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.

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.

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.

Corrigendum to“Point-of-care testing for lysine concentration in swine serum via blue-emissive carbon dots entrapped microfluidic chip”[Animal Nutrition 12(2023)236e244]

Section 2.1:Animal ethics approval number:HZAUSW-2002e0009 Change to:HZAUSW-2022e0011 Section 2.6:…200 mL solution of N-CDs(0.1 mg/mL)…Change to:…200 mL solution of N-CDs(1.5 mg/mL)…Section 3.1:…with the size ranging from 4 to 8 nm…Change to:…with the size ranging from 2 to 7 nm…

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.

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.

Transcending boundaries:Unleashing the potential of multi-organ point-of-care ultrasound in acute kidney injury

Acute kidney injury(AKI)is a clinical syndrome characterized by a rapid increase in serum creatinine levels or a decrease in urine output or both.In spite of thorough history-taking,physical examination,and laboratory analysis,there are limitations in the diagnostic process and clinical monitoring of AKI.Point-of-care ultrasonography(POCUS),a limited ultrasound study performed by clinicians at the bedside,has emerged as a valuable tool in different clinical settings.In this discussion,we explore the potential of POCUS performed by nephrologists to address specific questions encountered in the diagnosis and management of AKI patients.POCUS not only aids in excluding hydronephrosis but also provides real-time insights into hemodynamics,enabling formulation of individualized treatment plans.Further studies are required to assess the impact of multi-organ POCUS on pragmatic patient outcomes related to AKI,as well as its potential in risk stratification and identification of different levels of AKI severity and pathophysiological signatures.

Bow-and-arrow sign on point-of-care ultrasound for diagnosis of pacemaker lead-induced heart perforation:A case report and literature review

BACKGROUND Pacemaker lead-induced heart perforation is a rare but life-threatening complication of pacemaker implantation,and timely diagnosis remains a challenge for clinicians.Here,we report a case of pacemaker lead-induced cardiac perforation rapidly diagnosed by a“bow-and-arrow”sign on point-of-care ultrasound(POCUS).CASE SUMMARY A 74-year-old Chinese woman who had undergone permanent pacemaker implantation 26 d before suddenly developed severe dyspnea,chest pain,and hypotension.The patient had received emergency laparotomy for an incarcerated groin hernia and was transferred to the intensive care unit 6 d before.Computed tomography was not available due to unstable hemodynamic status,so POCUS was performed at the bedside and revealed severe pericardial effusion and cardiac tamponade.Subsequent pericardiocentesis yielded a large volume of bloody pericardial fluid.Further POCUS by an ultrasonographist revealed a unique“bow-and-arrow”sign indicating right ventricular(RV)apex perforation by the pacemaker lead,which facilitated the rapid diagnosis of lead perforation.Given the persistent drainage of pericardial bleeding,urgent off-pump open chest surgery was performed to repair the perforation.However,the patient died of shock and multiple organ dysfunction syndrome within 24 h post-surgery.In addition,we also performed a literature review on the sonographic features of RV apex perforation by lead.CONCLUSION POCUS enables the early diagnosis of pacemaker lead perforation at the bedside.A step-wise ultrasonographic approach and the“bow-and-arrow”sign on POCUS are helpful for rapid diagnosis of lead perforation.

Aquifer Test求群孔抽水试验水文地质参数

在水文地质条件复杂的地区,往往采用大型的群孔抽水试验充分揭露含水层特征,获取水文地质参数。用Aquifer Test软件求解水文地质参数,则方便实用、简捷高效,可快速输出拟合图形和求参结果。Aquifer Test提供了丰富的求参方案,求参必须结合当地当时的水文地质条件实际情况考虑,选择适合的方案和时空数据求取水文地质参数。

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.

Point-of-care ultrasound in diagnosis and management of congestive nephropathy

Congestive nephropathy is kidney dysfunction caused by the impact of elevated venous pressures on renal hemodynamics.As a part of cardiorenal syndrome,the diagnosis is usually made based on history and physical examination,with findings such as jugular venous distension,a third heart sound,and vital signs as supporting findings.More recently,however,these once though objective measures have come under scrutiny for their accuracy.At the same time,bedside ultrasound has increased in popularity and is routinely being used by clinicians to take some of the guess work out of making the diagnosis of volume overload and venous congestion.In this mini-review,we will discuss some of the traditional methods used to measure venous congestion,describe the role of point-of-care ultrasound and how it can ameliorate a clinician’s evaluation,and offer a description of venous excess ultrasound score,a relatively novel scoring technique used to objectively quantify congestion.While there is a paucity of published large scale clinical trials evaluating the potential benefit of ultrasonography in venous congestion compared to gold standard invasive measurements,more study is underway to solidify the role of this objective measure in daily clinical practice.

