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  Multiaperture sample positioning and analysis systemUSPTO Application #: 20070209935Title: Multiaperture sample positioning and analysis system Abstract: Systems for positioning and/or analyzing samples such as cells, vesicles, cellular organelles, and fragments, derivatives, and mixtures thereof, for electrical and/or optical analysis, especially relating to the presence and/or activity of ion channels. (end of abstract) Agent: Morgan, Lewis & Bockius, LLP - San Francisco, CA, US Inventors: Horst VOGEL, Christian Schmidt USPTO Applicaton #: 20070209935 - Class: 204403010 (USPTO) Related Patent Categories: Chemistry: Electrical And Wave Energy, Apparatus, Electrolytic, Analysis And Testing, Biological Material (e.g., Microbe, Enzyme, Antigen, Etc.) Analyzed, Tested, Or Included In Apparatus The Patent Description & Claims data below is from USPTO Patent Application 20070209935. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCES TO PRIORITY APPLICATIONS [0001] This application is a continuation of U.S. patent application Ser. No. 09/957,116, filed Sep. 19, 2001, which, in turn, is a continuation-in-part of the following U.S. patent applications: Ser. No. 09/581,837, filed Jun. 16, 2000; and Ser. No. 09/952,461, filed Sep. 14, 2000. U.S. patent application Ser. No. 09/581,837, in turn, claims priority from PCT Patent Application Serial No. PCT/IB98/01150, filed Jul. 28, 1998, which claims priority from Swiss Patent Application Serial No. 2903/97, filed Dec. 17, 1997. U.S. patent application Ser. No. 09/952,461, in turn, claims priority from Ser. No. 09/581,837, with priority claims as listed above, and the following U.S. provisional patent applications: Ser. No. 60/232,365, filed Sep. 14, 2000; Ser. No. 60/233,800, filed Sep. 19, 2000; and Ser. No. 60/322,178, filed Sep. 13, 2001. Each of the above-identified priority patent applications is incorporated herein by reference in its entirety for all purposes. CROSS-REFERENCES TO RELATED APPLICATIONS [0002] This application incorporates by reference in their entirety for all purposes the following patent applications: U.S. patent application Ser. No. 09/708,905, filed Nov. 8, 2000; PCT Patent Application Serial No. PCT/IB00/00095, filed Jan. 26, 2001; PCT Patent Application Serial No. PCT/IB00/00097, filed Jan. 26, 2001; U.S. Provisional Patent Application Ser. No. 60/353,411, filed Feb. 1, 2002; U.S. Provisional Patent Application Ser. No. ______, filed Mar. 1, 2002, titled MICROSTRUCTURED CARRIERS EXHIBITING ENHANCED BINDING OF MEMBRANOUS SAMPLES, and naming Cristina E. Davis, James A. DeRose, Yit-Shun Leung ki, and Christian Schmidt as inventors; U.S. Provisional Patent Application Ser. No. ______, filed Mar. 1, 2002, titled MICROSTRUCTURED CARRIERS WITH SURFACE MICRODOMAINS HAVING SELECTED HYDROPHOBICITY, and naming Andreas Brecht, Rosa A. Castillo, Cristina E. Davis, James A. DeRose, Anne-Lise Etter, Tom W. Gibbs, Wilma Lukas-Benotto, and Christian Schmidt as inventors; and U.S. Provisional Patent Application Ser. No. ______, filed Mar. 7, 2002, titled CARRIER SUPPORT ELEMENTS FOR HIGH-THROUGHPUT PATCH CLAMP SYSTEMS, and naming Andreas Brecht, Cristina E. Davis, Tom W. Gibbs, Alain Ramirez, and Christian Schmidt as inventors. FIELD OF THE INVENTION [0003] The invention relates to systems for positioning and/or analyzing samples. More particularly, the invention relates to systems for positioning and/or analyzing samples such as cells, vesicles, cellular organelles, and fragments, derivatives, and mixtures thereof, for electrical and/or optical analysis, especially relating to the presence and/or activity of ion channels. BACKGROUND OF THE INVENTION [0004] A variety of important biological processes occur at or within cell membranes. It therefore is not surprising that the biological function of membrane proteins has become an area of active research. Signal transduction processes in general, including nerve conduction, and neuroreceptors in particular have been shown to be influenced by pharmacologically active ingredients, making them obvious targets for drug development..sup.i Ion channels and ion transporters also have been shown to be an important class of therapeutic targets. In fact, interactions with ion channels have become a major potential source of adverse effects when administering a therapeutic agent, leading the Food and Drug Administration (FDA) and other government regulatory agencies to require safety profiling of potential therapeutics against certain ion channels. .sup.i J. P. Changeux (1993), "Chemical Signaling in the Brain," Sci. Am. Nov. Pages 30 ff; A. G. Gilman (1995), Angew. Chem. Int. Ed. Engl. 34:1406-1428; M. Rodbell (1995), Angew. Chem. Int. Ed. Engl. 34: 1420-1428. [0005] This understanding of the interactions between potential drugs and cell membrane components is beginning to play a crucial role in modern drug development. In view of the increasing number of known receptors and the rapidly growing libraries of potential pharmaceutical ingredients, there clearly is a need for highly sensitive screening methods that permit the analysis of a large number of different substances with high assay