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.

1 - 47 . (canceled)  
     
     
         48 . A multiaperture system for analyzing membranous samples selected from the group consisting of cells, vesicles, and cellular organelles, comprising: 
 a carrier having a plurality of apertures and substantially planar seal surfaces circling respective apertures, the carrier being adapted so that at least one of the samples can be sealed across at least one of the apertures and within the respective seal surface;    at least three fluid compartments each fluid compartment connected to another of the at least three fluid compartments on an opposite side of the carrier via at least one of the apertures; and    at least three electrodes, each electrode in electrical contact with at least one of the fluid compartments, wherein the electrodes are adapted to apply and/or measure at least one of an electrical potential and a current, across at least a portion of the at least one of the samples, after it is sealed across the at least one of the apertures;    wherein the fluid compartments and electrodes are separated on at least one side of the carrier to allow independent measurements;    wherein the maximum diameter of the aperture at the seal surface is between about 0.3 μm and about 7 μm.    
     
     
         49 . The system of  claim 48 , wherein the seal has an electrical resistance of greater than about 1 GΩ.  
     
     
         50 . The system of  claim 48 , wherein the membranous samples are selected from the group consisting of cells, vesicles, and biological organelles.  
     
     
         51 . The system of  claim 48 , wherein at least one electrode is used for measurement over more than one aperture.  
     
     
         52 . The system of  claim 48 , wherein several or all of the electrodes on one side of the carrier have a common electrical potential.  
     
     
         53 . The system of  claim 48 , the carrier having first and second sides, wherein one compartment is disposed on the first side of the carrier, and the remaining compartments are disposed on the second side of the carrier.  
     
     
         54 . The system of  claim 48 , wherein the system is configured for sequential measurements over at least two apertures.  
     
     
         55 . The system of  claim 48 , wherein the system is configured for parallel measurements over at least two apertures.  
     
     
         56 . The system of  claim 48 , further comprising a sample handling mechanism for adding, manipulating, exchanging, storing, and/or removing samples and sample components from at least one compartment.  
     
     
         57 . The system of  claim 48 , wherein the carrier is at least substantially planar.  
     
     
         58 . The system of  claim 48 , wherein the carrier has an electrically charged surface that attracts biological membranes.  
     
     
         59 . The system of  claim 48 , wherein the carrier has a surface that provides a molecule-specific bonding of cells, vesicles; or biological organelles on it.  
     
     
         60 . The system of  claim 48 , wherein the carrier is formed at least in part of materials selected from the group consisting of silicon, silicon derivatives, glass, and plastic.  
     
     
         61 . The system of  claim 48 , wherein the carrier comprises a silicon chip or a silicon wafer.  
     
     
         62 . The system of  claim 48 , the carrier having first and second sides, wherein the compartments on at least one of the first and second side of the carrier are open.  
     
     
         63 . The system of  claim 48 , wherein at least two fluid compartments are disposed on one side of the carrier, each of those compartments being in contact, via the apertures, with a single fluid compartment disposed on the other side of the carrier.  
     
     
         64 . The system of  claim 48 , further comprising an optical analysis mechanism configured for optical analysis samples positioned about at least one aperture.  
     
     
         65 . The system of  claim 64 , wherein the optical-analysis mechanism is configured for fluorescence measurements.  
     
     
         66 . The system of  claim 48 , further comprising a holder adapted to support the carrier.  
     
     
         67 . The system of  claim 48 , wherein the system includes a row of 8, 12, 16, 24, 32, or 48 apertures.