AVS 56th International Symposium & Exhibition | |
BioMEMS Focus Topic | Thursday Sessions |
Session BM+MN+MS+TF+BI-ThA |
Session: | Advances in Microfluidics for BioMEMS |
Presenter: | J. Shumaker-Parry, University of Utah |
Authors: | J. Liu, University of Utah M. Eddings, University of Utah A. Miles, Wasatch Microfluidics B. Gale, University of Utah J. Shumaker-Parry, University of Utah |
Correspondent: | Click to Email |
Analysis of biomolecule interactions based on surface plasmon resonance (SPR) microscopy provides a label-free approach to monitoring arrays of biomolecule interactions in real time. Typically the microarray sensing surface for these measurements is prepared ex situ and a single or few channel flow cell is used for the biomolecule interaction studies. The multiplexing nature then is derived from the microarray and the number of samples that can be run simultaneously is rather limited, diminishing the potential application for assays requiring a high-throughput approach due to a large number of samples. One example of this is the need to monitor for anti-drug antibodies from a large pool of patient samples during clinical trials of biotherapeutics. We demonstrate the capability of a multi-channel microfluidic flow cell array (MFCA) to expand the throughput capability when integrated with SPR microscopy. In addition, the MFCA provides an in situ approach to array fabrication that allows full characterization of the biomolecule immobilization process. We use the MFCA for delivery of sample solutions with continuous flow in 48 channels in parallel for rapid microarray creation and binding analysis while using SPR microscopy for real-time monitoring of these processes. Label-free measurement of antibody-antibody interactions demonstrates the capabilities of the integrated MFCA-SPR microscopy system and establishes the first steps of the development of a high-throughput, label-free immunogenicity assay. We demonstrate a limit of detection (LOD) of ~ 80 ng/ml for the particular antibody pair we studied. This LOD is ~6 times lower than the industry recommended immunogenicity assay detection limit. The high-throughput nature of the integrated system allows a large number of replicate experiments, including control experiments, to be performed simultaneously on the same sensor surface in a short time. The integrated system also will be applicable for more general high-throughput protein-array based analysis.