Quantum Biosensors on Chip - A Review from Electronic and Photonic Integrated Circuits to Future Integrated Quantum Photonic Circuits

At a Glance

Metadata	Details
Publication Date	2025-10-22
Journal	Microelectronics
Authors	Yasaman Torabi, Shahram Shirani, James P. Reilly
Institutions	Bell (Canada), McMaster University
Citations	1
Analysis	Full AI Review Included

Executive Summary

This review outlines the technological roadmap from classical Electronic Integrated Circuits (EICs) and Photonic Integrated Circuits (PICs) toward next-generation Integrated Quantum Photonic (IQP) biosensors, emphasizing scalability and high sensitivity.

Core Value Proposition: Quantum biosensors (QDs, NV centers) surpass the Standard Quantum Limit (SQL) by leveraging quantum phenomena (coherence, entanglement), achieving sensitivity approaching the Heisenberg Limit (1/N scaling).
Performance Benchmarks: NV center biosensors demonstrate the highest sensitivity, reaching limits of detection (LOD) as low as ~1 aM-fM, enabling single-molecule detection at room temperature.
Integration Trajectory: The pathway involves migrating from noise-susceptible EICs (SNR 15-30 dB) and complex PICs (SNR 30-50 dB) to IQP systems that combine quantum emitters, photonic waveguides, and CMOS-compatible detectors.
Key Quantum Platforms: NV centers in diamond offer room-temperature operation and high magnetic sensitivity (1 nT/√Hz). Quantum Dots (QDs) provide superior multiplexing capability via size-tunable, spectrally distinct emission.
IQP Components Demonstrated: Recent breakthroughs include the integration of quantum light sources, low-loss MEMS-based phase shifters (<0.5 dB loss, Vπ = 2 V), and CMOS-compatible single-photon avalanche diodes (SPADs) on silicon platforms.
Future Direction: Full IQP integration requires hybrid material platforms (SiC, LiNbO₃) for enhanced quantum coherence and 3D vertical stacking (TSV) to achieve mass-producible, portable diagnostic devices.

Technical Specifications

Parameter	Value	Unit	Context
Quantum Limit Scaling	1/√N	N/A	Standard Quantum Limit (SQL)
Quantum Limit Scaling	1/N	N/A	Heisenberg Limit (HL)
NV Center LOD	~1 aM-fM	M	Highest sensitivity quantum biosensing
Plasmonic Sensor LOD	~1 fM-pM	M	Quantum tunneling detection
QD Sensor LOD	~1 pM-nM	M	Fluorescence-based detection
NV Magnetometer Sensitivity	1	nT/√Hz	High-sensitivity magnetic field detection
Spin-Enhanced NV LOD	8.2 x 10^-19	M	HIV-1 RNA detection
Plasmonic Gap Distance (S)	0.5-2.8	nm	Quantum tunneling regime
DNA Conductivity (σ₀)	7.8	S/m	For gaps S < 3 nm
EIC Signal-to-Noise Ratio (SNR)	15-30	dB	Typical EIC biosensor performance
PIC Signal-to-Noise Ratio (SNR)	30-50	dB	Typical PIC biosensor performance
EIC Footprint	~0.01-10	mm²	Compact electronic integration
PIC Footprint	~1-100	mm²	Photonic integration
Bio-Impedance IC Power	<10	µW	Low-power CMOS circuit
Capacitive CMOS Resolution	4.5	fF	Cancer biomarker detection
CMOS Picoamp Readout Noise	7.2	pA_rms	Low-noise electrochemical array readout
Si₃N₄ MZI Sensitivity	6.8 x 10^-6	RIU	Refractive Index Unit sensitivity
Slotted Plasmonic Ring Sensitivity	1609	nm/RIU	Enhanced sensitivity via 10 nm slot width
Subwavelength Micro-ring Q-factor	~30,000	N/A	SARS-CoV-2 detection
MEMS Phase Shifter Loss	<0.5	dB	Low-loss IQP component
MEMS Phase Shifter Vπ	2	V	Low voltage control
Ge-Si SPAD Array Size	32 x 32	pixels	CMOS-compatible single-photon detection
Ge-Si SPAD Detection Probability	Up to 12	%	At 1310 nm, room temperature
NbN SNSPD Efficiency	91.6	%	Operating at 1.5 K (cryogenic)

Key Methodologies

The integration of quantum biosensing relies on reconciling the operational differences between quantum systems (coherence, low-temperature) and classical electronics (deterministic, ambient temperature).

