Fully Integrated Pneumatic-Free and Magnet-Free CMOS Ferrofluidic Platform for Comprehensive Biomolecular Processing.

Abstract

This article presents a fully integrated CMOS ferrofluidic platform featuring on-chip three-electrode electrochemical cells, temperature regulators, and magnetic sensors. The proposed platform consists of 25 ferrofluidic pixels and 2 magnetic sensors. Each ferrofluidic pixel comprises a spiral inductor, a three-electrode electrochemical cell, a temperature sensor, and a localized Joule heater. Unlike pneumatic-based platforms, this ferrofluidic platform does not require an external pneumatic pump to drive droplets. Instead, the on-chip spiral inductors generate magnetic fields to manipulate the ferrofluidic droplets. Additionally, these inductors are repurposed as heat radiators. The CMOS ferrofluidic platform is implemented using a 45-nm CMOS SOI process. Theoretical analyses of ferrofluidic control and magnetic sensing are conducted to understand the relationship between ferrofluidic movement conditions and the integrated magnetic sensor. The on-chip electrochemical potentiostat is characterized using various concentrations of methylene blue solution, and the variation in the electrochemical sensor is measured. As proof of concept, biological measurements with on-chip real-time recombinase polymerase amplification (RT-RPA) are demonstrated. The proposed platform offers a fully integrated solution for ferrofluidic manipulation, sensing, and temperature regulation without the need for external bulky equipment, thereby supporting advanced biomolecular processing. While RT-RPA is used here solely for demonstration purposes, our ferrofluidic multi-functional CMOS array platform is also capable of processing a wide range of other molecular analytes. This versatility underscores the platform's potential for broad applications in molecular diagnostics and bioanalytical research.