Biotechnology Resource Center (BRC)
The Orbitrap Fusion is an advanced tribrid mass spectrometry platform used to analyze and sequence proteins, peptides, and their modifications. The instrument can sequence 500 to 1000 peptides per minute. In less than two-hours, it is able to identify and quantify thousands of proteins in a single sample.
The most common applications for the instrument include in-depth proteome discovery experimentation, the characterization of complex protein modifications, and comprehensive qualitative or quantitative workflows on protein complexes. Using the latter, researchers are able to compare healthy and cancerous tissue samples. Their findings could result in further understanding the mechanisms of cancerous development or in the discovery of a protein biomarker that could be used as a target for developing new drugs.
The Genomics facility is home to several Illumina DNA sequencers. What was once an almost impossible task is now an automated sequencing system. Populations of DNA fragments are added to slides and placed inside the device. Using fluorescent dyes and lasers, the Illumina sequencers determine the precise order of nucleotides within millions to hundreds of millions of DNA fragments simultaneously. The facility has sequenced plants, pathogens, fungi, fish, invertebrates, and other animals. They have genotyped 1,500 different species, from snow leopards to gray whales to horses to oryxes. As a high throughput laboratory, they process around 150,000 samples each year for around 350 research groups at over 90 institutions.
The Zeiss Elyra Super Resolution microscope supports structured illumination (SR-SIM), total internal reflection fluorescence (TIRF), and localization-based (STORM/PALM) super resolution microscopies with 405, 488, 561, and 642 nanometer laser lines. It also includes definite focus focal-drift compensation and a Z-piezo stage insert for fast axial focusing. The instrument is equipped with two cameras: a pco.edge scientific complementary metal-oxide semiconductor (sCMOS) camera for structured illumination microscopies and an Andor Ixon Ultra 987 electron multiplying charged coupled device (EMCCD) camera for TIRF, STORM/PALM, and other time-lapse imaging. An objective heater is available for live mammalian cell imaging on the microscope stage. The BRC acquired the system in 2015 with funding from a National Science Foundation Major Research Instrumentation grant.
Jan Lammerding, Meinig School of Biomedical Engineering, uses super resolution structured illumination microscopy to study the molecular repair process by which cells can restore the integrity of their nuclear envelope after physical disruption.
The VisualSonics Vevo-2100 high-resolution ultrasound is designed around the same principles as a human ultrasound but is scaled down 100-fold for applicability to mouse cardiology, development, and cancer studies. Researchers can use the instrument for examining plant morphology or fluid flow in appropriately designed systems.
The Vevo-2100 generates 20 to 70 megahertz with phased array and solid state probes giving a resolution in the 50 to100 micrometer range. The instrument is particularly good for non-invasive imaging of anatomical structures and motion. A variety of doppler modes can be used to quantify the direction and magnitude of blood flow.
Cynthia A. Reinhart-King, Meinig School of Biomedical Engineering, uses the Vevo-2100 to measure arterial stiffness in mice models with different cardiovascular risk factors, such as age and lack of exercise. Arterial stiffening is used clinically to assess risk of cardiovascular disease and can be alleviated with treatments such as exercise.
The Xradia (Zeiss) Versa XRM-520 is referred to as a nano-CT or a 3D x-ray microscope. While most devices of this type have strict limits on the specimen’s physical size, the XRM-520 allows users to scan the entire specimen or smaller sub-regions. The focusing capability is particularly useful for examining specimens that are too rare or delicate to be sectioned destructively, such as fossils, museum specimens, or exotic materials. Researchers can create 4D and 5D+ datasets through repeated scanning of the same specimen. Researchers use the XRM-520 to visualize and measure structures in plants, insects, seeds, fossils, electronic/fluidic devices, materials constructs, and soft or dense biological tissue. Christopher J. Hernandez, Sibley School of Mechanical and Aerospace Engineering, uses the instrument to examine the mechanism of crack formation and recovery in bone microstructure.
The full-surround Plexiglas unit of the Zeiss LSM 880 provides a stable, heated, and humidified environment with carbon dioxide regulation that supports long-term imaging efforts. It has an automated stage for monitoring multiple positions or tiling large fields of view. It supports many laser lines (405, 458, 488, 514, 542, 561, and 633 nanometers), and fully spectrally resolvable emission channels. The linear array detector in the detection unit has a gallium arsenide phosphide photocathode, which is twice as sensitive as the multi-alkali photocathode on the older LSM710 module. The Zeiss LSM880 confocal/multiphoton microscope was acquired in 2015 with funding from a New York State health grant and a National Institute of Health shared instrumentation grant.
Tudorita Tumbar, Molecular Biology and Genetics, uses the i880 to image stem cell distribution and behavior in skin. Heidi L. Reesink and Alan J. Nixon, Clinical Sciences, use the microscope to simultaneously image the collagen structure in healthy articular cartilage and the thin layer of lubricin, a boundary lubricating glycoprotein, on the surface of cartilage.
The robots in the Genomics facility are automated liquid handlers, which transfer liquids and aid in processing samples by setting up enzymatic reactions for DNA sequencing and genotyping technologies. Researchers use the two robots, Tecan Genesis and Beckman Biomek FX to process DNA sequencing samples, using the Sanger sequencing method and next-generation genotyping for large-scale plant and animal breeding programs.
Utilizing the Tecan Genesis and the Beckman Biomek FX, the Genomics lab processes 150,000 samples per year, completing DNA sequencing for around 350 research groups at over 90 institutions.
The Biotechnology Resource Center (BRC) offers a range of core life science research facilities at Cornell University, administered by the Institute of Biotechnology, which also oversees the Center for Advanced Technology (CAT). The institute acts as a hub for biotechnological innovation,” says Jocelyn Rose, director of the Institute of Biotechnology. “The BRC provides an extensive suite of facilities for Cornell’s life science community, as well as outside campus, while the CAT is geared towards accelerating the commercialization of biotechnological breakthroughs by Cornell scientists. It’s a powerful synergy.” The BRC offers cutting-edge biotechnologies, expertise in their applications, technology testing and development, and consultation and training for investigators from Cornell and other institutions. The center consists of seven facilities that assist in different areas of life science research. Each facility provides individual consultations and holds regular seminars, workshops, and training events.
The Genomics facility specializes in DNA sequencing, real-time or digital polymerase chain reaction, sample preparation and quality control, and microarrays. The facility scientists provide expertise for designing large-scale genotyping and sequencing projects, sample preparation, data generation, and data analysis.
Protein identification and characterization, quantitative proteomics, small molecule profiling and quantitation, and sample preparation are services of the Proteomics and Mass Spectrometry facility. The Imaging facility has an array of devices to meet any life science research need, including high resolution x-ray CT, flow cytometry, confocal microscopy, multiphoton microscopy, and super resolution microscopy to name a few.
The Bioinformatics facility supports research at the BRC with advanced computations infrastructure and bioinformatics tools and techniques, laboratory information management system database development and resources, and software access and licensing.
The Advanced Technology Assessment facility effectively implements new technologies and novel applications with the potential for breakthrough discoveries in the life sciences. It assures that each facility in the BRC is equipped with cutting-edge technology.
“The BRC provides research opportunities that would not otherwise exist at Cornell,” says Tami Magnus, executive director of the Institute of Biotechnology. “Our extensive network of experienced staff, instrumentation, facilities, and partnerships within the scientific and economic development communities represent exceptional resources to promote life science research. We strive to maintain a reputation for excellence and provide services at the cutting edge of biotechnology.”