Quantum State Initialization and Readout:
- NV Centers: Electron spin states are initialized using green laser excitation and manipulated using microwave radiation. Readout is achieved by detecting spin-dependent fluorescence, which shifts based on local magnetic or chemical changes.
- Quantum Dots: Detection relies on size-tunable fluorescence emission. Target molecule binding alters the QD’s fluorescence properties, providing an optical signal.
Plasmonic Quantum Tunneling:
- Molecular binding events are detected by monitoring changes in electron tunneling current between closely spaced metal nanoparticles (e.g., gold). The current decreases exponentially with the nanogap distance, providing ultra-high sensitivity to minute molecular interactions.
Electronic Integrated Circuit (EIC) Integration:
- CMOS technology is used to transduce biochemical interactions (impedance, capacitance, current changes) into measurable electrical signals directly on-chip.
- MEMS structures (cantilevers, resonators) are integrated with EICs to enhance sensitivity by detecting mass or stress changes induced by biomolecular binding.
Photonic Integrated Circuit (PIC) Integration:
- Waveguide-based sensors (Mach-Zehnder Interferometers, Ring Resonators) exploit the evanescent field extending from the waveguide surface. Biomolecular binding alters the local refractive index (RIU), causing a measurable shift in optical phase or resonance wavelength.
- PICs utilize high refractive index contrast materials (Silicon, Si₃N₄) compatible with CMOS fabrication for high-speed, low-power operation.
Integrated Quantum Photonic (IQP) Architecture:
- Hybrid Material Platforms: Utilizing materials like Silicon Carbide (SiC) or Lithium Niobate (LiNbO₃) alongside silicon photonics to improve nonlinear optical properties and maintain room-temperature quantum coherence.
- On-Chip Components: Integrating quantum light sources (generating single or entangled photons), low-loss phase shifters (for quantum gate implementation), and single-photon detectors (SPADs/SNSPDs) onto a single silicon chip.
- 3D Integration: Future IQP manufacturing aims for vertical stacking of quantum, photonic, and electronic layers using Through-Silicon-Via (TSV) techniques to maximize density and scalability.

Commercial Applications

The convergence of quantum sensing and integrated circuit technology is poised to revolutionize several high-value sectors:

Sector	Technology Focus	Application Examples
Clinical Diagnostics	NV/QD Biosensors, PICs	Early detection of cancer biomarkers (fM sensitivity), viral detection (SARS-CoV-2 RNA), and respiratory antibody profiling.
Personalized Healthcare	EIC/CMOS Sensors	Wearable cardiovascular monitoring (bio-impedance ICs), real-time glucose sensing, and monitoring of oxidative stress in living cells (NV relaxometry).
Drug Discovery & Genomics	Quantum Computing, QDs	Accelerated molecular structure search, protein folding simulation, high-throughput DNA sequencing, and detection of antibiotic resistance.
Quantum Metrology	NV Magnetometers	Quantum-enhanced magnetoencephalography (MEG) for non-invasive brain activity monitoring, surpassing classical noise limits.
Environmental Monitoring	PIC Biosensors	Highly sensitive detection of water pollutants and toxins using rib-waveguide MZIs and slotted plasmonic ring resonators.
Quantum Hardware	IQP Systems	Development of compact, scalable quantum processors and communication systems utilizing integrated single-photon sources and detectors (SPADs, SNSPDs).

View Original Abstract

Quantum biosensors offer a promising route to overcome the sensitivity and specificity limitations of conventional biosensing technologies. Their ability to detect biochemical signals at extremely low concentrations makes them strong candidates for next-generation sensing systems. This paper reviews the current state of quantum biosensors and discusses their future implementation in chip-scale platforms that combine microelectronic and photonic technologies. It covers key quantum biosensing approaches including quantum dots (QDs), and nitrogen-vacancy (NV) centers. This paper also considers their potential compatibility with electronic integrated circuits (EICs), photonic integrated circuits (PICs) and integrated quantum photonic (IQP) systems for future biosensing applications. To our knowledge, this is the first review to systematically connect quantum biosensing technologies with the development of microelectronic and photonic chip-based devices. The goal is to clarify the technological trajectory toward compact, scalable, and high-performance quantum biosensing systems.

Tech Support

Original Source

DOI: https://doi.org/10.3390/microelectronics1020005

References

2025 - Advancements In Biosensor Technologies: From Nanobiosensors To Biocompatible And Optical Systems For Clinical And Environmental Applications
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2024 - A Multiplex “Disposable Photonics” Biosensor Platform and Its Application to Antibody Profiling in Upper Respiratory Disease [Crossref]