Multiplex electrochemical sensing platforms for the detection of breast cancer biomarkers.

Herein, advancements in electroanalytical devices for the simultaneous detection of diverse breast cancer (BC) markers are demonstrated. This article identifies several important areas of exploration for electrochemical diagnostics and highlights important factors that are pivotal for the successful deployment of novel bioanalytical devices. We have highlighted that the limits of detection (LOD) reported for the multiplex electrochemical biosensor can surpass the sensitivity displayed by current clinical standards such as ELISA, FISH, and PCR. HER-2; a breast cancer marker characterised by increased metastatic potential, more aggressive development, and poor clinical outcomes; can be sensed with a LOD of 0.5 ng/ml using electrochemical multiplex platforms, which falls within the range of that measured by ELISA (from picogram/ml to nanogram/ml). Electrochemical multiplex biosensors are reported with detection limits of 0.53 ng/ml and 0.21 U/ml for MUC-1 and CA 15-3, respectively, or 5.8 × 10-3 U/ml for CA 15-3 alone. The sensitivity of electrochemical assays is improved when compared to conventional analysis of MUC-1 protein which is detected at 11-12 ng/ml, and ≤30 U/ml for CA 15-3 in the current clinical blood tests. The LOD for micro-ribonucleic acid (miRNA) biomarkers analyzed by electrochemical multiplex assays were all notedly superior at 9.79 × 10-16 M, 3.58 × 10-15 M, and 2.54 × 10-16 M for miRNA-155, miRNA-21, and miRNA-16, respectively. The dogma in miRNA testing is the qRT-PCR method, which reports ranges in the ng/ml level for the same miRNAs. Breast cancer exosomes, which are being explored as a new frontier of biosensing, have been detected electrochemically with an LOD of 103-108 particles/mL and can exceed detection limits seen by the tracking and analysis of nanoparticles (∼ 107 particles/ml), flow cytometry, Western blotting and ELISA, etc. A range of concentration at 78-5,000 pg/ml for RANKL and 16-1,000 pg/ml for TNF is reported for ELISA assay while LOD values of 2.6 and 3.0 pg/ml for RANKL and TNF, respectively, are demonstrated by the electrochemical dual immunoassay platform. Finally, EGFR and VEGF markers can be quantified at much lower concentrations (0.01 and 0.005 pg/ml for EGFR and VEGF, respectively) as compared to their ELISA assays (EGRF at 0.31-20 ng/ml and VEGF at 31.3-2,000 pg/ml). In this study we hope to answer several questions: (1) Are the limits of detection (LODs) reported for multiplex electrochemical biosensors of clinical relevance and how do they compare to well-established methods like ELISA, FISH, or PCR? (2) Can a single sensor electrode be used for the detection of multiple markers from one blood drop? (3) What mechanism of electrochemical biosensing is the most promising, and what technological advancements are needed to utilize these devices for multiplex POC detection? (4) Can nanotechnology advance the sensitive and selective diagnostics of multiple BC biomarkers? (5) Are there preferred receptors (antibody, nucleic acid or their combinations) and preferred biosensor designs (complementary methods, sandwich-type protocols, antibody/aptamer concept, label-free protocol)? (6) Why are we still without FDA-approved electrochemical multiplex devices for BC screening?

Smart Wearable Nanopaper Patch for Continuous Multiplexed Optical Monitoring of Sweat Parameters.

Notwithstanding the substantial progress in optical wearable sensing devices, developing wearable optical sensors for simultaneous, real-time, and continuous monitoring of multiple biomarkers is still an important, yet unmet, demand. Aiming to address this need, we introduced for the first time a smart wearable optical sensor (SWOS) platform combining a multiplexed sweat sensor sticker with its IoT-enabled readout module. We employed our SWOS system for on-body continuous, real-time, and simultaneous fluorimetric monitoring of sweat volume (physical parameter) and pH (chemical marker). Herein, a variation in moisture (5-45 µL) or pH (4.0-7.0) causes a color/fluorescence change in the copper chloride/fluorescein immobilized within a transparent chitin nanopaper (ChNP) in a selective and reversible manner. Human experiments conducted on athletic volunteers during exercise confirm that our developed SWOS platform can be efficiently exploited for smart perspiration analysis toward personalized health monitoring. Moreover, our system can be further extended for the continuous and real-time multiplexed monitoring of various biomarkers (metabolites, proteins, or drugs) of sweat or other biofluids (for example, analyzing exhaled breath by integrating onto a facemask).

