Electrical Analysis Of Biological Membranes

Abstract

A biochip device for electrical analysis of biological membranes. The device may include a substrate assembly defining an array of apertures and including thin-film devices configured to sense an electrical property of biological membranes that seal the apertures. The device also may include an electrical interface coupled electrically to the thin-film devices and configured to electrically couple the thin-film devices to a control apparatus. The electrical interface may define a plurality of interface elements, and the apertures may be in excess over the interface elements.

1 . A method of performing an experiment on cells, comprising: 
 disposing cells adjacent an array of apertures, each aperture being included in an examination site having a sensor electrode configured to measure an electrical property of a cell membrane sealing the aperture;    measuring the electrical property for each aperture of the array;    identifying a subset of the apertures that are properly sealed by the cell membranes based on the measured electrical properties; and    selectively performing an additional operation on the identified subset.    
     
     
         2 . The method of  claim 1 , wherein selectively performing the additional operation includes exposing examination sites of the identified subset to at least one test agent.  
     
     
         3 . The method of  claim 2 , further comprising measuring an electrical property from the subset of apertures after exposing the examination sites to the at least one test agent.  
     
     
         4 . The method of  claim 2 , wherein each examination site includes a well for holding fluid, exposing including dispensing the at least one test agent to the well.  
     
     
         5 . The method of  claim 4 , wherein exposing includes dispensing different test agents to at least some of the wells.  
     
     
         6 . The method of  claim 1 , wherein disposing the cells includes placing the cells in wells separated by a fluid barrier.  
     
     
         7 . The method of  claim 1 , wherein disposing the cells includes applying a vacuum configured to pull cells against the apertures.  
     
     
         8 . The method of  claim 1 , wherein disposing the cells includes applying electrical signals to thin-film devices configured to enhance movement of cells.  
     
     
         9 . The method of  claim 8 , wherein applying the electrical signals includes energizing electrodes that generate electric fields.  
     
     
         10 . The method of  claim 8 , wherein applying the electrical signals includes energizing ultrasonic transducers.  
     
     
         11 . A method of performing an experiment on cells, comprising: 
 providing an array of examination sites, each site including an aperture and at least one circuit associated with the aperture, the at least one circuit including a switching device coupled to an electrode;    disposing cells at the examination sites;    selecting the switching device for each aperture to allow electrical signals to pass to the corresponding electrode; and    passing alignment signals to the electrodes when the corresponding switching devices are selected to promote movement of the cells toward alignment with the apertures.    
     
     
         12 . The method of  claim 11 , further comprising passing an excitation signal through at least a subset of the circuits associated with the apertures, the excitation signal being configured to allow measurement of an electrical property of the cells that seal apertures associated with the subset.  
     
     
         13 . The method of  claim 12 , wherein the switching device is a first switching device, the at least one circuit including a second switching device coupled to the electrode, passing the excitation signal including selecting the second switching device to operate the electrode.  
     
     
         14 . The method of  claim 12 , wherein the electrode is a first electrode and the switching device is a first switching device, the at least one circuit including a second switching device coupled to a second electrode, and wherein passing the excitation signal includes selecting the second switching device to operate the second electrode.  
     
     
         15 . The method of  claim 13 , further comprising sensing an electrical response produced by the excitation signal; and performing an operation selectively at the examination sites based on a comparison of the electrical response to a threshold value.  
     
     
         16 . The method of  claim 14 , further comprising sensing an electrical response produced by the excitation signal; and performing an operation selectively at the examination sites based on a comparison of the electrical response to a threshold value.  
     
     
         17 . The method of  claim 12 , wherein the electrode is a first electrode and the switching device is a first switching device, the at least one circuit including a second switching device coupled to an ultrasonic transducer, and wherein passing the excitation signal includes selecting the second switching device to operate the ultrasonic transducer.  
     
     
         18 . The method of  claim 14 , wherein the at least one circuit includes a third switching device coupled to an ultrasonic transducer, passing the excitation signal including selecting the third switching device to operate the ultrasonic transducer.  
     
     
         19 . The method of  claim 12 , the method further comprising energizing a thin-film device at the examination sites, the thin-film device being at least one of an ultrasonic transducer and a heater.  
     
     
         20 . The method of  claim 12 , wherein each examination site includes a pair of electrodes, the alignment signals and the excitation signal each being provided by a different electrode of the pair.  
     
     
         21 . A device for performing an experiment on cells, comprising: 
 means for disposing cells at an array of examination sites; each site including an aperture and at least one circuit associated with the aperture, the at least one circuit including a switching device coupled to an electrode    means for selecting the switching device for each aperture to allows electrical signals to pass to the corresponding electrode; and    means for passing alignment signals to the electrodes when the corresponding switching devices are selected to promote movement of the cells toward alignment with the apertures.