distance for the respective (the same) probe. For example, one could adjust the distance between probe 12 and sample 22 by means of the coarse positioning arrangement 30 and the piezo transducer 28 and use the detection result obtained by the detector 40 for this probe to control the distance of this probe (probe 12) with respect to the sample 22 by means of a feedback control loop 44 comprising the piezo transducer 28, the probe 12, the probe detector 40, and a feedback transformer 46. The feedback transformer 46 may comprise a high-voltage amplifier arrangement adapted to translate a control variable into a corresponding driving voltage sent to the piezo transducer 28.

This approach works quite well if the detection signal received for the respective local probe (in the example, probe 12) is strong enough with respect to noice. Even if the signal is strong enough to obtain the desired feedback control of the distance between the local probe and the sample, this approach has the advantage that there may be several interactions between the sample and the local probe, which might contribute to the detection signal. In the case of an atomic force microscopy probe (possibly of the cantilever type), for example, the forces between the probe tip and the surface of the sample may result from a multitude of interactions so that the central contrast mechanism on which the high resolution of atomic force microscopy is based will often become distorted.

The explained prior-art approach of controlling the distance of a measuring probe will completely fail if the detection signal received for the local probe is too small with respect to noise so that there is no signal on which the feedback control can be based.

In realization of an approach according to the present invention, the multiple local probe measuring device 10 has a plurality of local probes, namely the two local probes 12 and 14, with the detection results obtained for one of the local probes being used for the feedback control of the distances of both local probes with respect to the sample and the desired measurement information is obtained via the other local probe. The desired measurement information may comprise, for example, information with respect to the probe interaction versus distance between the respective probe and the sample surface.

In the diagram of FIG. 1, probe 12 is used for the feedback control of the distances of both probes 12 and 14 with respect to the sample surface and the detection results of probe 14 are evaluated to obtain the desired measurement information. As shown in FIG. 1, the probes 12 and 14 may have different distances with respect to the sample. In the situation shown in FIG. 1, the probe 14 has a larger distance with respect to the sample than probe 12. Accordingly, any interaction between the probes and the sample, which decreases with the distances, will give a stronger detection signal for probe 12 than for probe 14. For example, an interaction between sample 22 and probe 14 or another influence on probe 14 which gives a rise to a detection signal which is not strong enough for a feedback control of the distance, may give rise to a much higher detection signal for the other probe (probe 12) and may, accordingly, enable a feedback control of the distances.

Assuming that the local probes 12 and 14 are cantilever probes adapted to atomic force microscopy, FIG. 1 shows a situation in which probe 12 contacts the sample surface with relatively high reaction force (for example, 100 pN), giving rise to a corresponding deflection of the cantilever and a detection signal sufficiently strong to enable feedback control, whereas the other local probe is located well above the sample surface and interacts with the sample only weakly, so that only a weak deflection or weak deflections of the cantilever of probe 14 corresponding to interaction forces of a few pN may take place, which give rise to only weak detection signals possibly not sufficiently strong for enabling a feedback control of the distance. The interaction forces may be in the range of thermally induced fluctuation forces on the cantilever.

According to the approach of the invention, measurements of such weak interactions on a local probe are enabled under stabilized measurement conditions even for a long time, since the feedback control is based on the detection signals obtained for the other local probe which strongly interacts with the sample. Any piezo drift or mechanical or thermal instability of the mechanical connection loop between the probes 12 and 14, on the one hand, and the sample 22 on the other hand may be compensated by the feedback control stabilization of both local probes with respect to the sample obtained on the basis of the detection signal obtained for one local probe. Accordingly, the other local probe (probe 14) has stabilized measurement conditions (i.e., a stabilized distance with respect to the sample) to allow long-time measurements at high stability. Accordingly, even thermal fluctuations of the position (possibly deflection) of the local probe 14 may be analysed.

Referring again to the connection part 16 rigidly connecting the two local probes 12 and 14, the following should be mentioned. For high requirements with respect to the stabilisation, the connection part should be characterized by a coupling path between the two local probes, which has a path length in the order of magnitude of dimensions of the local probes themselves. Further, the rigidity of the mechanical coupling effected by the connection part should be such that it has associated a resonance frequency well above a limiting frequency associated with the detectors 40 and 42, so that any vibrations of the two local probes with respect to each other induced by vibrations of the connection part will not be detected. Further, if a resonance frequency can be associated with the local probes themselves, it is preferred that the resonance frequency associated with the connection part lies well above the resonance frequencies of the local probes.

