Point-of-care System Research Articles

Innovative Hydrophobic Valve Allows Complex Liquid Manipulations in a Self-Powered Channel-Based Microfluidic Device

We present an innovative, simple, and versatile hydrophobic valve enabling all-important complex liquid manipulations on self-powered, channel-based microfluidic devices and as such being extremely valuable for the design of highly demanding point-of-care (POC) platforms. The presented hydrophobic valve is made of filter paper treated with a fluorinated compound (i.e., Aquapel) and shows both superhydrophobic properties (contact angle up to 155°) and high resistance to liquid pressure (up to 9 kPa), while retaining gas permeability and utter fabrication simplicity. Whereas this valve can be integrated in any channel-based system and can be used both as a vent, to delay liquid displacement on chip, or as a barrier, to stop the liquid flow in a certain direction, in this work we demonstrate some of its capacities by combining it with our in house developed self-powered SIMPLE and iSIMPLE platforms. First, we integrated it with the infusion iSIMPLE pump, thus generating completely fail-proof activation regardless of how the operator is actuating the system. Second, we used hydrophobic valves as both barrier and vent in the same microfluidic chip, which allowed the combination of two SIMPLE pumps for splitting one sample in two parallel channels. This attribute is fundamental for achieving multiplex analysis on completely autonomous microfluidic platforms. Finally, we achieved an unprecedented liquid manipulation for a self-powered microfluidic platform, namely, shuttling of liquid, after a single user activation by combining for the first time SIMPLE and iSIMPLE with the developed hydrophobic vent and barrier, all in a single chip. These results convincingly demonstrated that the developed hydrophobic valve combined with SIMPLE/iSIMPLE presents an essential building block for an ideal POC system, which is self-powered, inexpensive, and robust and can perform complex bioassays upon a single user activation.

Determination of Free-PSA (fPSA) and fPSA/PSA-Ratio Using A Point-of-Care Device.

Prostate specific antigen (PSA) and free PSA (fPSA) are important tools for diagnosing prostate cancer (PC). Efforts are continuously undertaken to provide more patient-centered healthcare. The application of point-of-care (POC) systems for laboratory analyses represents a step in this direction. Previous investigations on total PSA measurements using a POC system (concile® Ω100 POC reader) showed good concordance with standard laboratory measurements. For the same POC reader a novel system for fPSA was developed. In the current study, we prospectively evaluated the quality of the POC system for fPSA. Sixty-four patients undergoing PSA measurements in our outpatient clinic between 06/2015 and 09/2015 were enrolled in the study. We measured total PSA (tPSA) and fPSA with a POC reader system (concile® Ω100) and a standard laboratory system (Siemens Immulite 2000®) and compared the respective results using linear regression analyses for PSA, fPSA, and fPSA/tPSA ratio (%fPSA). The coefficients of determination (r²) for fPSA and %fPSA were 0.85 (p < 0.001) and 0.82 (p < 0.001) in the subgroup with total PSA between 4 and 10 ng/mL. In the subgroup with tPSA ≤ 4 ng/mL, r² for fPSA concile® was 0.55 (p < 0.001) and 0.10 (p = 0.088) for %fPSA. In the subgroup of tPSA > 10 ng/mL the r² for fPSA and %fPSA was 0.50 (p = 0.022) and 0.50 (p = 0.022), respectively. The POC fPSA values correlated well with the laboratory analyses, specifically in the clinically relevant diagnostic range of tPSA 4 - 10 ng/mL. These results complement the tPSA data obtained previously and indicate the reliability of the fPSA method and the resulting %fPSA score.

Silica bead-based microfluidic device with integrated photodiodes for the rapid capture and detection of rolling circle amplification products in the femtomolar range

The rapid and sensitive detection of specific nucleic acid sequences at the point-of-care (PoC) is becoming increasingly in demand for a variety of emergent biomedical applications ranging from infectious disease diagnostics to the screening of antimicrobial resistance. To meet such demand, considerable efforts have been invested towards the development of portable and integrated analytical devices combining microfluidics with miniaturized signal transducers.Here, we demonstrate the combination of rolling circle amplification (RCA)-based nucleic acid amplification with an on-chip size-selective trapping of amplicons on silica beads (~8 nL capture chamber) coupled with a thin-film photodiode (200 × 200 µm area) fluorescence readout. Parameters such as the flow rate of the amplicon solution and trapping time were optimized as well as the photodiode measurement settings, providing minimum detection limits below 0.5 fM of targeted nucleic acids and requiring only 5 μL of pre-amplified sample. Finally, we evaluated the analytical performance of our approach by benchmarking it against a commercial instrument for RCA product (RCP) quantification and further investigated the effect of the number of RCA cycles and elongation times (ranging from 10 to 120 min). Moreover, we provide a demonstration of the application for diagnostic purposes by detecting RNA from influenza and Ebola viruses, thus highlighting its suitability for integrated PoC systems.

