Research Projects

One of our key areas of research is developing methods to study biological processes at the nano- and micro-scale. We are particularly interested in how cells interact with their environment, including cell-surface interactions, environmental and cell-cell signaling, and response to mechanical perturbation. To support these interests we have active research projects on biofilm imaging and analysis, antifouling and biofilm remediation, and cell patterning / printing.

Another focus of our group is the development of enabling technologies for biology and biological applications. In particular, we are leveraging established and emerging nanoscale technologies for high sensitivity biosensors. We are also developing novel resistive switching devices (memristors) for hybrid electronic platforms and for potential use in neuromorphic computing applications.

Cell-Surface Interactions
Bacterial cells have unique interactions with surfaces and microscale envrionments. Bacterial cells are commonly known to interact with surfaces in a variety of medical, industrial and natural environments. While cells can interact with surfaces individually, many bacteria can form complex communities known as biofilms in which cells are typically surrounded by a protective layer of extracellular polymeric substances (EPS) that mediate cell attachment, protect cells from dislodgement from the surface and provide mechanical stability. Comparatively little is known about the nanoscale material properties (including adhesive and cohesive strengths) of attached biofilms, making it difficult to generally predict how a biofilm may behave. Understanding how bacteria behave while attached to surfaces as part of a biofilm is highly important in medical and industrial applications. Biofilms in these environments can represent a hazardous and costly problem, causing biocorrosion, biofouling, infection and disease. It is therefore important to better understand the properties and characteristics of biofilms in order to develop better control and remediation techniques.

Integrated Confocal Microscopy and Atomic Force Microscopy (AFM) for Biofilm Analysis Our laboratory is currently working on methods to directly measure the biophysical properties of bacterial biofilms using atomic force microscopy (AFM). By coupling microfluidic fluid control with precision AFM measurement, we hope to better understand the dynamics of cell behavior under varying fluid shear conditions and during exposure to external chemical signals. This work is partially supported by the NSF Major Research Instrumentation Program, which allowed us to assemble a combined AFM – confocal laser scanning microscopy (CLSM) system. Using this unique research instrument, we are able to correlate optical images with AFM-based force, adhesion, and topography measurements, for an unparalleled view of bacterial and biofilm properties.

A) Microfluidic system for growth and maintenance of bacterial biofilms. B) Cross-section of the microfluidic growth chamber during combined AFM/confocal microscopy. C) Integrated Leica SP5 confocal microscope and Bruker/Veeco Catalyst Bioscope Atomic Force Microscope (AFM).

Top: Image of a 24 hour old Pseudomonas aeruginosa biofilm stained within the growth chamber of the device following removal of the roof. Cell plasma membranes have been stained with a fluorescent dye. Bottom: Enlarged views of the region in the box above. The lower right image is a 3D reconstruction of the region in the center image.

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Antifouling and Biofilm Remediation
Bacterial fouling of surfaces, and subsequent formation of biofilms is a major problem in medicine, industrial processes, and infrastructure. To combat fouling and biofilm formation, we are pursuing methods to limit bacterial attachment to surfaces and interrupt biofilm formation (or disrupt established biofilms). We are currently developing 3D nanomanufacturing strategies to create nanoscale topographical features that can be used for cell adhesion assays. These experiments will provide insight for the design of low-adhesion surfaces that could resist bacterial adhesion and colonization. We are also working with collaborators to develop molecular antagonists of biofilm formation and methods of delivering these antagonists for prophylactic or therapeutic treatment against biofilms.

Top: Microfluidic system for evaluating bacterial surface attachment. Bottom: Examples of a bright field image (showing surface topography) and fluorescent image (showing fluorescently tagged bacteria) which are used to determine the degree of surface attachment by various bacteria to topographically distinct surfaces.

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Cell Patterning and Printing
In addition to understanding how cells interact with surfaces, we are also interested in how bacteria (and other organisms) communicate within well-defined microenvironments. To better understand cell signaling behavior in microenvironments, we are interested in measuring the minimal distances needed for effective cell-to-cell communication and understanding the affects of cell density for surface attached organisms. To this end, we have pursued various patterning strategies to attach cells to surfaces in fixed geometric patterns, including development of a novel direct cell printing technology. Our current work includes the exploration of innate cell signaling (eg. quorum sensing), as well as signaling and cross-feeding in synthetic or evolved bacterial systems.

A) GFP-expressing S. typhimurium patterned on a printed array of antibodies. B) Live/Dead stained mouse embryonic stem cells growing in a printed droplet of 3D matrix material. C) Microscale cell-signaling study using printed E. coli “receiver” colonies which express GFP in response to quorum sensing signal molecules.

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Biosensor Development
Our laboratory has a strong background in lab-on-a-chip systems and novel biosensor platforms. An emerging biosensing strategy is to use state of the art semiconductor electronics for charge-based sensing of biomolecules. Our group is primarily focusing on field effect transistors (FETs) for sensitive detection and analysis of DNA hybridization and/or DNA damage events. A major focus of this work is to develop unique DNA immobilization strategies that optimize device sensitivity while also retaining native DNA structure and function. This includes the study of DNA interactions on materials used in modern nanoscale electronics, including high-K dielectrics, metal oxides, and compound semiconductors, as well as fabrication and testing of FET-based DNA sensors.

A) Conceptual image of a field effect transistor (FET) for DNA-based biosensing. B) Fluorescent imaging data (left) and quantitative surface attachment/hybridization data (right) from DNA immobilization studies on semiconductor device materials.

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Resistive Switching Devices (Re-RAM / memristors)
Memory resistors (a.k.a. Re-RAM, memristors, resistive memory) have been heralded as the fourth fundamental circuit element, along with the resistor, capacitor and inductor. Memristors are devices that exhibit multiple electrical resistances, depending on the voltage applied and/or current driven through them. This behavior is similar to “Hebbian learning” for biological memory formation, in which the history of signaling through a synapse dictates its state (on/off, memory/no memory). Our AFRL and AFOSR supported research on resistive switching focuses on development of memristors/Re-RAM for advanced computing and encryption applications, including neuromorphic computing. These projects, supported by the Air Force Research Laboratory and Air Force Office of Scientific Research, leverage the advanced 300mm wafer processing facilities at the CNSE Center for Semiconductor Research (CSR), and fundamental nanomaterials processing and development with our academic collaborators.