Q-BiC: A biocompatible integrated chip for in vitro and in vivo spin-based quantum sensing

Optically addressable spin-based quantum sensors enable nanoscale measurements of temperature, magnetic field, pH, and other physical properties of a system. Advancing the sensors beyond proof-of-principle demonstrations in living cells and multicellular organisms towards reliable, damage-free quantum sensing poses three distinct technical challenges. First, spin-based quantum sensing requires optical accessibility and microwave delivery. Second, any microelectronics must be biocompatible and designed for imaging living specimens. Third, efficient microwave delivery and temperature control are essential to reduce unwanted heating and to maintain an optimal biological environment. Here, we present the Quantum Biosensing Chip (Q-BiC), which facilitates microfluidic-compatible microwave delivery and includes on-chip temperature control. We demonstrate the use of Q-BiC in conjunction with nanodiamonds containing nitrogen vacancy centers to perform optically detected magnetic resonance in living systems. We quantify the biocompatibility of microwave excitation required for optically detected magnetic resonance both in vitro in HeLa cells and in vivo in the nematode Caenorhabditis elegans for temperature measurements and determine the microwave-exposure range allowed before detrimental effects are observed. In addition, we show that nanoscale quantum thermometry can be performed in immobilised but non-anaesthetised adult nematodes with minimal stress. These results enable the use of spin-based quantum sensors without damaging the biological system under study, facilitating the investigation of the local thermodynamic and viscoelastic properties of intracellular processes.

💡 Research Summary

The authors introduce the Quantum Biosensing Chip (Q‑BiC), a compact, microfluidic‑compatible platform that integrates microwave delivery, on‑chip temperature control, and a transparent imaging area to enable spin‑based quantum sensing in living biological specimens. The chip incorporates a 50 Ω‑matched coplanar waveguide (CPW) fabricated on a glass substrate, insulated with a thin layer of PDMS or Parylene C to minimize autofluorescence. Electromagnetic simulations and scanning‑NV microscopy confirm that the magnetic field generated by the CPW is uniform across the 5 mm‑long, 50 µm‑wide microwave line and matches the design predictions, providing reliable Rabi frequencies for NV spin manipulation.

Temperature regulation is achieved with two gold resistive heaters and an on‑chip resistive temperature detector (RTD). The RTD exhibits a linear resistance‑temperature relationship (η ≈ 0.003 K⁻¹) across 20–50 °C, enabling precise monitoring of the global sample temperature. A heat‑balance model (Cv dT/dt = εV²R_heater − k(T − T₀)) accurately predicts temperature rise at low voltages; at higher voltages convective losses become significant. By implementing a proportional‑integral‑derivative (PID) controller, the chip can step temperature in increments as small as 30 mK and maintain stability over long periods, which is essential for calibrating quantum sensors and compensating for external thermal disturbances such as the addition of liquids at different temperatures.

Biocompatibility is rigorously evaluated both in vitro (HeLa cells) and in vivo (adult Caenorhabditis elegans). For HeLa cells cultured in a PDMS well on the chip, continuous microwave exposure up to 21.8 dBm (≈0.15 W) for four hours does not alter the mean‑squared displacement (MSD) of intracellular vesicles, indicating that cellular viscosity and viability remain intact. At 25.6 dBm, MSD drops sharply within 20 minutes, and trypan‑blue staining confirms cell death within ~300 µm of the antenna, demonstrating a clear power threshold for safe operation.

In C. elegans, the authors immobilize non‑anaesthetized adults in a micro‑channel aligned with the microwave line. Optically detected magnetic resonance (ODMR) measurements on nanodiamond NV centers embedded in the worms remain stable up to 21.8 dBm, and a genetically encoded GFP stress reporter shows no activation, confirming that the microwave field does not induce physiological stress at these powers. The chip’s on‑chip thermometer records the global temperature increase, while the NV centers provide nanoscale thermometry, allowing the detection of minute local temperature changes without perturbing the organism.

Overall, Q‑BiC addresses three major challenges for quantum biosensing: (1) delivering a spatially uniform microwave field compatible with diverse biological sizes, (2) providing real‑time, high‑precision temperature control to mitigate heating artifacts, and (3) establishing safe microwave power limits for living cells and small organisms. By integrating these capabilities into a simple, sterilizable, and reusable device, the work paves the way for routine application of NV‑based quantum sensors in cell biology, neurobiology, and quantum‑level studies of intracellular processes. The platform’s ability to perform damage‑free, nanoscale measurements of temperature, magnetic fields, and potentially other parameters (e.g., pH) opens new avenues for probing the thermodynamic and viscoelastic properties of living matter with unprecedented spatial resolution.