Highly Sensitive Label-Free Detection of Small Molecules with an Optofluidic Microbubble Resonator

Abstract

The detection of small molecules has increasingly attracted the attention of researchers because of its important physiological function. In this manuscript, we propose a novel optical sensor which uses an optofluidic microbubble resonator (OFMBR) for the highly sensitive detection of small molecules. This paper demonstrates the binding of the small molecule biotin to surface-immobilized streptavidin with a detection limit reduced to 0.41 pM. Furthermore, binding specificity of four additional small molecules to surface-immobilized streptavidin is shown. A label-free OFMBR-based optical sensor has great potential in small molecule detection and drug screening because of its high sensitivity, low detection limit, and minimal sample consumption.

Optical Fiber Optofluidic Bio‐Chemical Sensors: A Review

“…Package structure diagrams of WGM coupling system: a) Full packaging; b) local packaging. [190,191] Importantly, the taper diameter in this structure was about an order of magnitude larger than that of a standard SMF taper coupler, thereby improving the mechanical strength of the system.…”

Microbubble Resonators for All-Optical Photoacoustics of Flowing Contrast Agents

“…Microbubble resonators are manufactured in house by heating a pressurized glass capillary [20][21][22] and thus producing a spherical bulge extending from the capillary stem: this bulge is the resonator itself. Since MBRs are produced from a capillary, they can be filled easily through a microfluidic circuit and have been widely used as optical sensors due to their high sensitivity towards refractive index perturbations [23][24][25][26] and mechanical perturbations. The latter property, which comes from the high mechanical quality factor of the MBR structure [27][28][29][30], is promising for PA detection since it lowers the limit of detection through constructive mechanical interference.…”

Acoustofluidic Measurements on Polymer-Coated Microbubbles: Primary and Secondary Bjerknes Forces

“…The acoustic manipulation of microbubbles (MBs) is a more recent application [ 5 , 6 ], which builds on the success of coated microbubbles as a contrast agent in ultrasound imaging [ 7 ] and focuses on their use in drug delivery [ 8 , 9 ] and bio-sensing applications [ 10 ]. Microstreaming generated from the oscillations of uncoated microbubbles (acoustically, thermally or chemically actuated) has been used for localised flow control, leading to dynamic switching in microfluidic chips [ 11 , 12 ], microswimmers’ propulsion [ 13 , 14 ] and localised probing of cell properties [ 15 , 16 ]. In these applications, microbubbles are potentially more effective than particles because their deformation can be controlled by an external agent, but they are often simply treated as particles with a higher compressibility.…”

“…In particular, we show evidence of a threshold pressure, above which phenomena classically attributed to bubble-bubble interactions (secondary Bjerknes forces [ 17 ]) can be observed. We propose a correction to the acoustic contrast factor to account for secondary Bjerknes forces and summarise our findings in a dynamical measurement of the compressibility of coated microbubbles: a key parameter for the uptake of microbubble-based therapies [ 8 ] and sensing applications [ 15 , 16 ]. Thanks to a direct estimation of key shell parameters—obtained by milling and compressing a selection of bubbles under a Focussed Ion Beam Scanning Electron Microscope (FIB-SEM)—we discuss our results in terms of the onset of volume oscillations [ 25 , 30 ] and of buckling [ 26 ].…”