Evidently, there still may occur several interactions between the local probe used for distance stabilization (probe 12 in FIG. 1) and sample 22. Often, however, there may be an interaction regime in which one of those interactions dominates the other interactions so that, in practice, there will be no significant distortion of the contrast mechanism relevant to the resolution of local probe microscopy. In any case, one might locate the sample in such a way with respect to the local probes so that only the local probe used for obtaining the measurement information interacts with the sample and the other local probe, which is used for the feedback control of the distances, interacts with a reference surface. In this case, there will be a well-defined interaction between the local probe used for the feedback control (in the following also referred to as "distance sensor") and the reference surface. Accordingly, the measurement condition for the other local probe (in the following also referred to as "interaction sensor") may be defined with reference to the detection results obtained for the distance sensor, allowing stabilized measurements at well-defined distances from the sample, for example, to obtain force-distance profiles without any distortions of the "distance axis" because of multiple interactions between the distance sensor and the sample.

The distance between the two local probes 12 and 14 in a height direction associated with the sample (in FIG. 1, the Z-direction) may be adjustable. In case of cantilever probes used in atomic force microscopy, a distance (height) of about 10 to 20 .mu.m may be appropriate. However, also other height differences (for example, about 1 to 100 .mu.m) may be appropriate depending on the sample and the measurement situation. The height difference may be adjustable, for example, by tilting a short face of a substrate integral with the cantilever probes against the sample surface.

Referring again to FIG. 1, the local probe measuring device 10 comprises a controller 48 adapted to control the piezo transducer via the feedback transformer 46. For example, the controller 48 sets a setpoint value (a desired value) representing a setpoint distance of local probe 12 with respect to the sample. The feedback control loop regulates the Z-position of the sample stage via the piezo transducer 28 so that a deviation between an actual value and the setpoint value approaches zero. The control characteristics of the feedback control loop may be selected as desired and may comprise at least one of an integral, differential, and proportional control characteristic.

The feedback transformer 46 may, at least in part, be realized by the controller 48 itself. This applies in particular when the controller is implemented on the basis of a digital processor. However, the feedback transformer 46 and the feedback control loop 44 may as well be implemented on the basis of analog electronic components. With respect to the setting of the setpoint value, the controller may even be implemented by means of a simple potentiometer or the like. Of course, a digital implementation of the controller and of the feedback control loop according to the state of the art is preferred.

The control scheme described so far may be supplemented by a second feedback control loop on the basis of measurement data referring to local measurements effected by the local probe serving as "interaction sensor", i.e. the "other local probe". This second feedback control loop should be characterized by a time constant shorter than a time constant characterizing the first control loop on the basis of measurement data referring to local measurements effected by the local probe serving as "distance sensor". One can think of the two feedback control loops as feedback control sub-loops of an overall feedback control loop. According to this supplemented control scheme, the feedback control on the basis of measurement data referring to the "distance sensor" may provide for a compensation of thermal drift or other drifts characterized by a rather long time constant, whereas the additional feedback control loop on the basis of measurement data referring to the "interaction sensor" may allow a detection of fine structures of the sample, i.e. topological details of the sample surface.

The controller 48 receives measurement data referring to the local measurements effected by the two local probes 12 and 14 from the detectors 40 and 42. The received measurement data can be evaluated with respect to the control of the piezo transducer, for example, to determine the appropriate setpoint value. Further, the received measurement data can be processed by the controller to obtain the desired measurement information. This information, as explained, is primarily contained in the measurement data referring to local probe 14 serving as an interaction sensor. However, also the measurement data referring to local probe 12 serving as a distance sensor may be evaluated to obtain the desired measurement information. This measurement information or/and the raw data obtained from the detectors 40 and 42 may be stored in any storage device and may be displayed on a monitor or printed via a graphics printers or the like.

