In liquid biopsy, biomarkers such as small nucleic acids, circulating tumor cells (CTCs), and extracellular vesicles (EVs) are used for cancer detection. Detecting CTCs is particularly important, as it provides insights into membrane proteins, glycan structures, and internal nucleic acids, but their rarity makes detection challenging amid millions of blood cells. To address this, we developed an innovative method using ion-sensitive field-effect transistors (ISFETs) combined with enzymatic signal amplification to detect cell membrane proteins with high sensitivity. We validated this approach with breast cancer cell lines, successfully detecting epidermal growth factor receptor (EGFR) on their membranes. The EGFR expression level among four breast cancer cell lines was compared, with results matching those from fluorescence-activated cell sorting (FACS). In addition, human epidermal growth factor receptor 2 (HER2) was also successfully detected by employing signal amplification based on enzymatic reactions. These cell-based transistors could offer advantages in miniaturization and the simultaneous analysis of multiple molecules on cell and EV membranes.
Sugita et al. (Sat,) studied this question.