Sweat-Based in Vitro Diagnostics(IVD):From Sample Collection to Point-of-Care Testing(POCT)

Sweat-based diagnostics offer an exciting avenue to noninvasively monitor analytes which had previously only been avail-able through painful blood draws.Sweat is enriched with physiologically valuable information,and recent proteomic studies have identified numerous critical analytes which have highly correlated levels in blood,interstitial fluid and sweat.How-ever,usage of sweat for health monitoring has not been studied extensively due to the substantial challenge of assembling a composite clinic-ready device.Recent advances in soft electronics have made this goal realizable,as these devices can perform electronic or optical monitoring on a flexible substrate using small volumes of liquid.While this field is still in its infancy,this review examines the physiological composition of sweat,various improvements in material science that improve sensor design,existing FDA approvals,methods of extracting sweat and comparisons to blood-based tests.Furthermore,this review assesses the critical challenges which must be overcome for this type of technology to make it out of research laboratories and into continuous clinical use.We believe that once properly harnessed,sweat-based diagnostics can provide patients a painless monitoring tool which can be customized to track a wide variety of medical conditions from the comfort of a patient’s own home.

Failure characterization of fully grouted rock bolts under triaxial testing

Confining stresses serve as a pivotal determinant in shaping the behavior of grouted rock bolts.Nonetheless,prior investigations have oversimplified the three-dimensional stress state,primarily assuming hydrostatic stress conditions.Under these conditions,it is assumed that the intermediate principal stress(σ_(2))equals the minimum principal stress(σ_(3)).This assumption overlooks the potential variations in magnitudes of in situ stress conditions along all three directions near an underground opening where a rock bolt is installed.In this study,a series of push tests was meticulously conducted under triaxial conditions.These tests involved applying non-uniform confining stresses(σ_(2)≠σ_(3))to cubic specimens,aiming to unveil the previously overlooked influence of intermediate principal stresses on the strength properties of rock bolts.The results show that as the confining stresses increase from zero to higher levels,the pre-failure behavior changes from linear to nonlinear forms,resulting in an increase in initial stiffness from 2.08 kN/mm to 32.51 kN/mm.The load-displacement curves further illuminate distinct post-failure behavior at elevated levels of confining stresses,characterized by enhanced stiffness.Notably,the peak load capacity ranged from 27.9 kN to 46.5 kN as confining stresses advanced from σ_(2)=σ_(3)=0 to σ_(2)=20 MPa and σ_(3)=10 MPa.Additionally,the outcomes highlight an influence of confining stress on the lateral deformation of samples.Lower levels of confinement prompt overall dilation in lateral deformation,while higher confinements maintain a state of shrinkage.Furthermore,diverse failure modes have been identified,intricately tied to the arrangement of confining stresses.Lower confinements tend to induce a splitting mode of failure,whereas higher loads bring about a shift towards a pure interfacial shear-off and shear-crushed failure mechanism.

C-CORE:Clustering by Code Representation to Prioritize Test Cases in Compiler Testing

Edge devices,due to their limited computational and storage resources,often require the use of compilers for program optimization.Therefore,ensuring the security and reliability of these compilers is of paramount importance in the emerging field of edge AI.One widely used testing method for this purpose is fuzz testing,which detects bugs by inputting random test cases into the target program.However,this process consumes significant time and resources.To improve the efficiency of compiler fuzz testing,it is common practice to utilize test case prioritization techniques.Some researchers use machine learning to predict the code coverage of test cases,aiming to maximize the test capability for the target compiler by increasing the overall predicted coverage of the test cases.Nevertheless,these methods can only forecast the code coverage of the compiler at a specific optimization level,potentially missing many optimization-related bugs.In this paper,we introduce C-CORE(short for Clustering by Code Representation),the first framework to prioritize test cases according to their code representations,which are derived directly from the source codes.This approach avoids being limited to specific compiler states and extends to a broader range of compiler bugs.Specifically,we first train a scaled pre-trained programming language model to capture as many common features as possible from the test cases generated by a fuzzer.Using this pre-trained model,we then train two downstream models:one for predicting the likelihood of triggering a bug and another for identifying code representations associated with bugs.Subsequently,we cluster the test cases according to their code representations and select the highest-scoring test case from each cluster as the high-quality test case.This reduction in redundant testing cases leads to time savings.Comprehensive evaluation results reveal that code representations are better at distinguishing test capabilities,and C-CORE significantly enhances testing efficiency.Across four datasets,C-CORE increases the average of the percentage of faults detected(APFD)value by 0.16 to 0.31 and reduces test time by over 50% in 46% of cases.When compared to the best results from approaches using predicted code coverage,C-CORE improves the APFD value by 1.1% to 12.3% and achieves an overall time-saving of 159.1%.