Chou Tzu-Hsuan, Yu Siyuan, Wilson Calder, Dawes Jacob, Park Jaehyeong, Marun Louis, Johnston Matthew L
IEEE Trans Biomed Circuits Syst. 2025 Aug;19(4):712-725. doi: 10.1109/TBCAS.2025.3576317.
This paper presents an impedance measurement system-on-chip (SoC) for flow cytometry (i.e. cell counting) applications. A source-differential, three-electrode sensing scheme is used in a microfluidic flow cell for particle detection. At the front-end, a lock-in amplifier architecture is used, including a high-gain TIA with 60 MHz bandwidth, passive mixers, and low-pass filters. The ac sensor signal is demodulated to extract in-phase (I) and quadrature (Q) baseband components to measure complex impedance. At the back-end, the SoC includes an 8-bit level-crossing ADC (LCADC) for digitizing I/Q signals, followed by real-time digital feature extraction and linear classification for real-time cell size determination. The SoC was fabricated in a 180 nm CMOS process. A measured prototype IC achieves 733 fA/$\sqrt{Hz}$ noise floor and 23 pArms input-referred noise from 1-1 kHz. Combined with a microfluidic flow cell, polymer beads in solution were used as cell surrogates to demonstrate particle counting. Measured results for particle diameters of 10 $\mu$m, 6 $\mu$m, 4.5 $\mu$m and 3 $\mu$m are shown. Following offline training, the SoC demonstrated on-chip classification of 4.5 $\mu$m and 6 $\mu$m beads with a prediction accuracy of 86.16% with pre-recorded data, and 73.6 % while performing real-time inline classification.
本文介绍了一种用于流式细胞术（即细胞计数）应用的片上阻抗测量系统（SoC）。在微流控流动池中采用源差分三电极传感方案进行粒子检测。在前端，采用锁相放大器架构，包括一个带宽为60 MHz的高增益跨阻放大器（TIA）、无源混频器和低通滤波器。对交流传感器信号进行解调，以提取同相（I）和正交（Q）基带分量来测量复阻抗。在后端，该SoC包括一个用于对I/Q信号进行数字化的8位过零模数转换器（LCADC），随后进行实时数字特征提取和线性分类以实时确定细胞大小。该SoC采用180 nm CMOS工艺制造。一个实测的原型集成电路在1 - 1 kHz范围内实现了733 fA/$\sqrt{Hz}$的本底噪声和23 pArms的输入参考噪声。结合微流控流动池，将溶液中的聚合物珠用作细胞替代物来演示粒子计数。展示了直径为10 $\mu$m、6 $\mu$m、4.5 $\mu$m和3 $\mu$m的粒子的测量结果。经过离线训练后，该SoC对4.5 $\mu$m和6 $\mu$m的珠子进行片上分类，对于预先记录的数据预测准确率为86.16%，在进行实时在线分类时准确率为73.6%。
