Point-of-care Research Articles

Improved sensitivity and automation of amulti-step upconversion lateral flow immunoassay using a3D-printed actuation mechanism.

The development of sensitive point-of-care (POC) assay platforms is of interest for reducing the cost and time of diagnostics. Lateral flow assays (LFAs) are the gold standard for POC systems, but their sensitivity as such is inadequate, for example, in the case of cardiac diagnostics. The performance can be improved by incorporating different steps, such as pre-incubation to prolong the interaction time between sample and reporter for immunocomplex formation, and washing steps for background reduction. However, for POC assays, manual steps by the assay conductor are not desired. In this research, upconverting nanoparticles (UCNPs) were coated with poly(acrylic acid) (PAA) and conjugated to anti-cTnI antibodies, yielding non-clustering particles with low non-specific binding. The performance of cTnI-LFA in the PAA-anti-cTnI-UCNPs was compared to thesame UCNPs with a commercial carboxyl surface. A kitchen-timer mechanism was embedded in a 3D-printed housing to produce a low-cost actuator facilitating a timed pre-incubation step for reporter and sample, and a washing step, to enable a multi-step cTnI-LFA with minimized manual labour. PAA-UCNPs showed improved mobility on nitrocellulose compared to those with a commercial surface. The mechanical actuator system was shown to improve sensitivity compared to a labour-intensive multi-step dipstick method, despite pre-incubation occurring during shaking and heating in the dipstick method. The limit of detection decreased from 7.6 to 1.5ng/L cTnI in human plasma. The presented actuator can be easily modified for sensitivity improvement in the LFA for different analytes via pre-incubation and washing steps.

An implementation science focused practice‐based research network for rural community pharmacies: RURAL‐CP

AbstractPractice‐based research networks (PBRNs) support the translation and evaluation of evidence‐based practices and interventions on a large scale and have primarily been used in primary care settings. Few pharmacy PBRNs exist. Our objective is to describe the composition and characteristics of the Rural Research Alliance of Community Pharmacies (RURAL‐CP), which is the first PBRN exclusively for rural community pharmacies. For each enrolled pharmacy, a pharmacist liaison completed a survey that assessed the pharmacy's operational characteristics, including business operations, human resource management, division of clinical responsibilities, technology and enhanced services, organizational context, and research priorities. Additionally, up to five other pharmacy staff members completed a brief survey on organizational context. Descriptive statistics were calculated. As of May 2023, there were 126 pharmacies across seven southeastern states that were enrolled in RURAL‐CP. Most pharmacies (91%) were independent pharmacies and operated 6 days per week (82%). On average, pharmacies employed 10 staff members and most trained student pharmacists. Pharmacies offered valuable services in their community, including immunizations, naloxone dispensing, and medication delivery. Blood glucose testing was the most common point‐of‐care (POC) test offered, and most pharmacies were interested in expanding POC offerings, particularly A1c testing and cholesterol screening. RURAL‐CP pharmacies have, on average, relatively strong organizational contexts and readiness for change. Pharmacists' top research priorities were expansion of clinical services, reimbursement, patient adherence, and addressing diabetes and hypertension. Although not generalizable to all rural pharmacies, results indicate that rural pharmacies deliver many important services in their communities and are interested in increasing services provided.

Implementation of Point of Care Sexually Transmitted Infections Testing in a Community Clinic Setting.

The rates of sexually transmitted infections (STIs) in the United States, including chlamydia and gonorrhea, are rising. Point-of-care (POC) testing could increase access to testing and treatment. This evaluation found POC STI testing to be concordant with the results of traditional laboratory testing for 100% of patients who were tested. Ninety-five percent of the patients reported being satisfied with the experience, and 66% preferred it to traditional laboratory testing. The most commonly reported reason for preferring the test was the short amount of time it took to receive results. However, insurance reimbursed less than 30% of what was billed for the POC tests. Low insurance reimbursement rates could be a barrier to implementation long-term financial sustainability of POC STI testing.

