A research team led by Jia Yanwei, assistant professor in the Institute of Microelectronics at the University of Macau (UM), has developed a semiconductor chip-based single-cell electrical impedance platform for drug screening, which can accurately distinguish cancer cells from non-cancerous cells from clinical tumor tissues and evaluate drug efficacy and toxicity simultaneously. The system is expected to be used by clinicians in medication guidance, thereby realizing the commercialization of research results and facilitating technological innovation in the Guangdong-Hong Kong-Macao Greater Bay Area. The research findings have been published in the internationally renowned journal Advanced Science and selected as the cover of the journal.
In recent years, precision medicine has emerged as a hot topic in the medical field. Precision medicine in oncology aims to tailor treatment strategies for individual cancer patients based on the distinctive cellular and molecular traits of their tumors, aiming for optimized therapeutic outcomes. Clinicians analyze genetic mutations or other molecular features of individual tumors to maximize treatment effectiveness. However, predicting outcomes solely based on mutations of specific genes poses challenges due to the intricate drug pathways involving numerous genes. A more direct approach involves screening drugs at the cellular level using primary tumor cells, promoting personalized cancer treatment. The application of microfluidic platforms has enabled drug screening using limited biopsy samples, thus achieving precision cancer treatment. Nevertheless, a significant challenge persists: Not all primary tumor cells are cancer cells.
The UM research team has therefore developed a system that integrates single-cell identification and drug screening on a semiconductor chip. This system can simultaneously assess drug efficacy against cancer cells and toxicity against non-cancerous cells. An integrated circuit for single-cell electrical impedance sensing was constructed on this semiconductor chip. This circuit is capable of sensing extremely weak signals, enabling differentiation between cancerous and non-cancerous cells without compromising cell viability. Single-cell identification was validated using breast, lung, and liver cell lines, as well as liver cancer samples from clinical patients. The diagnostic results of tumor tissue were consistent with clinical pathology. Following single-cell identification, drug screening was performed on the same chip to dually assess drug efficacy and toxicity in breast cancer models and clinical liver cancer patients. The on-chip drug screening results were validated by corresponding off-chip experiments using breast cell lines. The effectiveness or ineffectiveness of a drug screened on the IC-ECIS chip demonstrated consistency in the presence or absence of specific mutations in the drug-related genes determined via exome sequencing of individual liver tumors, validating the method for precision medicine.
According to the research team, semiconductor chip-based technology can provide clinicians and patients with reliable medication guidance, and low cost of equipment in comparison with that of gene sequencing. The technology enable mass production and the realization of precision medicine for all. Furthermore, this technology has achieved scientific and technological transformation, with Zhuhai ProMed Precise Medical Technology Co., Ltd. incubating it for industrialization and clinical application at the Third Affiliated Hospital of Sun Yat-sen University and the First Affiliated Hospital of Guangzhou Medical University.
The corresponding author of the study is Professor Jia, while UM doctoral student Hui Wenhao and Professor Lei Ka-Meng are the co-first authors. Wang Ping, chief physician of the First Affiliated Hospital of Guangzhou Medical University, and Yi Shuhong, chief physician of the Third Affiliated Hospital of Sun Yat-sen University, are also co-corresponding authors. UM professors Rui Martins and Mak Pui In, and the technical and management team of the State Key Laboratory of Analog and Mixed-Signal VLSI also made significant contributions to the study.
This work was supported by the Macau Science and Technology Development Fund (FDCT) [FDCT 0029/2021/A1, FDCT0168/2023/RIA3, FDCT004/2023/SKL]; University of Macau [MYRG2023-00034-IME, MYRG-GRG2023-00092-IME], and Dr. Stanley Ho Medical Development Foundation [SHMDFOIRFS/2024/001].
The article can be viewed at: https://advanced.onlinelibrary.wiley.com/doi/full/10.1002/advs.202503131
