Abstract
Biosensing based on whispering-gallery mode (WGM) resonators has been continuously studied with great attention due to its excellent sensitivity guaranteeing the label-free detection. However, its practical impact is insignificant to date despite notable achievements in academic research. Here, we demonstrate a novel practical platform of on-chip WGM sensors integrated with microfluidic channels. By placing silicon nanoclusters as a stable active compound in micro-resonators, the sensor chip can be operated with a remote pump and readout, which simplifies the chip integration and connection to the external setup. In addition, silicon nanoclusters having large absorption cross-section over broad wavelength range allow active sensing for the first time with an LED pump in a top-illumination scheme which significantly reduces the complexity and cost of the measurement setup. The nano-slot structure of 25 nm gap width is embedded in the resonator where the target bio-molecules are selectively detected with the sensitivity enhanced by strongly confined mode-field. The sensitivity confirmed by real-time measurements for the streptavidin-biotin complex is 0.012 nm/nM, improved over 20 times larger than the previously reported WGM sensors with remote readout.
Highlights
We developed label-free sensors with active whispering-gallery mode (WGM) resonators integrated with microfluidic channels in a practical form which is free from the strict evanescent coupling scheme relying on tapered fiber
The sensitivity of this device confirmed by real-time measurements for the streptavidin-biotin complex is 0.012 nm/nM, which is more than 20 times larger than that of the previously reported active WGM sensors without direct physical coupling
Since the characteristic parameters such as kon and Kd attained by analyzing the dynamics of the streptavidin-biotin complex agree well with the previously reported values, it is concluded that the nano-slot structure having 25 nm gap introduced to enhance the sensitivity doesn’t distort the molecular dynamics significantly
Summary
Sensing based on WGM resonators has been considered as one of the most promising approaches to realize lab-on-a-Chip (LoC) devices for label-free detection of bio/chemical molecules and particles.[1, 2, 3, 4] Since the sensing event is observed by the frequency shift of WGM resonance caused by the fractional perturbation of mode volume, any kinds of particles having the refractive index different from that of the environment can be detected without the need for the labeling.[1, 5] This versatile method providing outstanding sensitivity by means of high quality factor and small mode volume of WGM resonators has been verified by the detection of various kinds of nanoparticles including polystyrene beads, viruses, and DNA.[2, 6, 7, 8, 9, 10] In addition, it has demonstrated great potential for the analysis of molecular dynamics based on the real-time measurement of specific biomolecule interactions.[3, 10] Since WGM resonators can be fabricated on a chip in micrometer-scale footprint, it has been expected that this approach can be implemented in a form of miniaturized devices integrated on a chip.[1, 11, 12] despite these benefits, most of the WGM-based sensing researches primarily remain in scientific interest apart from the development of practical LoC devices.[1]. Bus waveguides monolithically implemented on a resonator chip are fairly robust but requires high microfabrication precision to define the gap and additional effort to implement light coupling at the end of the waveguides such as an end-fire coupling.[14] To overcome this limitation, the concept of the WGM sensor based on optically active resonators has emerged for promising alternatives.[1] In this approach, pump light focused to the active resonators induces the emission spectrum peaks along with the resonance modes which are detected by a spectrometer through free-space optics. Large absorption and emission cross-section of silicon nanoclusters allow pumping and proving remotely through free-space optics, [19, 20] which guarantees simple integration with microfluidic channels It permits the use of an LED as a pumping source for the first time, which significantly reduce the complexity and cost of the measurement setup. The molecular detection with this active WGM sensor is demonstrated with the streptavidin-biotin complex, which shows that device sensitivity is 0.012 nm / nM, which is over 20 times larger than that of the previous WGM sensors with remote readout
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