On this page:
- Cellular Imaging and Analysis
- Cellular Reprogramming
- Fluidic Systems
- Intelligent Systems
- Mass Spectrometry
- Nucleic Acid Synthesis and Function
- Pathology Workflow
- Science Management Group
Cellular Imaging and Analysis
The goals of the Cellular Imaging and Analysis Program are to develop novel technologies and tools that address the complexity of cellular systems. Cellular heterogeneity is a key feature of biological systems that require analysis at high resolution across many cells. Rather than average-based methods of bulk analysis, we are focused on studying cells at the single-cell level to understand the distributions of biological events and features.
Our research projects span a wide variety of biological disciplines, including Pathology, Stem Cells, and Cancer Biology. We have a state-of-the-art cell culture facility, live-cell imaging and analysis core, and capabilities for 3D fluorescence microscopy. We combine all of these technologies into our research activities to address the challenges of studying biological systems.
The overall objective of the Cellular Reprogramming program at Agilent Labs is to develop next generation technologies and platform solutions for the advanced manipulation and engineering of organisms, cells, and tissues for, basic biology, cancer research, pharmaceutical drug development and applied markets. Agilent Labs is building on a strong foundation of technologies important for these efforts, e.g. DNA oligo library and RNA synthesis to drive new method development to enable higher throughput directed mutagenesis and evolution of genes and pathways, e.g. using Crispr-Cas9-based technologies, gene-specific expression control at the genome level and directed engineering of entire genomes. As part of this effort, we are using our proprietary TC-RNA chemistry which can be used to readily synthesize single guide RNAs of 100nt or longer to explore performance enhancements that can be achieved from chemical modifications of guide RNAs for Crispr. In addition, to creating new reagents and methods for manipulating genomes and their functions, we are also working to advance tailored measurements to broaden the range of information obtained from each reprogrammed cell including, e.g. high throughput multi-omics measurements for characterization, embedded cell bio-sensors and "selectors" for directed evolution, and quantitative QC methods to determine stem-cell pluripotency and differentiation. We are also working to leverage and extend our expertise in informatics, automation and microfluidics to develop high throughput platforms to design experiments and perform integrated functions. Agilent Labs is leveraging its own deep expertise in many of the disciplines required to make breakthroughs in the areas described above and also engages in multiple external collaborations with leading academic, government and industrial labs to join forces in mutually beneficial ways to drive further development and application of these new technologies.
Hendel A; Bak RO; Clark JT, Kennedy AB, Ryan DE, Roy S, Steinfeld I, Lunstad BD, Kaiser RJ, Wilkens AB, Bacchetta R, Tsalenko A, Dellinger D, Bruhn L, Porteus MH. “Chemically modified guide RNAs enhance CRISPR-Cas genome editing in human primary cells. ” Nature Biotechnology, 2015 Sep;33(9):985-9. doi: 10.1038/nbt.3290. Epub 2015 Jun 29. http://www.ncbi.nlm.nih.gov/pubmed/26121415
The Fluidics Program at Agilent labs develops innovative solutions for the Life Sciences, Diagnostics, and Genomics businesses. For example, a high-sensitivity nano LC/MS chip was developed using microfabrication techniques. This chip was successfully transferred to the HPLC-MS business unit and commercialized. With excellent prototyping capabilities including a programmable femtosecond laser and a Class 1000 cleanroom with lithography, electrochemical etching, and mems processes, the Fluidics Program is well positioned to launch projects addressing the needs other business units within LDG.
Integrated HPLC chip with gradient generator and electrospray for mass spectrometry:
The Intelligent Systems program aims to advance data acquisition, data analysis and data tracking with informative algorithms, visual analytics, and adaptive, measurement-responsive instruments.
This program spans a range of domains including classic bioinformatics and computational biology, next generation sequence analysis, image analysis for digital pathology as well as development of complete analytical systems for reasoning across diverse data sets. We also conduct advanced research in novel user interfaces and visual analytics relevant to these domains. Using novel software, visualization and computational solutions we strive to provide to the most accurate quantitative representation and interpretation of diverse biological data across many different measurement platforms. In addition, we are interested in analytical approaches that optimize measurement information content and increase the cost effectiveness of instruments through both real time and offline analysis of the instrument data from complex samples.
