Miniaturization of fluorescence sensing in optofluidic devices

Abstract

Successful development of a micro-total-analysis system (µTAS, lab-on-a-chip) is strictly related to the degree of miniaturization, integration, autonomy, sensitivity, selectivity, and repeatability of its detector. Fluorescence sensing is an optical detection method used for a large variety of biological and chemical assays, and its full integration within lab-on-a-chip devices remains a challenge. Important achievements were reported during the last few years, including improvements of previously reported methodologies, as well as new integration strategies. However, a universal paradigm remains elusive. This review considers achievements in the field of fluorescence sensing miniaturization, starting from off-chip approaches, representing miniaturized versions of their lab counter-parts, continuing gradually with strategies that aim to fully integrate fluorescence detection on-chip, and reporting the results around integration strategies based on optical-fiber-based designs, optical layer integrated designs, CMOS-based fluorescence sensing, and organic electronics. Further successful development in this field would enable the implementation of sensing networks in specific environments that, when coupled to Internet-of-Things (IoT) and artificial intelligence (AI), could provide real-time data collection and, therefore, revolutionize fields like health, environmental, and industrial sensing.

Microfluidic Flow Sensing Approaches

“…However, the making of the sensor would be quite complicated with the fiber alignment, and direct contact of the flowing fluid with the fiber cantilever is also required. In another report using the optical approach for flow sensing, miniaturized fluorescence sensing is attempted for micro molecular tagging velocimetry in microfluidics [76], but these methods are not cost-effective and yet to reach the small footprint.…”

New bioimaging avenues for organs‐on‐chips by integration of bioluminescence

“…Notwithstanding these options, the vast majority of organ-on-a-chip current readouts are microscopy-based, typically combined with sacrificial off-chip analytical techniques (eg, qPCR, FACS, mass spectroscopy, and ELISA). 28 Optical methods offer several advantages, which render them highly suitable for merging with organ-on-a-chip platforms, such as being nondestructive, robust, sensitive, and, importantly, compatible with in situ and/or inline monitoring, 29 as elegantly depicted in the example in Figure 1D. Well known by the required mild conditions and noninvasiveness, luminescence-based biosensors are based on imaging light emission resulting from thermo, electrogenerated-, or chemi-BL reactions.…”

“…It is widely accepted that from all optical methods, fluorescence sensing is still the most popular detection method used in organ-on-chip platforms. 29 Indeed, most of the readouts compatible with organs-on-chips so far reported in literature remain heavily dependent on fluorescencebased microscopy assessment. [45][46][47] Fluorescence-based analysis is typically reliant on prelabeled cells or demand invasive end-point procedures, such as cell fixation, necessary for further processing for immunohistochemistry or histological staining.…”

Emerging optofluidic technologies for biodiagnostic applications

“…The integration features of optofluidic technology can (1) accelerate the reaction speed due to the short diffusion distance, high surface‐to‐volume ratio, and efficient heat transfer [ 10 ] ; (2) improve the sensitivity due to the efficient mass transfer in a small volume and enhanced light–matter interaction using on‐chip optical modules such as optofluidic laser [ 11 ] ; (3) reduce the cost due to the lower reagent and sample consumption [ 12 ] ; (4) miniaturize the diagnostic system because of the integrated optics in chips. [ 13 ] Those advantages make the optofluidics a promising solution for biodiagnosis. The advances of optofluidic technology will be useful for addressing global health issues such as the current COVID‐19 pandemic in many aspects, from the direct detection of the COVID‐19 virus using optofluidic genetic detection system to antibody‐based blood diagnosis test using optofluidic protein detection tool, and to antibody screening for therapeutic purpose using optofluidic cell analysis platform.…”