So far, only a control of the distances of the local probes 12 and 14 with respect to the sample 22 has been considered. With this control, a relative movement of the local probes 12 and 14 with respect to the sample 22 in the Z-direction can be effected, for example, to obtain force-distance profiles. Further, the controller 48 is adapted to control the piezo transducer 28 to effect a lateral scanning or sampling of the sample 22 in the X- and Y-directions. With this lateral scanning, a topographic imaging of the sample by the probes 12 and 14 may be effected. In case that the sample that has a planar surface or any changes of the sample height occur over lateral distances larger than the lateral distance between the two local probes 12 and 14, the provision of an additional distance sensor allows easy scanning of the sample by the interaction sensor in a "distance mode" or "lift mode" in which the respective distance between the interaction sensor and the sample surface can be maintained at high stability. This "distance" mode may even be used in case of a sample having height variations with lateral dimensions in the order of the lateral distance between the two probes. In such a case, one can, in a first step, measure the topography of the sample by means of the distance sensor. After this first pass across the sample surface, the distance of the interaction sensor 14 can be controlled at high stability on the basis of the measurement data obtained during the first pass, so that in a second pass across the sample surface, the interaction between the sample surface and the interaction sensor can be measured for a defined distance between the interaction sensor and the sample surface. Generally, the stabilization of distance relations or generally of measurement conditions, on the basis of measurement data obtained for an additional local probe can be used advantageously for any measurement scheme of the respective local probe microscopy technique.

A central requirement for the measurement scheme according to the invention described above, is independent detection of measurement data for the distance sensor and the interaction sensor. If there is a plurality of distance sensors, for example, three or more sensors arranged around one interaction sensor, independent detection for all sensors is desired. However, there might be cases where independent detection for the distance sensors or a plurality of distance sensors, on the one hand, and the interaction sensor or a plurality of interaction sensors, on the other, is sufficient for certain measurement situations.

An independent detection of measurement data for a plurality of local probes can be obtained for all detection principles used in the context of local probe microscopy. In the case of deflecting cantilever probes, for example, one might use piezo-electrical cantilevers, each of which produces its own electrical deflection signals used for the feedback control or measurements of interactions with the sample, respectively.

Further, independent optical detection of cantilever deflections is possible. FIG. 2 shows a cantilever substrate having a plurality of cantilevers. There are two laser beams 50 and 52, one being directed against the back of the triangular cantilever 20 and the other being directed against the back of the neighboring triangular cantilever 54. For example, cantilever 20 may serve as a distance sensor and cantilever 54 as an interaction sensor.

The laser beams are reflected by the cantilever backs onto a respective position-sensitive sensor, for example, a segmented photo-diode, giving rise to deflection signals representing the deflection of the respective cantilever. Since both cantilevers have associated there own laser beam and their own position-sensitive detector, the deflections of both cantilevers may be detected independently of each other.

Besides the possible configurations mentioned so far, many other configurations are possible. For example, it is not necessary that the distance sensor and the interaction sensor are of the same local probe microscopy type. For many measurement situations, it will be appropriate to use local probe microscopy probes of the same probe type for the distance sensor and the interaction sensor, for example, two atomic force microscopy probes or two scanning tunneling microscopy probes and the like. In other situations, it might be appropriate to use different local probe microscopy probes for the distance sensor and the interaction sensor, for example, a local probe of the scanning tunneling microscopy type for the distance sensor and a local probe of the atomic force microscopy or scanning force microscopy type for the interaction sensor. Correspondingly, the same applies to cases where a plurality of interaction sensors or/and a plurality of distance sensors are used.

Further, the detection principle according to which data representing the local measurement effected by the respective local probe are detected may be different or may be the same. Generally, any detection principle which appears appropriate with respect to the type of the respective local probe can be chosen to obtain measurement data representing the local measurements effected by the respective local probe. In case of the cantilever probes shown in FIG. 2, two cantilevers are simultaneously probed by laser beams to measure the deflection of the respective cantilever. Other detection principles to measure cantilever deflections are known and need not be enumerated here. In case of local probes of the scanning tunneling microscopy type, one would measure a tunneling current resulting from a quantum mechanical interaction between a probe tip and the sample.

In case of local probes of the scanning near-field optical microscopy type, an optical far-field resulting from a near-field illumination of a sample through a sub-wavelength sized aperture has to be detected to obtain a resolution beyond the Abbe diffraction limit. Such a measurement situation is shown in FIG. 3. A cantilever 100 serving as a local probe has an aperture 102, which is illuminated via an optical fiber 104 by optical radiation having a longer wavelength than the size of the aperture. An optical near-field on the other side of the end portion of the cantilever interacts with the sample 106 and gives rise to a far field which can be detected by a detector 108. The height of the aperture end portion of the cantilever 100 over the sample 106 can, according to the principles of the invention explained above, be controlled on the basis of interactions of another local probe, preferably another cantilever probe serving as a distance sensor. The cantilever 100, or even only the aperture 102, may be regarded as an interaction sensor in the sense of the principles of the invention explained above, irrespective of the fact that in case of a measurement situation as shown in FIG. 3, there no detection of data referring to the interaction sensor per se, but a detection of data referring to an interaction between the interaction sensor (the aperture 102), an optical field (generally an interaction field), and a sample, with no direct interaction between the detector and the interaction sensor.

