Internet-of-medical-things integrated point-of-care biosensing devices for infectious diseases: Toward better preparedness for futuristic pandemics.

Microbial pathogens have threatened the world due to their pathogenicity and ability to spread in communities. The conventional laboratory-based diagnostics of microbes such as bacteria and viruses need bulky expensive experimental instruments and skilled personnel which limits their usage in resource-limited settings. The biosensors-based point-of-care (POC) diagnostics have shown huge potential to detect microbial pathogens in a faster, cost-effective, and user-friendly manner. The use of various transducers such as electrochemical and optical along with microfluidic integrated biosensors further enhances the sensitivity and selectivity of detection. Additionally, microfluidic-based biosensors offer the advantages of multiplexed detection of analyte and the ability to deal with nanoliters volume of fluid in an integrated portable platform. In the present review, we discussed the design and fabrication of POCT devices for the detection of microbial pathogens which include bacteria, viruses, fungi, and parasites. The electrochemical techniques and current advances in this field in terms of integrated electrochemical platforms that include mainly microfluidic- based approaches and smartphone and Internet-of-things (IoT) and Internet-of-Medical-Things (IoMT) integrated systems have been highlighted. Further, the availability of commercial biosensors for the detection of microbial pathogens will be briefed. In the end, the challenges while fabrication of POC biosensors and expected future advances in the field of biosensing have been discussed. The integrated biosensor-based platforms with the IoT/IoMT usually collect the data to track the community spread of infectious diseases which would be beneficial in terms of better preparedness for current and futuristic pandemics and is expected to prevent social and economic losses.

Epitope imprinted polymeric materials: application in electrochemical detection of disease biomarkers.

Epitope imprinting is a promising method for creating specialized recognition sites that resemble natural biorecognition elements. Epitope-imprinted materials have gained a lot of attention recently in a variety of fields, including bioanalysis, drug delivery, and clinical therapy. The vast applications of epitope imprinted polymers are due to the flexibility in choosing monomers, the simplicity in obtaining templates, specificity toward targets, and resistance to harsh environments along with being cost effective in nature. The "epitope imprinting technique," which uses only a tiny subunit of the target as the template during imprinting, offers a way around various drawbacks inherent to biomacromolecule systems i.e., traditional molecular imprinting techniques with regards to the large size of proteins, such as the size, complexity, accessibility, and conformational flexibility of the template. Electrochemical based sensors are proven to be promising tool for the quick, real-time monitoring of biomarkers. This review unravels epitope imprinting techniques, approaches, and strategies and highlights the applicability of these techniques for the electrochemical quantification of biomarkers for timely disease monitoring. In addition, some challenges are discussed along with future prospective developments.

MXene-modified molecularly imprinted polymers as an artificial bio-recognition platform for efficient electrochemical sensing: progress and perspectives.

The development of efficient electrochemical sensors of exceptional features, molecularly imprinted polymers (MIPs), has been extensively utilized due to their great vitality as an alternative to bio-recognition elements. MIPs as an artificial bio-recognition element are getting significant attention due to their affordability, easy processability, and scaling-up capabilities. However, the challenge of longer stability and higher sensitivity associated with MIP-based sensing technology is still a remaining challenge. This can be addressed by modifying MIPs with electro-active nano-systems. Correspondingly, MXene is an emerging material of choice to make MIP-based sensing platforms more efficient and develop a bio-active-free sensing system. This review highlights state-of-the-art MXene-modified MIP electrochemical sensing platforms to overcome the associated limitations of pristine MIPs. As a proof-of-concept, the sensitive and selective detection of markers for health monitoring can be efficiently fulfilled by the high-performance MXene-MIP nanocomposite-based electrochemical sensor. Moreover, the challenges associated with this research area along with the potential solutions are also discussed. An attempt has been made to explore MXene-MIP nanocomposites as a next-generation sensing platform suitable for point-of-care testing (POCT) applications.

Next-Generation Intelligent MXene-Based Electrochemical Aptasensors for Point-of-Care Cancer Diagnostics.

