Abstract Resubmission: Develop Point-of-Care Volumetric-Bar-Chart-Chip for Drug Quantitation This proposal is a resubmission of a three-year R01 (DA035868-01) renewal. During the last grant period, we published 40 peer-reviewed papers and applied for 4 patents, with 17 publications and 2 patents directly resulted from this grant award support. We still have numerous raw data and 4 pending publications from this grant. The original patent featured in the grant, Volumetric-Bar-Chart-Chip (V-Chip) patent, was officially issued in 2015 (US9097710 B2) and licensed to Etta Healthcare and Ovagen. Our lab chip system is also a winner of 2015 R&D 100 award. In the resubmission, we focus on further developing the quantitation capability and point- of-care user friendliness of the V-Chip platform for drug quantitation. Key innovations and changes we incorporated to address the reviewers' concerns include: 1. Improving the design of the V-chip so that the device is more robust for quantitation and user-friendly in a point of care setting. This includes modifying the on-chip meter bar to eliminate the need for separate calibration, eliminating the need for manual pipetting by the integration of on-chip pumps, and changing the manual glass etching process to computer-guided laser-based production. 2. Adding more data on PtNP conjugation to prove the technical feasibility. 3. Changing the contact PI to Dr. Ping Wang as the focus of the proposal shifts to clinical validation and end-user pilot testing. We will assess clinical sensitivity, clinical specificity, intra- and inter-user variability in a clinical environment (Hospital of University of Pennsylvania) with targeted end-users. These changes should demonstrate the clinical value and robustness of our device. Current non-invasive (or minimal-invasive) point-of-care (POC) platforms to assist the therapeutics for Substance Use Disorder (SUD) are facing challenges of non-quantitation, inaccuracy, non-compatible with diverse biological specimens, long assay time, and requirement for sophisticated instrument and/or expertise for readout. Here, we propose an Integrated Competitive Multiplexed Volumetric Bar Chart Chip (ICV- Chip) to assay drug targets in urine, whole blood, and saliva. The ICV-Chip platform is quantitative, sensitive, accurate, fast, portable, convenient and low cost. The ICV-Chip bioassay is non/minimally invasive and able to assess the patients' adherence to their medical treatment by the integration of an adherence marker Acetazolamide. The development of the ICV-Chip thus overcomes most of the current technology limits and opens up the possibility of instrument-free personalized assessment of drug abuse.