Pain Point and Proposed Solution: Gastrointestinal (GI) diseases, such as inflammatory bowel disease and colorectal cancer, would significantly benefit from protein-biomarker diagnostics at the site of a lesion. This is because conventional imaging methods such as ultrasound, MRI, and x-ray computed tomography cannot assess this molecular-level information. While immunoassay technologies are capable of quantifying disease biomarkers in vitro, current assay technologies are too large to be utilized for the assessment of gastrointestinal health, in vivo. Therefore, the objective of this project is to develop a miniaturized, diagnostics assay, which can be scaled down to capsule-sized dimensions. Technological Innovation: The initial microfluidic assay will focus on the detection of hemoglobin as a model biomarker for intestinal bleeding. The microfluidic device will be engineered to perform electrochemical immunoassays on a miniaturized scale within a fully autonomous microfluidic system.
The specific aims of the project are the following: (1) Design an electrochemical ELISA for hemoglobin, and optimize under conditions that mimic intestinal fluid. (2) Design a miniaturized and autonomous microfluidic device, based on capillary- driven flow, for one-step detection of this protein biomarker. (3) Validate and optimize the platform using human intestinal fluid. Broader Impacts of the Technology: In the near-term, this platform could be coupled with an endoscope, allowing for direct analysis of the GI tract during endoscopy, or as a long-term objective, it could be incorporated into a capsule-based in vivo diagnostic device, allowing for periodic sampling of fluid along the gastrointestinal tract. This latter objective, in particular, could lead to a minimally invasive means of screening for a panel of gastrointestinal biomarkers, thereby providing a thorough assessment of gastrointestinal health for patients, and even healthy individuals. Further, as an immediately translational application, such a platform could be extended to point-of-care (POC) diagnostics involving serum-borne biomarkers, such as anti-TTG2 for celiac disease, or cardiac troponins I and T for acute myocardial infarction. Training Potential: The proposed training plan provides an opportunity for me to leverage my current scientific background in fluid dynamics, nanotechnology and sensor development, while expanding my skill set to include microfluidics, surface patterning and modification, device fabrication, and bioengineering - all of which will be essential for achieving my future career goal of leading an academic lab that utilizes nanomaterials to probe biological systems. In addition, the project provides a unique opportunity to work in collaboration with experts across a variety of fields, including biochemistry, bioengineering, microfluidics, gastroenterology, and radiology. Through these interactions, I will expand not only my breadth of knowledge, but also my academic network, building contacts across disciplines, and enabling future collaborations.
The objective of this project is to develop a miniaturized microfluidic immunoassay, which detects biomarkers of gastrointestinal (GI) disease and can be scaled down to capsule- sized dimensions. In the near-term, such a platform could be coupled with an endoscope, allowing for direct, molecular-level analysis of the gastrointestinal tract during endoscopy, or as a long-term objective, it could be incorporated into a capsule-based diagnostic device, allowing for periodic sampling of fluid along the gastrointestinal tract. This latter initiative could ultimately lead to the development of a minimally invasive diagnostic platform for the assessment of gastrointestinal health in diseased patients, and even healthy individuals.
| Hilmer, Andrew J; Jeffrey, R Brooke; Park, Walter G et al. (2017) Cholestyramine as a promising, strong anion exchange resin for direct capture of genetic biomarkers from raw pancreatic fluids. Biotechnol Bioeng 114:934-938 |
