The Infineon biochip uses a three-dimensional micro-array, a network of fine micro-channels that run between the upper and the lower side of the chip, in contrast to traditional glass substrate, planar biochips that have a two-dimensional sensor surface. Using a special etching process, about one million channels are formed per square centimeter of chip surface, each with a diameter of only 10 µm and a depth of half a millimeter. For the FTC, about 100 of these channels are used per probe molecule, with each chip typically being configured with 100 to 400 probe molecules or gene sections or spots.
Two characteristics of the FTC technology speed test times and increase the sensitivity of analysis compared to currently used, planar biochip technology. The molecules to be analysed are repeatedly pumped through the chip. In this manner, the reaction speed during hybridisation is no longer dependent on time-consuming diffusion and is much higher than with the planar biochips. Owing to the channel structure, a hundred times more molecules can react with each other, compared than with alternative biochips, which makes the assay more sensitive.
Analysis using the FTC is a multi-step process. The micro-channels of the biochip are prepared by MetriGenix, which populates the chip with segments of known genes that fix themselves on the walls of the micro-channels. Then the gene sample to be analysed is repeatedly pumped back and forth through the pores in the so-called Flow-Thru technique. This will cause matching genes of the sample to bind with the known genes on the pore wall. A luminescent dye that is added in another step will bind with the gene segments that have been matched in the chip and emit light. Captured by a Charge Coupled Device (CCD) camera and forwarded to a computer, the result can be evaluated on the screen.
"By further developing existing semiconductor technologies, Infineon will develop and produce cost-effective chip-based solutions in the field of biotechnology", stated Dr. Thomas Klaue, Director of Business Development and responsible manager for Infineon's biochip activities. "Together with competent partners, we provide complete system solutions that use innovative technologies to simplify, improve, and accelerate pharmaceutical development and medical diagnostics and make them more affordable."
Due to its special physical characteristics and design, the FTC technology offers numerous advantages: high sensitivity, a large reactive surface, a high signal-to-noise ratio though the use of silicon substrates, short assay times - about two to three hours instead of the usual half or full day as with present techniques - low re-agent consumption, and an automated hybridisation and evaluation process. The bottom line is reliable results within a short period of time at low costs and with easy handling.
For example, these chip-based system solutions accelerate the examination and evaluation of active agents in pharmaceutical development and make them more cost-effective than with the existing methods. In this manner, biochips contribute significantly to reducing the cost of pharmaceutical development.
Currently, pharmaceutical companies typically invest an average of 12 to 15 years into the development and test phase of a new drug. Because every acceleration of this process can improve the patients' chances for successful treatment, the new Infineon chip and test systems make an important contribution to the industry. Using new, chip-based analysis methods, the pharmaceutical industry expects time savings of one to two years in the development of a new drug. For a "blockbuster" drug - a popular, widely used medication - reducing time to market by just one year can mean increased revenues of up to 500 million euro.
Infineon plans to work with industry partners to further develop the Flow-Thru system for diagnostic purposes. This could enable physicians to determine the right medication for patients in their offices. Based on a blood sample, the physician could collect information about the specific reaction to a drug, about side effects and reaction times. This would mean significant progress in the treatment of diseases such as depression or hypertension, where the time until a medication takes effect is most critical.
For the practical application of the FTC, Infineon offers a complete system solution for biomolecular analysis. The "4D Array System" was jointly developed with United States specialist company MetriGenix, and is used by pharmaceutical and biotechnological companies for biological research, pharmaceutical screening and genetic or medical diagnostics.
The 4D Array System comprises the biochips as well as a hybridisation and an evaluation unit. The chip is safely contained in a cartridge through which the substances to be analysed are delivered to the chip. The system solution also includes the specific gene probes ("wetware") on the chip, which represent the actual biological content ("theme chip"). In this process, less than 100 selected, specific genes are applied to the theme chip in order to avoid unnecessary data ballast. Only those genes are used that are required by the customer to solve a specific problem.
The United States company MetriGenix together with Infineon developed the complete Flow-Thru Chip solution. This consists of Flow-Thru-Chips, a hybridisation unit (left) and an evaluation apparatus (right) with an integrated high-sensitivity camera.
Photo courtesy of Infineon Technologies.
Currently, a number of specific assays, equipped with the appropriate gene structures for specific diseases, are available for the 4D Array System. The range comprises arrays for examinations for lung and breast cancer, tissue proliferation, and inflammation, as well as an array for the detection of neural changes that are the cause of diseases such as Alzheimer's, Parkinson's or Multiple Sclerosis. In addition, custom arrays are available that provide specific genes with complexities of 50 to 192 samples based on customer specifications.
Apart from their underlying technology, biochips can be distinguished by their evaluation method, which may be optical or electronic. Optical biochips and matching analysis systems, such as the 4D Array System from Infineon/MetriGenix, are available now. Infineon's electronic DNA chip is scheduled for release into the market in about two or three years' time. A third technology, Infineon's "Neuro-Chip" is still in the research phase.
For Infineon, one of the most important future trends in the health care industry is the convergence of therapy and diagnostics. Here, especially the electronic DNA chip will play an important part in solving the task of determining the right drug in the right dosage for the right patient in the shortest possible time.
Personalised medicine to be applied in the doctor's office calls for small, cost-effective, easy to handle diagnostic analysis devices. Given the fact that it still takes an average of six months to find the right medication for a patient, the opportunities for biochips become obvious. New diagnostic methods such as biochips will make it possible in the near future to administer medication much more selectively and cost-effectively.
Infineon presents the commercially available Flow-Thru Chip system solution at the Bio-Analytica trade show from April 1 to 4, 2003 in Munich. The system is priced at about 60.000 euro and includes a hybridisation unit and an evaluation apparatus with an integrated high-sensitivity camera. More Infineon news is available in this VMW issue's article Neuro-Chip from Infineon measures electrical activity in living cells to further brain research.