Novel nanostructured indium tin oxide electrode for electrochemical immunosensors: Suitability for the detection of TNF-α

The need for new and innovative point of care (POC) systems providing a feasible alternative to costly and time consuming standard laboratory techniques is becoming more evident every day, particularly in the case of cardiovascular diseases. Coupling optical and electrochemical principles for highly specific and sensitive detection of biomarkers could boost the successful implementation of POC systems in biomedical environments. We suggest indium tin oxide (ITO) as a promising material for working electrodes in optoelectrochemical sensors, owing to the rare combination of high electrical conductivity and optical transparency it presents. Moreover, the nanostructured nature of the electrodes' surface is crucial for an eventual miniaturization of the POC system. In this work, we describe the construction and characterization of a nanostructured ITO electrode modified with aryl diazonium salt as transparent substrate for electrochemical immunosensors. The developed electrode was tested for the detection of tumour necrosis factor α (TNF-α), a cardiac biomarker playing an important role in the prevention of heart failure. Macro and microscopic evidences (gathered from electrochemical and spectral techniques) of covalent bonding and high surface coverage are provided. Specific interaction between antigen (TNF-α) and monoclonal antibody (Ab-TNF-α) was verified by fluorescence patterning, confirming the proper bio-recognition of the cytokine. As a proof-of-concept, results of electrochemical impedance spectroscopy (EIS) show stabilized semi-quantitative label-free detection of TNF-α at several concentrations (from 10 pg/mL to 100 pg/mL). These preliminary results demonstrate the feasibility of using transparent substrates for the detection of cytokines at low concentrations, and the consequent application in POC systems for the monitoring of cardiovascular diseases.

Point-of-Care HbA1c—A Case for Diabetes Screening and Diagnosis

Background: Hemoglobin A1C (A1C) is routinely used to screen, diagnose, and monitor diabetes. A1C is the desired tool to assess glycemic status as it reflects 90 days of glycemic control and does not require fasting. Point-of-care (POC) A1C offers rapid turnaround enabling direct patient engagement. POC A1C tests are indicated for monitoring, but not screening or diagnosis, due to perceived inaccuracy and imprecision. To counter this impression, we evaluated the performance of two POC A1C analyzers relative to the clinical laboratory (CL). Method: Blood from 48 subjects was collected with A1C values from 4.8-12.0% A1C. Capillary blood was analyzed on the PTS Diagnostics A1CNow®+ system and Siemens DCA Vantage® while venous blood was tested at external labs on the Tosoh G8 and Roche Cobas® c513 as CL comparators. For reference, venous blood was analyzed on the Roche Cobas Integra® 400 plus. Regression analysis was used to evaluate accuracy and paired differences to measure bias. Clinical risk was calculated using A1C category cut points of &amp;lt; 5.7, 5.7-6.4, and ≥ 6.5% A1C. Chi-squared test was used to assess differences between methods. Precision was performed on the POC systems using 10 replicates at approx. 4.5, 7, and 10% A1C. Results: Average paired biases were identical for the POC and CL analyzers (-0.04% A1C). Slopes were 0.97, 0.99, and 0.97 for the A1CNow+, DCA, and CL analyzers (p = 0.71) and intercepts were 0.15, 0.04, and 0.12 (p = 0.99). Regression values were 0.987, 0.996, and 0.998, respectively. Clinical risk agreement was 94% for A1CNow+, 100% for the DCA, and 98% for CL analyzers (p = 0.17). Pooled precision was 3.3% CV for A1CNow+ and 1.7% CV for DCA. Conclusion: The A1CNow+ and DCA were shown to be as accurate as the clinical lab in measuring A1C values. Risk analysis showed no statistical differences between the CL and POC analyzers in classifying diabetes. The A1CNow+ and DCA are valuable tools in evaluating the diabetic state and provide physicians with real-time information to better care for patients. Disclosure C.J. Szablowski: Employee; Self; PTS Diagnostics. E. Suscha: Employee; Self; PTS Diagnostics. K. Davis: Employee; Self; PTS Diagnostics. C.Z. Xie: Employee; Self; PTS Diagnostics. K. Moskowitz: Employee; Self; PTS Diagnostics. Stock/Shareholder; Self; PTS Diagnostics. J.H. Anderson: Employee; Self; PTS Diagnostics. Board Member; Self; GENEREX Biotechnology. A. Mechley: Consultant; Self; PTS Diagnostics.