Other interaction fields influencing or bringing about an interaction between a local probe and a sample comprise electrostatic fields, magnetic fields, and electromagnetic fields. Further, an interaction between a local probe and a sample may be influenced or even brought about by interaction media (for example, fluids, gases, gas mixture or liquids) which interact with the sample or/and with the respective local probe. To hold such an interaction medium, the device shown in FIG. 1 has a medium receptacle symbolized by broken line 110. Dependent on the sample, the interaction medium may be simply water or air.

The range of possible measurements which can be effected by using a local probe measuring device having a plurality of local probes can be extended significantly if probes are used which are functionalized with respect to the sample. For example, it is possible to bind sensing molecules to an AFM tip or to colloidal fields attached to an AFM cantilever. The molecules bound to the AFM probe can then be used as chemical sensors to detect forces between molecules on the tip and target molecules on a surface. This allows extremely high-sensitivity chemical sensing. As with chemically modified probes, one may tailor AFM probes to sense specific biological reactions. One could, for example, the binding forces of individual ligand-receptor pairs. To this end, an AFM probe tip may be coated with receptor molecules. Another example is the measurement of interaction forces between complementary DNA strains. To this end, one could bind DNA to a sample surface, on the one hand, and to a spherical probe attached to an AFM cantilever, on the other. There are many other examples of possible applications. Reference is had to the numerous literature about scanning probe microscopy and the different probing technologies developed so far. For all measurement situations in which the measurement results depend on the distance of the respective local probe of a sample, the principles of the present invention which allow independent measurement of the distance can be used advantageously. More generally: in any local probing technique in which well-defined local measurement conditions are desirable, the principles of the present invention which allow stabilization of these local measurement conditions on the basis of measurement data referring to local measurements effected by at least one other local probe can be used advantageously. If these local measurement conditions refer not only to the distance or to other parameters, the additional local probe can be denoted as measurement condition sensor instead of distance sensor.

In the following, some specific examples of preferred applications of a local probe measuring device of the atomic force microscopy type according to the invention will be given with reference to FIGS. 4 to 6. It is assumed that cantilever probes are used as local probes.

FIGS. 4a) and b) show schematically examples of force spectroscopy measurements. FIG. 4a), in the upper of the diagram, shows a force-distance profile which can be obtained if a cantilever substrate 200 is moved towards a sample surface 202 at a defined velocity until the probe tip 204 contacts the surface 202 and is retracted thereafter. During this positioning cycle, the force detected by the cantilever is recorded as a function of the distance between the substrate 202 and the surface. This distance can, according to the invention, be calibrated or measured by means of an additional cantilever serving as a distance sensor, since the height distance between the sensors can be measured with high accuracy, for example in advance of the spectroscopic measurements. Accordingly, the cantilever 206 having the tip 204 shown in FIG. 4 can be denoted as an interaction cantilever.

The shape of the force-distance profile shown in the diagram can be explained as follows. Near the sample surface there is a potential resulting from the interaction between the sample and the cantilever tip. The force sensed by the cantilever is given by the gradiant of this potential as a function of the distance between the sample surface and the tip. Near the sample, the tip jumps into contact with the sample if the potential has a gradient larger than the elastic force constant of the cantilever. As soon as there is a hard contact between the tip and the sample surface, the force on the cantilever is primarily governed by the spring constant of the cantilever.

During the retraction of the substrate with the cantilever, there are generally larger forces acting on the tip, which give rise to the hysterisis shown in the force-distance profile.

In the lower part of FIG. 4a), the gap between the tip and the surface is shown as a function of the distance between the substrate and the surface.

FIG. 4b) shows a schematic example of an intra-molecular force spectroscopy measurement result. During intra-molecular force spectroscopy measurements, molecules such as DNA strains, proteins, and so on, are stretched between a surface and an atomic force tip. The tension forces acting on the cantilever are recorded as a function of the distance. According to the invention, the distance can be measured or calibrated at high precision on the basis of deflection measurements relating to an additional cantilever, the distance cantilever. Another example, are inter-molecular force spectroscopy measurements which can be used, for example, for the measurement of adhesion forces between cells, binding forces between specific molecules, for example, ligand-receptor combinations.

