http://www.anl.gov/OPA/news98/biobackgrounder.htmTitle:
This page has been accessed * times since June 29, 1998. Background Q & ABiochip Commercialization ProjectMotorola Inc., Packard Instrument Co., Argonne National Laboratory
The goal is to develop and commercialize a new technology that can decode the genetic structures of living things thousands of times faster than existing technology. The technology uses biochips, robots and computers to automate the massively parallel detection of gene mutations and to simultaneously analyze the activity of thousands of genes in healthy and diseased cells and tissues. Who are the partners and what special capabilities does each provide? The partners are Motorola Inc., Packard Instrument Company and the U.S. Department of Energy's Argonne National Laboratory. Each brings special expertise and capabilities to the project.
By combining Motorola’s mass production capabilities, Packard’s core competencies in bioanalytical equipment and reagents, and Argonne and Engelhardt intellectual property and know-how, the partners believe they can make the biochip technology accessible to a broad range of markets for a wide range of applications. Motorola and Packard will contribute a total of $19 million over five years to support the joint-research agreement, making it one of the largest biotechnology joint-research agreements ever signed by a U.S. Department of Energy laboratory. Argonne's contribution, in conjunction with its Moscow research partner the Russian Academy of Science's Engelhardt Institute of Molecular Biology, is intellectual property in the form of 19 inventions related to biological microchips. The 19 inventions, which have been licensed exclusively to Motorola and Packard, are the result of more than $10 million in research support since 1994 by the US. Department of Energy, the Defense Advanced Research Projects Agency, the Russian Academy of Sciences, and the Russian Human Genome Program. What roles will Packard, Argonne and Motorola play in the alliance?
Motorola will use Packard’s patented nanoliter liquid-handling technology to develop the capabilities to mass produce biochips for specific markets and applications. Packard will develop two instruments -- the BioChip Arrayer and the BioChip Imager -- that together will create a single system for dispensing assays onto the biochips and analyzing the reactions.
What are the benefits of commercializing biochip manufacturing? Commercialization and mass production of biochips will greatly reduce costs and make biochips and their associated analytical technology widely available to researchers. Through miniaturization and automation, this technology and its associated analytical equipment will greatly reduce the amount of a sample needed for analysis and increase the number of samples that can be analyzed simultaneously. For example, conventional drug screening typically costs $4 to $5 per sample. Packard estimates that through miniaturization costs can be brought down to 40 cents -- or even to 4 cents -- per sample. The wide availability of biochip technology will lead to rapid and major advances in medical diagnostics and treatment, drug development, environmental remediation, and agricultural products.
The Argonne/Engelhardt biochips use micro-gel technology. Thousands of micro-gels are affixed to the surface of each biochip. As many as 10,000 or more micro-gels are contained in an area about the size of one microscopic slide. When performing an assay test, each micro-gel is like a micro-test tube. The advantage of this technology is that it provides a 3-dimensional platform to perform assay tests, allowing multiple layers of DNA to be stacked for greater sensitivity and accuracy. Because the gels are 3-dimensional, they can immobilize and assay important biological molecules such as proteins, RNA, and cDNA (cDNA is DNA made from "messenger RNA," a special type of RNA that serves as a template for synthesizing proteins). By using this technology in combination with liquid-handling instruments, such as those developed by Packard, researchers will be able to dispense DNA samples directly onto the biochips in their own labs. They will no longer need to provide proprietary research information to chip manufacturers. Moreover, a wide variety of biological targets can be immobilized on the biochip, including DNA, gene fragments and proteins. Who are the potential customers for this technology? Initially, the market will be pharmaceutical companies, research facilities, biotechnology firms and academic research institutions worldwide. Ultimately, it will be used in hospitals and clinical laboratories. How large is the potential market for products based on this technology? Nearly every pharmaceutical company, genetics research organization and biomedical research and diagnostic institution in the world is a potential customer of this technology, so the market potential is enormous. This technology is an extension of three revolutions in modern biology: the discovery of DNA, genetic engineering, and the use of genes to cure disease. DNA microchips are fuelling this third revolution by providing an automated, high-throughput technology that allows scientists to map out genetic codes found in DNA, creating a potential multi-billion-dollar market in the biopharmaceutical industry. Currently, genomics, the understanding of the human genome for developing therapeutic products to treat disease, is the most successful application for DNA microchips, but with the introduction of a practical biochip for genotyping, applications for clinical diagnostics are not far behind. How