Circuit and method to non-invasively detect the electrical potential of a cell or neuron

Abstract

A system and method for non-invasively measuring the electrical potential radiated by a cell. To do this, a probe is positioned within ten microns distance from the cell for receiving the signal. Also, a reference potential is determined for the cell's environment. A sensor records the signal and compares the reference potential to the cell's signal to measure the electrical potential of the cell.

1 . A system for non-invasively measuring the electrical potential of a cell in a nutrient bath according to a signal radiated by the cell, said system comprising: 
 a probe including a capacitive electrode covered by an electrically insulating material and being positioned within a predetermined distance from the cell to receive the signal therefrom;    a reference electrode immersed into the bath to determine a reference potential for the nutrient bath;    a sensor electronically connected to said probe for recording the signal radiated by the cell in the nutrient bath; and    a sensor means for comparing the reference potential to the signal radiated from the cell to measure the electrical potential of the cell.    
   
   
       2 . A system as recited in  claim 1  wherein said predetermined distance is in a range between one-half micron (0.5 μm) and ten microns (100 μm).  
   
   
       3 . A system as recited in  claim 1  wherein said probe has a detection surface and the cell and said detection surface have a substantially same spatial extent.  
   
   
       4 . A system as recited in  claim 1  wherein a cell-probe capacitance is established when said probe is within said predetermined distance, and wherein the cell-probe capacitance is less than approximately one one-hundredth picofarad (0.01 pF).  
   
   
       5 . A system as recited in  claim 1  wherein the signal radiated by the cell has a frequency greater than about ten Hertz (>10 Hz) and said sensor records the signal with a signal to noise ratio (SNR) greater than one (SNR>1).  
   
   
       6 . A system as recited in  claim 1  wherein the cell is a biological entity.  
   
   
       7 . A system as recited in  claim 6  wherein the biological entity is selected from a group consisting of animal cells, plant cells, neurons, bacterial specimens and amoebae.  
   
   
       8 . A system as recited in  claim 1  wherein said sensor records signals radiated from a plurality of cells.  
   
   
       9 . A system as recited in  claim 1  wherein said probe comprises: 
 an electrode covered by an electrically insulating material;    a guard partially surrounding said covered electrode; and    a means for maintaining said guard at substantially the same potential as said electrode to minimize capacitive coupling between said electrode and the bath.    
   
   
       10 . A system as recited in  claim 9  wherein said probe further comprises a conducting layer and a means for controlling the potential of said conducting layer to a predetermined potential relative to said reference potential to minimize the distortion of electric fields within the nutrient bath.  
   
   
       11 . A system for non-invasively measuring the electrical potential of a cell according to a signal radiated by the cell, said system comprising: 
 a means for maintaining the cell for radiation of a signal therefrom;    a means for positioning a cell within a predetermined distance from a detecting surface for receipt of the signal from the cell by the detecting surface;    a means electrically connected to said positioning means for recording the signal radiated by the cell in said maintaining means; and    a sensor means for using the signal radiated from the cell to measure the electrical potential of the cell.    
   
   
       12 . A system as recited in  claim 11  further comprising: 
 a means for determining a reference potential for the maintaining means; and    a means for comparing the reference potential to the signal to measure the electrical potential of the cell.    
   
   
       13 . A system as recited in  claim 11  wherein said maintaining means is a nutrient bath.  
   
   
       14 . A system as recited in  claim 11  wherein said positioning means is a probe.  
   
   
       15 . A system as recited in  claim 11  wherein said recording means is a sensor.  
   
   
       16 . A system as recited in  claim 11  wherein said predetermined distance is in a range between one-half micron (0.5 μm) and ten microns (10 μm).  
   
   
       17 . A system as recited in  claim 11  wherein the cells and said conducting surface have a substantially same spatial extent.  
   
   
       18 . A system as recited in  claim 11  herein the signal radiated by the cell has a frequency greater than about ten Hertz (>10 Hz) and said recording means records the signal with a signal to noise ratio (SNR) greater than one (SNR>1).  
   
   
       19 . A system as recited in  claim 11  wherein the cell is a biological entity selected from a group consisting of animal cells, plant cells, neurons, bacterial specimens and amoebae.  
   
   
       20 . A method for non-invasively measuring the electrical potential of a cell according to a signal radiated by the cell, said system comprising: 
 maintaining the cell in a nutrient bath for radiation of a signal from the cell;    positioning a cell within a predetermined distance from a probe, said probe including a capacitive electrode covered with an electrically insulating material said material having a conducting surface for receipt of the signal from the cell by the conducting surface;    determining a reference potential for the nutrient bath;    recording the signal radiated by the cell in the nutrient bath; and    comparing the reference potential of the nutrient bath to the signal radiated from the cell to measure the electrical potential of the cell.    
   
   
       21 . A method as recited in  claim 20  wherein said predetermined distance is in a range between one-half micron (0.5 cm) and ten microns (10 μm), wherein the signal radiated by the cell has a frequency greater than about ten Hertz (>10 Hz) and is recorded in said recording step with a signal to noise ratio (SNR) greater than one (SNR>1).  
   
   
       22 . A method as recited in  claim 21  wherein the cell is a biological entity selected from a group consisting of animal cells, plant cells, neurons, bacterial specimens and amoebae.  
   
   
       23 . A method as recited in  claim 20  further comprising the steps of: 
 exposing the cell to an agent selected from the group of agents consisting of a biological agent, a chemical agent and a pharmacological agent;    recording the signal radiated by the exposed cell in the nutrient bath; and    comparing the reference potential of the nutrient bath to the signal radiated from the exposed cell to measure the electrical potential of the exposed cell.