FIG. 4c) schematically shows the behavior of an oscillating cantilever as a function of a lever distance with respect to a surface. The cantilever is externally driven to oscillate at a certain frequency. The interactions between the oscillating cantilever and the sample, in particular, the sample surface, lead to a dependency of the oscillating amplitude of the distance. This dependency can be evaluated to obtain information about the interactions. According to the invention, the distance can be measured or calibrated on the basis of an additional cantilever, the distance sensor.

Instead of an oscillation of the cantilever by external driving, one can also use the thermal noise, i.e., thermal position fluctuations of the cantilever, to obtain information about the interaction between the cantilever and the sample surface.

FIG. 5, in diagram a), shows a frequency spectrum representing thermally induced vibrations of a cantilever at a distance 1000 nm of a surface. Diagram b) shows a corresponding positional autocorrelation function. Diagram c) shows a corresponding positional autocorrelation function for a distance of only 100 nm. From the measurement data, a number of parameters characterizing the thermally induced vibrations of the cantilever may be calculated, for example, a resonance frequency and a damping coefficient.

Since thermal noise measurements require relatively long measurement periods, it is very important to compensate any thermal drift to maintain stable measurement conditions, in particular, with respect to the distance. According to the invention, this can be effected by means of a second cantilever, the distance sensor. Further, since there are changes of the thermally induced cantilever oscillations on a minute distance scale, it is very important to measure at well-defined distances. According to the invention, this can be effected via the additional cantilever, the distance sensor.

The high sensitivity of noise measurements for interactions between the cantilever and the surface and, possibly, a surrounding medium can be seen, in particular, in FIG. 6. Diagrams a) and b) show a noise spectrum and a corresponding positional autocorrelation function for a so-called "soft contact" of the cantilever tip on the surface, i.e., in this case, forces between the surface and the cantilever lower than 20 pN, whereas diagrams c) arid d) show the spectrum and the corresponding positional autocorrelation function for a so-called "hard contact" between the cantilever tip and the surface, i.e., forces above 500 pN between the cantilever and the surface. If a cantilever probe measuring device according to the invention is used, stable measurement conditions (for example, defined "soft contact" conditions) can be maintained even over a long measurement period, since at least one additional cantilever, the distance sensor, allows a defined adjustment of the distance via feedback control.

Another embodiment of a multiple local probe measuring device according to the invention is shown in FIG. 7. Some aspects of the invention and some advantages which may be achieved on basis of the invention are summarized as follows with reference to FIG. 7:

According to the invention it is possible to eliminate out-of-plane drift, i.e. drift and noise in the vertical direction with respect to the sample. To this end, a local probe device having multiple sensors is used. For effecting measurements and the like, the multiple sensors are used simultaneously.

For example, after the distance sensor 12 in FIG. 7 (in the following and in FIG. 7 also denoted as D-sensor) has made contact with the surface S (the surface of a sample or a reference surface), it is possible to control the distance d between this and all other sensors of the same substrate carrier and the surface S with a typical atomic force microscopy (AFM) detection setup.

The enlargement (FIG. 7a) shows the details of the local probe arrangement as it was described above. The distance between the measurement or interaction sensor 14 (in the following and in FIG. 7 also denoted as M-sensor) and the sample surface can be actively controlled with local probe resolution as soon as the D-sensor has made contact with the surface. At this point the M-sensor can (but by no means must) be some .mu.m above the sample surface if the geometry is chosen appropriately. The two tasks of measurement and distance control are split up between the two sensors. Here it is assumed that the sensors are provided in the form of levers or cantilevers.

The high stability typical for contact mode AFM is not only kept but translated to all other non-contacted sensors on the array. The distance lever (D-lever) will detect all noise that would change the distance between sensor array and sample and will control and stabilize it according to the specifications of the feedback. All out-of-sample plane drift components can therefore be compensated completely.

The M-lever signal may be used to do measurements at any distance from the surface for any lengths of time as well as in contact with the surface at normal forces determined only by the sensitivity of the detection system and the thermal noise amplitude of the cantilever used. It is not dependent on the interaction characteristics of the M-lever with the sample and neither is it altered by the way a feedback would react to the M-lever signals.

