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• Shared operational amplifier-based readout capable of multimodal measurements. • Lightweight, multiplexed electrochemical sensors on flexible textile threads. • Miniaturized sensing platform for multiple analyte detection. • Probe platform validation with oxygen and pH monitoring. High throughput screening (HTS) based on microwell (or bioreactor) arrays is a well-established approach for rapid screening and identification of lead molecules or target analytes for drug discovery and other applications in biotechnology. However, it has been challenging to scale up these platforms due to the lack of integrated sensors to monitor the microenvironment of each microwell in the array needed. In this work, we present a practical solution for a miniaturized multiplexed sensing system with integrated circuitry capable of performing continuous electrochemical potentiometric and amperometric measurements. The platform uses lightweight multiplexed electrochemical sensors implemented on thin textile threads, all of which share a single operational amplifier (op-amp) and a switch network for both voltage and current measurements. The resulting platform forgoes the need for large-area sensors or bulky multichannel potentiostat with a simple readout circuitry capable of multimodal measurements. The design and validation of the multiplexed sensing system have been reported in the context of measuring pH and oxygen (O 2), which are crucial biomarkers for any HTS application. The thread-based pH and O 2 sensors possess sensitivities of ∼65.87 mV/pH for the pH sensor (n = 3) and 0.6621 nA/mg L-1 for the O 2 sensor (n = 3). This architecture is modular such that it can be easily extended to monitoring multiple biomarkers employing thread-based sensors and sharing the same readout circuitry, making it a practical and versatile tool for biotechnology research. [Display omitted] [ABSTRACT FROM AUTHOR]