Suspensions of micro- and nanoparticles are widely used in bioassays for detection of optically labeled molecules. Researchers from Southeast University in Nanjing, China,1 have now developed a new ‘label-free’ method enabling highly sensitive detection without markers. “Labeling is an expensive process that can be inefficient because the labels themselves may hinder interactions and activities of the biomolecules,” says Zhongze Gu, leader the research team.

Fig. 1: A collection of photonic beads.

Furthermore, markers may be toxic and thus unsuitable for in vivo applications. The advantage of this group’s label-free detection protocol is that the optical properties of the host matrix are directly modified by the target biomolecules, and no indirect imaging with markers is necessary.

This label-free approach is based on highly reflecting, spherical photonic crystals—photonic beads (Fig. 1). To fabricate the photonic beads, a tiny drop of aqueous solution containing polystyrene spheres and ultrafine silica particles was placed into silicone oil. The oil was then heated, causing the water from the spherical droplet to evaporate and the polystyrene spheres to form a regular pattern, and the tiny silica particles to fill the spaces between the polystyrene spheres. The beads were then calcinated, so that the polystyrene spheres within them evaporated, leaving only the biocompatible silica framework that formed the photonic crystal beads.The fabrication process is flexible, and parameters such as the reflecting wavelength of the beads can be easily tuned by varying the size of the polystyrene spheres.

To detect biomolecules, antibodies were embedded within the photonic crystal structure. Attachment of biomolecules to the antigens, resulted in a shift of the reflection spectrum of the beads as a function of biomolecule concentration. This procedure enables multiplex detection, where photonic beads of different colors are loaded with different antigens. Each colored bead then shifts its spectrum differently, depending on the presence of biomolecules specific to its antigens.

This method has commercial potential. “We believe that our technology will be widely applied in drug research and medical diagnostics, particularly once bead decoding is automized and also applied to the detection of bioreactions,” says Gu.