Benchmarking the Sensitivity and Specificity of the Herringbone Microfluidic Device for Rare Particle Capture

项目总结

PROJECT SUMMARY Many new technologies are developed and validated on the bench of the investigator, but few have the opportunity to test their performance with blinded, control samples. The lack of standards can be due to the novelty of technology or processing conditions, or simply the uncertainly of the underlying biology within patients. This is particularly challenging for liquid biopsy assays, as universal standards are desperately lacking, further slowing down future translation to the clinic. Through our work with the RADx-Rad program, we have begun validation testing for the parent technology featured in our R01 application: the ‘herringbone chip’, or EVHB-Chip. The use of their blinded samples has been powerful, both validating our internal findings, while also catching the attention of the regulatory agencies and other researchers. For this proposed study, we will conduct our most complex validation panel yet, a full challenge panel to evaluate specificity and sensitivity of our assay, testing over 100 blinded samples. This work will be done quickly, as we have all the tools and staff in place to test these samples in one month’s time. We will have full data harmonization with the NIH DCC, to ensure consistency, data standardization, and data deposits to the dbGAP database. Each sample is uniquely barcoded and the contents will include a set concentration of nanoscale analytes for us to test with the concentration varying from 1x to 4x our limit of detection. Contaminating analytes are also added to these samples, to allow for specificity to be determined. We will run each sample through our device, extract the RNA using our automated system, quantify the amount of and types of RNA transcripts detected and share the data with the DCC. This will trigger an automatic data unblinding, data transformation and analysis, allowing us to quickly assess device performance. In addition to getting this critical device validation work completed, the resulting publication will establish a new standard for diagnostic device development, which includes multi-party R&D efforts.