A very small research project in lab analysis

Ultra small lab-on-a-chip devices could revolutionize many tests and bring new diagnostic tools to underdeveloped regions

Xudong (Sherman) Fan and his experimental model for an improved Lab on Chip device. Fan's work not only includes microfluidics, like that used in the close-up LoC photo shown above, but also adds sensitive optical detection functionality. This improvement provides both delivery and detection of liquids in the LoC at nano-liter volume. Photo by Steve Morse.

Laboratory equipment for medical diagnoses and scientific evaluation can fill a room and cost a small fortune. Using nanotechnology advances, scientists across the world are looking to shrink such machines down to something that can reside on a computer chip.

One researcher, Xudong (Sherman) Fan, assistant professor of bioengineering at the University of Missouri, is looking to help make these new devices more efficient.

A lab-on-a-chip (LOC) handles extremely small fluid volumes and is used to integrate one or more laboratory functions on a single device of only millimeters to a few square centimeters in size. It is a subset of a broader concept, micro fluidics, which involves very small mechanical flow control devices like pumps, valves and sensors.

LOCs are used to improve many fluid-based laboratory tests including ion channel screening and biochemical assays. In blood sample preparation, they can crack cells to extract DNA.

LOCs are better than conventional lab techniques because very small fluid volumes can complete their reactions faster than larger volumes. Certain chemical reactions that require heat, for example, occur more quickly because it takes less energy to heat a small volume rather than a larger one. If a regent is needed for the reaction, less of that material is needed.

They hold great promise in fighting cancer by providing real-time PCR testing that can detect bacteria, viruses and cancer cells. Through an immunoassay, they can also detect cancers based on antigen-antibody reactions. By using a process involving electrical fields, dielectrophoresis, LOCs can also detect cancer cells and bacteria.

Fan's research in MU's Bond Life Sciences Center is looking to combine micro fluidics and sensing technology into one function on an LOC. Micro fluidics involves the channels and valves that guide the fluid through the LOC. The sensors provide the data that the scientists are looking for.

Combining these now separate functions will even further reduce the already small fluid levels needed to perform a scientific evaluation. This will shorten the detection time, lower the cost of the test and reduce the sample volume needed for the test.

Fan said his technology would allow researchers to use samples of only a few nanoliters—a billionth of a liter—instead of samples tens of thousands of times that large, which are needed now.

The most immediate application for Fan's work will provide less expensive and easier blood analysis, vapor analysis and cancer detection. Fan said the technology has several other applications, including environmental testing and new kinds of lasers as well as detection of cancer, other diseases and improved explosives.

Lab-on-a-chip technology promises to improve global health, particularly through the development of new point-of-care testing devices. In countries with few healthcare resources like full-scale labs, infectious diseases could be diagnosed immediately in the patient's home.

One active area of LOC research involves ways to diagnose and manage HIV infections. It is estimated that around 90 percent of people with the disease have never been tested for it. The typical test to determine and monitor HIV measures the number of CD4+ T lymphocytesin a person's blood. At the moment, flow cytometry is the gold standard for obtaining CD4 counts, but flow cytometry is a complicated technique that is not available in most developing areas because it requires trained technicians and expensive equipment.

Using very small samples of contagious, radioactive or bio-hazardous materials also makes these tests safer than conventional methods. Because such small amounts of testing materials are used, LOCs can often be used once and then safely disposed of.

Before coming to MU in 2004, Fan worked on biological sensors for 3M. His work to combine micro fluidics and sensing technology focuses on developing opto-fluidic ring resonators, a type of sensor in which light travels along the wall of a small glass tube, or capillary, containing a liquid or gas to be analyzed.

The capillary's properties allow the light to make thousands of loops around the sample. This allows much more of the light's energy to interact with the sample than in other types of light-based sensors, in which the light and the sample might only meet one time or a few times.

To improve LOC operation in medicine, Fan is also using fluorescence resonant energy transfer—a method that allows researchers studying diseases to detect whether certain types of molecules bind with each other. Fan's group is trying to advance the technique to the point that it can detect single molecules, which he said is "probably five years down the road."

Binding is really important, Fan said, because it is a key to how diseases occur and how they can be prevented. The technique relies on "tagging" molecules with fluorescent markers of different colors. When two of these molecules bind with each other, one marker transfers energy to the other, which changes how much of each color is observed.

The lab's work has captured the imagination of the scientific community. In August, Fan received the first part of a five-year, $400,000 grant from the National Science Foundation to continue his work as part of that group's Faculty Early Career Development program. A scientific paper that Fan presented was chosen by the Institute of Electrical and Electronics Engineers as the Sensors Journal Best Paper of 2008.

Such recognitions are no small feat.

Posted Nov. 6, 2008
Story by Randy Mertens