SERS biosensor with plastic antibodies for detection of a cancer biomarker protein.

Surface-enhanced Raman scattering (SERS) is a powerful method for detecting breast cancer-specific biomarkers due to its extraordinary enhancement effects obtained by localized surface plasmon resonance (LSPR) in metallic nanostructures at hotspots. In this research, gold nanostars (AuNSs) were used as SERS probes to detect a cancer biomarker at very low concentrations. To this end, we combined molecularly imprinted polymers (MIPs) as a detection layer with SERS for the detection of the biomarker CA 15-3 in point-of-care (PoC) analysis. This required two main steps: (i) the deposition of MIPs on a gold electrode, followed by a second step (ii) antibody binding with AuNSs containing a suitable Raman reporter to enhance Raman signaling (SERS). The MPan sensor was prepared by electropolymerization of the monomer aniline in the presence of CA 15-3. The template molecule was then extracted from the polymer using sodium dodecyl sulfate (SDS). In parallel, a control material was prepared in the absence of the protein (NPan). Surface modification for the control was performed using electrochemical techniques such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The performance of the sensor was evaluated using the SERS technique, in which the MPan sensor is first incubated with the protein and then exposed to the SERS probe. Under optimized conditions, the device showed a linear response to CA 15-3 concentrations from 0.016 to 248.51 U mL-1 in a PBS buffer at pH 7.4 in 1000-fold diluted serum. Overall, this approach demonstrates the potential of SERS as an optical reader and opens a new avenue for biosensing applications.

Development of colorimetric cellulose-based test-strip for the rapid detection of antibodies against SARS-CoV2 virus.

Given the pandemic situation, there is an urgent need for an accurate test to monitor antibodies anti-SARS-CoV-2, providing crucial epidemiological and clinical information to monitor the evolution of coronavirus disease in 2019 (COVID-19) and to stratify the immunized and asymptomatic population. Therefore, this paper describes a new cellulose-based test strip for rapid and cost-effective quantitative detection of antibodies to SARS-CoV2 virus by colorimetric transduction. For this purpose, Whatman paper was chemically modified with sodium metaperiodate to introduce aldehyde groups on its surface. Subsequently, the spike protein of the virus is covalently bound by forming an imine group. The chemical control of cellulose paper modification was evaluated by Fourier transform infrared spectroscopy, thermogravimetry and contact angle analysis. Colorimetric detection of the antibodies was performed by a conventional staining method using Ponceau S solution as the dye. Color analysis was performed after image acquisition with a smartphone using Image J software. The color intensity varied linearly with the logarithm of the anti-S concentration (from 10 ng/mL to 1 µg/mL) in 500-fold diluted serum samples when plotted against the green coordinate extracted from digital images. The test strip was selective in the presence of nucleocapsid antibodies, urea, glucose, and bovine serum albumin with less than 15% interference, and detection of antibodies in human serum was successfully performed. Overall, this is a simple and affordable design that can be readily used for mass population screening and does not require sophisticated equipment or qualified personnel. Supplementary Information: The online version contains supplementary material available at 10.1007/s10570-022-04808-y.

Colorimetric Paper-Based Sensors against Cancer Biomarkers.

Cancer is a major cause of mortality and morbidity worldwide. Detection and quantification of cancer biomarkers plays a critical role in cancer early diagnosis, screening, and treatment. Clinicians, particularly in developing countries, deal with high costs and limited resources for diagnostic systems. Using low-cost substrates to develop sensor devices could be very helpful. The interest in paper-based sensors with colorimetric detection increased exponentially in the last decade as they meet the criteria for point-of-care (PoC) devices. Cellulose and different nanomaterials have been used as substrate and colorimetric probes, respectively, for these types of devices in their different designs as spot tests, lateral-flow assays, dipsticks, and microfluidic paper-based devices (µPADs), offering low-cost and disposable devices. However, the main challenge with these devices is their low sensitivity and lack of efficiency in performing quantitative measurements. This review includes an overview of the use of paper for the development of sensing devices focusing on colorimetric detection and their application to cancer biomarkers. We highlight recent works reporting the use of paper in the development of colorimetric sensors for cancer biomarkers, such as proteins, nucleic acids, and others. Finally, we discuss the main advantages of these types of devices and highlight their major pitfalls.

