The Science and Art of Miniaturizing Diagnostic Medical Devices

On Wednesday, February 13, Marc Madou, Chancellor's Professor of mechanical and aerospace engineering and biomedical engineering at the University of California, Irvine, will hold a keynote presentation at the MD&M West Conference on "The Science (and Art) of Miniaturizing Medical Devices: A Closer Look at CD Technology in Molecular Diagnostics."

A subfield of microfluidics, CD microfluidics concentrates on the behavior, control, and manipulation of fluids in the microdomain. In this technology, fluidic channels and reservoirs are embedded in a CD-like plastic substrate that is spun using a motor. Exploiting centrifugal forces to achieve fluid propulsion, the system can perform a range of fluidic functions, including valving, decanting, calibration, mixing, metering, sample splitting, and separation. These functions are then combined with such analytical measurement techniques as optical imaging, absorbance, fluorescence spectroscopy, and mass spectrometry, enabling the CD platform to perform a host of medical and clinical diagnostics.

In a conversation with MPMN, Madou explains how his CD technology could eventually improve the practice of medical diagnostics and perhaps enable doctors in the future to run medical tests by simply popping a disk into an ordinary CD player.

MPMN: Please describe your CD technology and why you think it can play a role in medical device applications.

Madou: Our CD technology takes advantage of the same rotating platform that is used to play music and movies. However, many people have perhaps not recognized that in this very inexpensive CD player there is a sophisticated optical platform that can do three things for us at a very inexpensive cost. First, it's a microscope. Thus, it can easily be turned into a device for visualizing objects as small as cells. And of course, microscopy is used often in biomedical technology. Second, because the CD spins, it can function as a centrifuge. Third, CD technology is an inexpensive plastic disposable item. Thus, instead of employing glass slides, microtubes, or polymerase chain reaction (PCR) tubes, the CD contains chambers that we carve into the plastic. Lateral, flat structures, these chambers can contain a liquid, just like a PCR sample in a little tube.

For years, people have used silicon technology as an entry into manufacturing inexpensive disposables. Similarly, we are using the CD as a disposable item. However, the CD can also serve as an infrastructure for performing many biomedical applications, including immunoassays and blood gas, blood electrolyte, or DNA analyses. We have been addressing all of these technologies with our CD platform.

MPMN: How can your CD technology serve as an avenue for miniaturizing medical devices?

Madou: In addition to the CD's three primary characteristics, the technology can also act as a pump. In almost all medical diagnostic applications, you need a pump. In addition, the pump requires tubing. In our case, we don't need tubes because the rotating CD, performing as a pump, contains leads in the plastic disk. This feature promotes miniaturization because the disposable CD can serve as a small pump. And because the CD is symmetrical, it can easily be multiplexed. If you think of the CD as a pie, we can divide it into many small segments. Depending on size of the segments, the rim of a single CD can be used to perform 1,056 immunoassays.

MPMN: That explains the science behind your technology, but where does the art come in?

Madou: The art of solving problems that we can't solve simply through engineering comes from people that have worked with many manufacturing techniques and intuitively know if a technology is too complicated. For example, where should your heat source be located? Should it reside on the CD--the disposable part of our technology--or should it reside in the instrument used for running the CD? This is a partitioning question, and answering it helps us to design platforms to meet specific application needs. Thus, there's a huge difference between a CD application that's meant to perform high-throughput screening and one that's meant to perform a biomedical application. High-throughput screening can involve the use of a much more expensive CD, whereas in diagnostic applications, we try to put everything we can into the instrument and as little as possible into the disposable plastic CD.

In short, the element of art in our work comes down to understanding during the manufacturing process how much complexity we want to design into the instrument versus the disk. This requires good intuition.

MPMN: What are you and your colleagues striving for--a more complex CD or a more complex instrument? Or does it depend on the application?

Madou: When the microfluidics arena started, it was unfortunately quite heavily geared toward high-throughput screening for such applications as drugs. This trend misdirected the whole microfluidics field a bit because diagnostic applications are very different from high-throughput screening. For diagnostics--and that's mostly what we do with CDs--the equation is to achieve as little complexity as possible on the CD and shift as much cost and complexity as possible to the instrument. One reason why the cost factor in high-throughput screening differs from that in diagnostics is that in the former, you don't need to store the CD for a period of time. A robot pipettes liquids and a high-level technician operates the robot. Not so in the diagnostics arena.

MPMN: You've mentioned some of the potential applications for your technology, including diagnostics. What other medical device applications do you think your technology might eventually serve?

Madou: In my presentation at the MD&M West conference, I will highlight some of the products that are already on the market. Measuring blood gases and blood electrolytes was one of the easiest entries into the game. The next step up will be to develop DNA and nucleic acid analysis capability. We are working on both of these applications, but they aren't marketable yet. We also have several successful stations that perform very effective lysing and purification of DNA.

Thus, ours is a very generic platform because it is a smart centrifuge, an inexpensive disposable, and an optical system with very accurate positioning capability. It would be hard to develop such a technology from scratch. It has the backing of a huge CD industry behind it that enables us to work with these components at a low cost.