By measuring telltale molecules in the blood, doctors can determine patients’ cancer risk, monitor chronic diseases, and estimate the best time to perform in vitro fertilization. But current methods for detecting these molecules are time-consuming and relatively expensive, and they must be done in the lab rather than at a patient’s bedside. In hopes of providing a rapid, cheap alternative, a European consortium is developing a device for bedside diagnostics that integrates sensitive optical detectors with sample-handling microfluidics on the same chip. The device is being evaluated on clinical blood samples used to monitor hormone levels prior to in vitro fertilization treatments.
Simple chip: Microfluidic channels carved into a silicon chip are visible in this image as long rectangles. The channels hold waveguides, visible as pink lines, that converge on a single light sensor also integrated on the chip.
Other groups are also attempting to make such all-in-one diagnostic chips, using optical methods like the European group or using methods that rely on changes in electrical resistance. Optical methods are inherently more sensitive. However, measuring optical signals usually requires expensive, complex instruments. The European device does not. It features readout instrumentation integrated right on the chip, which makes the device simpler than other optical biomolecule detectors that must be read using something resembling a simplified fluorescence microscope. The European chip can be read out using an on-chip sensor that converts the optical signal into an electrical signal.
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“The idea was to develop a small chip that can be read out with simple electronics and detect a number of biomolecules at the same time,” says Konstantinos Misiakos, head of the Nemoslab project at Greece’s National Center for Scientific Research. The project is being funded by the European Union and a consortium including electronics companies ST Microelectronics (headquartered in Geneva, Switzerland) and Technobiochip (of Naples, Italy).
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The sensors are housed in a microfluidic channel carved into a silicon chip. The channel has nine bends, each of which is lined with a distinct silicon nitride waveguide that pipes light across the chip from each of nine light-emitting diodes to a single light-detector. Each waveguide is patterned with a different binding molecule, either an antibody or a strand of DNA selected for its ability to bind to a particular blood biomolecule such as a hormone.
When a blood sample flows into the channel, it passes over the waveguides, and the binding molecules pull their target out of the sample. When the biomolecules stick to the treated surface of the waveguide, the speed of light moving through the waveguide changes, creating a detectable change in the signal that’s picked up at the light sensor, which turns it into an electrical signal that can be read out. The prototype device can detect nine biomolecules at a time in blood serum.
“This approach has impressive potential,” says Michael McAlpine, assistant professor of mechanical and aerospace engineering and chemisty at Princeton University. However, the European device in its current form doesn’t match the sensitivity of other biomolecule sensors that can detect single molecules.
Misiakos says his group is evaluating ways to improve the device’s sensitivity, including increasing the length of the waveguides to amplify the optical signal. He expects that the chips would cost less than a dollar each to make in a silicon foundry.