P437 Feasibility study of a Point-of-Care assay for rapid determination of anti-TNFα biologics in capillary blood

Abstract Background Inflammatory bowel disease (IBD) patients benefit from therapeutic drug monitoring and personalized adjustment of anti-TNFα drugs such as adalimumab (ADL) and infliximab (IFX). Commercially available rapid assays allow the fast and easy measurement of ADL and IFX. Unfortunately, most ADL and IFX in-vitro diagnostic assays rely on serum as analyte matrix. This is a critical hurdle in point-of-care (POC) analysis, as it requires laboratory professionals, additional laboratory instruments and is time consuming. Therefore, two recently developed rapid tests for the determination of ADL and IFX that only require capillary blood (CB) or EDTA whole blood (WB) without further treatment are tested in a POC setup at three different study sites. The primary aim of this study is to demonstrate matrix equivalency of CB and EDTA WB compared to serum as reference. Methods This observational study was performed at three sites. Two sites in Switzerland, Clarunis Basel and Kantonsspital Baselland, and one site in France, Centre Hospitalier Universitaire de Saint-Étienne. Sample analysis was performed by healthcare professionals at the study sites with the established Quantum Blue® serum rapid tests and the newly developed capillary blood applications. Blood samples from patients under infliximab therapy were collected directly before infusion (trough level of drug). Samples from adalimumab-treated patients were collected irrespective of the injection schedule. In total, up to 100 IBD patients are anticipated in the study, 50 under infliximab therapy and 50 treated with adalimumab. This work evaluated the interim outcome after the analysis of 29 ADL and 18 IFX patients. Results Bland-Altmann analysis revealed a good agreement of CB and EDTA WB compared to serum for both IFX and ADL sample sets. The mean bias for the biologic’s trough level analysed in CB and compared to serum was 5.2% for IFX and -11.7% for ADL. Passing-Bablok analysis for CB versus serum resulted in a slope of 0.92 and an intercept at 0.08 for IFX and a slope of 0.86 and an intercept at -0.063 for ADL. A comparison of EDTA WB compared to serum revealed a mean bias of 7.8% for IFX and 7.4% for ADL. Passing-Bablok analysis for EDTA WB versus serum resulted in a slope of 1.00 and an intercept at 0.00 for IFX and a slope of 1.00 and an intercept at 0.30 for ADL. Conclusion The newly developed rapid Quantum Blue® assays for the determination of infliximab and adalimumab in capillary blood and EDTA whole blood are very well comparable to the analysis of either biologic in serum. This study furthermore demonstrated the assays are well suited to be used in a POC setting, such as infusion centres, rather than in a laboratory. Both assays are standardized to WHO reference material.

Rapid and visual identification of β-lactamase subtypes for precision antibiotic therapy

The abuse of antibiotics urgently requires rapid identification of drug-resistant bacteria at the point of care (POC). Here we report a visual paper sensor that allows rapid (0.25-3 h) discrimination of the subtypes of β-lactamase (the major cause of bacterial resistance) for precision antibiotic therapy. The sensor exhibits high performance in identifying antibiotic-resistant bacteria with 100 real samples from patients with diverse bacterial infections, demonstrating 100% clinical sensitivity and specificity. Further, this sensor can enhance the accuracy of antibiotic use from 48% empirically to 83%, and further from 50.6% to 97.6% after eliminating fungal infection cases. Our work provides a POC testing platform for guiding effective management of bacterial infections in both hospital and community settings.

Update on point-of-care-based coagulation treatment : Systems, reagents, device-specific treatment algorithms

Viscoelastic test (VET) procedures suitable for point-of-care (POC) testing are in widespread clinical use. Due to the expanded range of available devices and in particular due to the development of new test approaches and methods, the authors believe that an update of the current treatment algorithms is necessary. The aim of this article is to provide an overview of the currently available VET devices and the associated reagents. In addition, two treatment algorithms for the VET devices most commonly used in German-speaking countries are presented.

