Breast cancer is the second leading cause of cancer-related death in women. Approximately 50% of mortalities arise from estrogen receptor (ER)-positive tumors.[1] The major therapeutics for breast cancer are estrogen antagonists, like tamoxifen. Closely monitoring the antagonist in a patient would increase the efficacy of endocrine therapeutics while alleviating side effects during treatment. However, existing methods such as routine immunohistochemistry cannot effectively monitor estrogen antagonists because of their low throughput and high cost. To address these issues, we have devised a bioelectronic sensor of estrogen antagonists by grafting ER to the point of care (POC) glucometer.

Glucometers use a test strip containing glucose dehydrogenase (GDH), an enzyme that reacts with glucose in blood droplets and generates electric signals. To obtain an estrogenic regulated GDH, we inserted the ligand-binding domain of ER at all the 456 amino acids of the GDH. More than 7000 colonies were screened to identify the allosteric insertion sites globally. We find that the estrogenic regulated GDH can electrochemically detect a series of ER modulators as low as 1 nM with ≥40% dynamic range. Successful engineering of the classical glucose dehydrogenase yields a self-power antagonist sensor and establishes a platform for designing personalized diagnostics in a POC fashion.

[1] Torre, Lindsey A., et al. "Ovarian cancer statistics, 2018." CA: a cancer journal for clinicians 68.4 (2018): 284-296.