Additionally to the control or stabilization of the distance d, it may be provided for a control or stabilization of the lateral position of the M-sensor, possibly the M-lever. According to a particular aspect of the invention, the control or stabilization of the lateral position of at least one M-sensor is effected on basis of detection results obtained for at least one additional sensor sensitive to relative lateral movements between the additional sensor and the sample or reference surface. This additional sensor may be denoted as lateral drift sensor or lateral position sensor or as L-sensor. Possibly, the L-sensor simultaneously is sensitive also to the distance d and by use of an appropriate detection arrangement the information needed for the distance control or stabilization and the information needed for the lateral positional control or stabilization can be obtained independently of each other. In this case, the respective sensor is appropriately denoted as D/L-sensor and an additional D-sensor for the control and stabilization of the distance is not necessary.

Such a situation is exemplified in FIG. 8 which is based on FIG. 1. Probe 12, i.e. the D/L-sensor, is used for the feedback control or stabilization of the distances of both probes 12 and 14 with respect to the sample surface and for the feedback control or stabilization of the lateral position of both probes 12 and 14 with respect to the sample surface. As in FIG. 1, detection results referring to probe 14 (the M-sensor) are evaluated to obtain the desired measurement information. The feedback control or stabilization of the lateral positions comprises a feedback control or stabilization of the respective lateral position of both local probes with respect to one lateral coordinate (possibly the x- or the y-coordinate in FIG. 7) or a feedback control or stabilization of the respective lateral position with respect to two lateral coordinates (possibly the x- and the y-coordinate in FIG. 7), which completely define the lateral position of the respective local probe with respect to the sample (or a reference surface).

Possibly, two sensors sensitive to the lateral position are provided, one for obtaining the information needed for the lateral positional control or stabilization with respect to one lateral coordinate (possibly the x- coordinate) and one for obtaining the information needed for the lateral positional control or stabilization with respect to the other lateral coordinate (possibly the x-coordinate). If the axes of a reference coordinate system are appropriately chosen, these sensors may appropriately be denoted as X-sensor and Y-sensor or--if also the distance information can be obtained--as D/X-sensor and D/Y-sensor.

Accordingly, in addition to eliminating the out-of sample plane drift and noise as described before, the invention further makes it possible, to eliminate also all in-plane drift between the absolute positions of the M-sensor and the point facing it along the vertical axis on the sample surface by using one or more additional sensor(s) (possibly AFM cantilever sensor(s)) as L-sensor(s) or D/L-sensor(s).

An embodiment of a Multiple Sensor Lateral Stabilization System (MSLSS) in accordance with the invention is shown in FIG. 9. The system has a M-sensor in the form of a triangular cantilever (M-lever) and a D-sensor in the form of a triangular cantilever (D-lever) and a L-sensor in the form of a beam-shaped cantilever (L-lever). The D-lever serves to control the height or distance and the L-lever serves to detect lateral drifts along the y-axis and may accordingly be denoted as Y-sensor.

The embodiment of FIG. 9 employs the high sensitivity of a non-triangular, i.e. beam-shaped AFM lever to torsional forces. These torsional forces act on the lever, when the lever contacts the surface of the sample or the reference surface and the lever and the surface move relatively to each other, the movement having a movement component orthogonal to the longitudinal direction of the lever. With this one can detect and therefore control the in-plane, i.e. the lateral drifts, by using a proper feedback control.

The single L-sensor (the beam-shaped lever) is used to control the lateral drift of the sample along one in-plane axis (here the y-axis). The D-lever will control the height and while this is done, the L-lever, which is much softer than the D-lever with respect to torsional forces, can detect any lateral drifts along the y-axis. Such a beam-shaped cantilever for the use as L-sensor is readily available on commercial substrates. According to the geometry of commercial substrates, the respective cantilever can be used to correct the drift-components that change the sample's lateral position only along the array's base.

For the detection of the torsion of the L-lever and the deflection of the D-lever, a respective optical detection arrangement is provided which is based on detecting a deflection of a laser beam reflected from the respective lever because of a bending or torsion of this lever. The optical detection arrangement associated to the L-lever comprises a position-sensitive photo diode 200 for detecting the deflection of the laser beam 202. The optical detection arrangement associated to the D-lever comprises a position-sensitive photo diode 204 for detecting the deflection of the laser beam 206. According to FIG. 9, the laser beams shine on the levers along their longitudinal axis, before the beams are reflected onto the detectors 200 and 204.

Another embodiment of a Multiple Sensor Lateral Stabilization System (MSLSS) in accordance with the invention is shown in FIG. 10. The system has a M-sensor in the form of a triangular cantilever (M-lever) and a D/L-sensor in the form of a beam-shaped cantilever (D/L-lever). The D/L-lever serves to control the height or distance and to detect lateral drifts along the x-axis and accordingly may also be denoted as D/X-lever.