Epidemiology of Pathogenic Retroviruses and Domestic Cat Hepadnavirus in Community and Client-Owned Cats in Hong Kong.

Understanding the local epidemiology of feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) in Hong Kong will inform retrovirus prevention strategies. Domestic cat hepadnavirus (DCH), a novel hepatitis-B-like virus, is commonly detected among client-owned cats in Hong Kong, but community cats have not been studied. The aims of this study were to investigate the frequency and potential risk factors for (i) FeLV and FIV among community and client-owned cats and (ii) perform molecular detection of DCH among community cats in Hong Kong. Blood samples from 713 cats were obtained from client-owned (n = 415, residual diagnostic) and community cats (n = 298, at trap-neuter-return). Point-of-care (POC) testing for FeLV antigen and feline immunodeficiency virus (FIV) anti-p15 and p24 antibodies was performed. FeLV-positive samples were progressed to p27 sandwich enzyme-linked immunosorbent assay. Whole blood DNA was tested with qPCRs for FeLV U3 and gag, and nested PCRs where additional information was required. DCH qPCR was performed on a subset of community cats (n = 193). A single, regressive, FeLV infection was detected in a client-owned cat (1/415 FeLV U3 qPCR positive, 0.2%, 95% CI 0.0-1.3%). Five/415 client-owned cats tested presumably false FeLV-antigen positive (qPCR negative). No markers of FeLV infection were detected in community cats (0/298; 0%). FIV seroprevalence was much higher in community cats (46/298, 15.4%) than in client-owned cats (13/415, 3.1%) (p < 0.001). Mixed breed was a risk factor for FIV infection in client-owned cats. Neither sex nor age were associated with FIV infection. DCH DNA was detected in 34/193 (17.6%) community cats (median viral load 6.32 × 103 copies/reaction). FeLV infection is rare in Hong Kong, negatively impacting the positive predictive value of diagnostic tests. FeLV-antigen testing remains the screening test of choice, but confirmation of a positive result using FeLV qPCR is essential. FIV infection is common in community cats and the absence of a sex predisposition, seen previously in cats managed similarly, raises questions about virus-transmission dynamics in these groups. DCH infection is very common in Hong Kong, both in client-owned and community cats, highlighting the importance of understanding the pathogenic potential of this virus for cats.

Provider-Reported Barriers in Sexual Health Care Services for Women With Upstream Barriers: The Case of Syphilis and Congenital Syphilis in Southern Colorado, 2022.

Syphilis and congenital syphilis rates have increased sharply in Colorado in the past 5 years. Congenital syphilis is passed during pregnancy in utero and can cause lifelong physical, developmental, and neurologic problems for the child, or can lead to miscarriage, stillbirth, or early infant death. Congenital syphilis is easily prevented if the mother receives timely testing, treatment, and prenatal care. Providers can play a key role in preventing congenital syphilis for women with social vulnerabilities, who have a higher likelihood of syphilis and/or congenital syphilis infection. We surveyed 23 and interviewed 4 health care providers in southern Colorado in 2022 to record their experiences in providing sexual health care services. We asked providers with direct care experience about perceived barriers in effectively treating syphilis. The most significant barriers reported in the survey were the cost of treatment (26%) and the loss to follow-up (22%). Interviews revealed further challenges, including discretionary testing procedures, delays in screening results, treatment referral issues, and stigma around substance use and sexual activity. Elevated syphilis and congenital syphilis rates pose significant public health challenges. Coordinated interventions are necessary to effectively reduce the transmission of syphilis and congenital syphilis among women with upstream barriers. Potential care solutions include expanding rapid, point-of care testing and treatment options, supporting bicillin delivery or web-based inventory systems, offering anti-stigma training for providers, offering mental and behavioral health resources at providers' clinics, and expanding partnerships with syringe access programs.

