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.

Public Health Relevance

Resubmission: Develop Point-of-Care Volumetric-Bar-Chart-Chip for Drug Quantitation Current point-of-care (POC) methods for the measurement of illicit drugs suffer from non- quantitation, low accuracy, low throughput and long turn-around time. In this application, we proposed to develop an Integrated Competitive Volumetric Bar Chart Chip (ICV-Chip) to assay multiple drug targets in diverse clinical samples, which integrates the abilities to fully address the above-mentioned limitations. The development of the ICV-Chip holds the potential to meet the challenges listed in the PA-16-076 grant mechanism.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
3R01DA035868-06S1
Application #
10111962
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Moore, Holly Marie
Project Start
2013-07-15
Project End
2021-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
6
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Pathology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Li, Ying; Uddayasankar, Uvaraj; He, Bangshun et al. (2017) Fast, Sensitive, and Quantitative Point-of-Care Platform for the Assessment of Drugs of Abuse in Urine, Serum, and Whole Blood. Anal Chem 89:8273-8281
Li, Ying; Xuan, Jie; Song, Yujun et al. (2016) Nanoporous Glass Integrated in Volumetric Bar-Chart Chip for Point-of-Care Diagnostics of Non-Small Cell Lung Cancer. ACS Nano 10:1640-7
Jo, Myeong Chan; Qin, Lidong (2016) Microfluidic Platforms for Yeast-Based Aging Studies. Small 12:5787-5801
Song, Yujun; Wang, Yuzhen; Qi, Wenjin et al. (2016) Integrative volumetric bar-chart chip for rapid and quantitative point-of-care detection of myocardial infarction biomarkers. Lab Chip 16:2955-62
Zhang, Kai; Gao, Min; Chong, Zechen et al. (2016) Single-cell isolation by a modular single-cell pipette for RNA-sequencing. Lab Chip 16:4742-4748
Han, Xin; Liu, Zongbin; Zhao, Li et al. (2016) Microfluidic Cell Deformability Assay for Rapid and Efficient Kinase Screening with the CRISPR-Cas9 System. Angew Chem Int Ed Engl 55:8561-5

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