IEEE Trans Biomed Circuits Syst. 2023 Apr;17(2):257-272. doi: 10.1109/TBCAS.2023.3244570. Epub 2023 May 10.
The article presents for the first time a pill-based ingestible electronics with CMOS integrated multiplexed fluorescence bio-molecular sensor arrays, bi-directional wireless communication and packaged optics in a FDA-approved capsule for in-vivo bio-molecular sensing. The silicon chip integrates both the sensor array, and the ultra-low-power (ULP) wireless system that allows offloading sensor computing to an external base station that can reconfigure the sensor measurement time, and its dynamic range, allowing optimized high sensitivity measurement under low power consumption. The integrated receiver achieves -59 dBm receiver sensitivity dissipating 121 µW of power. The integrated transmitter operates in a dual mode FSK/OOK delivering -15 dBm of power. The 15-pixel fluorescence sensor array follows an electronic-optic co-design methodology and integrates the nano-optical filters with integrated sub-wavelength metal layers that achieves high extinction ratio (39 dB), thereby eliminating the need for bulky external optical filters. The chip integrates photo-detection circuitry and on-chip 10-bit digitation, and achieves measured sensitivity of 1.6 attomoles of fluorescence labels on surface, and between 100 pM to 1 nM of target DNA detection limit per pixel. The complete package includes a CMOS fluorescent sensor chip with integrated filter, a prototyped UV LED and optical waveguide, functionalized bioslip, off-chip power management and Tx/Rx antenna that fits in a standard FDA approved capsule size 000.
本文首次提出了一种基于药丸的可摄入式电子产品,它将 CMOS 集成的多路复用荧光生物分子传感器阵列、双向无线通信和封装光学器件集成在一个经 FDA 批准的胶囊中,用于体内生物分子传感。硅芯片集成了传感器阵列和超低功耗 (ULP) 无线系统,允许将传感器计算卸载到外部基站,从而可以重新配置传感器测量时间及其动态范围,以在低功耗下实现优化的高灵敏度测量。集成接收器的接收灵敏度为-59 dBm,功耗为 121 µW。集成发射器采用双频移键控/开关键控 (FSK/OOK) 工作模式,输出功率为-15 dBm。15 像素荧光传感器阵列采用电子光学协同设计方法,集成了纳米光学滤波器和集成亚波长金属层,实现了高消光比(39 dB),从而无需使用体积庞大的外部光学滤波器。该芯片集成了光电检测电路和片上 10 位数字化,在表面上实现了 1.6 飞摩尔的荧光标记灵敏度,每个像素的目标 DNA 检测限为 100 pM 至 1 nM。完整的封装包括一个带有集成滤波器的 CMOS 荧光传感器芯片、一个原型化的 UV LED 和光波导、功能化的生物滑液、片外电源管理以及适合标准 FDA 批准的 000 号胶囊尺寸的 Tx/Rx 天线。