Microfluidics Stream Their Way into Medical TestsIBM researchers developed a portable diagnostic chip that quantitatively measures a number of diseases.by Ashley Glowinski, Associate Editor
Luc Gervais, IBM Researcher, Zurich Research Laboratory, demonstrates the point-of-care diagnostic chip he developed with fellow IBM researcher Emmanuel Delamarche. | Capillary-driven microfluidics could drastically change point-of-care diagnostics, thanks to IBM researchers Luc Gervais and Emmanuel Delamarche.
At IBM’s Zurich Research Laboratory, the scientists created a one-step immunoassay by combining microfluidic elements and reagents such as analyte molecules, detection antibodies (dAbs) and capture antibodies (cAbs). Only a 5-µL sample of human serum is needed to prompt the sandwich immunoassay, which is read using a fluorescence microscope. The microfluidic functional elements comprise a reaction chamber sealed with polydimethysiloxane (PDMS) substrate, as well as a sample collector, delay valves, a deposition zone for dAbs, a capillary pump, and vents.1
“Our main goal was to develop a device that is quantitative and easy to use by non-trained medical personnel,” said Gervais. “A lot of labs are working on a chip. In many cases you have a chip alongside numerous electrical components and tubes, so it’s not really a lab on a chip; it’s a chip in a lab.”
The device, which is compact due to no moving parts, is comparable to lateral flow tests, such as a pregnancy test. In both instances, capillary forces detect the liquid and detection is done using a sandwich immunoassay, binding two different antibodies to the protein users want to analyze. According to Gervais, antibodies will, however, spread in all directions throughout the membranes that compose the pregnancy tests, creating undefined regions and thus making it a qualitative measurement.
“In the case of our one-step chip, we have very well-defined microchannels that help us to have the exact volume we want for analysis and the exact flow rate we want on the chip,” said Gervais. “The deposition regions for the dAbs and cAbs are clearly defined, which allows us to use small samples and have small detection regions that can be multiplex to analyze many different proteins at the same time. This makes the test quantitative, so we can get a concentration reading of the protein we want to analyze.”
While the prototype used in the study detected cardiac marker C-reactive proteins (CRPs), chips can also be used to provide a quantitative test for cancer, allergies, viruses, bacteria, and any disease with known protein markers.
In addition to fabricating a versatile chip that fully works with capillary forces, Delamarche and Gervais proved PDMS, which is used in research but typically not for disposable labware,1 has potential as a biological substrate for diagnostic tests and labs.
“This is the first study in which the lifetime of antibodies or proteins on PDMS were clearly demonstrated, and in which we showed that there’s no real disadvantage using PDMS up to a duration of six months to a year,” said Gervais.
Coris BioConcept and IBM are currently working together to bring the diagnostic one-step chips to the market. The researchers hope the devices will eventually be fabricated using plastic components and available for use in hospitals. Additionally, IBM plans to integrate their silicon technology experience with other biological researchers in order to develop point-of-care products, including company Neuro-Zone, which is developing devices to detect brain cells for neurological diseases.
Gervais predicts that in the future, microfluidic technology will enable multiplexing of proteins on a chip and the detection of RNA and DNA. He also expects that more personalized medicine and low-cost portable devices, as well as the connection of these devices to online medical records, will continue to expand the biological research landscape.
“Doctors and patients will benefit because the time to results will be a lot faster, and doctors will be able to administer treatments in a more timely fashion,” Gervais said. “This will ultimately save patients’ lives.”
1. Delamarche, Emmanuel and Luc Gervais. 2009. Toward One-Step Point-of-Care Immunodiagnostics Using Capillary-Driven Microfluidics and PDMS Substrates. Lab
on a Chip, The Royal Society of Chemistry. 3330-3337.
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