Colorimetric cellulose-based test-strip for rapid detection of amyloid ß-42.

An innovative sensing assay is described for point-of-care (PoC) quantification of a biomarker of Alzheimer's disease, amyloid ß-42 (Aß-42). This device is based on a cellulose paper-dye test strip platform in which the corresponding detection layer is integrated by applying a molecularly imprinted polymer (MIP) to the cellulose paper surface. Briefly, the cellulose paper is chemically modified with a silane to subsequently apply the MIP detection layer. The imprinting process is confirmed by the parallel preparation of a control material, namely a non-imprinted polymer (NIP). The chemical changes of the surface were evaluated by Fourier transform infrared spectroscopy (FTIR), contact angle, and thermogravimetric analysis (TG). Proteins and peptides can be quantified by conventional staining methods. For this purpose, Coomassie blue (CB) was used as a staining dye for the detection and quantification of Aß-42. Quantitative determination is made possible by taking a photograph and applying an appropriate mathematical treatment to the color coordinates provided by the ImageJ program. The MIP shows a linear range between 1.0 ng/mL and 10 µg/mL and a detection limit of 0.71 ng/mL. Overall, this cellulose-based assay is suitable for the detection of peptides or proteins in a sample by visual comparison of color change. The test strip provides a simple, instrument-free, and cost-effective method with high chemical stability, capable of detecting very small amounts of peptides or proteins in a sample, and can be used for the detection of any (bio)molecule of interest.

Imprinting Technology in Electrochemical Biomimetic Sensors.

Biosensors are a promising tool offering the possibility of low cost and fast analytical screening in point-of-care diagnostics and for on-site detection in the field. Most biosensors in routine use ensure their selectivity/specificity by including natural receptors as biorecognition element. These materials are however too expensive and hard to obtain for every biochemical molecule of interest in environmental and clinical practice. Molecularly imprinted polymers have emerged through time as an alternative to natural antibodies in biosensors. In theory, these materials are stable and robust, presenting much higher capacity to resist to harsher conditions of pH, temperature, pressure or organic solvents. In addition, these synthetic materials are much cheaper than their natural counterparts while offering equivalent affinity and sensitivity in the molecular recognition of the target analyte. Imprinting technology and biosensors have met quite recently, relying mostly on electrochemical detection and enabling a direct reading of different analytes, while promoting significant advances in various fields of use. Thus, this review encompasses such developments and describes a general overview for building promising biomimetic materials as biorecognition elements in electrochemical sensors. It includes different molecular imprinting strategies such as the choice of polymer material, imprinting methodology and assembly on the transduction platform. Their interface with the most recent nanostructured supports acting as standard conductive materials within electrochemical biomimetic sensors is pointed out.

Screen-printed electrode produced by printed-circuit board technology. Application to Cancer Biomarker Detection by means of plastic antibody as sensing material.

