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1. Biofabrication in Microfluidics
Biofabrication is considered as a convergent fabrication paradigm that bridges between biotechnology and microfabrication. Fundamentally, transfer of signals in biology is via ions and small molecules, while in microfabricated devices the transmitting components are electrons and photons. Microfabrication uses top-down methods to pattern surfaces with permanent features. Biological components are labile and the construction starts with bottom-up genetic information to code amino acid sequence and protein folding. As such, the use of biological components and mechanisms for construction represents an enabling strategy to interface microfabrication with biology. Biofabrication in microfluidics integrates the power of microfabricated devices with the molecular recognition of biology. By consuming less fluid volume and offering faster and parallel process control, advances in microfluidic technology are revolutionizing integrated platforms with applications in biology, biochemistry, medicine and biotechnology studies. Biofabrication in microfluidics encompasses the benefits of microfluidic technology to construct biological systems that offers unprecedented capabilities.
Our research group exploits device-imposed electrical signals, flow-driven chemical gradients, air-bubble initiated 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. The assembled biopolymers and proteins in microfluidic networks are spatially and temporally programmable. Electrodeposited chitosan and alginate scaffolds have enabled the conjugation of nucleic acids, proteins, metabolic enzymes and cells in microfluidics. Biofabricated chitosan membrane and polyelectrolyte complex membranes (PECM) allow selective penetration of small molecules while prohibiting macrobiomolecues such as antibodies diffusing through the freestanding membranes. We envisioned that biofabrication in microfluidics can be implemented to a wide-spectrum 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 treatments, disruption of the healthy microbiome, and, more drastically, the development of antibiotic resistance, which can deprive future effective antibiotic treatments when needed. Timely microbial susceptibility to narrow-spectrum antibiotics at the clinic site is impractical because standard antibiotic susceptibility testing (AST) takes 2~3 days and requires well-equipped facilities and skilled laborers. We are prototyping a fast and precise AST platform to provide insights into effective treatments of 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 affect 30-50% of the population in the United States, stimulate 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 cell and molecular mechanisms of cancer treatment-induced OM and the anti-mucositis effects of KGF will aid in identifying effective future treatments. This study evaluates a previously developed oral mucositis on a chip (OM-OC) as a screening platform for anti-mucositis treatments, using KGF as a well-studied example. Mucositis effects were induced by cisplatin, radiation, and combined treatment followed by a recovery period.
Current funding: NIH, VA.
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 between individual cells, clusters of cells and populations exist in complex networks that, in sum, guide behaviors. There are few experimental approaches that 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 in situ organize cells in microenvironments with spatiotemporal control and programmability. Established synthetic ecosystems with polymicrobial interactions within diffusion length scale represent the significant first step towards modeling the complex interactions among organisms found within microbiomes.
Completed funding: NIH.
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