The COVID-19 pandemic is an ongoing global challenge for public health systems. Ultrasensitive and early identification of infection is critical to prevent widespread COVID-19 infection by presymptomatic and asymptomatic individuals, especially in the community and in-home settings. We demonstrate a multiplexed, portable, wireless electrochemical platform for ultra-rapid detection of COVID-19: the SARS-CoV-2 RapidPlex. It detects viral antigen nucleocapsid protein, IgM and IgG antibodies, as well as the inflammatory biomarker C-reactive protein, based on our mass-producible laser-engraved graphene electrodes. We demonstrate ultrasensitive, highly selective, and rapid electrochemical detection in the physiologically relevant ranges. We successfully evaluated the applicability of our SARS-CoV-2 RapidPlex platform with COVID-19 positive and negative blood and saliva samples. Based on this pilot study, our multiplexed immunosensor platform may allow for high frequency at-home testing for COVID-19 telemedicine diagnosis and monitoring.
Digital health facilitated by wearable/portable electronics and big data analytics holds great potential in empowering patients with real‐time diagnostics tools and information. The detection of a majority of biomarkers at trace levels in body fluids using mobile health (mHealth) devices requires bioaffinity sensors that rely on “bioreceptors” for specific recognition. Portable point‐of‐care testing (POCT) bioaffinity sensors have demonstrated their broad utility for diverse applications ranging from health monitoring to disease diagnosis and management. In addition, flexible and stretchable electronics‐enabled wearable platforms have emerged in the past decade as an interesting approach in the ambulatory collection of real‐time data. Herein, the technological advancements of mHealth bioaffinity sensors evolved from laboratory assays to portable POCT devices, and to wearable electronics, are synthesized. The involved recognition events in the mHealth affinity biosensors enabled by bioreceptors (e.g., antibodies, DNAs, aptamers, and molecularly imprinted polymers) are discussed along with their transduction mechanisms (e.g., electrochemical and optical) and system‐level integration technologies. Finally, an outlook of the field is provided and key technological bottlenecks to overcome identified, in order to achieve a new sensing paradigm in wearable bioaffinity platforms.
MicroRNAs (miRs) have emerged as important clinical biomarkers with both diagnostic and prognostic value for relevant diseases, such as cancer. MiRs pose unique challenges for detection and are currently detected by northern blotting, real-time PCR, and microarray techniques. These expensive, complicated, and time-consuming techniques are not feasible for on-site miR determination. In this study, amperometric magnetobiosensors involving RNA-binding viral protein p19 as a selective biorecognition element were developed for miR quantification. The p19-based magnetosensors were able to detect 0.4 fmol of a synthetic target and endogenous miR-21 (selected as a model for its role in a wide variety of cancers) in only 2 h in total RNA extracted from cancer cells and human breast-tumor specimens without PCR amplification and sample preprocessing. These results open up formidable perspectives for the diagnosis and prognosis of human cancers and for drug-discovery programs.
Nanoparticles composed of Prussian Blue, PB, and the cyanometalate structural analogues, CuFe, FeCoFe, and FeCo, are examined as inorganic clusters that mimic the functions of peroxidases. PB acts as a superior catalyst for the oxidation of dopamine to aminochrome by HO. The oxidation of dopamine by HO in the presence of PB is 6-fold faster than in the presence of CuFe. The cluster FeCo does not catalyze the oxidation of dopamine to aminochrome. The most efficient catalyst for the generation of chemiluminescence by the oxidation of luminol by HO is, however, FeCo, and PB lacks any catalytic activity toward the generation of chemiluminescence. The order of catalyzed chemiluminescence generation is FeCo ≫ CuFe > FeCoFe. The clusters PB, CuFe, FeCoFe, and FeCo mimic the functions of NADH peroxidase. The catalyzed oxidation of NADH by HO to form NAD follows the order PB ≫ CuFe ∼ FeCoFe, FeCo. The efficient generation of chemiluminescence by the FeCo-catalyzed oxidation of luminol by HO is used to develop a glucose sensor. The aerobic oxidation of glucose in the presence of glucose oxidase, GOx, yields gluconic acid and HO. The chemiluminescence intensities formed by the GOx-generated HO relate to the concentration of glucose, thus providing a quantitative readout signal for the concentrations of glucose.
This paper describes two different electrochemical affinity biosensing approaches for the simple, fast and bisulfite and PCR-free quantification of 5-methylated cytosines (5-mC) in DNA using the anti-5-mC antibody as biorecognition element. One of the biosensing approaches used the anti-5-mC as capture bioreceptor and a sandwich type immunoassay, while the other one involved the use of a specific DNA probe and the anti-5-mC as a detector bioreceptor of the captured methylated DNA. Both strategies, named for simplicity in the text as immunosensor and DNA sensor, respectively, were implemented on the surface of magnetic microparticles and the transduction was accomplished by amperometry at screen-printed carbon electrodes by means of the hydrogen peroxide/hydroquinone system. The resulting amperometric biosensors demonstrated reproducibility throughout the entire protocol, sensitive determination with no need for using amplification strategies, and competitiveness with the conventional enzyme-linked immunosorbent assay methodology and the few electrochemical biosensors reported so far in terms of simplicity, sensitivity and assay time. The DNA sensor exhibited higher sensitivity and allowed the detection of the gene-specific methylations conversely to the immunosensor, which detected global DNA methylation. In addition, the DNA sensor demonstrated successful applicability for 1 h-analysis of specific methylation in two relevant tumor suppressor genes in spiked biological fluids and in genomic DNA extracted from human glioblastoma cells.
Autoantibodies raised against tumor-associated antigens have shown high promise as clinical biomarkers for reliable diagnosis, prognosis, and therapy monitoring of cancer. An electrochemical disposable biosensor for the specific and sensitive determination of p53-specific autoantibodies has been developed for the first time in this work. This biosensor involves the use of magnetic microcarriers (MBs) modified with covalently immobilized HaloTag fusion p53 protein as solid supports for the selective capture of specific autoantibodies. After magnetic capture of the modified MBs onto screen-printed carbon working electrodes, the amperometric signal using the system hydroquinone/HO was related to the levels of p53-autoantibodies in the sample. The biosensor was applied for the analysis of sera from 24 patients with high-risk of developing colorectal cancer and 6 from patients already diagnosed with colorectal (4) and ovarian (2) cancer. The developed biosensor was able to determine p53 autoantibodies with a sensitivity higher than that of a commercial standard ELISA using a just-in-time produced protein in a simpler protocol with less sample volume and easily miniaturized and cost-effective instrumentation.
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