The diagnostic Accuracy of Visual versus automated dipstick proteinuria testing in Pregnancy: A systematic review and Meta-Analysis

Objective: To evaluate the diagnostic accuracy of point-of-care (POC) tests for detecting proteinuria in pregnant women.Design:Systematic review and meta-analysis.Data Sources:MEDLINE and EMBASE databases were searched from inception to 13 November 2020.Eligibility Criteria and Data Analysis:Included studies measured the sensitivity and specificity ofPOC proteinuria testing compared to laboratory reference standards (protein-creatinine ratio (PCR), 24-hour urine collection). Bivariate meta-analyses determined pooled sensitivity and specificity. Random-effects inverse-variance model determinedheterogeneity.Main Outcome Measures:The primary outcome was overall sensitivity and specificity, stratified by method of POC testing and reference standard. Secondary outcomes were sensitivity and specificity within thesubgroupstest brand, reference standard, and hypertension status.Results: 1078 studies were identified, 17 studies comprising 23 comparisons were included. The meta-analysis included 13 studies with 19 comparisons. Pooled sensitivity and specificity of visual dipsticks against PCR was 72 % (95 % CI: 56 % to 84 %) and 92 % (95 % CI: 76 % to 98 %), respectively. Pooled sensitivity and specificity of visual dipsticks against 24-hour collection was 69 % (55 % to 80 %) and 70 % (51 % to 84 %), respectively. Pooled sensitivity and specificity for automated readers against PCR was 73 % (53 % to 86 %) and 91 % (83 % to 95 %), respectively. Pooled sensitivity and specificity of automated readers against 24-hour collection was 65 % (42 % to 83 %) and 82 % (46 % to 96 %), respectively.Conclusion: Visual dipsticks have comparable accuracy to automated readers, yet are notadequate as a rule-out test for proteinuria. Proteinuria POC testing maybe beneficial inantenatal care when repeatfollow-up tests are performed.PROSPERO Registration Number: CRD42021231914.

Accuracy of a Continuous Glucose Monitor During Pediatric Type 1 Diabetes Inpatient Admissions.

Objective: Continuous glucose monitors (CGMs) used for type 1 diabetes management are associated with lower hemoglobin A1c. CGMs are not approved for inpatient use, when close glucose monitoring and intensive insulin management are essential for optimal health. Accuracy data from adult hospitalizations have been published, but pediatric data are limited. Design and Methods: This retrospective review of Dexcom G6 data from youth with type 1 diabetes during hospitalization assessed CGMs and matched (within 5 min) point-of-care (POC) and laboratory glucose values. Glucose values >400 and <40 mg/dL were excluded due to sensor reporting capabilities. Standard methods for CGM accuracy were used including mean absolute relative difference (MARD), Clarke Error Grids, and percentage of CGM values within 15%/20%/30% if glucose value is >100 mg/dL and 15/20/30 mg/dL if value is ≤100 mg/dL. Results: A total of 1120 POC and 288 laboratory-matched pairs were collected from 83 unique patients (median age 12.0 years, 68.7% non-Hispanic white, 54.2% male) during 100 admissions. For POC values, overall, MARD was 11.8%, that on the medical floor was 13.5%, and that in the intensive care unit was 7.9%. The MARD for all laboratory values was 6.5%. In total, 98% of matched pairs were within Clarke Error Grid A and B zones. Conclusions: Findings from our pediatric population were similar to accuracy reported in hospitalized adults, indicating the potential role for CGM use during pediatric hospitalizations. Additional research is needed to assess accuracy under various conditions, including medication use, as well as development of safe hospital protocols for successful CGM implementation for routine inpatient care.

The Cascade of Care for Early Infant Diagnosis in Zimbabwe: Point of Care HIV Testing at Birth and 6-8 Weeks.

