Protein Engineering & Expression of Recombinant Immunotherapeutics
Our research efforts in this area are conducted under the Cornell University/ Ludwig Institute for Cancer Research (LICR) Partnership. Currently, we are exploring a number of parallel routes for the expression of therapeutic agents that have promise in the clinic. We are evaluating existing approaches, working to develop novel and improved techniques for protein expression, and constructing rational approaches to scale-up these systems.
In our laboratory, a major focus is on the development and optimization of microbial-based expression systems for tumor antigens and tumor-antigen-specific antibody fragments and their subsequent downstream purification. Through the use of our new cGMP-certified Biologics Production Facility, we will carry out the large-scale production of highly purified cancer immunotherapeutics suitable for testing in early-phase human clinical trials.
Micro-/Nanofabrication of Integrated Sensor Devices
The Sensors Group of the Batt Lab focuses on a variety of biosensor technologies aimed at detecting a wide array of biomolecules and biological agents. The goal of these projects is to provide both highly sensitive as well as highly portable detection systems that can be used outside of the confines of a laboratory. In this way, a variety of biomolecules and/or biological agents can be detected quickly and easily. Current sensor-related projects that have been undertaken in the lab include a miniaturized, PCR-based biosensor, as well as a surface plasmon resonance (SPR)-based biosensor. While the PCR-based sensor is primarily aimed at detecting microbial pathogens, the SPR-based sensor is ideally designed for the detection of biological molecules, including protein and DNA.
Much of the biosensor fabrication that is done in our lab is performed at the Cornell Nanofabrication Facility (CNF). The CNF facilities provide the necessary equipment and cleanrooms for semiconductor processing and chip fabrication. Silicon, glass and other substrates can be patterned, etched, deposited onto, and further modified on the micro- and nanoscales, yielding almost any type of sensor configuration imaginable. Much of the sensor work in the Batt Lab focuses on microfluidic-based systems, which can often be constructed from polymeric materials such as poly(dimethylsiloxane) (PDMS), that can be formed from a microfabricated mold. In this way, intricate micro-scale molds are fabricated in the CNF while the test structures themselves are regularly cast in our own laboratory.
In addition to biosensor fabrication, our laboratory is also interested in the electronic and microfluidic control systems that can automate sensor functions. We are currently collaborating with researchers from the Alliance for Nanomedical Technologies to create a general testing platform for micofluidic devices, referred to as the microFLUIDICS DESKTOP. The DESKTOP is designed to provide an on-board power supply, electronics and control systems to automate a variety of microfluidics-based sensors. This includes microfluidic pumps, micro-valve actuation, temperature control and optical detection systems. A schematic of the DESKTOP is shown in Figure 1 below.
Figure 1. The microFLUIDICS DESKTOP This self-contained unit provides on-board power, processing, temperature control, microfluidic control, and optical detection in a shoe-box sized platform. The DESKTOP is designed for the testing and integration of microfluidics-based biosensors.
In summary, our research group has an active and ongoing interest in biosensor technology. We have a variety of sensors that are presently undergoing development, and we are also engaged in a number of collaborative efforts with researchers from other laboratories that are aiming to develop similar technologies.
Specific Projects and Relevant Lab Personnel
- Construction of a miniaturized PCR-based biosensor
- Microfabrication of a totally integrated optical biosensor
- Development and characterization of novel surface chemistries for optical- and field effect transistor (FET)-based biosensor applications
Synthesis of Biologically Inspired Nanostructures for Advanced Materials Processing
The limit to precise manufacture of reproducibly functioning quantum confined materials for advanced electronics, photonics, and magnetics is fast approaching. The use of conventional integrated circuit techniques involving lithograthy followed etching has limited success in producing the ultrasmall structures that are needed for these advances. Biomolecule based self- or directed- assembly of nanostructures hold promise as a means of better control for uniformity of size and quality and emergence of desired properties.
Crystalline bacterial cell surface layer (S-layer) proteins have been optimized during billions years of biological evolution as building blocks of one of the simplest self-assembly systems. S-layer proteins form the outmost cell envelope component of a broad spectrum of bacteria and archaea. S-layer lattices exhibit either oblique, square or hexagonal lattice symmetry with unit cell dimensions in the range of 3-30 nm. S-layers are generally 5-10 nm thick and show pores of identical size (diameter, 2-8 nm) and morphology.
Previous studies on S-layers have shown that the periodic structure can be exploited as a template for the formation of regular arrays of molecules and particles. In addition, some S-layer proteins can be separated into monomers and reassemble into two-dimensional arrays on surfaces of a broad spectrum of materials and interfaces.
Our research project is focusing on formation of arrays of quantum dots, nanoparticles, semiconductor nanowires and carbon nanotubes. These high-density and ordered array structures should provide novel functional materials for application in electronics, photonics and magnetics, such as storage arrays, light emitting displays, sensors and lasers.
Specific Projects and Relevant Lab Personnel
- Development of novel, in situ biofabrication techniques to create PHA microstructures within microfluidic systems
- Synthesis and characterization of novel organic/inorganic hybrid materials based on PHAs and silicone polymers for microfluidics applications
- Design and engineering of novel genetic constructs for the expression of recombinant S-layer proteins with desired self-assembly properties
- Use of bacterial and archaeal S-layers for arraying highly fluorescent, water-soluble quantum dots on ultra-flat silicon substrates for novel opto-electronics applications
- Synthesis and arraying of magnetic nanoparticles for catalysis of carbon nanotube growth
Description of Images
The images shown on this page demonstrate the self-organization of gold nanoparticles by biomolecular templating using 2-D crystalline S-layer protein arrays.
Top Left:
Tapping mode-atomic force microscope (AFM) image of an S-layer fragment purified from Deinococcus radiodurans.
Bottom Right:
Low- and high-resolution transmission electron microscopy (TEM) images showing micrometer-sized patches of ordered 5 nm-sized gold nanoparticles.
Individuals interested in undergraduate research, graduate school training, postdoctoral training, or technical positions are encouraged to contact Professor Batt at the following address:
Dr. Carl A. Batt
Director, Cornell University/Ludwig Institute for Cancer Research Partnership
312 Stocking Hall
Cornell University
Ithaca, NY 14853-7201
Phone: (607) 254-5376
Fax: (607) 607-255-8741
E-Mail: cab10@cornell.edu