Electrochemical biosensors for point-of-care testing

Point-of-care testing(POCT)is the practice of diagnosing and monitoring diseases where the patient is located,as opposed to traditional treatment conducted solely in a medical laboratory or other clinical setting.POCT has been less common in the recent past due to a lack of portable medical devices capable of facilitating effective medical testing.However,recent growth has occurred in this field due to advances in diagnostic technologies,device miniaturization,and progress in wearable electronics.Among these developments,electrochemical sensors have attracted interest in the POCT field due to their high sensitivity,compact size,and affordability.They are used in various applications,from disease diagnosis to health status monitoring.In this paper we explore recent advancements in electrochemical sensors,the methods of fabricating them,and the various types of sensing mechanisms that can be used.Furthermore,we delve into methods for immobilizing specific biorecognition elements,including enzymes,antibodies,and aptamers,onto electrode surfaces and how these sensors are used in real-world POCT settings.

Wave-shaped microfluidic chip assisted point-of-care testing for accurate and rapid diagnosis of infections

Background:Early diagnosis and classification of infections increase the cure rate while decreasing complications,which is significant for severe infections,especially for war surgery.However,traditional methods rely on laborious operations and bulky devices.On the other hand,point-of-care(POC)methods suffer from limited robustness and accuracy.Therefore,it is of urgent demand to develop POC devices for rapid and accurate diagnosis of infections to fulfill on-site militarized requirements.Methods:We developed a wave-shaped microfluidic chip(WMC)assisted multiplexed detection platform(WMC-MDP).WMC-MDP reduces detection time and improves repeatability through premixing of the samples and reaction of the reagents.We further combined the detection platform with the streptavidin–biotin(SA-B)amplified system to enhance the sensitivity while using chemiluminescence(CL)intensity as signal readout.We realized simultaneous detection of C-reactive protein(CRP),procalcitonin(PCT),and interleukin-6(IL-6)on the detection platform and evaluated the sensitivity,linear range,selectivity,and repeatability.Finally,we finished detecting 15 samples from volunteers and compared the results with commercial ELISA kits.Results:Detection of CRP,PCT,and IL-6 exhibited good linear relationships between CL intensities and concentrations in the range of 1.25–40μg/ml,0.4–12.8 ng/ml,and 50–1600 pg/ml,respectively.The limit of detection of CRP,PCT,and IL-6 were 0.54μg/ml,0.11 ng/ml,and 16.25 pg/ml,respectively.WMC-MDP is capable of good adequate selectivity and repeatability.The whole detection procedure takes only 22 min that meets the requirements of a POC device.Results of 15 samples from volunteers were consistent with the results detected by commercial ELISA kits.Conclusions:WMC-MDP allows simultaneous,rapid,and sensitive detection of CRP,PCT,and IL-6 with satisfactory selectivity and repeatability,requiring minimal manipulation.However,WMC-MDP takes advantage of being a microfluidic device showing the coefficients of variation less than 10%enabling WMC-MDP to be a type of point-of-care testing(POCT).Therefore,WMC-MDP provides a promising alternative to POCT of multiple biomarkers.We believe the practical application of WMC-MDP in militarized fields will revolutionize infection diagnosis for soldiers.

A Point-of-Care Test System for Biochemical Blood Analysis Based on ADUC824

A point-of-care test system has been studied in this paper.It was used to determine substances in blood such as Hemoglobin (HB),Aspartate Aminotransferase (AST),Creatine Kinase (CK) and so on.Based on the principle of amperometric determination,the research on detecting weak current signals was carried on.At the same time as to the weak signals (nA level),magnifying,sampling and processing the signals were also studied.Controlled by ADUC824 and assisted by other units, every substance could be determined automatically and rapidly integrated with the corresponding biosensor.In the experiment, the minimum detectable current of the instrument (YT2005-1) is 0.2 nA.With regard to the 1 nA which the experiment demanded,it could be up to the mustard.And the system can provide results in 180 s with a long term stability.

