Milan, Italy--A group of European researchers is building optical sensors directly into the structure of labs-on-chips, paving the way for on-the-spot medical diagnostics. The HIBISCUS (Hybrid Integrated BIophotonic Sensors Created by Ultrafast laser Systems) consortium, which includes both academic and industrial partners, uses femtosecond laser micromachining to create waveguides on chips.
The "lab-on-a-chip" concept relies on microfluidics, in which miniscule volumes of sample liquids move along microscopic channels cut into materials such as silicon, glass, and plastic. The technology has progressed phenomenally: it is now possible to separate samples at the molecular level on a chip no larger than a postage stamp. But the lab-on-chip hype usually fails to address a big problem: usually, large-scale equipment is needed to detect and identify the molecules flowing inside the microfluidic chips. The fluidics is certainly at the microscale, but the optical molecular detection is firmly rooted in the macro world.
Laser lights the way
The EU-funded project inscribes features into microfluidic chips, making integrated optical detection a possibility for the first time. Femtosecond laser micromachining had already been used to cut intricate components, like gears and motors, into silicon, but the HIBISCUS team was able to inscribe waveguides into labs-on-chips. The waveguides channel light into the chip, across the microfluidic channels, and back out of the chip where it is detected.
Now it is possible to shine a light source (usually a laser) into the sample fluid and detect its absorption or other optical activity directly in the chip, rather than having to take a sample from the chip and analyze it with laboratory equipment.
In one demonstration, small changes in the refractive index of a sample flowing in a microchannel were detected using an optical interferometer. In this case, the waveguides were laid out so that one passed through a microfluidic channel while the other one passed just above it. The liquid flowing in the channel induced a change in the path length of the light between the two waveguides, which was picked up by the interferometer.
HIBISCUS has made prototype labs-on-chips with integrated waveguides for several biological applications, including a DNA-fragment separation and detection assay (which could be used to detect specific disease markers in patient samples) and a chemical microreactor for protein synthesis.
The dream of Giulio Cerullo, a researcher from Politecnico di Milano who coordinated the project, is that the lab-on-chip could help doctors perform virtually immediate medical diagnoses in their own practices. They could take a sample from a patient and immediately run it through a small device, which would be able to detect marker molecules (protein markers for a disease or the telltale DNA sequence of a genetic disorder).
"Once you make detection part of the lab-on-chip, you have miniaturization of an entire analytical laboratory," says Cerullo. "It brings diagnosis to the point of care. A patient goes home without that awful sense of uncertainty hanging over them until they get their test results back. Or they can receive urgent medical treatment--a day or two's advance on treatment can mean life or death for some cancer patients."
The HIBISCUS consortium includes three commercial partners that are all exploiting the results of the project. High Q Laser in Austria is already selling the femtosecond laser that it developed for the project. Lionix, based in the Netherlands, manufactures microfluidic chips and is now looking to make labs-on-chips that incorporate the waveguides. The Dutch firm Zebra Bioscience is developing kits for point-of-care diagnostics.
Cerullo reckons that an integrated lab-on-chip would not be prohibitively expensive for medical professionals. He estimates that the initial investment for a lab-on-chip manufacturer to set up the micromachining technology for the waveguides would be around €200,000. Total investment to manufacture fully integrated labs-on-chips may reach several million euros. But this outlay is relatively low once it is spread across the millions of disposable chips that could be sold to medical practices and hospitals around the globe.
The integrated optical detection also makes feasible the idea of using microfluidics as an efficient and more eco-friendly production method for pharmaceutical products.
"Our project is the last piece in the lab-on-chip puzzle," says Cerullo. "It will open the door to many exciting applications, especially much faster, on-the-spot medical diagnosis."
HIBISCUS received funding from the ICT strand of the EU's Sixth Framework Programme for research; ICT Results was the source of this information.
--posted by John Wallace