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The Story Behind: Microfluidics
A microdrop in the bucket
It's hard to believe, but many of the recent advances in genomics, proteomics and pharmaceuticals owe their success in part to the inkjet printer. These fields of research rely heavily on microfluidics, the study of the behaviour of fluid in very small volumes - microliters, nanoliters and picoliters, volumes thousands of times smaller than a dewdrop.
It could be argued that microfluidics, a sub-discipline of nanotechnology, has been a scientific discipline for nearly 30 years now, since it was originally developed and commercially used in the early 1980s by microelectronics engineers to develop the inkjet printer. Essentially, tiny tubes delivered the ink to the printer head; in colour printers, the placement of these tubes either isolate or combined different inks to produce the full RGB (or CMYK) colour spectrum in precise detail.
It's a concept similar to the integrated circuit microchip that revolutionized electronics, allowing radios, computers, mobile phones and all sorts of other devices to get smaller and smaller. But, the high cost, rigidity and fragility of the silicon microchip is impractical in microfluidics. There wasn't much impetus to search for a solution until the mid-1990s, when it became clear to several researchers that microfluidics was the path to answering troublesome biological questions such as what is the difference between the DNA of a cancerous cell and a healthy cell? How to analyze a gene sequence? How to tailor a drug to a specific disease symptom?
To find that, they had to work at the molecular level, looking at cells, genes, DNA and even individual proteins in fluid quantities as small as a microlitre - one millionth of a litre. The concept of microfluidics was out there, scientists just needed the tools to work with it.
In a ‘life-sized' laboratory, there are chambers for collecting and combining fluids, valves and channels for moving them through a closed system, sensors for measuring pressure, among other devices. The equipment is versatile enough that one configuration allows scientists to conduct a variety of experiments. What chemistry, biology and bioengineering researchers needed to do was miniaturize their laboratories.
It was a group of researchers at Stanford University who began looking for research applications for the technology behind the inkjet. It turns out that it's not such a big jump from engineering printers to engineering a lab on a chip (LOC), as this technology has come to be called. All it took was some creative thinking.
First comes the valve
Enter Stephen Quake, PhD, of Stanford University. Fuelled by a desire to make the process of getting answers in biology less labour intensive - why does it take months and a hundred thousand dollars to decode a human genome? - he started looking for ways to automate the process.
Since the early 1990s, researchers had been able to create a LOC that would conduct a single function, but what kind of lab is that? The problem with building multifunctional labs lay primarily with silicon. Using micromachined silicon chips was a great idea for the electronics industry, but it wasn't doing any good in practical biological applications. Silicon is rigid, and making valves that wouldn't leak the fluids they were supposed to control was proving next-to-impossible; making multiple valves that fit and functioned on the same chip was simply impossible.
Quake heard of Harvard chemist George Whitesides' success with elastomeric materials, the same type of rubber used to caulk around ordinary household plumbing such as toilets and sinks. Deciding that was the way to go, Quake and his team developed a micromechanical valve using only elastomeric material. Once the valve was developed, it was an easy leap to design an Integrated Fluid Circuit (IFC), complete with chambers, channels, pumps, valves and flow sensors - essentially an entire laboratory - on a single chip as small as a postage stamp.
Quake's IFC was essentially the stepping stone for a host of microfluidic devices. Microfluidics researchers are now creating and customizing micro laboratories capable of manipulating a single bacteria or a strand of DNA. In fact, it is now possible to use these LOCs to dissect single strands of DNA.
An IFC recently developed at Stanford University is a cell-culture chip that has 100 chambers to hold individual cells plus the microscopic plumbing necessary to add any combination of 16 different chemical inputs to those chambers. This IFC will hopefully be used by researchers in a number of different studies, with stem-cell research and antibiotic effects on bacteria among the most likely. Another microfluidic chip can be used to prepare purified proteins for medical and scientific research. Previously, purifying these proteins was a difficult, expensive and slow process.
The medical profession is turning to microfluidic devices not just for research but also diagnosis. Stanford University researchers have been developing a microfluidic device that can diagnose HIV and other diseases in just 10 minutes, as opposed to more than an hour via other laboratory methods. In Singapore, scientists are working to create a LOC that can detect exposure to a nerve gas agent such as sarin in a patient's blood. The idea is that first responders can test victims at the site of a terrorist attack, identifying those who need immediate treatment.
Read more about the inventors: Stephen R. Quake (US), Marc A. Unger (US), Hou-Pu Chu (US), Todd A. Thorsen (US), Axel Scherer (US)