The Usefulness and Limitations of Point-of-care Cardiac Troponin Measurement in the Emergency Department.

Objective This study was carried out to examine the usefulness of point-of-care (POC) cardiac troponin in diagnosing acute coronary syndrome (ACS) and to understand the limitations of a POC cardiac troponin I/T-based diagnoses. Methods Patients whose cardiac troponin levels were measured in the emergency department using a POC system (AQT System; Radiometer, Tokyo, Japan) between January and December 2016 were retrospectively examined (N=1,449). Patients who were < 20 years of age or who were admitted with cardiopulmonary arrest were excluded. The sensitivity and specificity of the POC cardiac troponin levels for the diagnosis of ACS were determined. Result One hundred and twenty of 1,449 total patients had ACS (acute myocardial infarction, n=88; unstable angina n=32). On comparing the receiver operating characteristic (ROC) curves, the area under the curve (AUC) values for POC cardiac troponin I and cardiac troponin T were 0.833 and 0.786, respectively. The sensitivity and specificity of POC cardiac troponin I when using the 99th percentile (0.023 ng/mL) as the diagnostic cut-off value were 69.0% and 88.1%, respectively. The sensitivity of POC cardiac troponin I (99th percentile) was higher in the patients sampled > 3 hours after symptom onset (83.3%) than in those sampled ≤ 3 hours after symptom onset (58.8%, p < 0.01). Conclusion When sampled > 3 hours after the onset of symptoms, the POC cardiac troponin I level is considered to be suitable for use in diagnosing ACS. However, when sampled ≤ 3 hours after the onset of symptoms, careful interpretation of POC cardiac troponins is therefore required to rule out ACS.

An integrated all foil based micro device for point of care diagnostic applications

Point-of-Care (POC) diagnostics often fail to meet the market requirements of low cost and advanced functionality, and are often limited to lateral flow based serological diagnostics with reduced sensitivity and specificity. We report here on an integrated microfluidic absorbance measurement device fabricated by roll-to-roll (R2R) compatible manufacturing processes, suitable for low cost POC systems. It is a device exclusively made of foils and takes external light from a low cost LED and converts the point light source to a homogeneous light via a foil based optical filter at the bottom of the device. The light is converted to an electrical signal by an amorphous organic semiconductor (OSC) material, integrated with screen-printed carbon finger on top of the device for electrical measurement. As a proof of principle, we demonstrate DNA hybridization assay, where the target DNA is coupled to magnetic beads for absorbance measurement. The device successfully distinguishes between matched and mismatched DNA hybridization and can differentiate between 1 μM, 50 nM and 2.5 nM DNA target concentrations. The inherent characteristics of the substrates and R2R fabrication concept significantly reduce the cost, making it suitable for POC applications at resource-limited settings.

Field evaluation of HIV point-of-care testing for early infant diagnosis in Cape Town, South Africa.

BackgroundEarly infant HIV diagnosis (EID) coverage and uptake remains challenging. Point-of-care (POC) testing may improve access and turn-around-times, but, while several POC technologies are in development there are few data on their implementation in the field.MethodsWe conducted an implementation study of the Alere q Detect POC system for EID at two public sector health facilities in Cape Town. HIV-exposed neonates undergoing routine EID testing at a large maternity hospital and a primary care clinic received both laboratory-based HIV PCR testing per local protocols and a POC test. We analysed the performance of POC versus laboratory testing, and conducted semi-structured interviews with providers to assess acceptability and implementation issues.ResultsOverall 478 specimens were taken: 311 tests were performed at the obstetric hospital (median child age, 1 days) and 167 six-week tests in primary care (median child age, 42 days). 9.0% of all tests resulted in an error with no differences by site; most errors resolved with retesting. POC was more sensitive (100%; lower 95% CI, 39.8%) and specific (100%, lower 95% CI, 98%) among older children tested in primary care compared with birth testing in hospital (90.0%, 95% CI, 55.5–99.8% and 100.0%, lower 95% CI, 98.4%, respectively). Negative predictive value was high (>99%) at both sites. In interviews, providers felt the device was simple to use and facilitated decision-making in the management of infants. However, many wanted clarity on the cause of errors on the POC device to help guide repeat testing.ConclusionsPOC EID testing performs well in field implementation in health care facilities and appears highly acceptable to health care providers.