Delayed diagnosis of cancer using conventional diagnostic modalities needs to be addressed to reduce the mortality rate of cancer. Recently, 2D nanomaterial-enabled advanced biosensors have shown potential towards the early diagnosis of cancer. The high surface area, surface functional groups availability, and excellent electrical conductivity of MXene make it the 2D material of choice for the fabrication of advanced electrochemical biosensors for disease diagnostics. MXene-enabled electrochemical aptasensors have shown great promise for the detection of cancer biomarkers with a femtomolar limit of detection. Additionally, the stability, ease of synthesis, good reproducibility, and high specificity offered by MXene-enabled aptasensors hold promise to be the mainstream diagnostic approach. In this review, the design and fabrication of MXene-based electrochemical aptasensors for the detection of cancer biomarkers have been discussed. Besides, various synthetic processes and useful properties of MXenes which can be tuned and optimized easily and efficiently to fabricate sensitive biosensors have been elucidated. Further, futuristic sensing applications along with challenges will be deliberated herein.

High throughput molecularly imprinted polymers based electrochemical nanosensors for point-of-care diagnostics of COVID-19.

The importance of early diagnosis of infectious disease has been revealed well by the COVID-19 pandemic. The current methods for testing SARS-CoV-2 mainly utilize biorecognition elements. The process of production of these biorecognition elements is not only tedious, time-consuming but also costly. The molecularly imprinted polymers recently have gained considerable attention as they are stable and also offer high selectivity and specificity than conventional labels. The present review discussed the MIPs-based electrochemical nano-sensors diagnostic of SARS-CoV-2.

TG/HDL Ratio: A marker for insulin resistance and atherosclerosis in prediabetics or not?

BACKGROUND: The spectrum of Diabetes Mellitus and various complications associated with it have been regarded as major global health challenges. Raised TG/HDL has been regarded as one of the valid markers for Insulin resistance. It leads to increased risk of CVD by causing Insulin resistance and also by its own effect on the vessel wall. Detection of raised TG/HDL ratio and early intervention before the patients develop clinical disease can help in mitigation of future consequences of CVD. AIMS: The aim of our study was to compare TG/HDL ratio between prediabetics and controls and further to look for any correlation between the TG/HDL ratio value with HOMA-IR and Carotid Intima Media Thickness (CIMT) in prediabetics. SETTINGS AND DESIGNS: A cross sectional study. METHODS AND MATERIAL: Study was done at ABVIMS and Dr RML Hospital, New Delhi. 60 prediabetics and 60 age, sex, BMI matched controls were employed. In both cases and controls fasting and postprandial blood glucose, glycated Hemoglobin (HbA1C) and fasting Insulin levels were measured. HOMA-IR values in both the groups were calculated using fasting glucose and Insulin levels. Serum lipid profile was obtained and TG/HDL ratio was analysed in two groups. Values obtained were compared between the two groups. CIMT was only measured in cases using B mode ultrasonography. STATISTICAL ANALYSIS AND RESULTS: Median (IQR) of fasting plasma Insulin (µIU/ml) in cases was 11.3 (10.175-13.505) versus that in controls being 5.73 (4.3-7.1). HOMA-IR (IQR) values in cases and controls were 3.12 (2.73 - 3.595) and 1.21 (0.918 - 1.505) respectively. Median (IQR) for TG/HDL ratio was 3.26 (2.712 - 4) for cases and 2.05 (1.755- 2.502) for controls. However no correlation was observed between either the mean CIMT (mm) or HOMA-IR with TG/HDL ratio. CONCLUSIONS: Diabetes Mellitus and its various complications are of a great burden to society. Diagnosing the risk factors early before the onset of these manifestations can help us in combating these major issues. One of the risk factors among them is raised TG/HDL ratio. Early detection of elevated TG/HDL in prediabetics may serve in early detection of atherosclerotic complications and help physicians in framing primary preventive strategies for tackling ASCVD in patients with prediabetes and full-blown Diabetes.

Transthyretin - A Novel Biomarker for Insulin Resistance and Atherosclerosis Risk in Prediabetics.

