Optical lab-on-chip IDs multiple blood molecules simultaneously, with greater sensitivity and speed

JULY 20, 2009--A lab-on-a-chip device, created by European researchers to identify lab-on-a-chip , is being used to measure fertility hormones and to detect genes associated with certain types of cancer. Under development by the EU-funded NEMOSLAB project, the chip can simultaneously test a sample for several different molecules at the point of care. The project aims to produce results while a patient is still visiting with his/her doctor instead of requiring delays while samples are analyzed in a remote lab.

"The question was whether we could combine silicon or other semiconductor technologies with the bioassay techniques and the diagnostic technologies," explains project coordinator Konstantinos Misiakos of Greece's National Center of Scientific Research (Athens). "Some of the technologies were innovative or state of the art at the time the project started, some others were more or less conventional."

NEMOSLAB (Nano Engineered Monolithic Optoelectronic transducers for highly Sensitive and LAbel-free Biosensing), a just-concluded project begun in January 2006, launched with a goal of producing a monolithic lab on a chip that uses a silicon optoelectronic transducer for protein and DNA detection. It involves partners from Greece, Germany, Italy and Denmark.

The project uses an optical technique to recognize the presence of selected biological molecules. Light passes down a silicon nitride waveguide--a flat, rectangular pipe about 8 microns wide and 0.15 microns thick--to a detector which converts it to an electrical signal.

The waveguide is coated with a probe molecule that binds to target molecules (an antibody that will bind with a specific protein, or a strand of DNA that will bind with a complementary strand in the sample fluid). "We chose the probes to be very selective for the molecules we want to detect," says collaborator Sotiris Kakabakos. "They have been tested right on the chip but also with conventional methods which select those probes to be very specific for the analyte to be determined."

A microfluidics system within the chip passes the sample--usually blood serum--over the waveguide. When a target molecule in the sample binds to the surface of the waveguide the optical properties are changed and the amount of light arriving at the detector also changes. The step in the signal is distinctive.

Each NEMOSLAB chip contains nine waveguides, which are exposed to the sample at the same time and can be primed to detect different molecules. The entire chip is fabricated as a single unit. An electronics package collects the signals from the waveguides and produces the results within a few minutes of the sample being introduced.

One of the NEMOSLAB partners, an infertility treatment center in Dortmund, Germany, is interested in using the device to monitor hormone levels in the blood of women seeking to conceive a baby through in-vitro fertilization. The NEMOSLAB device can test for nine different hormones at the same time. Misiakos says, "We can't claim the physics is new, but the realization of the physics into an integrated and small format through the mature silicon technology is new. Our advantage is that we have all the optical components monolithically integrated on the silicon chip."

Current technology requires women to travel to a clinic for such tests; a NEMOSLAB device would enable them to conduct the tests themselves at home.

The project has also developed a set of probes for detecting the BRCA1 gene which is associated with breast and ovarian cancer. Several different mutations of the gene can be sensed at the same time. This opens up the possibility of screening for a predisposition to these conditions.

The portability of the device makes it suitable for applications such as environmental monitoring--for instance for field testing for agrochemicals in water supplies--and food safety.

Commercialization is still a ways off; further work is needed on aspects such as the sample preparation. "We cannot just put in a drop of blood to get results. It has to be treated and that is not yet integrated on the device," says Misiakos. Further work is also needed on the read-out electronics so that the whole device can be made more compact. "The read-out electronics are quite small but we cannot claim that this is a hand-held device. It's portable at this time but not hand-held as we would like." There are also questions to be resolved about the long-term stability of the molecular probes coating the waveguides.

NEMOSLAB's is not the only viable approach to such tests; other groups are working on electrochemical, microbalance and acoustic methods for detecting molecules. "We are much more sensitive, though, compared to acoustic devices or to several electrochemical devices," says Kakabakos. "Also we have much faster results." And, he says, the fully integrated transducer is unique.

NEMOSLAB received funding from the ICT strand of the EU's Sixth Framework Programme for research. See the original article in ICT Results. And, learn more at the NEMOSLAB site.

Posted by Barbara G. Goode, [email protected], for BioOptics World.