The business of chemical analysis has a long history, possibly going back to the 1600s. But modern analytical chemistry truly began in the 1830s with the German chemist Robert Wilhelm Bunsen, who discovered that each element gives off a characteristic spectrum of light when heated. He developed the technique of emission spectroscopy and the Bunsen burner to heat elements. Then, he went on to perfect a battery made of zinc and carbon using nitric acid with which he extracted metals from their salts by electrolysis.
Despite some obvious advances, chemical analysis of any type remained an awkward, laborious process throughout the 19th and 20th centuries, much as it had been in Bunsen's time. It also continued to require a great deal of laboratory equipment and time. Nevertheless, efforts were always underway to streamline analytical processes — whether in science, medicine, or industry — and make them more widely available and easier to use.
As far back as the mid-1950s, micro-technology began to develop and by the mid-'60s it was being applied to chips used as pressure sensors. Soon, that technology was being used for various applications, including making sensors for airbags in automobiles. It was at that point that scientists began using Micro Electro Mechanical Systems — or MEMS — to handle minute quantities of fluids.
In the process, they developed tiny capillary channels, mixers, valves, pumps, and measuring devices. The term "lab on a chip" arose in connection with these experiments. The first actual chip-based analytical system was built at Stanford University in 1974 for gas chromatography.
Intense interest in this field grew throughout the 1980s and '90s. But big advances only came in the mid-'90s, as researchers realized how useful lab on a chip technology could be for genetic research. DNA micro-arrays for genetic analysis were developed, and DARPA began funding research on portable biological and chemical warfare detection systems.
As computer chip technology, microelectronics, and micro-mechanical systems increased in sophistication over the past decade, research efforts focused on reducing an entire analytical chemistry laboratory and all of its functions to something that could be carried around and used in the field. But even so, progress was stymied because samples usually had to be prepared separately, in a full-scale lab, before being processed by the miniaturized lab on a chip.
But now, at last, according to the journal Angewandte Chemie,1 a team in Singapore has developed a rapid test for genetic diagnosis that uses a single drop of fluid containing nanoparticles. That drop is moved across a chip by a magnetic field. This not only miniaturizes the entire process, but it reduces the time for analysis from hours to minutes.
For example, a drop of blood can be mixed with the drop containing nanoparticles and then placed on the chip. The nanoparticles contain antibodies that bind to cells in the blood. The magnetic field physically pulls the bound cells out of the fluid and moves those selected cells to the next station on the chip.
Enzymes can then be delivered to the selected cells for various functions. So, for example, a single drop of blood could be used to discover a cancer that would otherwise be undetectable. Best of all, the whole process takes just 17 minutes.
Because of the extreme miniaturization of the channels and small amounts of chemicals in these devices, they can also be used to mimic biological systems. According to a Chemical & Engineering News cover story,2 researchers are using lab on a chip technology to gain a whole new level of understanding of the chemical processes underlying high blood pressure, stroke, sickle cell disease, and other disorders.
They have even created what's being called a "lung on a chip," which mimics lung function in a "diseased state" so that scientists can investigate how pneumonia, cystic fibrosis, and asthma work at the molecular level.
Lab on a chip technology has already made an impact on the world. For example, the most recent reported outbreak of the disease known as severe acute respiratory syndrome — or SARS — which began on the border between China and Hong Kong, was identified using a micro-array chip. Because of the ability to rapidly analyze the virus, the disease was quickly controlled, saving many lives.
At a recent annual meeting of the Society for General Microbiology in England, scientists announced advances in identifying viruses that attack chickens, cattle, pigs, sheep, and other farm animals.3 Bird flu, foot-and-mouth disease, and other emerging viruses will soon be quickly identified using a screening chip that the scientists are developing. They already have a working micro-array chip that contains specific virus genes that react with any viruses in the sample being tested. These genes show up as colored spots on glass slides. This lab on a chip can test for multiple viruses at the same time.
Before the invention of the lab on a chip, the only way of detecting a virus was to wait until the animal became ill enough to have symptoms, then take a blood sample and send it to the lab. The analysis could take days. With a lab on a chip like the one being developed, an untrained person could sample every animal in a matter of minutes.
Diseased animals could be removed before others were contaminated. The device can detect 300 different virus strains that infect humans, animals, and even insects. It was used successfully to detect a virus that kills poultry and to discover foot-and-mouth disease in cattle. The chip has the great advantage that you don't have to know what you're looking for to use it.
It's hard to overstate the long-term potential of this emerging technology. As a new generation of scientists takes hold of lab on a chip technology, the possibilities for its uses become almost limitless — just as they did when a new generation of engineers and tinkerers took hold of computer chips in the 1970s.
