Detection of biological signals from a live mammalian muscle using an early stage diamond quantum sensor
At a Glance
Section titled âAt a Glanceâ| Metadata | Details |
|---|---|
| Publication Date | 2021-01-28 |
| Journal | Scientific Reports |
| Authors | James L. Webb, Luca Troise, Nikolaj Winther Hansen, Christoffer Olsson, Adam M. Wojciechowski |
| Institutions | Technical University of Denmark, Jagiellonian University |
| Citations | 62 |
| Analysis | Full AI Review Included |
Executive Summary
Section titled âExecutive SummaryâThis research presents the first successful detection of magnetic signals generated by action potentials in live mammalian muscle tissue using a diamond Nitrogen Vacancy (NV) quantum sensor.
- Core Value Proposition: Demonstrated a non-invasive, non-contact method for sensing biological electrical activity using a room-temperature diamond quantum sensor, overcoming the need for cryogenic cooling and bulky shielding required by Superconducting Quantum Interference Devices (SQUIDs).
- Performance in Noise: Achieved a magnetic field sensitivity floor of 50 pT/sqrt(Hz) in an ordinary, unshielded laboratory environment, leveraging the high dynamic range (estimated 42 ”T) of the NV sensor to prevent saturation by background noise.
- Signal Recovery: The weak biological signal (maximum 250 pT amplitude) was successfully recovered from dominant 50 Hz and 150 Hz mains noise using advanced digital signal processing, including bandpass filtering (20 Hz to 1.5 kHz) and adaptive notch filtering.
- Biological Validation: Signals were generated via optogenetic stimulation (470 nm blue light) of genetically modified mouse muscle, and the magnetic readout showed consistency with electrical probe data, confirming the signal was free of motion artifacts.
- Technical Milestone: The experiment validates the feasibility of using diamond quantum sensors for biosensing in mammals, serving as a crucial early step toward the ultimate goal of microscopic, high-spatial-resolution imaging of electrical activity in neural networks.
Technical Specifications
Section titled âTechnical Specificationsâ| Parameter | Value | Unit | Context |
|---|---|---|---|
| Magnetic Field Sensitivity Floor | 50 | pT/sqrt(Hz) | Measured noise floor (white noise) |
| Estimated Shot Noise Limit | 8 | pT/sqrt(Hz) | Theoretical limit |
| Raw Signal Dynamic Range | ±1 | ”T | Observed range, dominated by noise/drift |
| Estimated Dynamic Range (No Saturation Loss) | 42 | ”T | Assuming 1 MHz ODMR linewidth |
| Biological Signal Amplitude (Max) | 250 | pT | After filtering and averaging |
| Measurement Bandwidth (Lock-in) | 4.8 | kHz | Defined by 30 ”s lock-in time constant |
| Biological Signal Bandwidth | DC up to 1.5 | kHz | Frequency range of the action potential signal |
| Diamond Orientation | [100] | N/A | Electronic-grade single crystal |
| NV Layer Thickness | 20 | ”m | Grown by Chemical Vapor Deposition (CVD) |
| Nitrogen-14 Concentration (Gas Phase) | 5 | ppm | Optimized during CVD growth |
| Proton Irradiation Fluence | 3 x 1015 | protons/cm2 | Used for NV creation (2.25 MeV energy) |
| Annealing Temperature/Time | 800 °C / 4 | h | Post-irradiation processing |
| NV- Density | 0.1 to 1 | ppm | Resulting concentration |
| ODMR Linewidth | 1 | MHz | Measured for N-14 hyperfine transition |
| ODMR Contrast | 1.5 | percent | Measured for N-14 hyperfine transition |
| Laser Wavelength (Pump) | 532 | nm | Green laser (CW scheme) |
| Laser Power (Pump) | Up to 2 | W | Delivered to diamond |
| DC Bias Magnetic Field | ~1.5 | mT | Applied parallel to the (110) direction |
| Sample Temperature | 34 | °C | Maintained during measurement |
| Sample-Sensor Separation | ~66 | ”m | 16 ”m Al foil + 50 ”m Kapton tape |
Key Methodologies
Section titled âKey MethodologiesâThe experiment utilized a continuous wave (CW) Optically Detected Magnetic Resonance (ODMR) scheme in an inverted microscope setup, coupled with advanced digital signal processing to extract the weak biological signal.
