Single-cell impedance sensing on integrated circuit chip for fast tumor diagnosis

Accurate and prompt tumor diagnosis plays a critical role in surgical decision-making to minimize damage to patients with benign tumors and maximize the cure rate of cancer patients. Although imaging, molecular testing, and histopathology assist in preoperative and postoperative tumor assessments, a fast, automated, and easy-to-operate method for intraoperative tumor diagnosis is lacking. Here, we introduce an innovative integrated circuit-based single-cell electric cell-substrate impedance sensing (IC-ECIS) platform capable of rapid intraoperative differentiation between cancerous and non-cancerous tumors. Fabricated on a semiconductor chip, this system captures ultra-weak single-cell impedance signals with exceptional sensitivity for single-cell discrimination for cancer risk evaluation. The implementation of a polymer-embedded silicon fan-out (P-eSiFO) packaging approach has reduced post-fabrication costs to under $1 per chip and allowed the microelectrodes batch processing on multi-project wafer chips. The diagnostic results can be obtained in 20 min without compromising cell viability. Clinical tumor samples from the thyroid, liver, gallbladder, bile duct, breast, and pancreas were tested on-chip to evaluate cancer risk. The on-chip diagnostic findings aligned with traditional histopathological analysis and flow cytometry results. This technology provides a fast, stable, automated, and low-sample-consumption diagnostic solution for tumors, paving the way for large-scale implementation of semiconductor-based diagnostic tools in precision oncology and personalized medicine.