Routine birth testing of HIV-exposed infants (HEI) using point of care (POC) nucleic acid testing may allow for earlier diagnosis and treatment of infants living with HIV, but more data are needed on retention in care for those diagnosed at birth and re-testing for those with a negative HIV birth test. POC birth testing (within 48 hours of birth) was offered to all HEI born at 10 public maternities in Zimbabwe from November 2018 to July 2019. Data were abstracted from routine registers, including information on re-testing at 6-8 weeks for infants testing HIV-negative at birth and 6-month retention in care among infants diagnosed with HIV at birth. Of 2854 eligible HEIs, 2806 (98.3%) received POC HIV birth testing. Thirty-nine infants with HIV were identified (1.4%), and 23 (59%) were started on antiretroviral therapy (ART). Twenty infants (51%) remained on ART at 6 months. Of the 2694 infants who tested negative at birth, 1229 (46.5%) had a documented retest at 6-8 weeks. 7 (0.6%) of those infants tested HIV-positive. The uptake of POC birth testing was high in study facilities, but low rates of ART initiation after a positive birth test, despite high retention on ART through 6 months, diminish the impact of POC birth testing and must be addressed. Among infants who tested negative at birth, rates of testing at 6-8 weeks of life (46%) were slightly lower than national rates of testing at the same age without a birth test (56%) during the study period. Improving infant HIV testing rates at 6-8 weeks, regardless of birth testing, should be a priority.

Pre-hospital rule-out of non-ST-segment elevation acute coronary syndrome by a single troponin: final one-year outcomes of the ARTICA randomised trial.

The healthcare burden of acute chest pain is enormous. In the randomized ARTICA trial, we showed that pre-hospital identification of low-risk patients and rule-out of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) with point-of-care (POC) troponin measurement reduces 30-day healthcare costs with low major adverse cardiac events (MACE) incidence. Here we present the final 1-year results of the ARTICA trial. Low-risk patients with suspected NSTE-ACS were randomized to pre-hospital rule-out with POC troponin measurement or emergency department (ED) transfer. Primary 1-year outcome was healthcare costs. Secondary outcomes were safety, quality of life (QoL), and cost-effectiveness. Safety was defined as a 1-year MACE consisting of ACS, unplanned revascularization, or all-cause death. QoL was measured with EuroQol-5D-5L questionnaires. Cost-effectiveness was defined as 1-year healthcare costs difference per QoL difference. Follow-up was completed for all 863 patients. Healthcare costs were significantly lower in the pre-hospital strategy (€1932±€2784 vs. €2649±€2750), mean difference €717 [95% confidence interval (CI) €347 to €1087; P<0.001]. In the total population, the 1-year MACE rate was comparable between groups [5.1% (22/434) in the pre-hospital strategy vs. 4.2% (18/429) in the ED strategy; P=0.54]. In the ruled-out ACS population, 1-year MACE remained low [1.7% (7/419) vs. 1.4% (6/417)], risk difference 0.2% (95% CI -1.4% to 1.9%; P=0.79). QoL showed no significant difference between strategies. Pre-hospital rule-out of NSTE-ACS with POC troponin testing in low-risk patients is cost-effective, as expressed by a sustainable healthcare cost reduction and no significant effect on QoL. One-year MACE remained low for both strategies.

Microneedle Sensors for Point-of-Care Diagnostics.

Point-of-care (POC) has the capacity to support low-cost, accurate and real-time actionable diagnostic data. Microneedle sensors have received considerable attention as an emerging technique to evolve blood-based diagnostics owing to their direct and painless access to a rich source of biomarkers from interstitial fluid. This review systematically summarizes the recent innovations in microneedle sensors with a particular focus on their utility in POC diagnostics and personalized medicine. The integration of various sensing techniques, mostly electrochemical and optical sensing, has been established in diverse architectures of "lab-on-a-microneedle" platforms. Microneedle sensors with tailored geometries, mechanical flexibility, and biocompatibility are constructed with a variety of materials and fabrication methods. Microneedles categorized into four types: metals, inorganics, polymers, and hydrogels, have been elaborated with state-of-the-art bioengineering strategies for minimally invasive, continuous, and multiplexed sensing. Microneedle sensors have been employed to detect a wide range of biomarkers from electrolytes, metabolites, polysaccharides, nucleic acids, proteins to drugs. Insightful perspectives are outlined from biofluid, microneedles, biosensors, POC devices, and theragnostic instruments, which depict a bright future of the upcoming personalized and intelligent health management.