A smartphone-based automated fluorescence analysis system for point-of-care testing of Hg(Ⅱ)

This work demonstrates a smartphone-based automated fluorescence analysis system(SAFAS)for point-of-care testing(POCT)of Hg(Ⅱ).This system consists of three modules.The smartphone module is used to provide an excitation light source,and to collect and analyze fluorescent images.The dark box module is applied to integrate the desired optical elements and offers a dark environment.The cost of the integrated dark box mainly includes the upper cover,box body,lower bottom,¯xture and some optical elements which is about$109.The chip module is used for fluorescence sensing,which is composed of an upper plate,bottom plate and cloth-based chip.Due to the integration of multiple smartphone functions,the SAFAS eliminates the need for additional power sources,light sources and analysis systems.The dark box and upper and bottom plates are made by 3D printer.The cloth-based chip(about$0.005 for each chip)is fabricated using the wax screenprinting technique,with no need for expensive and complex fabrication equipments.To our knowledge,the cloth-based microfluidic fluorescence detection method combined with smartphone functions is first reported.By using optimal conditions,the designed system can realize the quantitative detection of Hg(Ⅱ),which has a linear range of 0.001–100μgmL^(-1)and a detection limit of 0.5 ngmL^(-1).Additionally,the SAFAS has been successfully applied for detecting Hg(Ⅱ)in actual water samples,with recoveries of 100.1%–111%,RSDs of 3.88%–9.74%,and fast detection time of about 1 min.Obviously,the proposed SAFAS has the advantages of high sensitivity,wide dynamic range,acceptable reproducibility,good stability and low cost.Therefore,it is believed that the presented SAFAS has great potential to perform the POCT of Hg(II)in different water samples.

Point-of-Care Testing Using Three Dimensional Optical Biosensor Based on Microfluidic Technology

We have presented a three dimensional optical protein chip that fulfills the demanding for point-of-care diagnostics in terms of ease-of-use (one step assay), miniaturization (5 μl). The artful combination of magnetic nanoparticles on chip and total internal reflection imaging (TIRI) technology permits the sensitive and rapid detection of hs-CRP (high-sensitivity C-reactive protein). The whole test was complete within 10 min using “all in one step” assay with a limit of detection of 0.1 ng/mL hs-CRP. The measuring range for hs-CRP could be extended to 10 ng/mL. The chip can also be used to detect more parameters in blood samples.

Point-of-Care Testing vs. Laboratory Testing during High Patient Volume Situations

Introduction: Our aim was to determine what patient volume, if any, in-laboratory testing provides results faster than Point-of-Care-Testing (POCT). Methods: To evaluate POCT effectiveness during high volume situations, POCT was compared to in-laboratory testing during busy periods with large numbers of patients. Our setting was an urban level 1 trauma center with an academic emergency medicine department (ED) and annual patient volume of 70,000. Patients seen requiring laboratory testing during peak volume between 11 a.m. and 7 p.m. were enrolled over a five-week period. One tube of blood was sent to the laboratory and the other tube was run in the ED using POCT. Turnaround time was recorded as time from when the tube was received to when the result was available. We also completed a time-motion study to assess the number of POCT machines that would be needed to process the entire average hourly hospital laboratory volume. Results: We collected 539 hematology and chemistry specimens. The POCT group was significantly faster than in-laboratory testing, with mean POCT [complete blood count (CBC) and chemistry] 3.5 minutes compared to in-laboratory CBC test time of 30.9 minutes and chemistry test time of 55 minutes. As the volume of samples peaked, there was a slight but insignificant decrease in POCT turnaround time. If POCT was used to process the entire average hospital laboratory volume which approached 54 samples an hour, 3 POCT machines would be necessary to maintain turnaround times. Conclusion: Even during ED high volume situations, POCT provided results significantly faster than in-laboratory testing.

