SIEMENS

Question: How much information can you squeeze out of a drop of blood or water, a cubic centimeter of air, or a few voxels worth of imaging data? Answer: More and more with each passing day. Across the board, from nanowires designed to wring information from cells (see article "If Nanoelectronics and Living Cells Converge...") to spectroscopic analyses that identify the constituents of factory emissions (see article "Quality: Light Tells a New Story") and the distribution of atmospheric carbon dioxide (see article "Eyes on the Earth"), and from programs that identify the genetic signatures of new viruses (see article "Identifying Invisible Invaders") to microchips that can identify antibiotics, hormones and bacteria in a drop of water (see article "Sensor Systems Based on Cells"), scientists are finding an expanding universe of information in smaller and smaller spaces.

At Siemens, one of the most far-reaching developments to emerge from this trend is a growing understanding of how we can extract health-related information from the nano-sized offspring of genomic activity – nucleic acids and proteins. Cardiac biomarkers are a case in point. Take troponins, for instance – proteins released by cardiac cells in response to damaging events, such as an infarction. “What’s needed if a heart attack is suspected is a rapid, inexpensive, automated test to measure troponin levels that can be administered on the spot and can provide actionable information,” says Siemens Principal Research Scientist Dr. Walter Gumbrecht, who is recognized as a world leader in socalled “lab-on-a-chip” technology.

With a view to providing that kind of information, Dr. Gumbrecht has teamed up with Michael Pugia, PhD, one of Siemens’ 12 “Inventors of the Year 2009” and a leader in the field of microfluidic diagnostic systems. Based at Siemens Healthcare Diagnostics in Elkhart, Indiana, Pugia is credited with 203 inventions and 140 patents. Now, he and Gumbrecht have come up with a concept called an “electrochemical camera” that can squeeze remarkable amounts of information out of any liquid it is programmed to analyze.

The device combines pixel-sized resolution based on CMOS microchip sensing (thus the term “camera”) with a revolutionary paper-like substance imbued with a range of “catcher” molecules that respond to target substances. The combination is brilliantly economical because instead of exposing the chip to liquids, only a disposable strip of “paper” is affected. The paper is mounted on the chip and the two are placed in a reader. The paper is then exposed to a target body liquid, as well as reagents that are piezo-jetted onto the paper’s surface to catalyze reactions with the substances searched for.

If a doctor suspects that a patient may be experiencing a heart attack, the reader would expose a drop of the patient’s blood to reagents that would activate troponin-sensing catcher molecules in the paper. “When they bind with target substances, these catchers emit electrons to the chip’s sensors,” explains Pugia. “Within seconds, the device not only confirms the presence of troponin, but provides a read-out of its level.”

Desktop Diagnostics. Probably still several years away from market introduction, electrochemical camera technology could change the face of diagnostics. “Because it relies on processes that are extremely rapid and reliable, It would open the door to desktop testing in the doctor’s office or emergency room for conditions such as stroke and infarction, and could make it possible to test patients before they enter a hospital for dangerous bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), a major cause of hospital-acquired infections and deaths,” says Gumbrecht.

The technology also holds the potential for improved accuracy in the treatment of chronic conditions, such as diabetes. Desktop testing for blood-based diabetes biomarkers – now under development at Siemens – would make on-the-spot adjustments to treatment possible, thus eliminating millions of follow-up visits and reducing healthcare costs. Working along these lines, Pugia and his team have discovered a new marker for a gene fragment that controls the body’s insulin production. “Regular testing quantifor the level of this marker,” says Pugia, “could lead to new treatments for the disease, and even the ability to forestall it.

Similar advantages hold for the application of the new technology to PSA (prostatespecific antigen) tests, which are administered to tens of millions of men worldwide each year. “I believe that a PSA test running on an electrochemical camerabased device will be competitive with central lab tests,” says Hanjoon Ryu, Senior Vice President for Point of Care Testing at Siemens Healthcare Diagnostics in Deerfield, Illinois. What’s more, he points out, thanks to the reusability of its chip, the technology may be affordable enough to even serve rural populations in the Third World.

A technology that could bring affordable molecular-level testing to a doctor’s desktop, whether his or her office is in Manhattan or a dusty village in Mozambique, offers vast advantages for patients and healthcare systems. “For the first time, patients will be able to get answers to many fundamental diagnostic questions directly from their physicians,” says Ryu. “By the same token, this trend could take a huge amount of pressure off of hospitals, which are today congested with patients suffering from minor conditions.”

And that trend, once set in motion, will accelerate rapidly. Already, electrochemical camera technology can detect nearly 100 proteins – many of them in less than a minute. “Looking ahead,“ says Pugia, “we expect to discover a growing number of proteins, and thus be able to work with partners to engineer a wider spectrum of catcher molecules to detect and quantify them.”