According to FIG. 10, a position sensitive detector 210 for the laser beam 212 reflected from the D/L-lever is used, which can simultaneously detect the bending (representing the distance) and the torsion (representing the lateral drift along the x-axis) of the D/L-lever. By substituting the height or distance signal coming from this L-lever for the one from a separate D-lever (not shown here), one has the ability to control one axis of lateral drift and the vertical drifts with just one lever. Accordingly, a separate D-lever is not needed. As detector 200 a split quadrant photo-diode may be used, as shown in FIG. 10.

However, this use of just one D/L-lever has the drawback that lateral drift along the long lever axis will induce bending of the lever that cannot be distinguished from height changes without an additional signal.

In order to detect drift in both lateral directions, there are e.g. the following possibilities: i) As L-sensor a L-lever may be used which is much softer than the D-lever with respect to torsion and bending (FIG. 11). ii) Two properly oriented beam-shaped cantilever sensors are used, one of which serves to detect drift in the first lateral direction and the other serves to detect lateral drift in the second lateral direction (FIG. 12). If the lateral directions correspond to the x- and y-directions (as in FIG. 12 ), the two levers are appropriately denoted as X-lever (or L.sub.X -lever) and Y-lever (or L.sub.Y -lever).

It should be emphasised, that the examples of FIGS. 11 and 12 serve to exemplify the principle of lateral control and stabilization. The concept of the invention can be realized with various other geometries as well as other types of local probe sensors.

According to the setup of FIG. 11, a D-lever and a separate L-lever are used. The L-Lever is a non-triangular lever, which is particularly sensitive to torsional forces, i.e. drift in the direction of y. One can get a full set of lateral drift signals, i.e. (x,y), because the L-lever is much softer not only with respect to torsion but also with respect to bending than the D-lever. In this case, a lateral drift along x will cause bending of the L-lever and accordingly be detectable with the L-lever. Accordingly, the lateral drift along x can be compensated for before it changes the height signal of the D-lever.

According to the setup of FIG. 12, another configuration to detect both in-plane drift components is used. Instead of using one beam-shaped and one triangular lever, two non-triangular L-cantilevers are used. As mentioned already, the two beam-shaped (non-triangular) cantilevers are very sensitive to torsional forces. To detect lateral drift along the x and the y axis both, the two L-cantilevers are oriented at 45.degree. with respect to the substrate and at 90.degree. with respect to each other. A corresponding sensor array can be fabricated on basis of the same technology conventionally used for substrates which are commercially available.

FIG. 12 shows a possible full configuration of levers on a single chip. The (x,y,d)-position of the M(easurement)-lever will be controlled by the D-lever, the X- or L.sub.X -lever and the Y- or L.sub.Y -lever. As explained in the following, the d-position can also be controlled artifact-free by using the d-signals from the two L-levers (which accordingly may be denoted as D/X- and D/Y-levers).

By shining the laser beam onto the L-levers along their long axis, one can detect height and torsional (lateral x- and y-) signals. Since the two L-sensors are oriented at 90.degree. with respect to each other, they deliver two independent torsional signals capable of detecting drifts along the two directions in the sample-plane. Because each L-lever supplies an isolated torsional signal along the normal force axis of the other L-lever, this setup allows to eliminate artifacts in the normal-force detection and therefore in the height control arising from drifts along the long lever axis, as they could still occur in the situation of FIG. 10. The detector 200 (e.g. a split quadrant photo diode) delivers a torsion signal representing the drift along the y-axis and a bending signal representing the distance d. The detector 210 (e.g. a split quadrant photo diode) delivers a torsion signal representing the drift along the y-axis and a bending signal representing the distance d. According to a more detailed analysis, there is a lateral drift term and a distance term [d] in the bending signal of the respective detector. The lateral drift term [d(x)] of the bending signal of detector 200 refers to lateral drift along the x-axis. The lateral drift term [d(y)] of the bending signal of detector 210 refers to lateral drift along the y-axis. The control effected on basis of the torsion signal of detector 200 allows to eliminate the lateral drift term of the bending signal of detector 210, so that the bending signal basically only has the distance term [d]. The control effected on basis of the torsion signal of detector 210 allows to eliminate the lateral drift term of the bending signal of detector 200, so that the bending signal basically only has the distance term [d]. Accordingly, there is no need for a separate D-lever.

The setup of FIG. 12 is especially useful for larger vertical scans, since the height detection signal will stay linear for comparatively large changes in the distance d.