Recent progress on rapid diagnosis of COVID-19 by point-of-care testing platforms

The outbreak of COVID-19 has drawn great attention around the world.SARS-CoV-2 is a highly infectious virus with occult transmission by many mutations and a long incubation period.In particular,the emergence of asymptomatic infections has made the epidemic even more severe.Therefore,early diagnosis and timely management of suspected cases are essential measures to control the spread of the virus.Developing simple,portable,and accurate diagnostic techniques for SARS-CoV-2 is the key to epidemic prevention.The advantages of point-of-care testing technology make it play an increasingly important role in viral detection and screening.This review summarizes the point-of-care testing platforms developed by nucleic acid detection,immunological detection,and nanomaterial-based biosensors detection.Furthermore,this paper provides a prospect for designing future highly accurate,cheap,and convenient SARS-CoV-2 diagnostic technology.

SPEED:an integrated,smartphone-operated,handheld digital PCR Device for point-of-care testing

This study elaborates on the design,fabrication,and data analysis details of SPEED,a recently proposed smartphonebased digital polymerase chain reaction(dPCR)device.The dPCR chips incorporate partition diameters ranging from 50μm to 5μm,and these partitions are organized into six distinct blocks to facilitate image processing.Due to the superior thermal conductivity of Si and its potential for mass production,the dPCR chips were fabricated on a Si substrate.A temperature control system based on a high-power density Peltier element and a preheating/cooling PCR protocol user interface shortening the thermal cycle time.The optical design employs four 470 nm light-emitting diodes as light sources,with filters and mirrors effectively managing the light emitted during PCR.An algorithm is utilized for image processing and illumination nonuniformity correction including conversion to a monochromatic format,partition identification,skew correction,and the generation of an image correction mask.We validated the device using a range of deoxyribonucleic acid targets,demonstrating its potential applicability across multiple fields.Therefore,we provide guidance and verification of the design and testing of the recently proposed SPEED device.

Recent Advances and Applications in Paper-Based Devices for Point-of-Care Testing

Point-of-care testing(POCT),as a portable and user-friendly technology,can obtain accurate test results immediately at the sampling point.Nowadays,microfluidic paper-based analysis devices(μPads)have attracted the eye of the public and accelerated the development of POCT.A variety of detection methods are combined withμPads to realize precise,rapid and sensitive POCT.This article mainly introduced the development of electrochemistry and optical detection methods onμPads for POCT and their applications on disease analysis,environmental monitoring and food control in the past 5 years.Finally,the challenges and future development prospects ofμPads for POCT were discussed.

Paper-Based Electrochemical Biosensors for Point-of-Care Testing of Neurotransmitters

Abstract Neurotransmitters are important biological molecules related to several nervous system diseases(NSDs).Point-of-care test-ing(POCT)of neurotransmitters is of great importance in preclinical research and early diagnosis of NSDs.Among various POCT platforms,paper-based electrochemical biosensors have achieved great advances in detection of neurotransmitters,thus taking a significant role in POCT of neurotransmitters nowadays.This review gives an overview of the recent advances of paper-based electrochemical biosensors for POCT of neurotransmitters.We first introduce the types of neurotransmitters and biological sample sources mainly used for neurotransmitter detection.Second,we review the components and the traditional fabrication technologies for paper-based electrochemical POCT biosensors,and then the functional modification methods of biosensor surfaces and three-dimensional fabrication methods for further enhancement of their detection performance.Then,we list examples of paper-based electrochemical biosensors used for detecting different neurotransmitters in biologi-cal samples.Last,we give a conclusion and promising development direction of paper-based electrochemical biosensors for neurotransmitters detection.The purpose of this review is to introduce the paper-based electrochemical biosensors as an emerging technology for POCT of neurotransmitters,offering a reference for readers and researchers for early diagnosis of NSDs using POCT technologies.

