Aptamer-based rapid diagnosis for point-of-care application

Abstract

Aptasensors have attracted considerable interest and widespread application in point-of-care testing worldwide. One of the biggest challenges of a point-of-care (POC) is the reduction of treatment time compared to central facilities that diagnose and monitor the applications. Over the past decades, biosensors have been introduced that offer more reliable, cost-effective, and accurate detection methods. Aptamer-based biosensors have unprecedented advantages over biosensors that use natural receptors such as antibodies and enzymes. In the current epidemic, point-of-care testing (POCT) is advantageous because it is easy to use, more accessible, faster to detect, and has high accuracy and sensitivity, reducing the burden of testing on healthcare systems. POCT is beneficial for daily epidemic control as well as early detection and treatment. This review provides detailed information on the various design strategies and virus detection methods using aptamer-based sensors. In addition, we discussed the importance of different aptamers and their detection principles. Aptasensors with higher sensitivity, specificity, and flexibility are critically discussed to establish simple, cost-effective, and rapid detection methods. POC-based aptasensors' diagnostic applications are classified and summarised based on infectious and infectious diseases. Finally, the design factors to be considered are outlined to meet the future of rapid POC-based sensors.

Keywords: Aptamer; Biosensors; Diagnosis; Point of care.

Fig. 1

Patent analysis and significant players in aptamer-based biosensor

Fig. 2

Scheme of SELEX. a The initial oligonucleotide pool (IOP) incubated with a target molecule. b Unbound oligonucleotides separated from bound molecules by washing steps. c Bound oligonucleotides eluted from the target molecule. d Eluted oligonucleotides amplified using the PCR (DNA-SELEX) or RT-PCR (RNA-SELEX) technique. e The enriched pool is then subjected to further rounds of selection. f After 5–15 rounds, aptamers are cloned and analysed in detail

Fig. 3

Aptamer-based assay formats. (i) a Small-molecule target buried within the binding pockets of aptamer structures; b single-site format; c dual-site (sandwich) binding format with two aptamers; and d “sandwich” binding format with an aptamer and an antibody (Song et al. 2008). (ii) a Sandwich mode; b Target-induced structure switching (TISS) mode; c Target-induced dissociation (TID) mode; d Competitive replacement (CR) mode(Prante et al. 2020). (iii) a Sandwich-based aptasensing; b Displacement -based aptasensing; c Folding -based aptasensing (Radi and Abd-Ellatief 2021)

Fig. 4

Trends in POC-based aptasensor

Fig. 5

Electrochemical-based aptasensor (i) A Schematic illustration depicting a selective modification of gold electrodes with different cytokine-binding aptamers. A pair of half-ring-shaped Au electrodes fabricated on glass slides are embedded inside one PEG hydrogel and incubated with antibodies for immune cell capture. Upon injection of cells, T cells and human monocytes are bound on Ab-modified glass regions. Two cytokine-binding aptamers are respectively modified on individually addressable electrodes for detecting cytokine release in real-time B Electrode layout, where the overall device size is half of a glass slide (25 mm 37.5 mm) C 300 mm diameter of PEG wells are used to capture approximately 400 cells inside one well (Liu et al. 2012a), (ii) The immobilisation of aptamer and aptabody at a layer formed by electro polymerization of a mixture of multi-walled carbon nanotubes (MWCNTs) with methylene blue (MB) (Hianik and Wang 2009), (iii) SD-EASs for the detection of Ampi A (Yang et al. 2017), iv) The fabrication of dual-signalling electrochemical aptasensor (Cao et al. 2017), (v) Immobilisation of Streptavidin by physical absorption onto the gold surface (Citartan and Tang 2019), (vi) Myoglobin detection with an electrochemical aptasensor with Y-shaped DNA architecture. Apt aptamer, MCH 6-mercapto-1-hexanol, SPGE screen-printed gold electrode (Taghdisi et al. 2016)

Fig. 6

Optical-based aptasensor: (i) Angiogenin detection strategy based on streptavidin-triggered amplified fluorescence polarisation (Musumeci et al. 2017), (ii) Elastase detection strategy based on competitive binding involving the elastase aptamer, a molecular beacon and a short DNA sequence (Musumeci et al. 2017), (iii) Selective colorimetric method for detection of cancer cells by employing DNA probe 1,2–functionalised gold nanoparticles and AS1411 aptamer (Borghei et al. 2017), (iv) The illustration of the aptasensor for pLDH detection (Jeon et al. 2013), (v) Selective label-free surface plasmon resonance (SPR) preparation for the specific detection of human-activated protein C-APC (Koyun et al. 2019)

Fig. 7

Mass-sensitive-based aptasensors: (i) QCM-based biosensors are promising tools for the rapid detection of infections (Lim et al. 2020), (ii) Aptamer-based QCM biosensor for salmonella detection (Ozalp et al. 2015) (iii) The schematic process of the QCM-based aptasensor for detection of S. Typhimurium (R. Wang et al. 2017a, b). (iv) schematic representation of the DNA-QCM virus sensor (Afzal et al. 2017), (v) Microcantilever Array Biosensor for Simultaneous Detection of Carcinoembryonic Antigens and α-Fetoprotein (Li et al. 2019)

Fig. 8

Aptasensor POC applications. (1) Aptamer-based detection of food allergen peanut protein (Stidham et al. 2022), (2) SPR-based biosensor for lung cancer detection using dendrimers as surface enhancement polymers (Altintas and Tothill 2013), (3) miRNA sensor-based peptide nucleic acid and nanographene oxide (PANGO) (Ryoo et al. 2013), (4) Label-free electrochemical monitoring of vasopressin in aptamer-based microfluidic biosensors (He et al. 2013), (5) Aptamer-based sensor for plasma protein detection(Zamay et al. 2016), (6) Aptamer detection of cadmium from water sample for environmental monitoring (McConnell et al. 2020), (7) DNA aptamers targeting Leishmania infantum H₃ protein (Frezza et al. 2020), (8) The fluorescent aptasensor for OTA determination based on the conformational change of aptamer (Guo et al. 2020), (9) Electrochemical nanoporous membrane-based detection of dengue(Rai et al. 2012), (10) DNA-based electrochemical biosensing platforms (Torres-Chavolla and Alocilja 2011)