Medical Device & Diagnostic Industry Magazine
MDDI Article Index

An MD&DI August 1997 Column

R&D HORIZONS

Fighting to switch the industry focus away from automotive applications, medical-use micromachines are introducing some amazing new technologies that are cheaper than their standard-size counterparts.

The trick to making successful--that is, practical--micromachines may well be to resist the urge to make them too small.

For the better part of two decades, engineers made micromachines ever smaller, a quest that doomed them to being laboratory curiosities, explains Henry Guckel, a micromachining pioneer. "Six years ago at a conference, I told my students that we should have copyrighted the pictures of our inventions because that was the only value of the devices they were making," says Guckel, IBM-Bascom professor of engineering and electrical and computer engineering at the University of Wisconsin (UW) in Madison. "We produced devices that looked beautiful but had absolutely no application. Today the emphasis is on making devices that have potential uses."

The majority of micromachines currently available in medical applications are designed to obtain precise pressure readings. This pressure sensor is used with catheters. Its size can be compared to the surrounding salt crystals. Photo courtesy of Lucas NovaSensor (Fremont, CA).

Micromachines are to the medical device industry what fleas are to a flea circus--imperceptible to the eye, yet capable of accomplishing extraordinary feats. Most micromachines currently used in medical practice record pressure in different parts of the body, delivering precise readings unobtrusively and inexpensively. But the potential of micromachine technology goes well beyond that. Accelerometers, which improve the operation of pacemakers, are being integrated into the medical mainstream. On the horizon are devices that will play primary roles in health-care delivery, such as pumps that deliver microquantities of drugs or that assist damaged hearts. Perhaps most intriguing are micromachines that will quickly and effectively identify infectious disease.

"Medical applications are going to grow very dramatically, particularly with the growth of home diagnostics," predicts Roger Grace, president of Roger Grace Associates (San Francisco), a high-technology marketing consulting firm. "There are a lot of people working on applications for urinalysis and blood analysis in which MEMS [microelectromechanical systems] will be a basic element."

MEMS are a subset of micromachines sculpted from silicon, as are semiconductors, and are typically fabricated in batches from 2500 to 15,000. The current flag bearers of MEMS technology are already engineering marvels. An entire device may be only a few millimeters in diameter. The ultrathin membranes etched into the silicon of pressure sensors can respond to changes as small as 0.1 psi. Electronic resistors planted in membranes can record changes in blood pressure or respiration, or in intrauterine pressure during birth. Other sensors have been placed in infusion pumps and dialysis equipment, where exact pressure measurements are needed to ensure proper flow.

Micromachine use in pacemakers is still evolving. These sensors detect patient motion and signal pacemakers to increase heart activity. Accelerometers also use electronic resistors to measure changes. Rather than being embedded in a membrane, the resistors, supported by tiny beams, recognize changes in the position of a mass.

Companies with deep pockets have bought into these evolving technologies. Sales are being driven by rock-bottom prices. Disposable blood pressure sensors are typically less than $2, compared to reusable devices that may cost $250 or more.

Some of the major companies taking advantage of this technology include Abbott, Baxter, Bird Products, Cardiac Pacemakers, Inc., CAS Medical, IVAC, Medex, Utah Medical, and Zimmer Patient Care. Their products and services include disposable blood pressure sensors, respiration and ventilation equipment integrated with MEMS sensors, pacemakers guided by microaccelerometers, infusion pumps, dialysis, and platelet phoresis.

This disposable blood pressure sensor from Lucas NovaSensor (Fremont, CA) incorporates a micromachined silicon sensor.

But today's offerings are just the beginning. Medical applications still only account for a small portion of the micromachine market. Leading the technology's commercialization is the automotive industry, which uses accelerometers to trigger the inflation of air bags and pressure sensors to relay information about oil and fuel.

The micromachine industry could grow to worldwide annual revenues of $12 billion by the year 2000, according to industry estimates.

A number of companies, such as EG&G IC Sensors (Milpitas, CA) and Lucas NovaSensor (Fremont, CA), are aggressively pursuing medical opportunities. Lucas NovaSensor is the world's largest producer of disposable blood pressure sensors, with volumes in excess of 8 million pieces a year. EG&G is not far behind.

A major challenge is to make medical products in a large enough volume to be cost-effective, says Harold Joseph, director of sales and marketing at EG&G. "The real drive has been to get the cost low, particularly for hospitals, where the benefit of micromachines is to provide a disposable part versus one that is cleaned and reused," says Joseph. To achieve the necessary volumes, EG&G is developing multiuse sensors--accelerometers, for example--that can be used for both automotive and medical applications with minor modifications.

But for EG&G and Lucas NovaSensor, pressure sensors and accelerometers are just paying the rent until the next generation of technology is born. A particularly hot area involves microfluidics, the ability to move, store, and otherwise manage small quantities of fluids. Developed at the UW in Madison and named after a German acronym for lithography, electroplating, and molding, LIGA is used to build the tiny pumps needed to move these fluids. One of the companies licensing the LIGA process is manufacturing a disposable micropump, which is being incorporated into intravenous lines for drug delivery. "It improves the metering accuracy of a drug tremendously," explains Guckel. "I especially like the product because it is a throwaway."

Micropumps are stepping stones to a number of applications. One of the most exciting is being pursued by MEMStek (Vancouver, WA), a start-up company and licensee of the UW technology. Nearing commercialization at MEMStek is a pumping system that might be used to speed up in vitro diagnostics.

John Skardon, director of marketing at MEMStek, notes that there are several common functions in all laboratory and analytical tests from electrophoresis to immunoassay. "What the functions all have in common is the ability to move milliliters and microliters of sample from point A to point B," he says. "We have attacked this particular part of the testing by creating what we think is the smallest soon-to-be commercially-available pump."