Point-of-care testing for lysine concentration in swine serum via blue-emissive carbon dot-entrapped microfluidic chip

Lysine is one of the essential amino acids and plays a vital role in the growth,development and health of pigs.Blood lysine concentration is a direct indication of lysine status;however,current methods can not satisfy the demands for rapid and on-site lysine concentration measurement of swine serum.Here,we developed blue-emissive nitrogen-doped carbon dots as a fluorescence probe for the determination of lysine with high fluorescence quantum yield,stability,sensitivity and specificity.The carbon dots were entrapped within hydrogel microstructures to fabricate microfluidic chips for rapid assay for lysine quantification.We further developed an imaging attachment to integrate the microfluidic chip and a smartphone into a portable point-of-care testing platform.This platform requires only 3μL sample and has a linear detection range of 25 to 300μmol/L with a limit of detection less than 16μmol/L,which covers the normal range of lysine concentration in swine serum.We tested lysine concentration in swine serum using this platform with high accuracy,low sample consumption,and within 3 min.Together,these results may provide a rapid and portable platform for dynamic monitoring of swine lysine status and contribute to precise feed formula modulation with low-protein diet strategy.

Rapid Absolute Determination Platform of Nucleic Acid for Point-of-care Testing

Nowadays nucleic acid tests are promising to be considered as point-of-care testing（POCT）. However, no such devices are currently available that can perform all the functions, including absolute nucleic acid determination, worldwide on-site detection, rapid analysis and real-time results reporting via ubiquitous mobile networks simultaneously with full package and automated means of measurement. In this study, we presented a compact low-cost portable POC automated testing platform with all attributes mentioned above. A disposable self-priming compartmentalization（SPC） microfluidic chip is used to conduct isothermal amplification. The platform also includes a micro-computer controlled heating unit, an inexpensive optical imaging setup, and a mobile device with customized software. It may become a useful tool for the rapid on-site detection of infectious diseases as well as other pathogens.

Evaluation of hand infections in the emergency department using point-of-care ultrasound

BACKGROUND:We aimed to evaluate the utility of point-of-care ultrasound(POCUS)in the assessment of hand infections that present to the emergency department(ED)and its impact on medical decision making and patient management.METHODS:We conducted a retrospective review of patients who presented to two urban academic EDs with clinical presentations concerning for skin and soft tissue infections(SSTI)of the hand between December 2015 and December 2021.Two trained POCUS fellowship physicians reviewed an ED POCUS database for POCUS examinations of the hand.We then reviewed patients’electronic health records(EHR)for demographic characteristics,history,physical examination findings,ED course,additional imaging studies,consultations,impact of POCUS on patient care and final disposition.RESULTS:We included a total of 50 cases(28 male,22 female)in the final analysis.The most common presenting symptoms and exam findings were pain(100%),swelling(90%),and erythema(74%).The most common sonographic findings were edema(76%),soft tissue swelling(78%),and fluid surrounding the tendon(57%).POCUS was used in medical decision making 68%of the time(n=34),with the use of POCUS leading to changes in management 38%of the time(n=19).POCUS use led to early antibiotic use(11/19),early consultation(10/19),and led to the performance of a required procedure(8/19).The POCUS diagnosis was consistent with the discharge diagnosis of flexor tenosynovitis 8/12 times,abscess 12/16 times,and cellulitis 14/20 times.CONCLUSION:POCUS is beneficial for evaluating of hand infections that present to the ED and can be used as an important part of medical decision making to expedite patient care.

Seeing beneath the surface:Harnessing point-of-care ultrasound for internal jugular vein evaluation

Point-of-care ultrasound(POCUS)of the internal jugular vein(IJV)offers a noninvasive means of estimating right atrial pressure(RAP),especially in cases where the inferior vena cava is inaccessible or unreliable due to conditions such as liver disease or abdominal surgery.While many clinicians are familiar with visually assessing jugular venous pressure through the internal jugular vein,this method lacks sensitivity.The utilization of POCUS significantly enhances the visualization of the vein,leading to a more accurate identification.It has been demonstrated that combining IJV POCUS with physical examination enhances the specificity of RAP estimation.This review aims to provide a comprehensive summary of the various sonographic techniques available for estimating RAP from the internal jugular vein,drawing upon existing data.