OBJECTIVE: The aim of the study was to compare serum levels of Transthyretin in prediabetics and controls and to correlate levels of same with HOMA-IR and mean CIMT Method: It was a case control study in which 60 prediabetic patients and 60 controls (age, sex, BMI matched) were employed. Plasma levels of glucose (fasting and postprandial), glycated hemoglobin (HbA1c), and serum levels of insulin (fasting) were measured in both cases and controls. HOMA-IR values in both the groups were calculated using fasting plasma glucose and serum insulin levels. Serum Transthyretin levels were measured using ELISA. The values obtained were compared between cases and controls. In cases, obtained serum levels of Transthyretin were correlated with HOMA-IR values and mean CIMT (measured in cases only using B-mode ultrasonography). RESULTS: Median (IQR) of serum levels of insulin (fasting in µIU/ml) in cases {11.3 (10.175-13.505)} was significantly higher than that of controls {5.73 (4.3-7.1)}. HOMA-IR median (IQR) in cases and controls was 3.12 (2.73-3.595) and 1.21(0.918- 1.505) respectively. Median (IQR) for serum levels of Transthyretin was also significantly higher in cases as compared to controls [46.74 (30.43-81.225) and 22.38 (16.628-27.89) respectively]. Significant positive correlations were observed between serum levels of Transthyretin with both HOMA-IR and mean CIMT (with correlation coefficients being 0.288 and 0.536 respectively). Univariate linear regression analysis showed that with increase in serum Transthyretin by 1 mg/ dl, mean CIMT increases by 0.001 mm. CONCLUSION: Individuals with impaired glucose tolerance have been found to have increased risk of atherosclerosis as compared to normoglycemics after excluding other risk factors. Assessment for the risk of same with the help of novel markers can help in diagnosis and intervention at an early stage and thereby preventing risk of further complications.

Serum Retinol Binding Protein-4 Levels in Prediabetics - Novel Biomarker of Insulin Resistance and Atherosclerosis.

BACKGROUND: Atherosclerotic cardiovascular diseases are the leading cause of morbidity and mortality in both diabetics and prediabetics. In insulin resistant states, increased levels of various adipose derived cytokine (adipokine) have been found to have an important role in the process of atherosclerosis. One such novel adipokine is RBP4, (belonging to lipokalin family) which also by exerting an inflammatory process has a role in the pathogenesis of insulin resistance and CVD.. Early detection of all these inflammatory cytokines may immensely help us in prognosticating the pace of disease besides instituting early interventional manuevers. OBJECTIVE: The aim of the study was to compare serum levels of RBP4 in prediabetics and controls and to correlate levels of RBP4 with HOMA-IR and CIMT. METHODS: 60 prediabetic patients and 60 age, sex, BMI matched controls were employed in the case control study. In both cases and controls serum levels of fasting and postprandial blood glucose, glycated hemoglobin (HbA1c) and fasting insulin levels were measured. HOMA-IR values in both the groups were calculated using fasting glucose and insulin levels. Serum RBP4 levels were measured using ELISA. The values obtained were compared between cases and controls. CIMT was only measured in cases using B-mode ultrasonography. RESULTS: Median (IQR) of fasting plasma insulin levels (uIU/ml)in cases was 11.3 (10.175-13.505) versus that of controls which was 5.73 (4.3-7.1). HOMA-IR median (IQR) in cases and controls was 3.12 (2.73-3.595) and 1.21(0.918-1.505) respectively. Median (IQR) for RBP4 in cases was 67.4 (46.166-111.088) which was significantly higher as compared to controls 33.92 (23.902-52.45). Significant positive correlation was seen between RBP4 with both, HOMA-IR and mean CIMT with correlation coefficients of 0.3693 and 0.621 respectively. On performing univariate linear regression analysis it was found that with increase in serum RBP4 levels by 1 mg/L, HOMA-IR and mean CIMT significantly increased by 0.007 units and 0.001 mm respectively. METHODS: 60 prediabetic patients and 60 age, sex, BMI matched controls were employed in the case control study. In both cases and controls serum levels of fasting and postprandial blood glucose, glycated hemoglobin (HbA1c) and fasting insulin levels were measured. HOMA-IR values in both the groups were calculated using fasting glucose and insulin levels. Serum RBP4 levels were measured using ELISA. The values obtained were compared between cases and controls. CIMT was only measured in cases using B-mode ultrasonography. CONCLUSION: Prediabetics have been found to have more risk of cardiovascular events as compared to normoglycemics. Early assessment of the same with the use of novel biomarkers like RBP4 can be considered for early detection of atherosclerosis in prediabetic individuals. It may further help in early intervention and thus prevention from future complications.

Rapid diagnosis of SARS-CoV-2 using potential point-of-care electrochemical immunosensor: Toward the future prospects.