Point-of-care diagnosis of pre-eclampsia based on microfiber Bragg grating biosensor

Pre-eclampsia is a serious multi-organ complication that severely threatens the safety of pregnant women and infants. To accurate and timely diagnose pre-eclampsia, point-of-care (POC) biosensing of the specific biomarkers is urgently required. However, one of the key biomarkers of pre-eclampsia, placental growth factor (PlGF), has a reduced level of expression in patients, which challenges the quantification capability and Limit-of-detection (LOD) of biosensors. Herein, we reported a microfiber Bragg grating biosensor for the quantification of PlGF in clinical serum samples. The Bragg grating was inscribed in a unilateral tapered fiber to generate the segmented Fabry-Perot spectrum for improving the capability of detection. Furthermore, a temperature-calibrated Bragg grating was added to enable dual parametric detection of PlGF and temperature simultaneously for removing the crosstalk. Finally, the biosensor was envisaged to be perfectly compatible with microfluidic chips, and thus dramatically reducing the sample consumption to as small as 10 μL. The proposed biosensor can respond to PlGF with concentrations ranging from 5 to 120 pg mL−1, attaining a LOD of 5 pg mL−1 of clinical relevance. More importantly, the biosensor achieved micro volume detection of clinical serum samples from patients, and the ROC curve with an AUC of 0.977 confirmed the viability of the device. Our study paves the way to a new idea for cost-effective and high-precision screening of patients with pre-eclampsia, and hence envisages a promising prospect for point-of-care (POC) diagnosis of patients with pre-eclampsia.

Point-of-care potentials of lateral flow-based field screening for Mycoplasma bovis infections: a literature review.

Point-of-care (POC) field screening for tools for Mycoplasma bovis (M. bovis) is still lacking due to the requirement for a simple, robust field-applicable test that does not entail specialized laboratory equipment. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, this review identifies the methodologies that were retrieved based on our search strategy that have been reported for the diagnosis of m. bovis infection between 2014 and diagnostics. A search criterion was generated to curate 103 articles, which were reduced in number (to 46), following the screening guidelines of PRISMA. The 43 articles included in the study present 25 different assay methods. The assay methods were grouped as microbiological culture, serological assay, PCR-based assay, LAMP-based assay, NGS-based assay, or lateral flow assay. We, however, focus our discussion on the three lateral flow-based assays relative to others, highlighting the advantages they present above the other techniques and their potential applicability as a POC diagnostic test for M. bovis infections. We therefore call for further research on developing a lateral flow-based screening tool that could revolutionize the diagnosis of M. bovis infection.

Construction of a label-free electrochemical biosensing system utilizing Fe3O4/α-Fe2O3@Au with magnetic-induced self-assembly for the detection of EGFR glycoprotein

A label-free electrochemical biosensing system was developed for the sensitive detection of epidermal growth factor receptor (EGFR), which was frequently overexpressed in lung cancer, breast cancer, and glioblastoma. Magnetic Fe3O4/α-Fe2O3@Au nanocomposites were utilized as the signal amplifiers and for the immobilization matrix of specific probes (ssDNA-APT) in the biosensors. The Fe3O4/α-Fe2O3@Au/ssDNA-APT biosensors were formed through Au–S binding on this matrix and were immobilized onto a magnetic glassy carbon electrode (MGCE) using magnetic-induced self-assembly. The performance of the EGFR detection system was verified using differential pulse voltammetry (DPV). The system exhibited a wide linear range from 0.1 ng/mL to 1000 ng/mL (R2 = 0.9947), with a limit of detection (LOD) of 0.18 ng/mL. Furthermore, the repeatability, stability, selectivity, and ability for real sample analysis were investigated. With its simplicity and reliability, this biosensing system has the potential to be developed as a valuable tool in clinical EGFR detection, offering a promising candidate for point-of-care (POC) testing.