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Diamond Synthesis and NV Creation:
- A [100] oriented electronic-grade single crystal diamond was overgrown with a 20 ”m nitrogen-doped layer (5 ppm N-14) via Chemical Vapor Deposition (CVD).
- NV centers were created by 2.25 MeV proton irradiation (3 x 1015 protons/cm2 fluence), followed by annealing at 800 °C for 4 hours.
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Sensor Integration and Bias Field:
- The diamond was mounted on a microwave antenna and separated from the biological sample by a 16 ”m aluminum foil heat sink and 50 ”m Kapton tape insulator.
- A DC bias magnetic field of ~1.5 mT was applied using rare-earth magnets, aligned perpendicular to the main current propagation direction, to optimize NV sensitivity.
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ODMR Readout and Acquisition:
- The NV centers were optically pumped using a 532 nm green laser (up to 2 W) and read out via red fluorescence collected by a balanced photodetector.
- Microwaves (2.7-3 GHz) were applied using a three-frequency drive scheme, and the magnetic signal was detected using a lock-in amplifier with a 30 ”s time constant, yielding a 4.8 kHz measurement bandwidth.
- Electrical probe data was recorded simultaneously for reference, 3 mm away from the magnetic sensor location.
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Biological Stimulation:
- Mouse extensor digitorum longus (EDL) muscle, expressing Channelrhodopsin 2 (ChR2), was maintained in ACSF at 34 °C.
- Action potentials were triggered optogenetically using 5 ms pulses of 470 nm blue light, repeated every 2 seconds.
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Signal Processing and Averaging:
- Data was acquired in 60 s iterations (30 stimulations per iteration) over many hours (up to 16 h) to leverage 1/sqrt(N) noise reduction via averaging.
- Digital filtering was applied: a bandpass filter (20 Hz to 1.5 kHz) was used to match the expected biological signal spectrum, and adaptive windowed notch filters were applied in the frequency domain to remove high-amplitude background noise (e.g., 50 Hz and 150 Hz mains harmonics).
Commercial Applications
Section titled âCommercial ApplicationsâThis technology, leveraging the unique properties of NV diamond quantum sensors (room temperature operation, high bandwidth, high spatial resolution potential), is relevant to several high-tech sectors:
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Biomedical Imaging and Diagnostics:
- Non-Invasive Electrophysiology: Developing portable, room-temperature magnetometers for clinical use (e.g., in hospitals) to detect fast biological signals (kHz range) such as nerve impulses or cardiac activity, offering a competitive alternative to bulky, cryogenic SQUIDs.
- Microscopic Neural Mapping: Creating high-spatial-resolution (potential < 10 ”m) widefield imaging systems to map electrical activity in dissected tissue (e.g., brain slices) for neuroscience research, enabling non-invasive study of neural networks.
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Quantum Sensing Hardware:
- Robust Magnetometer Systems: Commercializing NV diamond sensors designed for operation in unshielded, noisy environments, utilizing the high dynamic range and integrated digital signal processing (e.g., fixed-width notch filter combs) for noise mitigation.
- Integrated Sensor Arrays: Developing multi-sensor diamond arrays fed by a single central laser source (via fiber optic coupling) to perform gradiometry, reducing common-mode noise and spatially resolving signal sources within tissue.
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Materials Science and Diamond Manufacturing:
- High-Quality CVD Diamond: Driving demand for isotopically purified, high-quality CVD diamond substrates necessary to achieve the required NV coherence times and sensitivity improvements for practical applications.