(1133-B) Moving towards patient-centric clinical trials with metabolomics analysis of dried blood samples using an at-home microsampling collection device
Monday, February 5, 2024
2:00 PM – 3:00 PM EST
Location: Exhibit Halls AB
Abstract: Clinical trials require significant resources and time and encounter challenges with sample collection due to volume restrictions and collection times being limited to the clinic visit. However, recent technological advancements in patient sample collection have the potential to reduce patient burden and enrich clinical trial data. Among these technologies are microsampling devices, which allow for at-home collection of dried whole blood microsamples (DBS) and digitally capture patient metadata. Advances in analytical technologies have enabled lower detection limits with smaller sample volumes. To realize the potential of these devices, analytical experiments are required for benchmarking test samples against current collection methods. In pilot studies, metabolomics analyses of whole blood were performed to determine if metabolites could be robustly detected from DBS. Metabolites can provide insight into disease biology and drug response, among other important insights.
Whole blood was collected from healthy donors and cancer patients in a microsampling device (Tasso-M20), which contained a cartridge with four 20 µL DBS discs per device. Benchmarking studies were performed to evaluate robustness and reproducibility over time, and by varying environmental conditions, including high temperature/humidity as well as room temperature storage up to 30 days. Stable isotope labeled metabolites were spiked into the cartridges and used as internal standards to evaluate robustness of protocol (% Recovery and RSD). An automated method using a liquid handler was developed for metabolite extraction from DBS. Polar metabolites, including over 200 central carbon metabolites, were separated using ion-pairing chromatography and detected by targeted mass spectrometry.
The study demonstrated that the method was robust and reproducible: >80% of detected metabolites had RSD < 20%, and 93% of metabolites were stable at 14-day room temperature storage. However, metabolite stability was affected by high heat/humidity storage: after 2 days, 10% of metabolites were significantly affected by these conditions. Metabolite abundances were compared in venous plasma and DBS from cancer patients and healthy donors. Similar metabolic trends were demonstrated between DBS and plasma; for example, the kynurenine abundance ratio (cancer/healthy) was 1.27 in DBS and 1.26 in plasma. Kynurenine and other cancer-relevant metabolites were detected from DBS collected longitudinally and demonstrated differential abundance between healthy donors and cancer patients. This work demonstrates the ability of microsampling devices to help improve data collection for clinical studies, enable more rapid and informed clinical decisions, and provide a valuable tool for discovery research.