Drift-Compensated Magnetic Biosensors Using Concurrent Dual-Frequency Oscillators

Magnetic biosensors that utilize magnetic nanoparticles (MNPs) as labels for biodetection assays have gained prominence in recent years due to their potential for use in rapid, accessible, and low-cost diagnostics devices. Resonance-shift-based magnetic biosensors are particularly suited for such applications, as they are readily implemented in standard CMOS processes, do not require external biasing or magnetic fields, and often do not require complex preparation chemistry. However, LC oscillator-based sensing cells suffer from drift induced by temperature fluctuations and other slow-varying noise sources, significantly degrading the signal-to-noise ratio (SNR) and impairing the achievable limit of detection. In this work, we propose a drift compensation approach utilizing a dual-frequency oscillator, operating concurrently at two widely spaced frequencies that track each other. The oscillator is designed such that the magnetic susceptibility of MNPs is large at the lower frequency but small and negative at the higher frequency. Thus, drift causes the oscillation frequencies to shift together, which can be canceled out, whereas the desired magnetic signal is encoded in the frequency difference. This enables simultaneous sensing and drift compensation, unlike previous approaches that utilize frequency switching. A proof-of-concept <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$2 \times 2$ </tex-math></inline-formula> array spectrometer integrated circuit (IC) is presented, which achieves sub-ppm sensitivity and can be completely powered and controlled from a laptop Universal Serial Bus (USB) interface. Each sensing cell consumes as little as 3.1 mW and is tunable over a wide frequency range of 1.2–1.65 GHz/2.9–4 GHz. A single-step, wash-free immunoassay to detect streptavidin is performed, highlighting the viability of the magnetic spectrometer IC for in vitro diagnostic bioassays.