iBMF - Research
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 and air-bubble initiated electrostatic interactions to guide the assembly of polysaccharides including chitosan, alginate and collagen in microfluidics. The signal-guided assembly of biopolymers in microfluidic networks is 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. Synthetic Ecosystems and Microbiomes
Signaling between cells guides biological phenotype. Communications between individual cells, clusters of cells and populations exist in complex networks that, in sum, guide behavior. 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 as one approach that enables in-situ organization of living cells in microenvironments with spatiotemporal control and programmability. Constructed bacterial biofilm mimics offer detailed understanding and subsequent control of population-based quorum sensing (QS) behaviors in a manner decoupled from cell number. Established synthetic ecosystems with multiple cell populations within diffusion length scale represent the significant first step towards modeling the complex interactions among organisms found within microbiomes.
3. Chemotaxis and chemotropism
Chemotaxis is the movement of an organism in response to a chemical stimulus. This signaling regulates individual organism behavior as well as the coordinated behaviors of a group of cells via the perception and a response to external signaling molecules. Chemotropism is the growth of organisms (or parts of an organism, including individual cells) such as bacteria and plants, navigated by chemical stimulus from outside of the organism or organism's part. Chemo-tropism is different from Chemotaxis, the major difference being that chemotropism is related to growth, while chemotaxis is related to locomotion. Biofabrication in microfluidics provide microenvironments with spatiotemporal precision in positioning cells and accuracy in providing chemical signals. We are developing novel microfluidic platforms to answer some important unresolved issues in bacterial chemotaxis and yeast chemotropism.
4. Highly Stable Lipid Bilayers
Engineering appropriate models of cellular structures and processes is essential in elucidating fundamental cellular mechanisms and in identifying useful targets for pharmaceutical drugs. Model lipid bilayers (LBs) have been long used to study membrane-associated proteins that are involved in ion channel transport, membrane fusion, and in regulation of signaling pathways. Conventionally, LBs are either manually painted or constructed with self-assembled monolayers across small apertures, followed by incorporation of membrane proteins. Although a wide range of biological studies have been performed using these techniques over the past half century, model LBs often collapse within hours. There is no stable LB system that can be monitored electrically, optically and allowing for rapid membrane bathing solution exchange at the same time. We aim to develop artificial cell membranes that address these challenges.
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. This study, in collaboration with Engineers and Scientists at CUA and ADA Foundation, aims to develop a microfluidic oral mucosa-on-a-chip system to rapidly assess layer remodeling and cell-specific responses to aspects of the oral environment including cytotoxic dental leachables and the cariogenic bacteria.
6. Separating but Communicating: Properties of Biofabricated Membranes
The biofabricated membranes in microfluidics feature some unique properties such as freestanding, mechanically robust, semipermeable to small molecules, molecularly microaligned, and ready for biofunctionalization. Open questions remain and ongoing efforts is made to answer including the details of the membrane properties, to what extend the properties can be tuned, and how the membranes can be optimized for different applications.