Review of Integrated Optical Biosensors for Point-Of-Care Applications

Abstract

This article reviews optical biosensors and their integration with microfluidic channels. The integrated biosensors have the advantages of higher accuracy and sensitivity because they can simultaneously monitor two or more parameters. They can further incorporate many functionalities such as electrical control and signal readout monolithically in a single semiconductor chip, making them ideal candidates for point-of-care testing. In this article, we discuss the applications by specifically looking into point-of-care testing (POCT) using integrated optical sensors. The requirement and future perspective of integrated optical biosensors for POC is addressed.

Keywords: integration; optical biosensors; point-of-care.

Figure 1

Schematic diagram of the fluorescence-based biosensor. Target analyte can be determined by FRET (Förster resonance energy transfer), FLIM (fluorescence lifetime imaging), FI (changes in fluorescence intensity), or FCS (fluorescence correlation spectroscopy).

Figure 2

Schematic diagram of the SERS (surface-enhanced Raman scattering) process using metal nanoparticles to enhance the sensitivity [39]. Reproduced with permission from [39]. Copyright (2016) Springer Open.

Figure 3

Illustration of the sensing mechanism of a photonic crystal (PC) biosensor.

Figure 4

Schematic of a guided mode resonance (GMR) sensor. The resonance can be observed from both the reflectance and transmittance spectra.

Figure 5

Schematic configuration of an surface plasmon resonance (SPR) biosensor.

Figure 6

(a) Schematic of channel layout and (inset) computational fluid dynamics simulation (CFD) mesh of mixing junction. (b) 3D (three-dimensional) CFD simulation result of the mixing junction. Reproduced with permission from [73]. Copyright (2008) OSA publishing.

Figure 7

(A) Schematic of the microfluidic multispectral flow cytometry (MMFC) system. Reproduced with permission from [76]. Copyright (2010) ACS publications. (B) Schematic representation of the fluorescence-activated droplet sorting (FADS) system. Reproduced with permission from [77]. Copyright (2009) Royal Society of Chemistry.

Figure 8

(A) The microfluidic device with on-chip total internal reflection fluorescence microscopy (TIRFM). Reproduced with permission from [78]. Copyright (2012) Springer. (B) A microfluidic microwell device for trapping fluorescent labeled single cells. Reproduced with permission from [79]. Copyright (2018) Springer.

Figure 9

Schematic structures of the microfluidic SERS sensor: (a) schematic details on the SERS-active substrate with patterned nanopillar forests and flat metal areas for self-detection. (b) The overview of the microfluidic SERS sensor with tubes inserted as the inlet and outlet for analyte transportation. Reproduced with permission from [84]. Copyright (2014) Wiley-VCH Vertag.

Figure 10

(A) Schematic diagram and (B) cross-section view of the particle-based microfluidic molecular separation (PMMS) SERS device. Reproduced with permission from [85]. Copyright (2019) Springer.

Figure 11

Droplet-based SERS microfluidics platform: ports 1–5 are used for the injection of sample, SERS-enhancement substrate, and their aggregation agent. Reproduced with permission from [86]. Copyright (2016) ACS publications.

Figure 12

Biomolecular detection by optofluidic localized surface plasmon resonance (LSPR) device. (A) Schematic of the LSPR system consisting of a light source; spectrometer; peristaltic pump; LSPR sensor attached to a commercial microchannel device; and motorized stage for real-time, multi-point (10 spots) immunoglobulin G (IgG) detection. Reproduced with permission from [90]. Copyright (2017) MDPI. (B) The LSPR sensor consists of a PDMS microfluidic channel embedded with the multi-parallel AuNR (Au nanorod) array pattern coated on the glass substrate that can be used for multiplex cytokine detection. Reproduced with permission from [92]. Copyright (2016) ACS publications. (C) The quake valve-based microfluidic device integrating the gold nanorod array pattern is used for multiplex cytokine detection. Reproduced with permission from [93]. Copyright (2018) ACS publications.

Figure 13

The microfluidic LSPR platform for on-chip cell manipulation followed by in situ biomolecular detection. (A) (a) Schematic of the device for matrix metalloproteinase 9 (MMP-9) detection. After cell stimulation, secreted-MMP-9 directly binds to the gold nanoslit array. Then, the amount of the MMP-9 secretion is measured as the transmission spectrum received. (b) The cell trapping microfluidics. Reproduced with permission from [94]. Copyright (2013) Wiley-VCH Vertag. (B) (a) Schematic of the adipocyte culture and LSPR sensing platform. The AuNR pattern coated on the glass substrate allows a multiplex cytokine measurement. The upper PDMS layer has a cylinder chamber for adipocyte culture. (b) The culture chamber surrounded by a block array provides a microenvironment for macrophage formation and can only allow the small secreted protein to pass through the gap for further LSPR sensing. Reproduced with permission from [95]. Copyright (2018) Royal Society of Chemistry.

Figure 14

PC-based biosensors integrated with a microfluidic device. (A) (a) Schematic diagram of PC biosensor chips for extracellular vesicle (EV) detection. (A) (b) The mechanism for EV label-free detection and the SEM (scanning electron microscopic) image of host EVs immobilized on the PC surface. (A) (c) The binding of specific EV will affect resonant reflection and cause a spectral shift of Δλr. Reproduced with permission from [96]. Copyright (2018) ACS publications. (B) (a) Schematic of a 96-well microplate integrated with PC-based biosensors. (B) (b) Photograph of the bottom of the 96-well microplate incorporating microfluidic channel integrated with PC-based biosensors. (B) (c) Spatial peak wavelength value (PWV) shift image detected by 2D spatial image instrument that could be calculated by PWV shift values. Reproduced with permission from [98]. Copyright (2007) Royal Society of Chemistry.

Figure 15

(A) (a) Schematic of the GMR optofluidic sensing system. (b) Schematic and (c) optical image of the disposable GMR biosensor chip. Reproduced with permission from [99]. Copyright (2017) Elsevier. (B) Schematic of the three-layer lab-on-chip system and optical read-out setup. Reproduced with permission from [100]. Copyright (2018) Royal Society of Chemistry.