This research work presents, for the first time, a screen-printed electrode (SPE) made on a PCB board with silver tracks (Ag) and a three electrode configuration (AgxO-working, AgxO-counter and Ag/AgxO-reference electrodes), following the same approach as printed-circuit boards (PCBs). This low cost and disposable device was tested for screening a cancer biomarker in point-of-care. The selected biomarker was carcinogenic embryonic antigen (CEA) protein, routinely used to follow-up the progression of specific cancer diseases. The biosensor was constructed by assembling a plastic antibody on the Ag-working electrode area, acting as the biorecognition element of the device. The protein molecules that were entrapped on the polymer and positioned at the outer surface of the polypyrrole (PPy) film were removed by protease action. The imprinting effect was tested by preparing non-imprinted (NPPy) material, including only PPy as biorecognition element. Infrared and Raman studies confirmed the surface modification of these electrodes. The ability of the sensing material to rebind CEA was measured by several electrochemical techniques: cyclic voltammetry (CV), impedance spectroscopy (EIS) and square wave voltammetry (SWV). The linear response ranged from 0.05 to 1.25 pg/mL against logarithm concentration. Overall, producing screen-printed electrodes by means of conventional PCB technology showed promising features, mostly regarding cost and prompt availability. The plastic antibody-based biosensor also seems to be a promising tool for screening CEA in point-of-care, with low response time, low cost, good sensitivity and high stability.

An electrochemically synthesized molecularly imprinted polymer for highly selective detection of breast cancer biomarker CA 15-3: a promising point-of-care biosensor.

In this study, a molecularly imprinted polymer film (MIP) was prepared on the surface of a disposable carbon screen-printed electrode (C-SPE) using (3-acrylamidopropyl)trimethylammonium chloride (AMPTMA) as a functional monomer and the cancer biomarker carbohydrate antigen 15-3 (CA 15-3) as a template. The MIP was synthesized by in situ electropolymerization (ELP) of the AMPTMA monomer in the presence of the CA 15-3 protein on the C-SPE surface. The target was subsequently removed from the polymer matrix by the action of proteinase K, resulting in imprinted cavities with a high affinity for CA 15-3. Electrochemical techniques such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to characterize the different phases of the sensor assembly. Chemical and morphological analysis was performed using RAMAN and scanning electron microscopy (SEM). CA 15-3 was successfully detected in a wide working range from 0.001 U mL-1 to 100 U mL-1 with a correlation coefficient (R2) of 0.994 in 20 min. The MIP sensor showed minimal interference with other cancer proteins (CEA and CA 125). Overall, the developed device provides a rapid, sensitive, and cost-effective response in the detection of CA 15-3. Importantly, this comprehensive approach appears suitable for point-of-care (PoC) use, particularly in a clinical context.

Prussian blue nanocubes with peroxidase-like activity for polyphenol detection in commercial beverages.

The present study describes an efficient method for the determination of polyphenol content in beverages based on a composite material of graphene oxide decorated with Prussian blue nanocubes (rGO/PBNCs). In this method, rGO/PBNCs act as a nanoenzyme with peroxidase-like catalytic activity and produce a colorimetric product in the presence of hydrogen peroxide and tetramethylbenzidine (TMB). To verify the effectiveness of the method, we used two model standards for antioxidants: gallic acid (GA) and tannic acid (TA). The method validation included a comparison of the performance of a natural enzyme and an artificial one (rGO/PBNCs) and two polyphenols in the analysis of commercial beverage samples. After optimization, a pH of 4, ambient temperature (22 °C), a reaction time of 2 minutes and an rGO/PBNCs concentration of 0.01 µg mL-1 were found to be the most favorable conditions. The detection limits obtained were 5.6 µmol L-1 for GA and 1.5 µmol L-1 for TA. Overall, rGO/PBNCs offer advantages over natural enzymes in terms of stability, versatility, scalability and durability, making them attractive candidates for a wide range of catalytic and sensory applications.

Irreversible colorimetric bio-based curcumin bilayer membranes for smart food packaging temperature control applications.

