December 24, 2002
Microfluidics to Revolutionize Biosciences

Forbes has a nice write-up on the microfluidic chip designs of Cal Tech biophysicist Stephen R. Quake

He and his group, along with Caltech's Axel Scherer, added a few clever twists. His chips, the size of a half-dollar or smaller, are made with two layers of rubber, relying on a technique similar to injection molding used to make toys. The bottom layer has hundreds or thousands of tiny intersecting liquid-handling channels, each about the width of a human hair (100 microns). The top layer contains hundreds of control channels through which pressurized water is pumped. Valves are formed where the control channels cross over the fluid channels. When pressurized water is fed over such an intersection, the pressure pushes down the thin layer of rubber, separating it from the fluid below, and it clamps shut the fluid channel below, like stepping on a hose. Quake's lab can make the chips with $30 bottles of rubber, an ultraviolet light to create molds and a convection oven to cure the rubber. A grad student can design and make a new chip in less than two days.

Quake predicts that his chips will have 100 times the number of cells and valves in a few years. These chips will be used for handheld instant blood chemistry testers, mini DNA sequences that are orders of magnitude smaller and cheaper than today's models, mini-labs for analysing the state of single cells, for testing large numbers of drugs against large numbers of cells in parallel, and countless other biochemical tasks that can be made orders of magnitude less expensive and less time-consuming.

Quake's chip technology is being commercialized by venture capital start-up Fluidigm. They have a picture of one of the chips on their web site. Fluidigm is developing this technology to lower the cost of polymerase chain reaction (PCR) which is widely used for DNA sequencing.

South San Francisco, CA, September 26, 2002 - Fluidigm Corporation and The California Institute of Technology announced today major advancements in complexity and function of microfluidic device technology. Using its novel fabrication technology, the MSL™(multi-layer soft lithography) process, Fluidigm has demonstrated a fluidic microprocessor that can run 20,000 PCR assays at sub-nanoliter volumes, the smallest documented volume of massively parallel PCR assays. This technology is being developed in the near term to run over 200,000 parallel assays. Fluidigm believes this fluidic architecture will make significant contributions in cancer detection research as well as in large scale genetic association studies.

At the same time, a group led by Dr. Stephen Quake, Associate Professor in the Department of Applied Physics at the California Institute of Technology and co-founder of Fluidigm, published an article in Science today describing a paradigm for large scale integration of microfluidic devices. These devices are capable of addressing and recovering the contents from one among thousands of individual picoliter chambers on the microfluidic chip.

Using new techniques of multiplexed addressing, Quake's group built chips with as many as 6,000 integrated microvalves and up to 1000 individually addressable picoliter chambers. These chips were used to demonstrate microfluidic memories and tools for high throughput screening. Additionally, on a separate device with over 2000 microvalves, they demonstrated the ability to load two different reagents and perform distinct assays in 250 sub-nanoliter reaction chambers and then recover the contents.

"We now have the tools in hand to design complex microfluidic systems and, through switchable isolation, recover contents from a single chamber for further investigation. These next-generation microfluidic devices should enable many new applications, both scientific and commercial," said Dr. Quake.

"Together, these advancements speak to the power of MSL technology to achieve large scale integration and the ability to make a commercial impact in microfluidics," said Gajus Worthington, President and CEO of Fluidigm. "PCR is the cornerstone of genomics applications. Fluidigm's microprocessor, coupled with the ability to recover results from the chip, offers the greatest level of miniaturization and integration of any platform," added Worthington.

Fluidigm hopes to leverage these advancements as it pursues genomics and proteomics applications. Fluidigm has already shipped a prototype product for protein crystallization that transforms decades-old methodologies to a chip-based format, vastly reducing sample input requirements and improving cost and labor by orders of magnitude.

Note as well Fluidigm's development of a prototype to automate protein crystallization which is used for the determination of 3 dimensional structure of proteins. Fluidigm is selling their Topaz prototype protein crystallization kit and they list the following benefits for it:

  • Sample input is reduced by 2 orders of magnitude, increasing experimentally accessible proteins by 100%.
  • As many as 144 crystallization experiments can be conducted in parallel.
  • Reagent consumption is reduced 100x.
  • Labor and storage costs are reduced 300x compared to the 20-year old technology currently in place.

There are countless uses for smaller cheaper mini chemistry labs. As this technology advances it will accelerate the rate of advance of biological science and biotechnology literally by orders of magnitude. The impact will be greater than the impact of computers to date because it will make possible the cure of diseases, the reversal of aging and the enhancement of human intellectual and physical performance.

Also see my previous post on the Quake lab's work.

Share |      Randall Parker, 2002 December 24 02:47 PM  Biotech Advance Rates

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