URBANA-CHAMPAIGN, Ill. – Sensitive detection of biomolecules is of great interest for applications such as drug development, virus detection, environmental monitoring and medical diagnostics. In contrast to optical biosensors based on surface plasmon resonance, interferometers or resonant cavities, integrated silicon-on-insulator microring sensors offer fast sample preparation and measurements, even on small sample quantities, and are exceptionally scalable, which will be key for multiplex analysis. Using this technique, researchers at the University of Illinois have demonstrated reliable, label-free detection of a clinically important cancer biomarker with a very low limit of detection.
Microring resonators can be used to detect specific molecules because their transmission spectra are very sensitive to refractive index changes in the surrounding material. The presence of other molecules has this effect and can be made selective for certain molecules if the surface is prepared in a specific way.
Optical microring resonators have found many applications to date in integrated optics and telecommunications, where they are used as wavelength selection filters. They consist of very small ring-shaped waveguides – typically a few micrometers in radius – with input and output couplers. They can be made in different materials using lithography processes known from semiconductor manufacturing. Light injected into the microring via the input waveguide travels around the circumference; certain wavelengths interfere resonantly with others already in the cavity, forming so-called whispering gallery modes. This can be observed in a sharp dip in the transmission at the output.
What makes these structures so attractive for sensing purposes is the fact that this resonance wavelength is strongly dependent upon the refractive index of the material surrounding the waveguide substrate. What makes them handy for the sensing of biomolecules is the fact that a capture protein can be attached to the sensor surface, enabling linkage with its complementary protein, called the analyte, to be tested. For this “functionalization,” the right chemical treatment of the waveguide surface is needed to prevent nonspecific protein adsorption.
Although this may sound a bit cumbersome, the good news is that, unlike most commercial biosensors, this method does not require molecules to be “labeled,” which can complicate detection and decrease reliability. Instead, reliability and accuracy are improved by the fact that a large number of individually addressable microrings can be made on a single substrate with little extra effort – which means that many tests can be run in parallel and compared. Due to the rings’ small size, this is even possible for small sample sizes. Alternatively, groups of rings can be functionalized for different target molecules, and a variety of tests can be performed in parallel on the same small sample. Furthermore, nonfunctionalized microrings can be used as control sensors and to compensate for potential environmental effects.
The University of Illinois team, led by professor Ryan C. Bailey, whose work was published in Analytical Chemistry (2009, 81 , pp. 9499-9506), aims to make such new proteomic technologies available for clinical use. The researchers demonstrated detection of the clinically important protein biomarker carcinoembryonic antigen (CEA) in undiluted serum using an initial-slope-based quantitation method.
CEA was detected at clinically relevant levels, and concentration was determined. Comparison with commercial enzyme-linked immunosorbent assay equipment showed that the label-free microring sensor platform has a comparable limit of detection (2 ng/mL) and superior accuracy in the measurement of CEA concentration across a three-orders-of-magnitude dynamic range. Based on this, the researchers say that their future goal is to extend the platform for highly multiplexed label-free bioanalysis.