Research into innovative food safety technologies has led to the development of smart packaging with embedded chemical sensors that can monitor food quality throughout the supply chain. Thermochromic materials (TM), which are able to dynamically change colour in response to temperature fluctuations, have proven to be reliable indicators of food quality in certain environments. Natural colourants such as curcumin are becoming increasingly popular for smart packaging due to their low toxicity, environmental friendliness and ability to change colour. The innovation in this research lies in the production of a bio-based bilayer membrane specifically designed for irreversible temperature monitoring. Membrane A was prepared by dissolving cellulose acetate and curcumin in acetone at room temperature, with glycerol serving as a plasticiser. At the same time, membrane B was carefully formulated by dissolving cellulose acetate and triethanolamine in acetone, with sorbitol as plasticiser. The preparation of these different membranes revealed a remarkable event: a gradual and irreversible colour transition from an initial yellow to a brick-red hue after 24 hours of storage at 25 °C. The chemical structure and morphological analyses of the membranes were performed using several techniques, including FTIR, DSC and SEM. The membrane labels were adhered to aluminium cans and their colorimetric response was observed over a period of 10 days. Minimal colour variations were observed, confirming the reproducibility and stability of the curcumin-based membranes as temperature sensors.

Novel biomimetic Prussian blue nanocubes-based biosensor for Tau-441 protein detection.

Tau protein is a promising biomarker for early diagnosis of Alzheimer's disease. Therefore, there is an urgent need to develop a simple and effective method for its detection. To this end, an innovative sensing device was developed using a carbon screen-printed electrode (C-SPE) decorated with graphene oxide/Prussian Blue nanocubes (GO/PBNCs) for the selective and sensitive determination of Tau-441 protein. The molecular imprinting polymer (MIP) was built on the GO/PBNCs/C-SPE by electropolymerizing 3-aminophenol (3-AMP) in the presence of the target protein using chronoamperometry, and the template was subsequently removed from the polymer matrix with oxalic acid. In parallel, a non-imprinted material (NIP) was also prepared in the absence of the target for comparison purposes. Scanning electron microscopy and transmission electron microscopy, were used to study the morphology of the modified electrode and electrochemical techniques were used to monitor the stepwise assembly of the sensor. Under optimized conditions, the sensing platform exhibited a linear range within 1.09 and 2.18 nmol/L and a detection limit of 0.01 pmol/L in spiked phosphate buffer solution (PBS). The MIP sensor showed minimal interference with uric acid and bovine albumin. The simplicity of production, affordable cost and promising performance make this sensor a potential strategic sensing platform for the detection of chemical and biological molecules.

Electrochemical miRNA-34a-based biosensor for the diagnosis of Alzheimer's disease.

Alzheimer's disease (AD) is the most common dementia type and a leading cause of death and disability in the elderly. Diagnosis is expensive and invasive, urging the development of new, affordable, and less invasive diagnostic tools. The identification of changes in the expression of non-coding RNAs prompts the development of diagnostic tools to detect disease-specific blood biomarkers. Building on this idea, this work reports a novel electrochemical microRNA (miRNA) biosensor for the diagnosis of AD, based on carbon screen-printed electrodes (C-SPEs) modified with two gold nanostructures and a complementary anti-miR-34a oligonucleotide probe. This biosensor showed good target affinity, reflected on a 100 pM to 1 µM linearity range and a limit of detection (LOD) of 39 pM in buffer and 94 aM in serum. Moreover, the biosensor's response was not affected by serum compounds, indicating selectivity for miR-34a. The biosensor also detected miR-34a in the cell culture medium of a common AD model, stimulated with a neurotoxin to increase miR-34a secretion. Overall, the proposed biosensor makes a solid case for the introduction of a novel, inexpensive, and minimally invasive tool for the early diagnosis of AD, based on the detection of a circulating miRNA overexpressed in this pathology.

Aptasensor for the Detection of Moraxella catarrhalis Adhesin UspA2.

