Design and Implementation of Current Readout for Biomedical Applications

In recent decades, miniature biosensors have emerged as a promising technique for medical and biological applications due to their comparable stability and sensitivity compared to traditional laboratory methods while offering significant cost and flexibility advantages. These biosensors have the ability to detect multiple analytes and physical conditions, allowing the design of smaller, smarter, and tailored systems.

However, despite the advantages of biosensors, their output signals are often relatively weak and are accompanied by strong background interference. Although laboratory methods can achieve accurate signal reading using various techniques or even multiple equipments, miniaturized biosensor systems can only rely on fully integrated readout electronics for signal filtering, amplification, and quantization, which is the main bottleneck for the wide deployment of biosensors in point-of-care testing or other applications. The challenges of biosensor readout design include increasing the dynamic range and readout speed, reducing power consumption and area, and achieving high signal fidelity within a reasonable testing cost.

This thesis focuses on optical biosignal readout to achieve low power consumption while achieving high dynamic range and signal linearity. In this research, a proof-of-concept prototype based on discrete components was first developed for a laser Doppler system readout, which offers a transimpedance gain of 151.4 dBΩ (3.9% higher than the state-of-the-art), a nonlinearity of 0.05%, and a dynamic range of 83.9 dB via a time-domain readout scheme.

These specifications highlight the capability of the designed system to effectively amplify and process the signals generated by the laser Doppler system while maintaining a high degree of linearity and a wide dynamic range, thereby demonstrating its potential for accurate and reliable readout in laser Doppler-based applications. Subsequently, a fully CMOS-integrated chip was designed in a standard 0.18 μm process to further improve the readout dynamic range to 124 dB for quantization of fluorescence and bioluminescence biosensor signals.

This design incorporates innovative features such as passive loop delay compensation, an asynchronous switching scheme, and a fully digital time domain comparator. It achieves state-of-the-art performance, that is, a dynamic range of 124 dB while maintaining linearity and sensitivity up to 98.3% and 1pA, respectively. It consumes only 210 μA current from a 1.8 V supply, with an input current range of 2 pA to 3.25 μA, and pA-level input-referred noise level. Finally, the designed chip is used to develop a miniaturized in vitro NanoLuc (NLuc) luciferase-based bioluminescence sensing system for biomolecule quantification. The pM-level detection limit of the designed system is comparable to the laboratory instrument, which has a detection limit of 10 pM under the same setup. It is important to note that the advantages of bench-top instruments come at the cost of increased size, complexity, and costs and often require experts to handle them. CMOS-based chips, on the other hand, excel in their small form factor, potential for low-cost manufacturing, and suitability for portable or wearable applications. This fabricated chip can be the foundation for developing a portable disease detection device, as demonstrated in a complete bioluminescence prototype system developed in this research.