From biochemical nanosensors to imaging to informatics to COVID-19 convalescent plasma - developing diagnostics and therapies for clinical medicine

Current cancer management follows a multipronged approach that include surgery, radiation, and chemotherapy. There is a pressing need for a platform technology to provide precision chemotherapy screening, drug delivery detection, and real-time therapy efficacy monitoring. We have developed single walled carbon nanotube (SWNT) sensors for the detection of chemotherapeutics, more recently for temozolomide (TMZ) and its byproduct 5-Amino-4-imidazolecarboxamide (AIC) with sensitivity at 5-500 μM and in vitro viability up to 7 days in TMZ treated glioblastoma cells. Sensors for irinotecan, cisplatin, and lomustine were developed with sensitivities at 50 μM. H2O2 sensors were used to measure the therapy efficacy of gemcitabine and irinotecan in pancreatic ductal adenocarcinoma in vitro and in vivo. Multiplexing these sensors could yield insights into delivery, diffusion, metabolism, and efficacy of chemotherapeutics in hours or days. Other strategies are being developed such as ratiometric approaches and wavelength-induced frequency filtering to improve performance and sensitivity. A fiber optic platform was developed as a minimally invasive form factor to integrate the sensor hydrogel, optical waveguide, and detection system. As a physician-scientist in NYC, my research rapidly shifted to the role of convalescent plasma (CP) in COVID-19. CP can be used to passively transfer antibodies from recently recovered patients to actively infected treatment-resistant patients. Initial studies revealed antibody neutralizing activity peaked at 31-35 days post symptom onset. Initial outcomes in severe and life-threatening COVID-19 hospitalized patients show CP as a potentially efficacious treatment for non-intubated patients. Retrospective study of 427 CP transfusion events yielded 12.9% of transfusion reaction rate with vast majority due to COVID-19 disease not CP. Increased risk was identified in patients with blood group B or cancer, and decreased risk for patients in their 80s.