CTC Purification System Based on Thermoresponsive NanoSubstrates

DESCRIPTION provided by applicant The goal of this SBIR Phase II proposal is to conduct the advanced development of the rd gen Thermoresponsive NanoVelcro assay in order to achieve rapid purification of circulating tumor cells CTCs from non small cell lung cancer NSCLC patient blood samples paving the way for CTC derived molecular signatures and functional readouts This project is led by Dr Garcia PI who has extensive experience in early stage development of the technology and has a background in surface chemistry microfluidics and in vitro diagnostic technologies He is supported by an interdisciplinary team comprising business development FDA expertise QC QA management nanotechnology support lung cancer clinical utility genetic analysis biostatistics industrial collaborators nd downstream potential customers NSCLC accounts for andgt of lung cancer cases Since NSCLCs are usually not very sensitive to chemotherapy and or radiation the advent of targeted therapy by epidermal growth factor receptor EGFR inhibitors offer a great treatment options to a sub population of NSCLC patients who carry oncogenic driver mutations in their EGFR genes To guide the implementation of targeted therapy invasive biopsy or surgery is employed to sample NSCLC tissues for determining the presence of these EGFR mutations However these invasive sampling procedures impose significant risk to the patients As an alternative CTCs can be captured repetitively and analyzed in a minimally invasive manner thus providing a systemic picture of the malignant clones that possess high metastatic capacity The proposed Thermoresponsive NanoVelcro assay is composed of two individual components i a digital fluidic handler with an embedded temperature control module and ii a custom designed chip holder in which a clamp down design allows instant assembly of a NanoVelcro substrate with an overlaid PDMS component will be designed and fabricated at CytoLumina To highlight the significance of our downstream studies we will gather serial blood samples from lung cancer patients We will collect the purified CTCs and subject them to mutational analysis for eight genes including EGFR Further the purified CTCs will be introduced to a variety of in vitro cell culture systems i e microfluidic and D cell culture platforms established by our joint team UCLA and CytoLumina to create viable CTC cell lines The personalized cell lines will be used to study patterns in drug susceptibility which is linked to the underlying genetic driver mutation PUBLIC HEALTH RELEVANCE A sub population of non small cell lung cancer NSCLC patients carries an oncogenic driver mutation in their genes that can be treated by epidermal growth factor receptor EGFR inhibitors CytoLuminaandapos s SBIR Phase II proposal aims to develop a circulating tumor cell CTC purification system capable of instant purification of NSCLC CTCs from patient blood samples which will facilitate efficient and minimally invasive identification o the mutation in these patients