Lab-on-a-chip: Vast promises,real restraint
Advances in lab-on-a-chip technology are driving development of low-cost, high-throughput applications for in-the-field diagnostics, cancer research, and other unmet needs in the healthcare field. Its cost- and time-saving benefits hold great appeal–but commercial factors are weighing on early development work.
by Sarah Fister Gale, contributing editor
Lab-on-a-chip technology is on the cusp of changing the field of diagnostics. These stamp-sized devices combine microfluidics and microelectronics on a single chip to perform complex tests using tiny amounts of material. Their size and scalability is freeing clinicians from their labs and enabling real time tests to be conducted on-the-go.
Researchers around the world are developing innovative applications for these devices that could break down barriers to gathering critical data in the field. Companies such as Caliper Life Sciences and Abbott Point of Care are already using commercial lab-on-a-chip devices for real-time testing, and dozens of projects are in development to find new ways to use this technology across a broad spectrum of clinical and diagnostic applications.
These innovations hold great promise for applications in cancer research, HIV diagnostics, blood sample preparation, bacteria detection, and environmental monitoring. The social and humanitarian implications are substantial–yet the true value of this technology, and the feature that will drive commercial adoption of these devices in the near term, is their ability to save substantial time and money.
Lab-on-a-chip technology delivers faster throughput using a fraction of the material required for conventional testing applications, and that translates to time and money saved, says Isaac Meek, genomics marketing manager for Caliper Life Sciences, a lab-on-a-chip technology solution provider in Hopkinton, MA. Caliper recently launched Lab Chip GX, an advanced nucleic acid separations system that dramatically reduces the time it takes to deliver test results.
“In typical nucleic acid separation, lab operators use gel electrophoresis, which applies an electric current to a gel matrix,” Meek points out. “It’s a time-consuming application that takes hours.” By transitioning the cell separation event to a microfluidic chip, the process speeds up dramatically. “Things happen very fast in the micro-world. We can detect separation at a high resolution in 30 to 80 seconds,” he says.
Cutting screening from hours to seconds means collecting more data in less time. Along with conducting more tests to develop broader data sets, Meek notes that it gives researchers incentive to assess the quality of samples before subjecting them to assays–rather than conducting the tests on faith alone, only to find out later that their results were skewed due to low quality samples.
“A lot of researchers won’t bother to test samples if it’s going to take days to get results,” he notes. “Faster throughput allows for better quality control and greater integration.”
Biofilms and cancer cells
As geometries and budgets continue to shrink, the cost- and time-saving benefits derived lab-on-a-chip applications hold great appeal for commercial applications, particularly as companies struggle to find ways to deliver higher-quality data in less time with less money.
However, most innovative applications are still in the research phase, as interdisciplinary teams of scientists, biologists, and mechanical engineers work in conjunction to develop new uses for these small-scale operations.
Several lab-on-a-chip development projects are underway at Johns Hopkins University in Baltimore, MD, notes Andre Levchenko, associate professor in the Whitaker Institute for Biomedical Engineering at the university’s Institute for NanoBioTechnology. Levchenko’s group is currently working with microfluidic devices to understand how cell tissue responds to chemicals in a micro-environment.
Closeup of the microfluidic device shows the tiny channels used by researchers in their biofilm experiments.
“Microfluidics give you the opportunity to control cells in space and time,” he says. “It’s the most important advantage and the ultimate reason people want to use this technology.”
That level of control is enabling his team to study how infections propagate within the human body and interact with its immune system, something that is difficult to reproduce in a lab. Infections develop complex biofilms that help them to resist defenses in the body; “because colonies of blood cells develop very differently in lab environments than they do in nature, it’s difficult to create and manage these biofilms in a lab, and the resulting data is hard to interpret,” he notes. But using microfluidics, his team has been able to create and study these biofilms in a controlled environment, leading to more precise and realistic results. “That is impossible to do otherwise.”
