Light-Addressable Regenerative Photoelectrochemical Biosensor Array with Self-Calibration for High-Throughput and Accurate Detection of Circulating Tumor Cells

Abstract

High-efficiency detection of circulating tumor cells (CTCs) provides real-time information for cancer diagnosis and therapy. The light-addressable photoelectrochemical biosensor array (LAPECBA) is the best candidate for rapid and high-throughput detection. However, strong background interference, baseline drift, and batch deviation hinder the further application of LAPECBA. Here, we reported a LAPECBA with self-calibration for high-throughput and accurate detection of CTCs. The α-Fe₂O₃/Bi₂S₃ heterojunction was synthesized as an electrode substrate material to enhance the photoelectric performance, and the aptamer-DNA concatemer (ADC) interface was constructed for high-efficiency capture of CTCs and release the CTCs with the assistance of ATP. Light-addressable multiplexed detection was achieved by constructing multiple regions on a single FTO electrode and sequentially exposing them with a laser pen. A self-calibration strategy was implemented by calculating the photocurrent differences between the detection channels and calibration channel to diminish the strong background interference, baseline drift, and batch deviation. Under optimal conditions, this LAPECBA could detect CTCs in the linear range of 50–1000 cells mL^–1 with a detection limit of 2 cells mL^–1 (S/N = 3). Additionally, the trapped CTCs were released by ATP-stimulated ADC disintegration, benefiting downstream analysis and demonstrating the high regenerative potential of LAPECBA. This self-calibrating LAPECBA exhibited great potential for accurate and high-throughput detection of CTCs in clinics.