Point-of-care continuous ^(13)C-methacetin breath test improves decision making in acute liver disease: Results of a pilot clinical trial

AIM: To assess the role of the 13C-methacetin breath test (MBT) in patients with acute liver disease. METHODS: Fifteen patients with severe acute liver disease from diverse etiologies were followed-up with 13C-MBT during the acute phase of their illnesses (range 3-116 d after treatment). Patients fasted for 8 h and ingested 75 mg of methacetin prior to the MBT. We compared results from standard clinical assessment, serum liver enzymes, synthetic function, and breath test scores. RESULTS: Thirteen patients recovered and two patients died. In patients that recovered, MBT parameters improved in parallel with improvements in lab results. Evidence of consistent improvement began on day 3 for MBT parameters and between days 7 and 9 for blood tests. Later convergence to normality occurred at an average of 9 d for MBT parameters and from 13 to 28 d for blood tests. In both patients that died, MBT parameters remained low despite fluctuating laboratory values. CONCLUSION: The 13C-MBT provides a rapid, noninvasive assessment of liver function in acute severe liver disease of diverse etiologies. The results of this pilot clinical trial suggest that the MBT may offer greater sensitivity than standard clinical tests for managing patients with severe acute liver disease.

Point-of-care ultrasonography in cirrhosis-related acute kidney injury:How I do it

Discerning the etiology of acute kidney injury(AKI)in cirrhotic patients remains a formidable challenge due to diverse and overlapping causes.The conventional approach of empiric albumin administration for suspected volume depletion may inadvertently lead to fluid overload.In the recent past,point-of-care ultrasonography(POCUS)has emerged as a valuable adjunct to clinical assessment,offering advantages in terms of diagnostic accuracy,rapidity,cost-effectiveness,and patient satisfaction.This review provides insights into the strategic use of POCUS in evaluating cirrhotic patients with AKI.The review distinguishes basic and advanced POCUS,emphasizing a 5-point basic POCUS protocol for efficient assessment.This protocol includes evaluations of the kidneys and urinary bladder for obstructive nephropathy,lung ultrasound for detecting extravascular lung water,inferior vena cava(IVC)ultrasound for estimating right atrial pressure,internal jugular vein ultrasound as an alternative to IVC assessment,and focused cardiac ultrasound for assessing left ventricular(LV)systolic function and identifying potential causes of a plethoric IVC.Advanced POCUS delves into additional Doppler parameters,including stroke volume and cardiac output,LV filling pressures and venous congestion assessment to diagnose or prevent iatrogenic fluid overload.POCUS,when employed judiciously,enhances the diagnostic precision in evaluating AKI in cirrhotic patients,guiding appropriate therapeutic interventions,and minimizing the risk of fluid-related complications.

Point-of-care ultrasonography spotlight:Could venous excess ultrasound serve as a shared language for internists and intensivists?

Point-of-care ultrasonography(POCUS),particularly venous excess ultrasound(VExUS)is emerging as a valuable bedside tool to gain real-time hemodynamic insights.This modality,derived from hepatic vein,portal vein,and intrarenal vessel Doppler patterns,offers a scoring system for dynamic venous congestion assessment.Such an assessment can be crucial in effective management of patients with heart failure exacerbation.It facilitates diagnosis,quantification of congestion,prognostication,and monitoring the efficacy of decongestive therapy.As such,it can effectively help to manage cardiorenal syndromes in various clinical settings.Extended or eVExUS explores additional veins,potentially broadening its applications.While VExUS demonstrates promising outcomes,challenges persist,particularly in cases involving renal and liver parenchymal disease,arrhythmias,and situations of pressure and volume overload overlap.Proficiency in utilizing spectral Doppler is pivotal for clinicians to effectively employ this tool.Hence,the integration of POCUS,especially advanced applications like VExUS,into routine clinical practice necessitates enhanced training across medical specialties.