Photothermal biosensing integrated with microfluidic paper-based analytical device for sensitive quantification of sarcosine

This article presents the development of a photothermal biosensing integrated with microfluidic paper-based analytical device (PT-μPAD) as a quantitative biosensor method for monitoring sarcosine in human control urine, plasma, and serum samples. The device utilizes gold nanoparticles (AuNPs) as both a peroxidase-like nanozyme and a photothermal substrate to enable sarcosine detection. In our PT-μPAD, hydrogen peroxide (H2O2) is generated through the oxidation of sarcosine by a sarcosine oxidase (SOx) enzyme. Subsequently, the H2O2 flows through the paper microchannels to the detection zone, where it etches the pre-deposited AuNPs, inducing a temperature change upon exposure by a 532 nm laser. The temperature variation is then measured using a portable and inexpensive infrared thermometer. Under optimized conditions, we obtained a linear range between 10.0 and 40.0 nmol L−1 (R2 = 0.9954) and a detection limit (LOD) of 32.0 pmol L−1. These values fall within the clinical range for sarcosine monitoring in prostate cancer diagnostics in humans. Moreover, our approach exhibits high selectivity without interfering effects. Recovery studies in various human control samples demonstrated a range of 99.05–102.11 % with the highest RSD of 2.25 %. The PT-μPAD was further validated for sarcosine determination in human control urine and compared with a commercial ELISA assay, revealing no significant difference between these two methods at a 95 % confidence level. Overall, our proposed sarcosine biosensor is well-suited for prostate cancer monitoring, given its affordability, sensitivity, and user-friendliness, even for unskilled individuals. Moreover, this strategy has promising prospects for broader applications, potentially detecting various biomarkers as a point-of-care (POC) diagnostic tool.

Low-Cost Biosensor Technologies for Rapid Detection of COVID-19 and Future Pandemics.

Many systems have been designed for the detection of SARS-CoV-2, which is the virus that causes COVID-19. SARS-CoV-2 is readily transmitted, resulting in the rapid spread of disease in human populations. Frequent testing at the point of care (POC) is a key aspect for controlling outbreaks caused by SARS-CoV-2 and other emerging pathogens, as the early identification of infected individuals can then be followed by appropriate measures of isolation or treatment, maximizing the chances of recovery and preventing infectious spread. Diagnostic tools used for high-frequency testing should be inexpensive, provide a rapid diagnostic response without sophisticated equipment, and be amenable to manufacturing on a large scale. The application of these devices should enable large-scale data collection, help control viral transmission, and prevent disease propagation. Here we review functional nanomaterial-based optical and electrochemical biosensors for accessible POC testing for COVID-19. These biosensors incorporate nanomaterials coupled with paper-based analytical devices and other inexpensive substrates, traditional lateral flow technology (antigen and antibody immunoassays), and innovative biosensing methods. We critically discuss the advantages and disadvantages of nanobiosensor-based approaches compared to widely used technologies such as PCR, ELISA, and LAMP. Moreover, we delineate the main technological, (bio)chemical, translational, and regulatory challenges associated with developing functional and reliable biosensors, which have prevented their translation into the clinic. Finally, we highlight how nanobiosensors, given their unique advantages over existing diagnostic tests, may help in future pandemics.

