IPF 2013-Manufacturing Challenges for Emerging Technologies: IV. Manufacturing Challenges: The Life Sciences
Tuesday, October 29, 2013 8:00 AM in Room 202 B
MS+AS+BA+BI+PS+TF-TuM-1 Microfluidics for Chemical Analysis
Liz Carr, Qing Bai, Reid Brennen, Sue Post, Greg Staples, Karen Seaward, Hongfeng Yin, Lynette Martinez, Debbie Ritchey, Kevin Killeen (Agilent Technologies)
Chemical analysis is an essential tool for pharmaceuticals, environmental testing, food safety, forensics, energy and many other industries. The need for faster, more accurate and more sensitive measurements continuously pushes the limits of measurement technology and creates opportunities for advances in chemical analysis instruments and applications. One way in which this need can be addressed is by incorporating microfluidic devices in High Pressure Liquid Chromatography (HPLC). Pressure-based microfluidic chips have enabled a new class of reproducible integrated workflow devices that combine sample preparation, enrichment, and HPLC separation with an integrated ESI/MS (Electrospray Ionization/Mass Spectrometry) interface for high sensitivity nanoflow Liquid Chromatography-Mass Spectrometry (LC-MS). These devices have most commonly been fabricated using polymer, ceramic, and glass materials but the next generation of higher capacity and throughput microfluidic chips for LC-MS requires materials and structures capable of ultra high pressure operation. In this work, we describe the fabrication and performance of diffusion-bonded metal chips for high performance nano- and microflow LC-MS operation. The microfabrication technology required to make these devices includes semiconductor fabrication standards such as photolithography and thin film deposition, as well as laser ablation, electrochemical etching, and diffusion bonding. These novel metal devices exhibit state of the art performance in resolution and throughput for microfluidic LC-MS chips. These chips are an example of improvements in measurement sensitivity, resolution, speed, and ease of use that have been made possible by utilizing microfluidic devices for chemical analysis.
MS+AS+BA+BI+PS+TF-TuM-3 Challenges in the Fabrication of Nanoscale Devices for DNA Base Sensing
Satyavolu Papa Rao, J. Bai, Eric Joseph, Robert Bruce, M. Lofaro, M. Krishnan, Markus Brink, M. Guillorn, Stephen M. Rossnagel, Qinhghuang Lin, J. Cotte, C. Jahnes, J. Smith, L. Gignac, K. Reuter, S.-W. Nam, Y. Astier, C. Wang, G. Stolovitsky, R. Goldblatt (IBM Research Division, T.J. Watson Research Center)
The fabrication of integrated circuits with increasingly fine geometries has required the development of advanced process technologies, which can be further refined for the purpose of building devices for biological applications. Applications such as sensing nucleotides in DNA require structures that are of the order of a few nanometers. This talk will focus on the specific challenges encountered in the fabrication of such nano-scale devices – broadly classified into materials-related challenges, unit-process challenges and process integration-related challenges. Issues such as dielectric integrity, metal recrystallization, and materials compatibility with chemistries used down-stream will be discussed. Dimension control during fabrication of ~10 nm sized structures was achieved through intense process development efforts of reactive ion etch and chemical mechanical planarization (both manufacturing-friendly techniques). Device layout issues that affect manufacturability will be presented. Finally, some of the important lessons learned in achieving a high yield of reliable devices through process-integration changes will also be discussed.
MS+AS+BA+BI+PS+TF-TuM-5 Nucleic Acid Synthesis and Applications
Steve Laderman (Agilent Technologies)
The pursuit of perfect and practical de novo chemical syntheses of nucleic acids has been the foundation of a broad range of life science accomplishments over many decades in the past. Its further pursuit is enabling a broad range of opportunities many decades into the future. These themes will be elucidated by examining the precedents and improvements enabling high throughput genomics for research and diagnostics through the manufacturing of high quality DNA microarrays and complex pools of long oligonucleotides. Looking forward, new ways to synthesize RNA will enable deeper understanding and improved manipulations of cells, tissues and organisms. At the same time, multiple applications of synthetic biology are motivating additional focus on further advances in flexibly and cost-effectively constructing perfect DNA.
MS+AS+BA+BI+PS+TF-TuM-9 Single Molecule, Real-Time DNA Sequencing
Stephen Turner (Pacific Biosciences)
In this talk, I'll convey the story of the development and commercialization of Pacific Biosciences' Single Molecule, Real-Time DNA Sequencing technology. I will start with an overview of the method, how it works, and how if differs from sequencing methods that came before it. I will continue with a discussion of some key technology milestones, with an emphasis on the technological advances in materials engineering and nanofabrication. I'll finish by showing some examples of how this technology has transformed the field of DNA sequencing and genome analysis.
MS+AS+BA+BI+PS+TF-TuM-11 Opportunities and Challenges in the Biobased Products Manufacturing
Jim Flatt, Shaun Bailey, Stan Bower, Dan Gibson, Sammy Farah, Justin Butler, John Hannon (Synthetic Genomics)
Biobased production of life’s necessities, including food, fuels, chemicals and medicines provides a foundation for sustainable and geographically distributed manufacturing processes. Biobased manufacturing utilizes photosynthetic processes directly through conversion of carbon dioxide and light energy or indirectly through conversion of renewable biomass feedstocks to products. Biological cells (biocatalysts) are the operating systems for these biobased manufacturing processes. Rapid advances in synthetic biology enable the engineering of biocatalysts which can produce a broader range of products than previously possible, at high yields and productivities necessary for achievement of desired economics. Improvements in biocatalysts are achieved through modifications of DNA, which is the software of living systems. Significant advances in the costs, fidelity and speed of DNA synthesis, along with improving understanding of gene function and regulation is enabling the more rapid development of biocatalysts which achieve required performance for commercially viable manufacturing processes. The current state of the art of synthetic biology and technology trends which will impact future development of biobased processes will be discussed. Additional market-specific and process-specific challenges exist, and will be discussed in context of the specific examples taken from manufacture of synthetic vaccines, biobased chemicals and fuels. Recently, Novartis and Synthetic Genomics demonstrated the ability to successfully produce vaccines for prevention of seasonal influenza using synthetic DNA constructs, which significantly reduces the time from influenza strain identification to production of the vaccine seed. Development of this revolutionary process required significant improvement of the fidelity of DNA synthesis and assembly, which provides insight into the challenge of engineering more complex biocatalysts. On the other end of the spectrum, phototrophic microalgae have great long-term potential to provide a sustainable and alternative source of food and liquid transportation fuels. Phototrophic microalgae can be cultivated using non-potable water on non-arable land. Techno-economic analysis (TEA) and life cycle assessment (LCA) both suggest that significant improvements in biocatalyst productivity and capital cost reduction will be required to achieve competitive economics. Maximum observed algal biomass productivities in the range of 20 to 25 g/m2/day are far lower than generally-agreed upon theoretically-achievable productivities based upon the actual solar energy available. Improvement of photosynthetic efficiency in mass culture is required for economical algal-based processes. Limited availability of light in mass culture also limits the maximum achievable cell density, which results in increased downstream processing costs. The challenges of “dilute solution economics” associated with commercial algae production and potential biological and engineering solutions will be discussed.