throughput per unit time, otherwise known as "high throughput screening" (or "HTS"). In particular, there is a need for automated and/or high throughput screening methods that are relevant to cell membrane components. [0006] At present, relatively traditional methods are used for the screening of pharmaceutical ingredients. Such methods include ligand binding assays and receptor function tests that are performed separately..sup.ii Although binding assays are relatively inexpensive, and amenable to high throughput, they require labeled high-affinity ligands, and generally are limited to assays for ligands that can compete effectively for labeled ligand. Fluorescent or fluorogenic reagents generally are compatible with high throughput assays, including the analysis of ion channels using fluorescent calcium indicators, and the evaluation of membrane potential effects with potential-sensitive dyes. However, such reagents typically are not sensitive enough for single cell measurements, and generally can provide only indirect measurements of the membrane component of interest. .sup.ii J. Hodgson (1992), Bio/Technology 9:973. [0007] The patch clamp was introduced by Neher and Sakmann in the early 1980s as a powerful technique for the direct study of drug effects on single receptors. In recognition of the strength of the method, Neher and Sakmann were awarded the Nobel prize in 1991. Classical patch-clamp methods often are used in conjunction with functional membrane receptor assays, including receptors coupled to G-proteins and ion channel-forming receptors..sup.iii This method is highly specific and extremely sensitive: it can, in principle, be used to measure the channel activity of individual receptor molecules. In doing so, glass micropipettes with an opening diameter of typically 1-0.1 .mu.m are pressed on the surface of a biological cell. The membrane surface that is covered by the micropipette is called a "patch." If the contact between the glass electrode and the cell membrane surface is sufficiently electrically isolating, the ion flow over the membrane patch can be measured electrically with the aid of microelectrodes, one placed in the glass pipette and the other placed in the milieu opposite the membrane..sup.iv A key advantage of this electrophysiological method is that it makes directly accessible the function of the corresponding channel-forming proteins or receptors coupled to channel-forming proteins via the measured electrical characteristics of the channel-forming proteins. .sup.iii J. Knowles (1997), "Medicines for the New Millennium Hunting Down Diseases [sic: Diseases]." Odyssey Vol. 3(1). .sup.iv O. P. Hamill, A. Marty, et al. (1981), "Improved Patch-clamp Techniques for High-resolution Current Recording from Cells and Cell-free Membrane Patches". Pflugers Arch 391(2):85-100. [0008] Unfortunately, several major limitations have prevented patch-clamp technology from revolutionizing receptor science and pharmaceutical drug development. For example, to produce high quality results, the patch-clamp method requires a tremendous effort in technical installation and highly qualified operators. Moreover, in addition to being expensive, a standard patch-clamp setup may require a long set-up time and have a high failure rate. [0009] Thus, there is a need for a system for positioning and/or analyzing cells that is rapid, facile, and suitable for multiarray analysis, such as the system provided by the invention. SUMMARY OF THE INVENTION [0010] The invention provides systems for positioning and/or analyzing samples such as cells, vesicles, cellular organelles, and fragments, derivatives, and mixtures thereof, for electrical and/or optical analysis, especially relating to the presence and/or activity of ion channels. BRIEF DESCRIPTION OF THE DRAWINGS [0011] FIG. 1 is a schematic view of a system for positioning and/or analyzing samples in accordance with aspects of the invention. [0012] FIG. 2 is a cross-sectional side view of a substrate chip prepared from Si/SiO.sub.2 in accordance with aspects of the invention. [0013] FIG. 3 is a cross-sectional side view of a measurement system having planar electrodes in accordance with aspects of the invention. [0014] FIG. 4 is a cross-sectional side view of a measurement system having point or wire electrodes in accordance with aspects of the invention. [0015] FIG. 5 is a cross-sectional side view of a measurement system having open fluid compartments in accordance with aspects of the invention. [0016] FIG. 6 is a top view of a measurement system having multiple measurement sites in accordance with aspects of the invention. [0017] FIG. 7 is a cross-sectional side view of the measurement system of FIG. 6, taken generally along line 7-7 in FIG. 6. [0018] FIG. 8 is a cross-sectional side view of a measurement system having optical measurement aids in accordance with aspects of the invention. Continue reading... Full patent description for Multiaperture sample positioning and analysis system Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Multiaperture sample positioning and analysis system patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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