The commercial applications for this type of device could have important implications for pharmaceutical development, says Levchenko, because it can be used to accurately screen drugs that are effective against these biofilms.
That control over environment may be equally beneficial in studying the properties of cancer cells without having to grow them in a lab. Researchers at Hopkins are also currently developing ways to use lab on chip devices to run tests on very small numbers of live cancer cells, eliminating the need for intermediate cultures, which can change cell properties and make test results irrelevant.
“Every project we are working on has potential for clinical or pharmaceutical development,” Levchenko says. “It’s a very exciting time for this research.”
Diagnostics to go
Along with offering greater control, elimination of lab testing also creates opportunities for portability, notes John McDevitt, a scientist at the University of Texas at Austin and research director of Austin-based McDevitt Research Laboratory, a developer of lab-on-a-chip sensor technology.
McDevitt’s team is in the clinical testing phase of an HIV immune function sensor that can cost-effectively deliver HIV test results in the field. The device analyzes sample micro-volumes of blood stained with fluorescent antibodies using a handheld device. The samples are captured on a membrane within a miniaturized flow cell and imaged through microscope optics.
“We used lab-on-a-chip technology to take a complex $50 test and miniaturize it, making it into something that is simple and dirt-cheap,” he says. The chip is made from injection molded plastic and the analyzer is based on digital camera technology, which together create an inexpensive tool that is scalable. McDevitt’s team is concurrently developing related applications for this technology to diagnose cardiac arrest and cancer, two major causes of death in the US. He anticipate those devices could be commercially available in two years.
“In the lab-on-a-chip industry, you have to make thoughtful choices about the applications you pursue,” he notes. “If you create a $10,000 diagnostic chip, it may be interesting in the academic world, but to be commercially viable you have to be able to achieve economic scale.”
He believes those lab-on-a-chip applications that target an unmet need for quick or better results–such as real-time diagnosis of cardiac arrests that don’t show up on an EKG–will have the biggest impact. “The key is to find something that’s not being done, or not being done well then to develop an application to fill that need,” he says.
Along with addressing specific clinical applications, McDevitt and other experts in the field see the programmable lab-on-a-chip as the next great innovation in this technology. Just as the Pentium chip changed the usability of microchips, a programmable lab-on-a-chip would speed development of applications and give users greater flexibility in the analysis tools they use and stock.
“Programmability is at the heart of all of our efforts,” McDevitt says. His group is focused on creating devices that can be adjusted to address multiple needs, rather than building new platforms for each application. “Economically it is much more feasible.”
Steven Werely, associate professor of mechanical engineering at Purdue University in West Lafayette, Indiana agrees. He is working on a project at Purdue funded by the National Science Foundation to develop a general purpose lab-on-a-chip that could be reconfigured by the end user for use in multiple applications.
“There are a number of operations that are common to lab-on-a-chip applications, and most people have special devices for each of them,” he points out. “We are trying to build a lab-on-a-chip that will perform the jobs of multiple applications.”
Werely’s programmable lab-on-a-chip (PLoC) system for general-purpose applications is based on an all-polydimethylsiloxane platform that comprises all essential components on chip, such as valves, pumps, channels, and mixers, to perform multiple-tasks. The fluidic operations are controlled by self-developed interface that allows users to program fluid operations, enabling a wide variety of applications to be realized on the same microchip.
“The development of the programmable manipulation creates a versatile platform that saves costs and effort, and will be feasible for various biological assays,” he says.
The project is underway now, although Werely notes that like many lab-on-a-chip projects, this is still in the development phase.
“A lot of people in universities are working on lab-on-a-chip applications, but right now, penetration in the marketplace is small,” he says. However, he’s optimistic about the progress he and other researchers are making. “In the next five years all of those academic applications will hit the market.”
McDevitt adds that along with creating a path for academicians to achieve business success, he sees a greater good occurring as a result of his work.
“We’d like to see lab-on-a-chip systems make healthcare affordable globally,” he says simply. “That’s where our scientific passions lie.”