Instead of shining the lasers on the L-levers along the long axis of the levers, one can alternatively choose such an arrangement that the lasers shine on the L-levers at a 90.degree. angle. This makes the detection system more sensitive to lateral drifts. However, in this case the height signal will have only a short linear range so that this arrangement should only be used for small vertical scans.

The arrangement with propagation of the laser beam along the longitudinal axis of the respective L-lever as in FIG. 12 is shown in a front view in FIG. 13a and in a view from above in FIG. 13b. Further, the arrangement with propagation of the laser beams substantially orthogonal to the respective L-lever is shown in a front view in FIG. 14a and in a view from above in FIG. 14b. The respective laser beams 202, 210 are drawn in interrupted lines. Only the D/X- and D/Y-levers are shown. The deflections of the reflected laser beams because of torsion and bending of the levers are indicated by arrows and it is indicated, which information can be obtained from these deflections.

As can be seen by comparing FIGS. 13 and 14, the two detection situations differ only by an exchange in the positions of the two lasers with respect to the two L-levers. One could thus change relatively quickly between a detection set-up optimized for large vertical scans or one with optimized detection of lateral drifts.

Mathematically, one may analyse the detection situation according to FIGS. 13 and 14 as follows:

According to a linear Ansatz, the torsion signals may be written as S.sub.X =a.sub.1.DELTA.x S.sub.Y =a.sub.2.DELTA.y.

Further, according to the linear Ansatz, the bending signals may be written as

In case of the arrangement of FIG. 13, a bending of the respective lever gives rise to a deflection of the reflected laser beam within a vertical plane defined by the laser beam incident onto the respective lever. A torsion of the respective lever gives rise to a deflection of the reflected laser beam basically orthogonal to this vertical plane of incidence.

In case of the arrangement of FIG. 14, a torsion of the respective lever gives rise to a deflection of the reflected laser beam within a vertical plane defined by the laser beam incident onto the respective lever. A bending of the respective lever gives rise to a deflection of the reflected laser beam basically orthogonal to this vertical plane of incidence.

It appears that the above linear Ansatz describes quite well the situation. Accordingly, it is in principle possible to make a vertical scan (changing the distance of the measurement sensor with respect to the sample) under controlled or stabilized conditions with respect to the lateral position. There may be influences on the torsion signals, which are not considered in the above Ansatz. E.g., if the distance is changed, the normal force on the tips of the L-levers will change. This might cause changes of the torsion. However, if a reference surface is used which is softer than the cantilever tip contacting the reference surface, the torsion of the cantilever will be maintained even under vertical scan conditions.

In any case, the lateral stabilization and control described in the foregoing is very effective for local measurements under constant distance conditions.

The concept of the MSLSS can be made even more powerful if one were to fabricate special samples, which could define the sample properties under the M-lever on the one side and offer a different surface for the D/L-lever(s) on the other side. In this way one can make sure that the surface under the D/L-levers is appropriate and optimal for the drift-correction signals. Such a surface could for example be very hard and especially adhesive for the D/L-Levers, to increase the lateral force signals, or--as has already been indicated above--it could be such that the tips could just penetrate a layer of some hundred nm, which is prepared on the hard surface underneath, in which they would then be `stuck` and fixed laterally.

The invention provides a local probe measuring device for effecting local measurements refering to a sample, comprising a first local probe for local measurements with respect to a sample or a reference surface, a second local probe for local measurements with respect to the sample or the reference surface, a measurement condition adjustment arrangement adapted to commonly adjust a first measurement condition of the first local probe with respect to the sample or the reference surface and a second measurement condition of the second local probe with respect to the sample or the reference surface, a detection arrangement comprising a first detection arrangement associated with the first local probe adapted to independently detect first measurement data referring to local measurements effected by said first local probe and a second detection arrangement associated with the second local probe adapted to independently detect second measurement data referring to local measurements effected by said second local probe. According to a different definition, the invention provides a local probe measuring device for effecting local measurements refering to a sample, comprising a plurality of local probes for local measurements with respect to a sample or a reference surface, a measurement condition adjustment arrangement adapted to commonly adjust measurement conditions of said local probes with respect to the sample or the reference surface, a plurality of detection arrangements, each being associated or adapted to be associated to one particular of said local probes and adapted to independently detect measurement data referring to local measurements effected by said particular local probe. Further, methods for effecting local measurements and local manipulations by means of multiple local probes are provided.

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