An undergraduate at Rensselaer Polytechnic Institute, for example, recently created a lab on a chip that makes sugars. That may sound simple and unimportant, but sugars are what make the human body — in fact, any living organism — function. Sugars are also the basis of many modern drugs. Sugars are among the most important and complex molecules in the body, controlling everything from metabolism to how cells communicate with one another.4
Sugars are created in a structure known as a "Golgi apparatus" that attaches highly-specialized arrangements of sugar molecules to proteins to make them able to communicate and to determine their ultimate function in the body. The artificial Golgi apparatus devised at Rensselaer does the same thing using electro-mechanical methods based on the enzymes found in a real Golgi apparatus.
A well-known, sugar-based drug is the anti-coagulant Heparin. As many will recall, it has been in the news recently, because shipments of the drug imported from China were contaminated. The Heparin that is available today is taken from the intestines of livestock, which was the source of the contamination.
For the first time, the artificial Golgi apparatus holds out the hope of creating artificial Heparin that would be impossible to contaminate. Researchers at Rensselaer are now busy attempting to make artificial Heparin to provide relief to millions of people suffering from heart disease, stroke, and other ailments that require the anti-coagulant.
Given this important trend, we offer the following six forecasts for your consideration:
First, lab on a chip technology will offer business opportunities similar to those brought on by the biotech revolution, which created giants like Amgen from tiny start-up companies. Those who can develop or identify winning lab on a chip applications will have business or investment opportunities that come around only once every few decades. This is the time for serious investors to research the subject and begin following the winners.
Second, many small, agile entrants will arise from university labs around the world, and they will be key players in the fight for dominance in the lab on a chip market. Competitors will proliferate as this technology is adopted worldwide. From a broad and deep mixture of basic research and technological developments, commercial applications will emerge that will form the foundation of many new companies and will create vast amounts of wealth in the coming years. While the corporate giants are already busy developing lab on a chip technology, their legacy cost structures and institutional cultures may hamper them from coming up with top-flight solutions.
At the same time, governmental entities, such as the National Institute of Standards and Technology (NIST), will be forging ahead with new developments as well. According to an article in the journal Applied Physics Letters,5 NIST recently introduced a lab on a chip that measures only a quarter inch square that can cool reagents to within a tenth of a degree of absolute zero, thereby creating one of the most sensitive chip-based labs ever invented. This breakthrough opens up whole new areas of analysis. In fact, this technology will be used initially for measuring the age of the universe by X-ray analysis of stardust.
Third, the ability to identify the genetic materials underlying pathogens quickly and cheaply will allow for early detection and treatment of cancer and viruses. Despite the broad range of uses one can imagine, the primary driving force behind this technology will be medical applications. In the longer term, lab on a chip devices will combine with nano-technology to create implantable therapeutic instruments that will actively attract and eliminate cancer cells or viruses, scavenging the body for the harmful agents before symptoms even have a chance to appear. This will make it possible for people to survive otherwise deadly diseases, such as certain types of second-stage breast cancer and even HIV/AIDS.
Fourth, with cheap and fast lab on a chip technology, food contamination will essentially become a thing of the past. Researchers in England have developed a lab on a chip that detects drug-resistant bacteria such as E. coli and salmonella.6 In just a few years, all food producers will be equipped with such devices, virtually eliminating the present-day dangers that come from the mass production of such foods as vegetables and beef, which are easily contaminated, resulting in illness and costly recalls. Workers armed with the new technology will perform tests in the field before contamination can spread. Any instance of contamination will be readily discovered and eliminated before the foods can be shipped.
Fifth, lab on a chip technology will make huge contributions to basic science. At Johns Hopkins Whiting School of Engineering and the School of Medicine, for example, a lab on a chip designed to mimic the chemical complexities of the brain is enhancing the understanding of how nerve cells work to form the nervous system.7 This is shedding new light on how nerves decide which direction to grow and how far to go, as well as what chemical signals allow them to communicate such information. This in turn will lead to an understanding of nerves that will allow for treatment of spinal cord injury and nervous system disorders. In addition, the technology will play a key role in developing new drugs. But scientific advances will go well beyond clinical medicine. Lab on a chip technology will push the frontiers of every science, from quantum mechanics to astrophysics.
Sixth, new advances will make this technology so cheap that it will find uses everywhere, even in the poorest nations of the world. For example, researchers at Harvard's Whitesides Research Group have demonstrated that fluid control in micro-devices can be achieved using ordinary paper.8 Today's microfluidic chips are made from more expensive materials like silicon, glass, or plastic, and they include small pumps and valves that add complexity and cost to the manufacturing process. The Harvard team created a microfluidic device on a tiny piece of paper. Because paper naturally absorbs fluids, there's no need for costly pumps or valves to spread a liquid that is being tested, such as blood or urine, across the chip. This simple approach promises to introduce an era of cheap, disposable tests that could be distributed by the millions to every corner of the globe.
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