The objective of the proposed research is to develop a microfluidics-guided digitally encoded combinatorial method, referred to as digital one-disc-one-compound (ODOC) array, integrating state-of-the-art combinatorial chemistry with emerging microfluidics, microfabrication, encoding and matrix theories, for discovery of cancer-targeting molecules with high throughput, high efficiency and high accuracy at low cost. As an indispensable tool for biology and medicine, combinatorial chemistry has enabled high-efficiency modular synthesis of biomolecules and high-throughput exploration of the lead compounds for specific biological targets. However, existing combinatorial strategies only allow either large-scale synthesis or chemical addressability, but not both. Moreover, high equipment cost and complex chemical processing limit their utility to laboratories only. Under the proposed research, we aim at addressing large- scale combinatorial synthesis, digital molecular identification, synthetic throughput, parallel screening, and quantitative analysis of combinatoria chemistry as a whole, by introducing batch-fabricated microdisc carriers with digital barcodes and matrix-directed combinatorial synthesis in reconfigurable microfluidic networks. Specifically, cancer integrin-targeting peptide libraries will be designed and synthesized on the digital ODOC array, followed by microfluidic quantitative screening of the cell-ligand interactions on the array Comprehensive structure-activity relationship (SAR) data obtained by quantitative cell binding of every single compound-disc facilitates design of focused libraries for rapid optimization of cancer-targeting ligands with higher specificity and affinity than those previously discovered. In brief, the proposed digital ODOC array, once developed, will provide a transformative paradigm for high-throughput high-efficiency screening, optimization, and characterization of biomolecules targeting at various types of cancer cell receptors.

Public Health Relevance

The objective of the proposed research is to develop a microfluidics-guided digitally encoded combinatorial method, referred to as digital one-disc-one-compound (ODOC) array, integrating state-of-the-art combinatorial chemistry with emerging microfluidics, microfabrication, encoding and matrix theories, for discovery of cancer-targeting molecules with high throughput, high efficiency and high accuracy at low cost.

Agency
National Institute of Health (NIH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA173243-02
Application #
8721896
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Dickherber, Anthony J
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Davis
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
City
Davis
State
CA
Country
United States
Zip Code
95618