Innovative point-of-care (PoC) diagnostic platforms are desirable to surpass the deficiencies of conventional laboratory diagnostic methods for bacterial infections and to tackle the growing antimicrobial resistance crisis. In this study, a workflow was implemented, comprising the identification of new aptamers with high affinity for the ubiquitous surface protein A2 (UspA2) of the bacterial pathogen Moraxella catarrhalis and the development of an electrochemical biosensor functionalized with the best-performing aptamer as a bioreceptor to detect UspA2. After cell-systematic evolution of ligands by exponential enrichment (cell-SELEX) was performed, next-generation sequencing was used to sequence the final aptamer pool. The most frequent aptamer sequences were further evaluated using bioinformatic tools. The two most promising aptamer candidates, Apt1 and Apt1_RC (Apt1 reverse complement), had Kd values of 214.4 and 3.4 nM, respectively. Finally, a simple and label-free electrochemical biosensor was functionalized with Apt1_RC. The aptasensor surface modifications were confirmed by impedance spectroscopy and cyclic voltammetry. The ability to detect UspA2 was evaluated by square wave voltammetry, exhibiting a linear detection range of 4.0 × 104-7.0 × 107 CFU mL-1, a square correlation coefficient superior to 0.99 and a limit of detection of 4.0 × 104 CFU mL-1 at pH 5.0. The workflow described has the potential to be part of a sensitive PoC diagnostic platform to detect and quantify M. catarrhalis from biological samples.

Development of a novel electrochemical biosensor based on plastic antibodies for detection of STEAP1 biomarker in cancer.

STEAP1 is a cell surface protein of the STEAP family whose main function focuses on intercellular communication and cell growth. STEAP1 is considered a promising putative biomarker and a candidate target for prostate cancer treatment. For specific and selective detection of STEAP1, a molecularly imprinted polymers (MIP) was developed on a screen-printed electrode (C-SPE) whose surface was modified with a nanocomposite based on carbon nanotubes decorated with dendritic platinum nanoparticles (CNTs- PAH /Pt). Then, the MIPs were produced on the modified C-SPE by electropolymerization of a mixture of STEAP1 and a monomer (pyrrole-2-carboxylic acid). Then, the protein was removed from the polymeric network by enzymatic treatment with trypsin, which created the specific template cavities for further STEAP1 detection. Electrochemical techniques such as EIS and CV were used to follow the chemical modification steps of C-SPE. The analytical performance of the biosensor was evaluated by SWV in PBS buffer and in lysates of neoplastic prostate cancer cells (LNCaP) extracts. The MIP material showing a linear range from 130 pg/ml to 13 µg/ml. Overall, the biosensor exhibits essential properties such as selectivity, sensitivity and reproducibility for its application in medical and clinical research diagnosis and/or prognosis of prostate cancer.

Paper-based aptasensor for colorimetric detection of osteopontin.

This work presents a novel cellulose-based aptasensor for the colorimetric detection of a cancer biomarker, osteopontin (OPN), in point-of-care (PoC) analysis. For this purpose, the cellulose paper was chemically modified with (mercaptopropyl)methyldimetoxisilane to attach the thiolated aptamer, which acts as a biological detection layer. The surface modification was checked by Fourier transform infrared spectroscopy and thermogravimetric analysis. Colorimetric detection was performed using a conventional staining solution, Bradford reagent. The color analysis was performed by evaluating the RGB coordinates provided by the ImageJ program from the photographs taken with a smartphone. Overall, the biosensor shows good sensitivity with a wide linear range (R > 0.998) of 5-1000 ng/mL and a detection limit lower than 5 ng/mL in buffer and commercial human serum solution, after 30 min of incubation. In addition, this aptasensor shows good selectivity to some interfering species such as bovine serum albumin and recombinant OPN. Analytical data obtained from spiked serum samples confirm the accuracy of the method. Importantly, it is a broad-spectrum method that tends to meet the criteria of REASSURED (real-time connectivity, ease of sampling, affordability, specificity, ease of use, speed and robustness, device freedom, and deliverability) for global testing.

