INV-18062
The development of ultrasensitive, miniature, and label-free bioanalytical detectors for medical diagnosis, drug discovery, and environmental monitoring has been a dream of scientists and biotechnologists. Such devices provide on-site and real-time information, which improves point-of-care diagnosis and high-throughput drug discovery. Chip scale calorimeter and chromatography are used for detection and quantification of bio-analytes. However, calorimeters such as thermal biosensors need a large sample volume, and it is challenging to be functionalized at chip scales. On-chip chromatography temporally separates the sample with minimal energy in a short time, but they are difficult to be integrated with sensitive detectors. Whispering gallery mode (WGM) techniques were offered as a promising solution to enhance the sensitivity of biosensors at small scales and provide rapid information about the composition of biochemical/chemical samples.
This invention introduces rapid, simple, and total analysis of chemical/biochemical reactions within a monolithic structure using WGM techniques and on-chip detectors.
This invention is a total analysis system (TAS) including WGM optical resonators with on-chip chemical/biochemical sensing or analysis device such as chromatography, or calorimetric, or biochemical reaction chamber. In the chromatography-coupled version of the invention, microbubbles are in the outlet or inlet of the chromatography column. The optical resonance is induced through the outer surface of microbubbles, where the chemical/biochemical reaction happens, and the binding of analytes is detected from the shift of resonance wavelength. In the calorimetric biosensor version of the invention, the microbubbles are integrated with the microfluidic channel. The biocatalyst of interest is placed in the microfluidic channel where the bio-analyte reacts and the changes in the reaction temperature are resonated in the temperature-dependent microbubble-based WGM resonators. The enclosed structure of microbubbles prevents analyte loss; moreover, the resonator’s quality factor called Q-factor, indicates the sensor performance in this invention reaches up to above 100 million. In this invention, microbubbles may be functionalized with various coating, or they may be made by wafer-scale glass techniques. The integration of microbubble-based resonator and on-chip chromatography or microfluidic channel into a single device automates all necessary steps in the chemical/biochemical analysis of a sample, which addresses the limitations of existing technologies.