Our group’s nanotechnology research comprises several different projects, which are summarized below. These projects are directed towards designing, constructing and implementing nanoscale structures that are useful for either interfacing, mimicking or characterizing biological systems.
Nanosensing and Actuation Using Cell Mimetics
Functional biomedical sensing devices will need to directly interface to the molecular-scale processes of biology. These devices must extract and process information from a complex environment of interacting non-linear biomolecular processes and, in an ideal embodiment, intervene in processes gone awry. Functionality at this level of complexity dictates the requirements of engineering functional nanoscale components within microscale structures. Further, we must employ processing schemes that are highly complex yet can be implemented in a very small volume. Nature’s answer to this design challenge is the cell, and the objective of this work is to develop sensors that mimic the dimensions and some portion of the functionality of a cell. Only by mimicking cellular features will effective operation and interfacing to biological systems be achieved. To achieve this ideal, we are exploiting recent advances in nanofabrication that allow for the synthesis of physical features on length scales ranging from nanometers to centimeters. These fabrication techniques allow for the construction of cellular mimetics that incorporate features such as semi-permeable membranes, chemical sensors and chemical actuators in a footprint of less than 100 µm. The nanostructured features are derived from the synthesis of carbon nanofibers that allow for control on the molecular scale. We are establishing the functional elements of cellular mimics and integrating these capabilities for demonstrations of sensing and actuation at the molecular and cellular scale.
Molecular Scale Patterning of Biofunctional Surfaces via Scanning Probe Lithography
Small molecules, proteins, and cells are naturally subjected to interactions with surfaces that alter their physical and chemical makeup. These alterations are often dictated by the precise spatial arrangement of organic species within complementary molecular assemblies on the interacting surface. Investigation of the role that molecular scale assembly and arrangement of biofunctional surfaces have on fundamental cellular processes or subcellular biochemical reactions requires the capacity to engineer surfaces with different organic species at the nanoscale. To that end, we are integrating and developing multiscale, biocompatible lithography techniques based on microcontact printing, atomic force nanografting and related scanning probe lithography processes to engineer biofunctional surfaces with nanoscale precision. Current studies focus on the use of microcontact printing to develop micro- or cellular-scale patterns of biofunctional and inert alkanethiols on gold surfaces. These surfaces are characterized via closed loop, contact mode AFM scanning in a liquid environment and selectively modified at the nanoscale via physical removal, or “scraping”, using the AFM tip as a lithographic tool. These areas are simultaneously backfilled with biofunctional molecules present in the liquid imaging cell and tested for interactions with proteins and whole cells. These surfaces, having biofunctional elements that span multiple length scales, will not only facilitate a more detailed understanding of fundamental biological processes, but they will also find broad application in the fields of tissue engineering, drug delivery, biosensor design, and high throughput screening.
Nanoscale Devices for Biomolecular Interfaces
Small, engineered organic molecules are vital components of nanobiotechnological systems. One major role they play is as molecular-scale devices, where they represent the ultimate in miniaturization for nano-scale engineering. We are particularly interested in light-operated devices that respond to light by undergoing molecular motion, such as azobenzene. Through appropriate chemical methods, azobenzene can be incorporated into more complex structures to couple this motion to downstream events, making the azobenzene a phototransducer. We are focused primarily on incorporating azobenzene into amino acid- and peptide-based molecules for applications of using light to direct movement of proteins within cells, to stimulate neuronal signaling in the retina, and to control association of materials.
Additionally, small organic molecules have a valuable structural role in nanoscale devices, as they can both stabilize synthetic nanomaterials and provide the physical link to biomolecules, cells, or tissues. We have recently initiated an effort to address the difficulty of forming stable nanoparticle-protein assemblies for biomedical applications.