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Toward a CMOS-integrated quantum diamond biosensor based on NV centers

Ioannis Varveris, Gianni D. Aliberti, Felix J. Barzilaij, Zhi Jin, Samantha A. van Rijs, Qiangrui Dong, Daan Brinks, Salahuddin Nur, Ryoichi Ishihara

Abstract

We report progress toward a CMOS-integrated quantum diamond biosensing platform that combines nitrogen-vacancy (NV) centers in diamond with a custom 40 nm CMOS Single-Photon Avalanche Diode (SPAD) array. The system integrates on-chip active quenching and digital readout with external FPGA-based photon counting, compact microwave delivery, and practical optical excitation and collection schemes to support widefield optically detected magnetic resonance (ODMR). System-level design considerations spanning fluorescence collection efficiency, detector count-rate capability, and microwave homogeneity are analyzed with biological compatibility and scalability in mind. Using superparamagnetic iron oxide nanoparticle (SPION)-labeled HEK293T cells as a representative use case, simple dipole-field estimates indicate that sub-$μ$T sensitivity is required to resolve ODMR shifts within typical ensemble linewidths. Based on the proposed architecture and efficiency analysis, a magnetic field sensitivity of approximately 90 nT/$\sqrt{\mathrm{Hz}}$ per pixel is estimated. These results outline a practical path from optics-heavy quantum diamond microscopes toward compact, CMOS-integrated NV-based biosensors for quantitative magnetic imaging in complex biological environments.

Toward a CMOS-integrated quantum diamond biosensor based on NV centers

Abstract

We report progress toward a CMOS-integrated quantum diamond biosensing platform that combines nitrogen-vacancy (NV) centers in diamond with a custom 40 nm CMOS Single-Photon Avalanche Diode (SPAD) array. The system integrates on-chip active quenching and digital readout with external FPGA-based photon counting, compact microwave delivery, and practical optical excitation and collection schemes to support widefield optically detected magnetic resonance (ODMR). System-level design considerations spanning fluorescence collection efficiency, detector count-rate capability, and microwave homogeneity are analyzed with biological compatibility and scalability in mind. Using superparamagnetic iron oxide nanoparticle (SPION)-labeled HEK293T cells as a representative use case, simple dipole-field estimates indicate that sub-T sensitivity is required to resolve ODMR shifts within typical ensemble linewidths. Based on the proposed architecture and efficiency analysis, a magnetic field sensitivity of approximately 90 nT/ per pixel is estimated. These results outline a practical path from optics-heavy quantum diamond microscopes toward compact, CMOS-integrated NV-based biosensors for quantitative magnetic imaging in complex biological environments.
Paper Structure (21 sections, 13 equations, 19 figures, 1 table)

This paper contains 21 sections, 13 equations, 19 figures, 1 table.

Figures (19)

  • Figure 1: Energy-level structure and ODMR principle of the negatively charged nitrogen-vacancy (NV$^-$) center. The ground and excited spin-triplet states exhibit a zero-field splitting of approximately 2.87 GHz between the $m_s = 0$ and $m_s = \pm1$ sublevels. Optical excitation (typically at 532 nm) induces spin-dependent fluorescence in the 600–800 nm range via intersystem crossings through intermediate singlet states. The right panel illustrates representative continuous-wave ODMR spectra: at zero magnetic field ($B = 0$), the $m_s = \pm1$ transitions are degenerate, while an applied magnetic field ($B \neq 0$) lifts this degeneracy through Zeeman splitting, resulting in two distinct resonance frequencies separated proportionally to the magnetic field component along the NV axis.
  • Figure 2: I-V characteristic of photodiodes. The conventional Avalanche Photo Diode (APD) gives an analog signal that is amplified by incoming light. The Single Photon Avalanche Diode (SPAD) is operated in reverse bias beyond breakdown voltage $V_{br}$, pushing it in the Geiger regime. An incoming photon triggers an avalanche, which becomes self-sustaining. Then, either passive or active quenching can be used to pull the voltage down and stop the avalanche. Lastly, the SPAD is allowed to recharge, making it ready for the next photon detection.
  • Figure 3: Layout of the SPAD chip with a $16 \times 16$ array, with on-chip active quenching and readout electronics.
  • Figure 4: Overview of the SPAD array. The array consists of 16x16 SPAD pixels, which are organized into rows. The pixel schematic is highlighted on the left. Each row has a Parallel In Serial Out (PISO) module (highlighted on the right), which makes the pixels accessible with their respective serial I/O.
  • Figure 5: Schematic of the SPAD circuit. The active quenching, hold-off and recharge is managed by the control circuit, which pulls the anode to $V_{DD}$ and $V_{SS}$ accordingly.
  • ...and 14 more figures