Measuring just 5 mm in diameter and 9 mm in length, including the motor, this device can be commanded to pump precise quantities, from tens of microliters to more than a milliliter, in one minute. "If you had a budget that would allow you to build three or four existing pumps into a device, you might be able to afford to use 10 of our pumps and reduce the number of valves and interconnects and in the process make the finished device operate quite a bit faster," Skardon says.

One of the most advanced near-term opportunities for microfluidics is DNA analysis. The technology's potential is evident in research at the MIT Lincoln Laboratory (Lexington, MA), where engineers are modifying capillary gel electrophoresis to take advantage of micromachines. The speed at which conventional gels can separate samples is determined by the voltage applied to the gel, according to lab investigator Albert Young, PhD. High voltages create heat that can skew the results. But microcapillaries 30 to 100 µm in diameter--about the diameter of a human hair--can disperse more heat than conventional gels.

"The heat gets extracted to the side walls very rapidly, and this allows you to drive the process much harder and get very fast separations," says Young. "So if you need to do a test quickly--for example, identify a bacterium in minutes rather than hours or days--there are a lot of advantages to making the test equipment small."

To get the DNA for this testing requires a polymerase chain reaction (PCR), wherein a DNA sample is amplified into larger quantities. Typically PCR uses carriers comprising pockets that hold reagent. These carriers cycle between two temperatures, a process called thermal cycling.

Engineers at Lucas NovaSensor have etched as many as 48 microwells into a silicon block 11 * 11 mm, with each well wired to allow precise thermal cycling. This use of micromachining requires less reagent and produces results much more quickly. "It also means potentially making these systems portable, bringing them right on-site," says Brian Wirth, marketing director at Lucas NovaSensor.

Wirth and his colleagues pride themselves on being at the leading edge of technology. Lucas NovaSensor was founded in 1985 on early research conducted at Stanford University, and the transducer lab continues to explore micromachine research. Among its projects are technologies that promise to forge the ultimate man-machine link. "The potential is to implant a mesh of microelectrodes into a nerve, let the nerve regenerate through the mesh, and then have this mesh serve as part of a closed-loop feedback mechanism," Wirth says. "It's a step toward becoming a bionic man."

Cutaway of a silicon micromachined accelerometer (EG&G, Milpitas, CA) used in pacemakers, activity/sleep monitors, and motion studies.

Such meshlike devices have the potential to precisely control prosthetic limbs. In turn, these sensors might be connected to micromachines that move the smallest surfaces on a prosthesis, making the actions of an artificial arm indistinguishable from those of a biological one. Alternatively, these devices might produce microelectrical signals to provide hearing to the deaf and sight to the blind. Experiments on frogs and rats in the Stanford Integrated Circuits Laboratory have established neural interfaces with cut nerves that have grown together, forming stable electrical links between on-chip microelectrodes and axons in peripheral and auditory nerves.

There are enormous obstacles to mak-ing these and other forward-reaching microtechnologies practical. Foremost among them are fabrication challenges--making mass quantities of devices that optimally fit the task for which they are being designed. This challenge has not been easy to meet, even for micromachines used in current and near-term applications.

Developers of these products have used a variety of etching processes, including chemicals and plasma. The etching is conducted under computer control, but silicon has an annoying habit of allowing electrochemical etching to occur only at 55° angles along the crystallographic planes of single-crystal silicon. "This limits not only the shape of the product but also the size," explains Wirth, "because if you start etching at 55° angles outward, the surface area has to get pretty big by the time you etch a thin diaphragm at the top."

Progress has been made by using advanced fabrication methods, such as deep reactive ion etching (DRIE). This technique provides greater control over the etching process than conventional methods, making deeper grooves that reduce the horizontal chip size and allow more flexible designs in silicon and custom sculpting. The end result is dramatic improvement in the capability to build microdevices. "With DRIE, you can literally sculpt structures," Wirth says.

Packaging, assembling, and testing are other challenges high on the list for improving micromachines. The massive growth of the semiconductor industry led to the development of cost-effective methods for manufacturing silicon devices. But packaging, assembling, and testing can be up to 95% of the total cost of a product whose strength in the market is its disposability, which requires low price. "The cost the customer incurs is the cost of buying, testing, and fitting the product into a package," Joseph explains.

To keep these costs low, EG&G is making products that fit into housings that have already been developed by their customers. For example, last October EG&G introduced the Model 1620 pressure sensor, which can be dropped directly into a vendor's disposable blood pressure housing.

Such drop-ins address an important part of the financial equation but not all of it. In the end, the components must be made efficiently and effectively. EG&G is adapting world-class manufacturing techniques, including C-cell manufacturing, to accomplish this goal. Adoption of this continuous-flow technique has dramatically improved yields, cut costs, and enhanced product quality, shrinking production cycle times from two weeks to eight hours on one product line and from six weeks to three days on another.

C-cells are characterized by physically grouping all the manufacturing equipment and resources necessary to produce a specific product rather than centralizing the work process to support a wide variety of different products. With this process in place, says Tom Spies, director of operations at EG&G, the company can "implement daily improvement and rapid responses to change in every product line."

This rapid response to opportunities in the manufacture of micromachines and their applications will be critical in making micromachines a significant part of the medical device industry. The products that now characterize medical applications are only the start. The future of micromachines, says Wirth, "is really up to the imagination of the design engineer."

Greg Freiherr is a contributing editor to MD&DI.

Copyright ©1997 Medical Device & Diagnostic Industry