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

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 an electrode covered by an electrically insulating material, a guard partially surrounding said 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, said probe 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 μum) and ten microns (10 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 cited 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 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.

10. 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 probe including an electrode covered by an electrically insulating material, a guard partially surrounding said electrode and a means for maintaining said guard at substantially the same potential as said electrode to minimize capacitive coupling between the electrode and the means for maintaining the cell and a detecting surface for receipt of the signal from the cell by the detecting surface, said surface being located on the insulating material;

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.

11. A system as recited in claim 10 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.

12. A system as recited in claim 10 wherein said maintaining means is a nutrient bath.

13. A system as recited in claim 10 wherein said recording means is a sensor.

14. A system as recited in claim 10 wherein said predetermined distance is in a range between one half micron (0.5 μm) and ten microns (10 μm).

15. A system as recited in claim 10 wherein the cells and said conducting surface have a substantially same spatial extent.

16. A system as recited in claim 10 wherein 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).

17. A system as recited in claim 10 wherein the cell is a biological entity selected from a group consisting of animal cells, plant cells, neurons, bacterial specimens and amoebae.

18. 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 the cell within a predetermined distance from a probe, said probe including an electrode covered with an electrically insulating material, and a guard partially surrounding said electrode, said material having a conducting surface for receipt of the signal from the cell by the conducting surface;

maintaining said guard at substantially the same potential as said electrode to minimize the capacitive coupling between the electrode and the nutrient bath;

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.

19. A method as recited in claim 18 wherein said predetermined distance is in a range between one half ten microns (0.5 μm), 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).

20. A method as recited in claim 19 wherein the cell is a biological entity selected from a group consisting of animal cells, plat cells, neurons, bacterial specimens and amoebae.

21. A method as recited in claim 18 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.

22. 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 guard partially surrounding an 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 nutrient bath and being positioned within a predetermined distance from the cell to receive the signal therefrom:

a reference electrode immersed into the nutrient 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.

23. A system as recited in claim 22 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.