Method and apparatus for sensing a time varying current passing through an ion channel
A capacitive sensing system is used to measure a time-varying ion current through a channel, such as an ion channel or protein pore. Such a capacitive system does not suffer problems of electrode corrosion and, when used with methods to control a build up of ion concentration, allows the use of measurement volumes around the channel with dimensions on a scale of nanometers.
1. An apparatus for sensing a time varying current passing through a channel provided in a membrane comprising:
a membrane including a channel located therein;
a voltage source for establishing a potential difference across the channel and driving an ionic current through the channel; and
a capacitive sensing electrode positioned to measure an electrical property of the membrane.
2. The apparatus according to claim 1 , further comprising:
a bath; and
a sensing volume separated from the bath by the membrane.
3. The apparatus according to claim 2 , wherein the voltage source further comprises a first electrode located in the bath and a second electrode located in the sensing volume.
4. The apparatus according to claim 3 , further comprising:
a first electrolyte in the bath and a second electrolyte in the sensing volume, wherein the second electrode is capacitively coupled to the second electrolyte, with negligible contribution from resistive current.
5. The apparatus according to claim 2 , wherein the voltage source comprises a first electrode located in the bath and the capacitive sensing electrode located in the sensing volume.
6. The apparatus according to claim 2 , further comprising:
means for adjusting an amplitude of a voltage of the voltage source to offset a build up of voltage in the sensing volume.
7. The apparatus according to claim 1 , further comprising: circuitry, coupled to the capacitive sensing electrode, for determining the ionic current.
8. The apparatus according to claim 1 , wherein the channel is selected from the group consisting of: an ion channel, a protein pore, a nanochannel and an engineered aperture.
9. The apparatus according to claim 1 , wherein the channel has two defined conductive states.
10. The apparatus according to claim 1 , wherein the membrane is formed from a bilipid or a liquid film.
11. The apparatus according to claim 1 , wherein the membrane constitutes a solid.
12. The apparatus according to claim 11 , wherein the membrane is formed from polycarbonate.
13. The apparatus according to claim 11 , wherein the membrane is formed from polyimide.
14. The apparatus according to claim 1 , wherein the sensing volume has a thickness less than approximately 1 mm.
15. The apparatus according to claim 1 , wherein the sensing volume has a thickness less than approximately 1 μm.
16. The apparatus according to claim 1 , wherein the sensing volume has a thickness less than approximately 10 nm.
17. The apparatus according to claim 1 , further comprising:
a substrate wherein the membrane is supported on the substrate.
18. The apparatus according to claim 17 , wherein the substrate is selected from the group consisting of: ultra thin viscous films, hydrophilic polymers, soft polymer cushions, aerogels, xerogels and tethers.
19. The apparatus according to claim 17 , wherein the substrate constitutes a solid surface provided with a through hole.
20. The apparatus according to claim 17 , wherein the voltage source further includes a first electrode located directly adjacent the channel opposite to the capacitive sensing electrode.
21. The apparatus according to claim 1 , further comprising:
means for maintaining a driving voltage at a low level to minimize the ionic current passing through the channel.
22. The apparatus according to claim 1 , further comprising:
means for producing a DC or quasi DC voltage across the channel by applying a driving current waveform with a net increasing signal over a desired time period.
23. A method of sensing a time varying current passing through a channel in a membrane located between a bath and a sensing volume comprising:
placing an analyte in the bath;
applying a driving voltage across the channel; and
measuring an electrical property of the membrane with a capacitive sensing electrode.
24. The method of claim 23 , in which the channel switches between defined conductivity states in a stochastic manner.
25. The method of claim 23 , further comprising: adjusting an amplitude of the voltage to offset a build up of voltage in the sensing volume.
26. The method of claim 23 , further comprising: maintaining the driving voltage at a low level to minimize an ionic current passing through the channel.
27. The method of claim 23 , further comprising: producing a DC or quasi DC voltage across the channel by applying a driving current waveform with a net increasing signal over a desired time period.