The great need for more efficient and effective oncologic drug development has driven the discovery and integration of biomarkers into all phases of clinical research. Further still, biomarkers are entering the clinical arena as early means of determining which patients are likely benefiting from a particular drug. One field of targeted therapy that has relied on biomarkers for many years is cancer immunotherapy which seeks to use """"""""vaccines"""""""" molecules to activate and direct immune cells, and their secreted cytokines and antibodies, against tumors. Several cytokines have been found to be informative in understanding the type of immune response (e.g., Th1 or Th2). Molecular analyses have suggested that a combination of these immune markers could predict which patients will have clinical benefit. ? ? Equipment currently used for measuring a panel of cytokines is: 1) very expensive 2) highly labor-intensive and 3) limited in sensitivity. There is a need for a technology that completely automates the measurement of user-configured panels of cytokines at increased sensitivity and more importantly that an individual investigator can afford. Such technology will accelerate the discovery process in oncological research initially and enable other areas of research as well. ? ? In phase I, we have successfully demonstrated a rapid and parallel immunoassay lab-on-a-chip based on manipulation of discrete sub-microliter droplets. Heterogeneous """"""""sandwich"""""""" assays were performed on IL-6 within 10 minutes, which includes completely automated washing steps on a programmable chip. During phase I, we resolved a number of research issues to demonstrate the feasibility of performing immunoassays on a digital microfluidic chip while in Phase II we will build on those results to: scale up the number of user-configured immunoassays performed on a chip to 384 by developing a chip that can perform 48 simultaneous cytokine immunoassays on each of 8 PBMC samples stimulated by 8 peptides; demonstrate reproducibility, linearity, range, LOD, recovery, inter/intra-assay variability on a statistically significant number of samples, perform method comparison, and develop cell handling capability on-chip for fully integrated operations. Our instrument (which will fit within the Materials and Supplies budget) and disposable chips would be priced to be affordable for individual investigators. ? ?

Public Health Relevance

Cancer immunotherapy research and development has been greatly benefiting from monitoring multiple biomarkers, most notably several panels of cytokines. This monitoring information on the biomarker profiles will help reveal the roles that proteins play in responding to treatment with cancer vaccines and eventually lead to better cancer therapies and its monitoring. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44CA114993-02
Application #
7481950
Study Section
Special Emphasis Panel (ZRG1-BCMB-L (11))
Program Officer
Evans, Gregory
Project Start
2005-04-01
Project End
2010-02-28
Budget Start
2008-03-19
Budget End
2009-02-28
Support Year
2
Fiscal Year
2008
Total Cost
$750,000
Indirect Cost
Name
Advanced Liquid Logic
Department
Type
DUNS #
140695474
City
Research Triangle Park
State
NC
Country
United States
Zip Code
27709
Sista, Ramakrishna S; Eckhardt, Allen E; Srinivasan, Vijay et al. (2008) Heterogeneous immunoassays using magnetic beads on a digital microfluidic platform. Lab Chip 8:2188-96
Sista, Ramakrishna; Hua, Zhishan; Thwar, Prasanna et al. (2008) Development of a digital microfluidic platform for point of care testing. Lab Chip 8:2091-104