Impact of point-of-care clinical decision support on referrer behavior, imaging volume, patient radiation dose exposure, and sustainability

ObjectivesWhen referring patients to radiology, it is important that the most appropriate test is chosen to avoid inappropriate imaging that may lead to delayed diagnosis, unnecessary radiation dose, worse patient outcome, and poor patient experience. The current radiology appropriateness guidance standard at our institution is via access to a standalone web-based clinical decision support tool (CDST). A point-of-care (POC) CDST that incorporates guidance directly into the physician workflow was implemented within a subset of head and neck cancer specialist referrers. The purpose of this audit was to evaluate the imaging pathway, pre- and post-implementation to assess changes in referral behavior.MethodsCT and MRI neck data were collected retrospectively to examine the relationship between imaging referrals pre- and post-POC CDST implementation. Effective radiation dose and estimated carbon emissions were also compared.ResultsThere was an overall reduction in absolute advanced imaging volume by 8.2%, and a reduction in duplicate CT and MRI imaging by 61%, p < 0.0001. There was also a shift in ordering behavior in favor of MRI (OR [95% CI] = 1.50 [1.02–2.22], p = 0.049). These changes resulted in an effective radiation dose reduction of 0.27 mSv per patient, or 13 equivalent chest x-rays saved per patient, p < 0.0001. Additionally, the reduction in unnecessary duplicate imaging led to a 13.5% reduction in carbon emissions, p = 0.0002.ConclusionsImplementation of the POC CDST resulted in a significant impact on advanced imaging volume, saved effective dose, and reduction in carbon emissions.Critical relevance statementThe implementation of a point-of-care clinical decision support tool may reduce multimodality ordering and advanced imaging volume, manifesting in reduced effective dose per patient and reduced estimated carbon emissions. Widespread utilization of the point-of-care clinical decision support tool has the potential to reduce imaging wait times.Key points• Implementation of the point-of-care clinical decision support tool reduced the number of patients who simultaneously had a CT and MRI ordered for the same clinical indication compared to a standalone web-based clinical decision support tool.• The point-of-care clinical decision support tool reduced the absolute number of CT/MRI scans requested compared to the standalone web-based clinical decision support tool.• Utilization of the point-of-care clinical decision support tool led to a significant reduction in the effective dose per patient compared to the standalone web-based clinical decision support tool.Graphical

Rapid and reliable diagnosis of Moraxella catarrhalis infection using loop-mediated isothermal amplification-based testing.

Moraxella catarrhalis (M. catarrhalis) was an important pathogen closely associated with respiratory tract infections. We employed the loop-mediated isothermal amplification (LAMP) coupled with nanoparticle-based lateral flow biosensor (LFB) and fluorescence testing technique for formulating two diagnostic methods for M. catarrhalis detection, termed M. catarrhalis-LAMP-LFB assay and M. catarrhalis-LAMP-FRT, respectively. The M. catarrhalis-LAMP-LFB system incorporated the use of biotin-14-dCTP and a forward loop primer (LF) with a hapten at the 5' end. This design in LAMP reaction enabled the production of double-labeled products that could be effectively analyzed using the lateral flow biosensor (LFB). For the M. catarrhalis-LAMP-FRT assay, the LF was modified with a sequence at 5' end, and a fluorophore, as well as a black hole quencher, were strategically labeled at the 5' end and within the middle of the new LF. The restriction endonuclease Nb.BsrDI could accurately recognize and cleave the newly synthesized double-strand terminal sequences, resulting in the separation of the fluorophore from the black hole quencher and releasing fluorescence signals. Both assays have been proven to be highly sensitive and specific, capable of detecting genomic DNA of M. catarrhalis at concentrations as low as 70 fg, with no cross-reactivity observed with non-M. catarrhalis pathogens. Furthermore, both methods successfully identified M. catarrhalis in all clinical samples within 1h that were confirmed positive by real-time PCR, exhibiting superior sensitivity than conventional culture methods. Herein, the newly developed two LAMP-based assays were rapid and reliable for M. catarrhalis detection and hold significant promise for deployment in point-of-care (POC) settings.