Development of a biosensor for phosphorylated Tau 181 protein detection in Early-Stage Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia in the elderly, and there are still no reliable methods for its early detection. Recently, the phosphorylated protein Tau181 (p-Tau181) was identified as a highly specific biomarker for AD. Therefore, in this work, a new strategy for the development of an electrochemical-based immunosensor for the detection of p-Tau181 is described. For this purpose, a carbon screen-printed electrode (C-SPE) was modified with platinum nanoparticles decorated with multi-walled carbon nanotubes (MWCNTs- PAH /Pt) to enable antibody binding. Scanning electron microscopy, transmission electron microscopy, Raman and X-ray photoelectron spectroscopy were used to study the morphology and crystallinity of the nanomaterials. Cyclic voltammetry and square-wave voltammetry were performed to compare the electrochemical properties of these electrodes. Under optimal conditions, the developed immunosensor exhibited a linear range from 8.6 to 1100 pg/mL, and the detection limit was estimated to be 0.24 pg/mL. This device showed excellent reproducibility and stability with remarkable selectivity for p-Tau181 in serum samples. Overall, this device enables minimally invasive clinical evaluation of p-Tau181 level with high sensitivity through simple operation, which makes this device a promising tool for future point-of-care purposes that will contribute to the technological development of clinical diagnostics.

Wine astringent compounds monitored by an electrochemical biosensor.

An innovative approach for monitoring astringent polyphenols in beverages (wines) is described, consisting of an electrochemical biosensor constructed by adsorbing salivary α-amylase or proline-rich protein (PRP) onto amined gold screen-printed electrodes. Interaction with polyphenols was tested using pentagalloyl glucose (PGG) as a standard, an important representative element for astringency. The analytical properties of the resulting biosensors were evaluated by electrochemical impedance spectroscopy at different pHs. The PRP-biosensor was able to bind to PGG with higher sensitivity, displaying lower limit of the linear range of 0.6 µM. Wine samples were tested to prove the concept and the concentrations obtained ranged from 0.17 to 4.7 µM, as expressed in PGG units. The effects of side-compounds on PRP and on α-amylase binding to PGG were tested (gallic acid, catechin, ethanol, glucose, fructose and glycerol) and considered negligible. Overall, concentrations > 1.0 µM in PGG units are signaling electrochemical impedance, providing a quantitative monitoring of astringent compounds.

Recent Advances in the Selection of Cancer-Specific Aptamers for the Development of Biosensors.

An early diagnosis has the potential to greatly decrease cancer mortality. For that purpose, specific cancer biomarkers have been molecularly targeted by aptamer sequences to enable an accurate and rapid detection. Aptamer-based biosensors for cancer diagnostics are a promising alternative to those using antibodies, due to their high affinity and specificity to the target molecules and advantageous production. Synthetic nucleic acid aptamers are generated by in vitro Systematic Evolution of Ligands by Exponential enrichment (SELEX) methodologies that have been improved over the years to enhance the efficacy and shorten the selection process. Aptamers have been successfully applied in electrochemical, optical, photoelectrochemical and piezoelectrical-based detection strategies. These aptasensors comprise a sensitive, accurate and inexpensive option for cancer detection being used as point-of-care devices. This review highlights the recent advances in cancer biomarkers, achievements and optimizations made in aptamer selection, as well as the different aptasensors developed for the detection of several cancer biomarkers.

Electrochemical Aptasensor for the Detection of the Key Virulence Factor YadA of Yersinia enterocolitica.

