Point-of-Care Prostate Specific Antigen Testing: Examining Translational Progress toward Clinical Implementation

Abstract

Prostate cancer (PCa) is the second most common male cancer and is attributable to over 375,000 deaths annually. Prostate specific antigen (PSA) is a key biomarker for PCa and therefore measuring patient PSA levels is an important aspect of the diagnostic pathway. Automated immunoassays are currently utilized for PSA analysis, but they require a laboratory setting with specialized equipment and trained personnel. This results in high diagnostic costs, extended therapeutic turnaround times, and restrictions on testing capabilities in resource-limited settings. Consequently, there is a strong drive to develop point-of-care (PoC) PSA tests that can offer accurate, low-cost, and rapid results at the time and place of the patient. However, many emerging PoC tests experience a trade-off between accuracy, affordability, and accessibility which distinctly limits their translational potential. This review comprehensively assesses the translational advantages and limitations of emerging laboratory-level and commercial PoC tests for PSA determination. Electrochemical and optical PSA sensors from 2013 to 2023 are systematically examined. Furthermore, we suggest how the translational potential of emerging tests can be optimized to achieve clinical implementation and thus improve PCa diagnosis globally.

Keywords: biosensors; electrochemical detection; healthcare devices; optical detection; point-of-care testing; prostate cancer; prostate specific antigen; translational progression.

Figure 1

Emerging sensors for electrochemical detection of PSA. (a) Peptides with functionalized AuNPs are immobilized on Au/paper-based working electrodes (PWEs). PSA introduction cleaves the peptides, which removes AuNPs and, thus, reduces the DPV signal. Adapted with permission from (70). Copyright 2018, American Chemistry Society. (b) PSA antibodies are electroinserted into Vero cells, which are then immobilized to AuNP-modified screen-printed carbon electrodes. Eight electrodes were inserted into a portable device for simultaneous CA measurements. Adapted from ref (68). Creative Commons CC BY license, MDPI. (c) Aptamers are immobilized to molybdenum disulfide-modified GCEs, and Si nanoprobes with electroactive tags are utilized for signal amplification. Introducing PSA liberates the Si nanoprobes and therefore reduces the SWV signal. Adapted with permission from ref (72). Copyright 2022 Elsevier. (d) Aptamers/PSA are immobilized to Au electrodes before electropolymerization of a dopamine layer. The PSA is then removed, which leaves exposed binding sites to allow direct detection using EIS. Adapted from ref (74). Creative Commons CC BY license, Elsevier.

Figure 2

Emerging sensors for optical detection of PSA. (a) Whole blood is directly added to a LFA in which antibody-modified AuNPs are immobilized to the conjugate pad. The optical density of the test/control lines is analyzed using a portable Cube reader. Adapted from ref (43). Creative Commons CC BY license, Elsevier. (b) Magnetic AuNPs modified with antibodies are immobilized to the conjugate pad of an LFA and a magnetic assay reader is utilized for quantitative PSA determination. Adapted with permission from ref (96). Copyright 2021 Elsevier. (c) A fluorometric immunochromatographic test strip (ICTS) is developed for the simultaneous detection of fPSA and tPSA using dual-color magnetic-quantum dot nanobeads (MQBs) conjugated with antibodies. Quantitative determination is performed by using a smartphone-based dual-color fluorescent lateral flow strip reader. Adapted with permission from ref (91). Copyright 2019 Elsevier. (d) Antibody-modified SiO₂NPs embedded with quantum dots (QDs) are immobilized to the conjugate pad of an ICTS and a smartphone-based reader is utilized for PSA determination. Adapted from ref (95). Creative Commons CC BY license, MDPI.