James P. Landers, PhD
Development of a Microfluidic Genetic Analysis (MGA) system
Current research is focused on the development of a microfluidic-based analysis that presents the user with a genetic analysis tool with sample in-answer out capabilities. The Microfluidic Genetic Analysis (MGA) system will be capable of accepting real-world samples (blood, tissue biopsies, histological slices, etc.) and executing a series of sample preparation and analysis steps. The sample preparation steps may include tissue disruption/lysis, nucleic acid and/or protein extraction, followed by labeling, PCR and then an analytical step that provides an interpretable read-out upon fluorescence detection (with or without separation). These processes involve chromatographic steps on chip-embedded solid phases, enzymatic reactions, and labeling chemistries, some of which may require elevated temperature control in certain domains on the integrated microfluidic device. In order for these devices to accomplish this within the nanospace of the microfluidic architecture, exquisite nanoliter volume fluidic control is required.
The proof of principle of the functionality and utility of the MGA system was first revealed in late 2006 for the detection of select infectious disease agents (B. Pertussis; B. Anthracis) from multiple sample types (nasal swab, blood, nasal aspirate) [Easley et al., Proc Natl Acad Sci U S A. 103(51):19272-7, 2006; Editor’s Choice Science 2007 Vol. 315 Pg 302: Research Highlight Nature Biotech. Vol. 25(1) Jan. 2007]. Subsequent efforts have been focused on creating a ‘cancer detection’ chip, one that could use the same functional elements to interrogate human genomic DNA for gene rearrangements associated with T-cell lymphoma. This work is on-going. More recent efforts have been in defining mechanisms for cell capture on a chip, whereby samples with heterogeneous cell populations could be probed for select cell types, which could be captured and concentrated. Our foray into this work was leveraged by forensic research funds from the National Institute of Justice (NIJ) to define a method whereby acoustic energy applied to a specific chamber on the chip would allow for a size-selective cell capture – in this case, application to sperm cell capture from vaginal swabs used in sexual assault cases. We are currently translating these advances into developing a Circulating Tumor Cell (CTC) chip to capture CTCs out of whole blood for both microscopic and molecular characterization. This allows us to bring the full force of advanced microfluidic technology to bear on cancer diagnostics.