Detection of Bacterial and Viral Pathogens Using Photonic Point-of-Care Devices

Abstract

Infectious diseases caused by bacteria and viruses are highly contagious and can easily be transmitted via air, water, body fluids, etc. Throughout human civilization, there have been several pandemic outbreaks, such as the Plague, Spanish Flu, Swine-Flu, and, recently, COVID-19, amongst many others. Early diagnosis not only increases the chance of quick recovery but also helps prevent the spread of infections. Conventional diagnostic techniques can provide reliable results but have several drawbacks, including costly devices, lengthy wait time, and requirement of trained professionals to operate the devices, making them inaccessible in low-resource settings. Thus, a significant effort has been directed towards point-of-care (POC) devices that enable rapid diagnosis of bacterial and viral infections. A majority of the POC devices are based on plasmonics and/or microfluidics-based platforms integrated with mobile readers and imaging systems. These techniques have been shown to provide rapid, sensitive detection of pathogens. The advantages of POC devices include low-cost, rapid results, and portability, which enables on-site testing anywhere across the globe. Here we aim to review the recent advances in novel POC technologies in detecting bacteria and viruses that led to a breakthrough in the modern healthcare industry.

Keywords: diagnostics; infectious diseases; lensless imaging; microfluidics; plasmonics; point-of-care devices; smartphone.

Figure 1

Flow diagram showing the process of sample testing using point-of care devices.

Figure 2

(A) Schematic of the enzyme-linked immunosorbent assay (M-ELISA) inside the microfluidic chip; (B) Magnetic actuation platform holding the microfluidic chip controlled by Arduino controller allowing bi-directional movement of the magnets; (C) Colorimetric changes in the chip were recorded using a smartphone; (D) Histogram plot of the saturation maximum pixel intensity (MPI) of the color following the M-ELISA assay on chip [62].

Figure 3

(A) Schematic of the flexible polyester film-based electrical sensing platform for HIV detection, including the capture of HIV through the use of anti-gp120 antibody coated magnetic beads, washing and lysis steps, and measurement of electrical impedance; (B) Detection of bacteria on cellulose paper, using a smartphone, based on nanoparticle aggregation assay. The following schematics depict the gold nanoparticle surface modification steps and the resultant aggregation assay which is detected by using a smartphone [71].

Figure 4

Representation of plasmon-based sensors and the different detection methods: (A) planar metallic thin-film-based biosensors and (B) localized surface plasmon resonance (LSPR)-based biosensors.

Figure 5

(A) Schematic of the fluorescence assay for detecting multiple pathogens, using a smartphone: The sample was added to a chip coated with microbeads, which are optically barcoded by quantum dots and are coated with bio-recognition element to capture a specific target molecule; (B) Photograph of the microwell chip containing different barcodes in each well; (C) Fluorescence image of the different quantum dot barcode array (Scale bar—20 µm); (D) Schematic of the smartphone device. Two excitation sources were used to excite the quantum dot barcoded chip independently. The optical emission is collected by a set of objective and eyepiece lenses and filtered using a long-pass filter and then imaged, using a smartphone camera; (E) Photograph of the smartphone device incorporated with the microwell chip. Used with permission, from Reference [131].

Figure 6

Schematic of a lensless digital holographic imaging system. A simple imaging system consists of a light source, complementary metal-oxide semiconductor (CMOS) sensor array, and a semi-transparent chip/substrate containing the sample.

Figure 7

(A) Schematic of the HSV-1 capture assay on a specially prepared chip. (B) Schematic of the portable lensless microscope with pixel super-resolution capability. The device weighs less than 500 gm and is about 25 cm in height [152]. Lensless microscopy was also used to detect Staphylococcus aureus directly in a contact lens [154]. The contact lenses were coated with multiple layers polyelectrolytes that enables the immobilization of antibody specific to the S. aureus onto them. Simulated experiments were performed by incubating the antibody-coated contact lens with artificial tear fluid containing the bacteria. This was followed by the addition of a secondary antibody-coated polystyrene microparticle (5 µm), which resulted in the formation of a sandwich structure. A portable lensless microscope was used to directly image and quantify the number of microparticles present on the curved surface of the contact lens. Up to 16 bacteria/µL could be detected by using this method.