New point-of-care (POC) diagnosis of bacterial infections are imperative to overcome the deficiencies of conventional methods, such as culture and molecular methods. In this study, we identified new aptamers that bind to the virulence factor Yersinia adhesin A (YadA) of Yersinia enterocolitica using cell-systematic evolution of ligands by exponential enrichment (cell-SELEX). Escherichia coli expressing YadA on the cell surface was used as a target cell. After eight cycles of selection, the final aptamer pool was sequenced by high throughput sequencing using the Illumina Novaseq platform. The sequencing data, analyzed using the Geneious software, was aligned, filtered and demultiplexed to obtain the key nucleotides possibly involved in the target binding. The most promising aptamer candidate, Apt1, bound specifically to YadA with a dissociation constant (Kd) of 11 nM. Apt1 was used to develop a simple electrochemical biosensor with a two-step, label-free design towards the detection of YadA. The sensor surface modifications and its ability to bind successfully and stably to YadA were confirmed by cyclic voltammetry, impedance spectroscopy and square wave voltammetry. The biosensor enabled the detection of YadA in a linear range between 7.0 × 104 and 7.0 × 107 CFU mL−1 and showed a square correlation coefficient >0.99. The standard deviation and the limit of detection was ~2.5% and 7.0 × 104 CFU mL−1, respectively. Overall, the results suggest that this novel biosensor incorporating Apt1 can potentially be used as a sensitive POC detection system to aid the diagnosis of Y. enterocolitica infections. Furthermore, this simple yet innovative approach could be replicated to select aptamers for other (bacterial) targets and to develop the corresponding biosensors for their detection.

Plastic Antibody of Polypyrrole/Multiwall Carbon Nanotubes on Screen-Printed Electrodes for Cystatin C Detection.

This work reports the design of a novel plastic antibody for cystatin C (Cys-C), an acute kidney injury biomarker, and its application in point-of-care (PoC) testing. The synthetic antibody was obtained by tailoring a molecularly imprinted polymer (MIP) on a carbon screen-printed electrode (SPE). The MIP was obtained by electropolymerizing pyrrole (Py) with carboxylated Py (Py-COOH) in the presence of Cys-C and multiwall carbon nanotubes (MWCNTs). Cys-C was removed from the molecularly imprinted poly(Py) matrix (MPPy) by urea treatment. As a control, a non-imprinted poly(Py) matrix (NPPy) was obtained by the same procedure, but without Cys-C. The assembly of the MIP material was evaluated in situ by Raman spectroscopy and the binding ability of Cys-C was evaluated by the cyclic voltammetry (CV) and differential pulse voltammetry (DPV) electrochemical techniques. The MIP sensor responses were measured by the DPV anodic peaks obtained in the presence of ferro/ferricyanide. The peak currents decreased linearly from 0.5 to 20.0 ng/mL of Cys-C at each 20 min successive incubation and a limit of detection below 0.5 ng/mL was obtained at pH 6.0. The MPPy/SPE was used to analyze Cys-C in spiked serum samples, showing recoveries <3%. This device showed promising features in terms of simplicity, cost and sensitivity for acute kidney injury diagnosis at the point of care.

Paper-Based Biosensors for COVID-19: A Review of Innovative Tools for Controlling the Pandemic.

The appearance and quick spread of the new severe acute respiratory syndrome coronavirus disease, COVID-19, brought major societal challenges. Importantly, suitable medical diagnosis procedures and smooth clinical management of the disease are an emergent need, which must be anchored on novel diagnostic methods and devices. Novel molecular diagnostic tools relying on nucleic acid amplification testing have emerged globally and are the current gold standard in COVID-19 diagnosis. However, the need for widespread testing methodologies for fast, effective testing in multiple epidemiological scenarios remains a crucial step in the fight against the COVID-19 pandemic. Biosensors have previously shown the potential for cost-effective and accessible diagnostics, finding applications in settings where conventional, laboratorial techniques may not be readily employed. Paper- and cellulose-based biosensors can be particularly relevant in pandemic times, for the renewability, possibility of mass production with sustainable methodologies, and safe environmental disposal. In this review, paper-based devices and platforms targeting SARS-CoV-2 are showcased and discussed, as a means to achieve quick and low-cost PoC diagnosis, including detection methodologies for viral genomic material, viral antigen detection, and serological antibody testing. Devices targeting inflammatory markers relevant for COVID-19 are also discussed, as fast, reliable bedside diagnostic tools for patient treatment and follow-up.