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. 2010 Nov 2;107(44):18777-82.
doi: 10.1073/pnas.1002562107. Epub 2010 Oct 11.

Monitoring Ion-Channel Function in Real Time Through Quantum Decoherence

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Monitoring Ion-Channel Function in Real Time Through Quantum Decoherence

Liam T Hall et al. Proc Natl Acad Sci U S A. .
Free PMC article

Abstract

In drug discovery, there is a clear and urgent need for detection of cell-membrane ion-channel operation with wide-field capability. Existing techniques are generally invasive or require specialized nanostructures. We show that quantum nanotechnology could provide a solution. The nitrogen-vacancy (NV) center in nanodiamond is of great interest as a single-atom quantum probe for nanoscale processes. However, until now nothing was known about the quantum behavior of a NV probe in a complex biological environment. We explore the quantum dynamics of a NV probe in proximity to the ion channel, lipid bilayer, and surrounding aqueous environment. Our theoretical results indicate that real-time detection of ion-channel operation at millisecond resolution is possible by directly monitoring the quantum decoherence of the NV probe. With the potential to scan and scale up to an array-based system, this conclusion may have wide-ranging implications for nanoscale biology and drug discovery.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Quantum decoherence imaging of ion-channel operation (simulations). (A) A single NV defect in a diamond nanocrystal is placed on an atomic force microscope tip. The unique properties of the NV atomic level scheme allows for optically induced readout and microwave control of magnetic (spin) sublevels. (B) The nearby cell membrane is host to channels permitting the flow of ions across the surface. The ion motion results in an effective fluctuating magnetic field at the NV position which decoheres the quantum state of the NV system. (C) This decoherence results in a decrease in fluorescence, which is most pronounced in regions close to the ion-channel opening. (D) Changes in fluorescence also permit the temporal tracking of ion-channel dynamics.
Fig. 2.
Fig. 2.
Details of the NV center structure, energy levels, and control scheme. (A) NV-center diamond lattice defect. (B) NV spin detection through optical excitation and emission cycle. Magnetic sublevels ms = 0 and ms =  ± 1 are split by a D = 2.88 GHz crystal field. Degeneracy between the ms =  ± 1 sublevels is lifted by a Zeeman shift, δω. Application of 532 nm green light induces a spin-dependent photoluminescence and pumping into the ms = 0 ground state. (C) Microwave and optical pulse sequences for coherent control and readout.
Fig. 3.
Fig. 3.
Sources of magnetic field fluctuations and their relative amplitudes. (A) Calculated magnetic field signals from water, ion-channel, and lipid bilayer sources at a probe standoff of 4 nm over a 1 ms timescale. (B) Comparison of σB for various sources of magnetic fields. (C) Fluctuation regime, Θ = fe/γpσB, for magnetic field sources vs. probe standoff. Rapidly fluctuating fields (Θ≫1) are said to be in the fast-fluctuating limit (FFL). Slowly fluctuating fields (Θ ≪ 1) are in the slow fluctuation limit (SFL). The ion-channel signal exists in the Θ ∼ 1 regime and therefore has an optimal dephasing effect on the NV probe.
Fig. 4.
Fig. 4.
Simulated spatial scans based on the ion channel as a dephasing source. Relative population differences are plotted for pixel dwell times of 10, 100 and 1,000 ms. Corresponding image acquisition times are 4, 40, and 400 s.
Fig. 5.
Fig. 5.
Temporal characteristics of the measurement protocol. (A) Dephasing rates due to the sources of magnetic field plotted as a function of probe standoff, hp. (B) Optimum temporal resolution as a function of crystal T2 times for hp = 2–6 nm. (C) Temporal resolution as a function of interrogation time, τ, for separations of 2–7 nm. The limits corresponding to T2 = 15 μs and T2 = 300 μs are shown as vertical dashed lines.
Fig. 6.
Fig. 6.
Theoretical results for the detection of ion-channel operation. (A) Plot illustrating the dependence of temporal resolution (δt) and signal variance (δP) on the number of data points included in the running average (Ns). (B) Simulated reconstruction of a sodium ion-channel signal with a 200 Hz switching rate using optical readout of an NV center (blue curve). The actual ion-channel state (on/off) is depicted by the dashed line, and the green line depicts the analytic confidence threshold. Fourier transforms of measurement records are shown in CE for standoffs of 4, 5, and 6 nm, respectively. Switching dynamics are clearly resolvable for hp < 6 nm, beyond which there is little contrast between decoherence due to the ion-channel signal and the background.

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