Moving toward smart biomedical sensing.

The development of novel biomedical sensors as highly promising devices/tools in early diagnosis and therapy monitoring of many diseases and disorders has recently witnessed unprecedented growth; more and faster than ever. Nonetheless, on the eve of Industry 5.0 and by learning from defects of current sensors in smart diagnostics of pandemics, there is still a long way to go to achieve the ideal biomedical sensors capable of meeting the growing needs and expectations for smart biomedical/diagnostic sensing through eHealth systems. Herein, an overview is provided to highlight the importance and necessity of an inevitable transition in the era of digital health/Healthcare 4.0 towards smart biomedical/diagnostic sensing and how to approach it via new digital technologies including Internet of Things (IoT), artificial intelligence, IoT gateways (smartphones, readers), etc. This review will bring together the different types of smartphone/reader-based biomedical sensors, which have been employing for a wide variety of optical/electrical/electrochemical biosensing applications and paving the way for future eHealth diagnostic devices by moving towards smart biomedical sensing. Here, alongside highlighting the characteristics/criteria that should be met by the developed sensors towards smart biomedical sensing, the challenging issues ahead are delineated along with a comprehensive outlook on this extremely necessary field.

Innovations and Challenges in Electroanalytical Tools for Rapid Biosurveillance of SARS-CoV-2.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, preventive social paradigms and vaccine development have undergone serious renovations, which drastically reduced the viral spread and increased collective immunity. Although the technological advancements in diagnostic systems for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) detection are groundbreaking, the lack of sensitive, robust, and consumer-end point-of-care (POC) devices with smartphone connectivity are conspicuously felt. Despite its revolutionary impact on biotechnology and molecular diagnostics, the reverse transcription polymerase chain reaction technique as the gold standard in COVID-19 diagnosis is not suitable for rapid testing. Today's POC tests are dominated by the lateral flow assay technique, with inadequate sensitivity and lack of internet connectivity. Herein, the biosensing advancements in Internet of Things (IoT)-integrated electroanalytical tools as superior POC devices for SARS-CoV-2 detection will be demonstrated. Meanwhile, the impeding factors pivotal for the successful deployment of such novel bioanalytical devices, including the incongruous standards, redundant guidelines, and the limitations of IoT modules will be discussed.

Towards smart personalized perspiration analysis: An IoT-integrated cellulose-based microfluidic wearable patch for smartphone fluorimetric multi-sensing of sweat biomarkers.

Practical obstacles, such as intricate designs and expensive equipment/materials, in the fabrication of wearable sweat sensors, have limited their feasibility as a personalized healthcare device. Herein, we have fabricated a cellulose-based wearable patch, which further paired with a smartphone-based fluorescence imaging module and a self-developed smartphone app for non-invasive and in situ multi-sensing of sweat biomarkers including glucose, lactate, pH, chloride, and volume. The developed Smart Wearable Sweat Patch (SWSP) sensor comprises highly fluorescent sensing probes embedded in paper substrates, and microfluidic channels consisted of cotton threads to harvest sweat from the skin surface and to transport it to the paper-based sensing probes. The imaging module was fabricated by a 3D printer, equipped with UV-LED lamps and an optical filter to provide the in situ capability of capturing digital images of the sensors via a smartphone. A smartphone app was also designed to quantify the concentration of the biomarkers via a detection algorithm. Additionally, we have recommended an Internet of Things (IoT)-based model for our developed SWSP sensor to promote its potential application for the future. The field studies on human subjects were also conducted to investigate the feasibility of our developed SWSP sensor for the analysis of sweat biomarkers. Our findings convincingly demonstrated the applicability of our developed SWSP sensor as a smart, user-friendly, ultra-low-cost (~0.03 $ per sweat patch), portable, selective, rapid, and non-invasive healthcare monitoring device for immense applications in health personalization, sports performance monitoring, and medical diagnostics.