Larry Kricha, M.D., professor of pathology and lab medicine at the University of Pennsylvania and director of the chemistry lab at UPenn Hospital
Less than 50 years ago, a single computer filled a room — today, it may not fill the palm of a hand. Similar and even greater changes are occurring in the design of laboratory equipment and for the same reason — our ever increasing ability to miniaturize and integrate electronic devices. According to at least one expert the next 50 years in microelectronics could change today’s laboratories as much as computing did over the last 50 years.
“The one technology that looks like it will have the greatest impact on the clinical laboratory, is the microchip,” said Larry Kricha, M.D., who spoke at a fall meeting of the American Association for Clinical Chemistry in Boston. Kricha is a professor of pathology and lab medicine at the University of Pennsylvania and director of the general chemistry lab at UPenn Hospital.
To illustrate his point about the potential magnitude of the change, Kricha referred to ENEAC, the first electronic computer. Built for use in World War II, ENEAC weighed over 30 tons, contained 1,800 vacuum tubes, and required a large, highly skilled staff to calculate trajectories. Now, a single person using a laptop computer that weighs less than 10 pounds can do even more complex calculations. Just like personal computers, laboratory devices are getting smaller, easier to use and less expensive.
Using another historical reference, Kricha compared the laboratory of Otto Folin circa 1900 to a typical clinical laboratory of today.
Kricha noted that today’s labs, in contrast to those in the 1900s, perform high volumes of tests, are highly automated and offer extensive testing menus.
The impetus to miniaturize analytic devices did not originate in the clinical diagnostic lab but in drug discovery labs where it is necessary to inexpensively perform millions of tests by conserving rare compounds. Point of care also has created a demand for small instruments.
Microminiaturization makes it possible to put several assay components into a single device and make that device “very, very small,” Kricha emphasized. While these devices are shrinking, they also are gaining capabilities.
Labs on a chip
One example of miniaturization in the chemistry lab is a microfluidic or “lab-on-a-chip” device. These devices separate small samples via chip architecture such as exit and entry ports and pillars and pathways that create gaps to isolate cells by size and enable reagents or markers to be added to a sample. These devices employ few or no electronics. The PCR chip or “flat test tube,” as Kricha calls it, is one example. A more complex lab on a chip is the bioelectronic chip, which combines fluidics and electronics. It separates material by breaking cells with an electric charge.
Other chip developers are working on what they call the “cellular phones” for DNA molecules. Kricha calls them, “talking test tubes.” Such devices consist of a 250-micron tube of silicon that contains a series of electronic devices and circuits such as ROM and an oscillator. It also includes a molecular recognition lab on its surface. These chips can be programmed to be identified by a unique signal. They then can be put in a sample and detected and identified later. In that way, they provide information on binding taking place within the sample.
Pluses and minuses of microlabs
As any cell phone or palm pilot user can attest, making things smaller changes the way humans interact with them. This, in turn, raises issues about the advantages and disadvantages of devices, even familiar ones. Just as the popularization of cell phones has raised issues of etiquette and safety, so too has the miniaturization of lab analyzers brought its pluses and minuses.
Kricha described the upside and downside.
Advantages
- Integration — all analysis steps on one chip and one device (isolate cells, extract inform amplification reactions, detect amplicond and download results to an information system)
- Mass production and low cost — microanalyzers can be made in few steps using just two or three masks
- Small and portable instruments — tests can be done at the bedside, doctor’s office, even the home
Disadvantages
- New technology always faces resistance
- Human interface — the only way in and out of some of the devices is a hole 500 microns in diameter
- No standard on size of devices, how to handle them and what the interface(s) should be.
- Degrees of miniaturization — the volumes in some are submicroliter, even nanoliter. If using a heterogeneous sample (i.e. blood) it’s very hard to take a small sample and have it be representative
- Detection limits are a difficult barrier to microminiaturization not easily overcome. You can’t take a serum or plasma sample and keep reducing the sample volume for a smaller and smaller analyzer that uses less and less of a sample because eventually you reach the detection limit.
Clearly, many of the obstacles facing lab microtechnology are technical and eventually will be overcome with continued research and development. Social and ethical issues, on the other hand, tend to be more difficult. As Kricha pointed out, it is not only simple tests and procedures that are being miniaturized and simplified by microtechnology but “more alarmingly” genetic tests. What we are talking about are “small analytical devices capable of doing the most sophisticated genetic tests we do — outside the laboratory and perhaps not completely controlled. This raises some ethical issues.”
Whether or not Kricha’s prediction — that the microchip is the technology that will have the greatest impact on the clinical laboratory — is correct, the trend toward miniaturization of technology marches on and continues to impact the world both inside and outside the lab.
