Title: Protein Analysis to Address Unmet Clinical Needs
Prof. H. Tom Soh, Depts. of EleDissctrical Engineering & Radiology, Stanford University; Chan-Zuckerberg Biohub
Prof. Michael J. Mahan, Dept. of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara
The capability to simultaneously measure the concentration of many (100+) specific protein targets in a single blood sample has the potential to provide insight into an individual’s health state and prove valuable in the early detection and effective treatment of many diseases. For such a method to realize clinical utility, however, stringent performance characteristics are necessary which pose significant technical challenges. Briefly, the technique must be extremely specific, sensitive, and precise in the measurement of its target, furthermore, it must be generalizable enough such that it can simultaneously measure many specific target proteins varying greatly in abundance, all in a single sample, assay run, and the same level of sample dilution. This requirement stems from the widespread inhibitory effects caused by complex media samples such as serum and plasma that cause artifacts such as dilutional nonlinearity in multiplexed assays, rendering results quantitatively entirely unreliable for many targets, the identities of which may vary from patient-to-patient. Currently, no existing technology can achieve all of the characteristics described above: simultaneous, precise, ultrasensitive, and highly multiplexed cytokine measurements, generalizable to targets varying vastly in physiological abundance, and all performed at a single dilution.
To address this unsolved problem, we have developed the Proximity Ligation-Assisted Sequencing (PLA-Seq) assay. In this presentation, I shall describe the unmatched performance characteristics of PLA-Seq, along with unique and novel tunability characteristics that enable it to achieve each of the requirements listed above. Empricial demonstration of these tuning mechanisms as well as the demonstrated performance of PLA-Seq in complex media shall be presented as well. Finally I will briefly describe numerous additional projects I have either substantially supported or led.