Coronavirus disease (COVID-19) is an emerging and highly infectious disease making global public health concern and socio-economic burden. It is caused due to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). It has the tendency to spread rapidly through person-to-person. Currently, several molecular diagnostic platforms such as PCR, qRT-PCR, reverse transcription loop-mediated isothermal amplification (RT-LAMP), CRISPR are utilized for the diagnosis of SARS-CoV-2. These conventional techniques are costly, time consuming and require sophisticated instrumentation facility with well trained personnel for testing. Hence, it is tough to provide testing en-masse to the people in developing countries. On the other hand, several serological biosensors such as lateral flow immunosensor, optical, electrochemical, microfluidics integrated electrochemical/fluorescence is currently utilized for the diagnosis of SARS-CoV-2. In current pandemic situation, there is an urgent need of rapid and efficient diagnosis on mass scale of SARS-CoV-2 for early stage detection. Early monitoring of viral infections can help to control and prevent the spreading of infections in large chunk of population. In this review, the SARS-CoV-2 and their biomarkers in biological samples, collection of samples and recently reported potential electrochemical immunosensors for the rapid diagnosis of SARS-CoV-2 are discussed.

SERS Based Lateral Flow Immunoassay for Point-of-Care Detection of SARS-CoV-2 in Clinical Samples.

The current scenario, an ongoing pandemic of COVID-19, places a dreadful burden on the healthcare system worldwide. Subsequently, there is a need for a rapid, user-friendly, and inexpensive on-site monitoring system for diagnosis. The early and rapid diagnosis of SARS-CoV-2 plays an important role in combating the outbreak. Although conventional methods such as PCR, RT-PCR, and ELISA, etc., offer a gold-standard solution to manage the pandemic, they cannot be implemented as a point-of-care (POC) testing arrangement. Moreover, surface-enhanced Raman spectroscopy (SERS) having a high enhancement factor provides quantitative results with high specificity, sensitivity, and multiplex detection ability but lacks in POC setup. In contrast, POC devices such as lateral flow immunoassay (LFIA) offer rapid, simple-to-use, cost-effective, reliable platform. However, LFIA has limitations in quantitative and sensitive analyses of SARS-CoV-2 detection. To resolve these concerns, herein we discuss a unique modality that is an integration of SERS with LFIA for quantitative analyses of SARS-CoV-2. The miniaturization ability of SERS-based devices makes them promising in biosensor application and has the potential to make a better alternative of conventional diagnostic methods. This review also demonstrates the commercially available and FDA/ICMR approved LFIA kits for on-site diagnosis of SARS-CoV-2.

Serum Heart Type Fatty Acid Binding Protein Levels in Prediabetes-An Invaluable Cardiovascular Biomarker.

BACKGROUND: The pathophysiological effects of diabetes on the heart and the rest of the cardiovascular system begins much earlier in its precedent stage of prediabetes and one major underlying defect is insulin resistance. Heart-type fatty acid binding protein (H-FABP) is a recently studied molecule inherent to the cardiac myocytes found to rise in both coronary and non-coronary heart diseases. The utility of the molecule in prediabetes and its relationship with insulin resistance is being studied. OBJECTIVE: The aim of the study is to compare serum levels of H-FABP in prediabetics and controls and correlate them with Homeostatic model assessment - insulin resistance (HOMA-IR). METHODS: 50 prediabetic patients and 50 age, sex and BMI matched controls were employed in the case control study. Serum fasting and postprandial blood sugars, glycosylated hemoglobin (HbA1c), fasting insulin levels were measured in cases and controls. HOMA-IR index was calculated from fasting glucose and insulin values. Serum H-FABP was measured in both cases and controls using Immunoturbidimetric method with anti- H-FABP coated latex reagent kits. The values were compared between both the groups. RESULTS: The mean serum fasting insulin level among cases was 12.22mIU/ml and that of the control group was 5.37mIU/ml (p value <0.0001). HOMA- IR mean values were 3.31 ± 1.56 and 1.16 ± 0.44 in cases and controls respectively (p- <0.001). The mean serum levels of H-FABP among cases and controls were 6.38± 2.76ng/ml and 3.24 ± 2.47 ng/ml respectively (p <0.0001). The correlation between the two variables, HOMA-IR and H-FABP was also found to be strongly positive (r=0.675). Linear regression analysis showed that for 1 unit increase in HOMA-IR, H-FABP increased by 1.095 and for 1 unit increase in Fasting insulin, H-FABP increased by 0.038. CONCLUSION: Prediabetics have a higher risk of cardiovascular morbidity when compared to normoglycemics with insulin resistance being the single most important contributor. Serum H-FABP levels are elevated in prediabetes representing a marker of subclinical cardiovascular disease (CVD).