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This paper proposes a low-noise readout circuit with a noise floor of 11 fArms/sq(Hz) and a bandwidth of 1.3 MHz. The novel electrostatic discharge (ESD) leakage current cancellation stage allows the circuit to detect sub-pA range current input. A total trans-impedance gain of 160 dB is obtained by a current preamplification stage with a 100 × current gain followed by a transimpedance amplifier (TIA) with a 1 Mohm feedback resistive gain. The reader is designed in a 0.18 μm CMOS process and consumes 5.6 mW from a 1.8 V supply.

Quantitative detection for nanomolar analytes is a challenge for surface-enhanced Raman scattering (SERS). In this report, a SERS method which combined with an internal standard method and a two-step centrifugation method was established for trace analysis of two drugs using a portable Raman spectrometer. Metformin hydrochloride was used as an internal standard for phenformin hydrochloride to increase the linearity of SERS detection, while, streptomycin sulfate was used for tigecycline. The two-step centrifugation method for sample preparation increased the density of hot spots and the concentration of analyte by accumulating silver nanoparticles. Therefore, the detection sensitivity was significantly improved. Furthermore, the repeatability of SERS signals was increased by adding 200 µL of the sample solution into a slit-type quartz cuvette to make the excitation light transmit through a heavy thickness sample solution. The RSDs of SERS signal intensity ratio of phenformin hydrochloride and tigecycline to internal standard were 1% and 1.6%, respectively. Finally, phenformin hydrochloride and tigecycline exhibited a good linearity in the range of 1–500 nM (R2 = 0.9976) and 10–750 nM (R2 = 0.9926), respectively. In a word, this method greatly improved the lower limit of quantitation of SERS, and laid foundation for rapid and convenient quantitative detection of low concentration drug in biological samples.