As study cohorts continue to grow in terms of numbers of samples as well diversity and size of data measurements, scalability is becoming increasingly important in both computation as well as visualization. To address this we are beginning to work with big data technologies toward an understanding of how these technologies can be best leveraged for analyzing life science and clinical diagnostic data.
Agilent Laboratories are focused on creating fundamental improvements in the performance and applications of mass spectrometry and data analysis. Leveraging the ingenuity of a multi-disciplined scientific and engineering team, we are researching many aspects of mass spectrometry ranging from sample handling and preparation, to detection, data acquisition, data processing and algorithms to create practical solutions for a wide variety of mass analysis needs. Our projects range in scope from defining and integrating new subsystems and code structures to developing leading edge solutions to enable higher sample throughput and use of smaller samples. In addition to inventing new concepts and approaches, we apply state-of-the-art technologies from many industries and disciplines to improve Agilent's mass spectrometry performance, quality and application range.
Nucleic Acid Synthesis and Function
Building on world-leading technologies for DNA and RNA synthesis, Agilent Labs is continuing to create the next generations of DNA and RNA synthesis methods to achieve longer lengths, higher quality and lower cost in order to advance research, engineering and diagnostics.
The recent discovery of multiple classes of biologically important non-coding RNAs, e.g. long non-coding RNAs, has led to an exploding interest in studying and exploiting the expanding world of functional RNAs. Agilent's proprietary TC-RNA chemistry has many advantages over legacy methods and enables synthesis of longer RNAs cost effectively including modifications at any position. It can also help enable more cost effective large scale synthesis of RNA oligonucleotides for therapeutic applications. In parallel with developing technologies for robust, high throughput manufacturing of RNAs using the TC-RNA chemistry we are engaging in a variety of external and internal collaborations exploring use of long RNAs for RNA structure-function studies, e.g. using NMR, X-ray crystallography, and single molecule fluorescence. In addition, we are evaluating the performance and utility of arrays of RNAs synthesized on glass surfaces for protein and small molecule binding studies.
Agilent's world-leading DNA oligo libraries are already key to a wide variety of products, e.g. Sure Select target enrichment kits, Sure FISH probes, and are being employed by Gen9 to assemble longer length DNAs, e.g. for synthetic biology related applications. Agilent Labs, in collaboration with Marv Caruther's lab at University of Colorado, is exploring breakthrough new methods for scalable DNA synthesis to extend Agilent's position as the premier provider of high complexity, long oligo libraries and to enable new applications to broaden the market for synthetic DNA. In addition to world leading nucleic acid chemists, Agilent Labs employs a variety of automated synthesis machines including a custom built DNA array writer with flexibility to explore new chemistries to enable a more seamless application of those chemistries to highly multiplexed manufacturing.
Advances in multiplexed measurement and information technologies in recent years have enabled researchers to do much more holistic analyses of complete genomes, transcriptomes, proteomes, metabolomes, etc. across many types of organisms. The use of such Omics technologies have yielded major advances in our fundamental understanding of living systems with far reaching impacts on endeavors such as improving human health, understanding and sustaining ecosystem function and biodiversity, and generating food plants to adapt and grow sustainably in changing environments. Agilent Labs has made major contributions to several Omics technologies including genomics and transcriptomics leveraging our DNA microarray platform, and metabolomics leveraging our GC- and LC-MS platforms. The overall goal of the current Omics program in Agilent Labs is to further increase speed, accuracy and utility of multiplex measurements of DNA, RNA, proteins, metabolites and their chemically modified forms by developing innovations in areas such as high throughput sample prep for metabolomics, more comprehensive tools for measurement of metabolite fluxes, and expansion of tools for profiling and functional characterization of the expanding world of non-coding RNAs.
The pathology workflow program is developing innovative solutions to support pathologists as they continually drive to improve patient outcomes. We are creating cutting edge workflow technologies to increase laboratory efficiency and quality of results. Our new tools and platforms are aimed at speeding the integration of emerging diagnostic assays into the pathology laboratory and supporting their new sample preparation requirements, imaging and data analysis. The Pathology Workflow program works in close collaboration with the cellular imaging and analysis and intelligent systems programs in Agilent Labs.
Science Management Group
The mission of Agilent Labs is to ensure the long-term viability and growth of Agilent’s businesses. To be successful, Agilent Labs must have a comprehensive understanding of the external science, engineering and technology trends and their impact and importance to Agilent’s customers.