RhIr@MoS2 nanohybrids based disposable microsensor for the point-of-care testing of NADH in real human serum

Dihydronicotinamide adenine dinucleotide(NADH)is an important enzyme in all living cells,which is found to be abnormally expressed in cancer cells.Since it is redox-active,an electrochemical detection method would be suitable for monitoring its concentration in biological fluids.Here we present a strategy for specific determination of NADH in real human serum by using RhIr@MoS2 nanohybrids based microsensor.To implement the protocol,RhIr nanocrysrals are in-situ grown onto MoS2 interlayers forming a nanohybrid structure(RhIr@MoS2).After being locally deposited on an electrochemical microsensor,it could be used for the analysis of NADH.The developed RhIr@MoS2 nanohybrids based microsensor possesses the ability for analyzing NADH at the applied potential of 0.07 V(much lower than most reported values).The detection limit is evaluated as low as 1 nmol/L even in bovine serum albumin(BSA)media.In addition,the sampling analysis of human serum from cancer patients and health controls shows that the microsensor displays good diagnostic sensitivity and specificity,illustrating that this developed detection technique is a relatively accurate method for measuring NADH in biological fluids.The proposed electrochemical microsensor assay also owns the benefits of convenience,disposable and easy processing,which make it a great possibility for future point-of-care cancer diagnosis.

DropLab:an automated magnetic digital microfluidic platform for sample-to-answer point-of-care testing—development and application to quantitative immunodiagnostics

In point-of-care testing(POCT),tests are performed near patients and results are given rapidly for timely clinical decisions.Immunodiagnostic assays are one of the most important analyses for detecting and quantifying protein-based biomarkers.However,existing POCT immunodiagnostics mainly rely on the lateral flow assay(LFA),which has limited sensitivity or quantification capability.Although other immunodiagnostic assays,such as enzyme-linked immunosorbent assays(ELISAs),offer more sensitive and quantitative results,they require complex liquid manipulations that are difficult to implement in POCT settings by conventional means.Here,we show the development of DropLab,an automated sample-in-answer-out POCT immunodiagnostic platform based on magnetic digital microfluidic(MDM)technology.DropLab performs microbead-based ELISA in droplets to offer more sensitive and quantitative testing results.The intricate liquid manipulations required for ELISA are accomplished by controlling droplets with magnetic microbeads using MDM technology,which enables us to achieve full automation and easy operations with DropLab.Four ELISAs(the sample in triplicates and a negative control)can be run in parallel on the thermoformed disposable chip,which greatly improves the throughput and accuracy compared to those of other POCT immunodiagnostic devices.DropLab was validated by measuring two protein targets and one antibody target.The testing results showed that the limit of detection(LOD)of DropLab matched that of the conventional ELISA in a microwell plate.DropLab brings MDM one step closer to being a viable medical technology that is ready for real-world POCT applications.

Point-of-care ultrasound in nephrology:A private practice viewpoint

Point-of-care ultrasound(POCUS)is a limited ultrasound examination performed by the clinician at the bedside,emerging as a complement to physical examination across various medical specialties.In the field of nephrology,its integration has been gradual,primarily limited to guiding procedures like temporary dialysis catheter placement or,in some cases,diagnostic kidney ultrasounds.In reality,the assessment of hemodynamic status at the bedside holds immense value for nephrologists,yet there exists limited awareness among practitioners regarding its implementation.While there is a growing trend towards incorporating multiorgan POCUS training in fellowship programs,private practice nephrologists remain relatively uninformed.This discussion explores the untapped potential of POCUS as a valuable diagnostic tool in everyday nephrology practice,demonstrating its effectiveness in diverse clinical settings,ranging from medical wards to outpatient dialysis units.Additionally,we delve into the challenges hindering its widespread adoption and consider the future trajectory of this innovative approach.