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1. Biofabrication in Microfluidics
Biofabrication is considered a convergent fabrication paradigm that bridges biotechnology and microfabrication. Fundamentally, biological signals are transmitted via ions and small molecules, whereas microfabricated devices use electrons and photons as transmitting components. Microfabrication uses top-down methods to pattern surfaces with permanent features. Biological components are labile, and construction starts with bottom-up genetic information that codes amino acid sequence and protein folding. As such, using biological components and mechanisms for construction enables interfacing microfabrication with biology. Biofabrication in microfluidics integrates the power of microfabricated devices with biology's molecular recognition. By using less fluid volume and enabling faster, parallel process control, advances in microfluidic technology are revolutionizing integrated platforms for applications in biology, biochemistry, medicine, and biotechnology. Biofabrication in microfluidics leverages microfluidic technology to construct biological systems with unprecedented capabilities.
Our research exploits electrical signals, flow-driven chemical gradients, electrostatic interactions, and simple surface tension to guide the assembly of polysaccharides, including chitosan and alginate, and the gelation of proteins, including collagen and gelatin methacrylate (GelMA), in microfluidics. Biofabricated chitosan membranes and polyelectrolyte complex membranes (PECMs) allow selective penetration of small molecules while preventing macrobiomolecules such as antibodies from diffusing through the freestanding membranes. By implementing a "fluitrode" concept to transmit small molecules and ions through channels and semipermeable membranes, similar to electrodes that transmit electrons, microfluidic networks can spatially and temporally program the assembly of biopolymers, proteins, and cell populations. Electrodeposited chitosan and alginate scaffolds have enabled the conjugation of nucleic acids, proteins, metabolic enzymes, and cells in microfluidics. We envision biofabrication in microfluidics for a wide range of applications, from biological and biochemical analysis to biomedical engineering studies.
2. Rapid antibiotic susceptibility testing (Rapid AST)
Bacteria cause widespread diseases, including urinary tract infections (UTI), acute lung infections, and bloodstream infections. Prescriptions to treat acute bacterial infections are often empiric, using broad-spectrum antibiotics at high doses, because the urgency of treatment does not allow for lab test results that take hours or days. However, this practice risks ineffective treatment, disruption of the healthy microbiome, and, more seriously, the development of antibiotic resistance, which can limit future effective antibiotic options when needed. Timely microbial susceptibility testing for narrow-spectrum antibiotics at the point of care is impractical because standard antibiotic susceptibility testing (AST) takes 2~3 days and requires well-equipped facilities and skilled staff. We are prototyping a fast, precise AST platform to provide insights into effective treatments for acute bacterial infections, such as sepsis, within 30 minutes. Our solution recognizes that motile bacteria, the primary source of common bacterial infections, swim away from effective antibiotic gradients and quickly lose their motility when exposed to survival doses of effective drugs.
Current funding: NIH, ITHC.
3. Mucosa-on-a-Chip
The oral mucosa is a layered tissue with an active microbiome. Pathologies such as periodontitis, which affects 30-50% of the population in the United States, have stimulated interest in studying inter-kingdom and host-pathogen interactions in the oral mucosa. Oral mucositis (OM) is a severe complication of cancer therapies caused by off-target cytotoxicity. Palifermin, which is recombinant human keratinocyte growth factor (KGF), is currently the only mitigating treatment available to a subset of OM patients. Determining the cellular and molecular mechanisms of cancer treatment-induced OM and KGF's anti-mucositis effects will help identify effective future treatments. This study evaluates a previously developed oral mucositis-on-a-chip (OM-OC) platform for screening anti-mucositis treatments, using KGF as a well-studied example. We are extending the mucosa-on-a-chip platform to screen more drug candidates and actively developing kidney-on-a-chip and skin-on-a-chip systems.
Current funding: NIH, VA, Glenn W. Bailey Foundation.
4. Direct methanol fuel cell (DMFC)
Hydrogen fuel cells have played an essential role in NASA explorations by providing electrical power besides drinking water as a byproduct, thanks to their lightweight, long-duration advantages over batteries. Commercial adoption of hydrogen fuel cells, however, is limited primarily by high costs and the need for hydrogen infrastructure. A Direct Methanol Fuel Cell (DMFC) is a valuable alternative, offering higher energy density in a compact system with an easily refuelable liquid fuel. Conventional DMFCs, however, rely on expensive proton exchange membranes and noble-metal catalysts and face technical hurdles including methanol crossover and sluggish reaction kinetics. We hypothesize that the core material costs and technical hurdles in DMFCs can be addressed by employing our patent-pending electrofabricated chitosan membranes as the anion exchange membranes (AEMs) in chitosan-based AEM-DMFCs. We expect to lower membrane cost, reduce methanol crossover, avoid using precious-metal catalysts, and improve reaction kinetics, hydroxide-ion conductivity, and alkaline stability.
Current funding: CUA Seed Grant.
5. Synthetic Ecosystems and Microbiomes
Communications among individual cells, cell clusters, and populations occur in complex networks that collectively guide behavior. Few experimental approaches enable high-content interrogation of individual and multicellular behaviors at length and time scales commensurate with the signal molecules and cells themselves. We exploit “biofabrication” in microfluidics to organize cells in situ in microenvironments with spatiotemporal control and programmability. Established synthetic ecosystems with polymicrobial interactions within the diffusion length scale represent a significant first step towards modeling the complex interactions among organisms found within microbiomes.
Current funding: Glenn W. Bailey Foundation.
Completed funding: NIH.
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