Paper-based biosensors as point-of-care diagnostic devices for the detection of cancers: a review of innovative techniques and clinical applications

Abstract

The development and rapid progression of cancer are major social problems. Medical diagnostic techniques and smooth clinical care of cancer are new necessities that must be supported by innovative diagnostic methods and technologies. Current molecular diagnostic tools based on the detection of blood protein markers are the most common tools for cancer diagnosis. Biosensors have already proven to be a cost-effective and accessible diagnostic tool that can be used where conventional laboratory methods are not readily available. Paper-based biosensors offer a new look at the world of analytical techniques by overcoming limitations through the creation of a simple device with significant advantages such as adaptability, biocompatibility, biodegradability, ease of use, large surface-to-volume ratio, and cost-effectiveness. In this review, we covered the characteristics of exosomes and their role in tumor growth and clinical diagnosis, followed by a discussion of various paper-based biosensors for exosome detection, such as dipsticks, lateral flow assays (LFA), and microfluidic paper-based devices (µPADs). We also discussed the various clinical studies on paper-based biosensors for exosome detection.

Keywords: biosensors; dipsticks; early diagnosis; lateral flow assay; microfluidic paper-based device; paper-based devices.

Figure 1

Schematic representation of exosome production, secretion, and transfer of cargo from donor cancer cells to the bloodstream and its therapeutic application. Exosomes are a type of extracellular vesicle released by both normal and cancer cells. Internal vesicles are formed by inward budding of the cellular compartments of the multivesicular body (MVB). When the MVBs fuse with the plasma membrane, these intracellular vesicles are released as exosomes that carry organic compounds specific to cancer cells, such as DNA, RNA, and proteins, into the various biological fluids, including serum and urine of cancer patients. Exosomes in the bloodstream have several biomedical applications, including diagnostic and prognostic applications, predictive and surveillance applications, and therapeutic applications such as drug delivery.

Figure 2

Schematic illustration of non-invasive detection of HER2-positive exosomes using a high-affinity capture probe and reformative tyramine signal amplification. HER2-positive exosomes play a crucial role in breast cancer diagnosis and therapy. First, exosomes are isolated from cell culture fluid or clinical samples and applied to the surface of a gold chip containing a capture probe. In the presence of HER2-positive exosomes, the capture probe binds to the HER2 protein and exposes the G4 sequence. The addition of hemin leads to the formation of a catalytically active G4-Hemin complex. In turn, the addition of tyramine promotes the catalysis of G4-Hemin, converting tyramine to a reactive oxidized intermediate with the help of H2O2, leading to the formation of a fluorescent signal. Exosomes are quantitatively detected by fluorescence intensity.

Figure 3

Schematic diagram representing the main steps of paper-based biosensors for isolation and measurement of circulating exosomes.