A combined microwave-optical biomolecular sensor with high sensitivity and selectivity is presented. The microwave sensor characterizes the dielectric properties of a medium using the oscillation frequency shift. To improve the sensor sensitivity beyond the 1/ $ {f^{{3}}}$ phase noise limit, a quadrature-oscillator-based reactance sensing scheme is proposed, which attenuates the 1/ $ {f^{{3}}}$ noise by 20 dB/decade. Further sensitivity enhancement is realized by a novel chopping technique that modulates the free-running frequencies of the coupled oscillators differentially while maintaining a fixed locking frequency. To achieve a higher selectivity, optical sensors are introduced to target specific biomolecules. Utilizing single-photon avalanche diodes, they detect both photon intensity and photon emission time. A biosensor prototype was fabricated in a 28 nm CMOS technology. The microwave sensor achieves 0.2 ppm/ $\sqrt {\text {Hz}}$ frequency sensitivity with 11.5 mW power consumption. The optical sensor shows 500/s dark count rate and 300 ps timing jitter at 1 V excess bias. A protein thermal denaturation experiment confirms the sensitivity and selectivity enhancement of the dual-modality biosensing platform.

中文翻译：

---

微波-光学双模态生物分子传感平台的设计与分析

提出了一种具有高灵敏度和选择性的组合微波光学生物分子传感器。微波传感器使用振荡频移来表征介质的介电特性。提高传感器灵敏度超过 1/ ${f^{{3}}}$ 相位噪声限制，提出了一种基于正交振荡器的电抗传感方案，它衰减了 1/ ${f^{{3}}}$ 噪声降低 20 dB/十倍频程。进一步的灵敏度增强是通过一种新颖的斩波技术实现的，该技术在保持固定锁定频率的同时对耦合振荡器的自由运行频率进行差分调制。为了实现更高的选择性，引入了光学传感器来靶向特定的生物分子。利用单光子雪崩二极管，它们可以检测光子强度和光子发射时间。生物传感器原型采用 28 nm CMOS 技术制造。微波传感器达到 0.2 ppm/ $\sqrt {\text {Hz}}$ 频率灵敏度为 11.5 mW 功耗。光学传感器在 1 V 过偏压下显示 500/s 暗计数率和 300 ps 定时抖动。蛋白质热变性实验证实了双模态生物传感平台的灵敏度和选择性增强。