quickly will this technology be on the market? For drug discovery, academic life science research and pharmaceutical research, biochips have immediate practical applications for polymorphism analysis (variations in DNA sequence among individuals), gene expression studies, and monitoring clinical trials. Within a few years, biochips could be routinely used to study cellular responses to drugs under investigation, to detect genetic differences between patient populations, and to determine the therapeutic effectiveness of new drug candidates. The transition into the clinical diagnostics market will take place in four to five years. Why is determining the human genome so important? Mapping, or sequencing the genome, the complete collection of genes that is nature's code for building and operating all organisms, is a major national research effort. Because humans have billions of gene pairs, the task is monumental -- sort of like determining the entire works of Shakespeare from a vat filled with Scrabble letters. This technology simplifies that chore by manufacturing DNA "microchips " -- arrays of short strands of DNA immobilized into gel elements fixed on a glass plate. A worldwide research effort is currently under way to map and sequence the human genome. How can biochips aid genomics research? The ability to determine thousands of different oligonucleotides on DNA sequences in the same assay procedure is very important to genomics as well as to medical diagnostics. In genomics, sequencing information and the detection of gene mutations are important for gene sequencing, gene discovery, genetic mapping, the study of drugs and environmental factors on gene expression and the screening of individuals for sequence variation (polymorphism). What specific applications will the biochips have in genomics?
How can the Argonne/Engelhardt approach speed up genetic research? The Argonne-Engelhardt approach promises to decode genomes and detect genetic mutations thousands of times faster than conventional technology by automating a process similar to a computer "word search" for unidentified DNA strands. For example, tests of the Argonne/Engelhardt technology led to the speedy identification of the genetic change in individuals with thalassemia, a defect in the blood's hemoglobin similar to sickle cell anemia. This disease, which appears only in the Mediterranean, is caused by a genetic defect that usually affects only one or two base pairs in the relevant gene. The Argonne-Engelhardt process identified the presence of that genetic mutation in the blood of thalassemia patients in only seconds. When using the Argonne/Engelhardt approach, scientists prepare two solutions: one containing short strands of known DNA and another containing unknown DNA. Less than a drop of each is applied to the biochip, then the unknown DNA sections are given a few minutes to pair up with known sections. A computer attached to a microscope analyzes the data and in a few seconds pieces the word puzzle together, thereby identifying genetic sequences and mutations. The biochip technique uses fluorescent "tags" or stains to indicate where known and unknown DNA bases have paired. When exposed to light of a specific energy, many molecules absorb some of the energy and become “excited.” This means that one or more or the molecule's electrons have risen to a higher energy state. In nature, high energy states tend to be unstable, so eventually the electron falls back down to a lower energy state, and emits light. This process is called “fluorescence.” Fluorescent light is like a fingerprint of the excited molecule. By measuring the light’s energy, scientists can identify the molecules that emitted it. The Argonne/Engelhardt process for decoding DNA uses this property to determine how well known strands of DNA have bonded with strands from a sample of unknown DNA. After known and unknown DNA segments have had time to pair -- a matter of seconds -- the biochip is loaded with fluorescent dyes that attach to specific bases. The dyes are more concentrated at sites where the bases form pairs. Packard has developed a specially designed two-wavelength imaging system to analyze the signals from the DNA samples and decode the unknown strands. By using biochips and robots to automate this entire process, an unknown DNA fragment can be decoded in a matter of minutes. The DNA bases are the four biological molecules that make up DNA, or deoxyribonucleic acid, the molecule that nature uses to spell out the blueprints and operating instructions of all living things. DNA is made up of two long spiral chains. Each link in one chain is physically bound to a corresponding link in the other chain. The links are made of only four DNA bases: adenine (A), cytosine (C), guanine (G) and thymine (T). Thus the language of DNA is written in only four letters: A, C, G and T. This short alphabet encodes thousands of genes that direct the construction of proteins, which make up the cells in our bodies and control most biological processes. When the links of the DNA spirals bind, A always binds with T in the adjoining spiral, and C always binds with G. An oligonucleotide is a short segment of a DNA chain. Typically, scientists call a DNA segment with fewer than 100 bases an “oligonucleotide.” A biochip is essentially a small glass slide with thousands of absorbent micro-gels fixed to its surface. A single biochip may contain 10,000 or more micro-gels in an area about the size of one microscopic slide. It provides a medium for matching known and unknown samples of DNA and automating the process of identifying the unknowns. |