Microgel assisted Lab-on-Fiber Optrode

Precision medicine is continuously demanding for novel point of care systems, potentially exploitable also for in-vivo analysis. Biosensing probes based on Lab-On-Fiber Technology have been recently developed to meet these challenges. However, devices exploiting standard label-free approaches (based on ligand/target molecule interaction) suffer from low sensitivity in all cases where the detection of small molecules at low concentrations is needed. Here we report on a platform developed through the combination of Lab-On-Fiber probes with microgels, which are directly integrated onto the resonant plasmonic nanostructure realized on the fiber tip. In response to binding events, the microgel network concentrates the target molecule and amplifies the optical response, leading to remarkable sensitivity enhancement. Moreover, by acting on the microgel degrees of freedom such as concentration and operating temperature, it is possible to control the limit of detection, tune the working range as well as the response time of the probe. These unique characteristics pave the way for advanced label-free biosensing platforms, suitably reconfigurable depending on the specific application.

Comparison of Point-of-Care Versus Laboratory Troponin Testing in an Emergency Department Setting.

There have been concerns regarding troponin results accuracy between point-of-care (POC) testing preformed in an emergency department (ED) setting and laboratory testing. The purpose of this study was to compare the results of cardiac troponin I testing as concerns POC testing and laboratory analysis as a way to show that these results are interchangeable. A retrospective chart review was performed from October 2012 through September 2013 to identify all patients who presented to the ED that received both a POC and laboratory troponin associated with the same blood draw. A total of 189 patients met inclusion criteria. Three laboratory samples were hemolyzed and not available for comparison. Of the remaining 186 samples, when a positive cutoff value of 0.034 ng/mL was used: 37 POC tests were positive and 149 POC tests were negative, sensitivity 0.85 (95% confidence interval [CI] = 0.69-0.94), specificity 0.98 (95% CI = 0.94-0.99), positive predictive value 91.9% (95% CI = 77-97.9%), and negative predictive value 96% (95% CI = 91.1-98.4%). When a POC troponin positive cutoff value of 0.12 ng/mL was used: 20 POC tests were positive and 164 were negative: sensitivity 1.0 (95% CI = 0.8-1.0), specificity 0.99 (95% CI = 0.95-1.0), positive predictive value 91% (95% CI = 69-98.4%), and negative predictive value 100% (95% CI = 97.1-100%). In an ED setting; POC testing is accurate and correlates well with laboratory testing. Considering that the POC analysis takes a fraction of time to yield results, the validity of its data is important. The results of this study show that the POC system is a suitable test for rapid evaluation of patients presenting to the ED. This correlation increased with a higher testing positive cutoff value (0.12 versus 0.034 ng/mL). These data can assist the emergency physician with rapid identification of evidence of cardiac injury and be assured that the results are accurate. POC lab testing should be considered whenever possible to provide the fastest troponin results.

Medical signal steganography using curvelet Transform

Steganography is the mechanism of protecting secret data which is sent through the common communication medium. Point of Care (PoC) system is used in most of the hospitals and health care centres. PoC system, it produces patient’s physiological readings like sugar level, pressure level, and medical signals like EEG, ECG and EMG etc. In order to consult with the doctors/experts those who are in some other locations, patient data and medical signals are to be sent to them. Medical steganography is the application of steganography for protecting medical data. In this work, a curvelet based medical steganography is implemented for one dimensional (1D) Medical signal like ECG, EMG and EEG. The results proved that, the curvelet based approach is best suited for 1D medical signal. We evaluate the performance of curvelet based approach using the metrics PSNR, MSE and payload. We obtained 35.89 % of average PSNR value for ECG signals, 21.47 % of average PSNR value for EMG signals and 22.57 % of average PSNR value for EEG signals. Keywords: Medical signal processing; ECG; EMG; EEG; Steganography; Encryption; Curvelet; Watermarking.

Field deployable platform for prognostic hepatic cancer screening.

267 Background: Hepatocellular carcinoma (HCC) incidence rates are increasing in many parts of the world particularly in low- and middle-income countries (LMICs). Although treatable if identified in the early stages in many LMICs patients are identified later in disease. A low cost point of care system that could identify patients at a higher risk of having HCC could be used as a screening tool to identify patients at an earlier stage. We are currently developing a low cost point of care hand held platform that can simultaneously evaluate the blood levels of common HCC markers. We present our preliminary findings on the limit of detection (LOD) of our system. Methods: Our device combines the rapid but qualitative results of a vertical flow assay with the quantitative capabilities of surface enhanced Raman scattering spectroscopy. Our final product will be able to simultaneously measure the blood levels of the five most proven markers of HCC: alphafetoprotein (AFP), lens-culinaris agglutinin binding alphafetoprotein (AFP-L3), des-gamma-carboxy prothrombin (DCP), core antibodies to hepatitis B virus (HBV), and core antibodies to hepatitis C virus (HCV). In this pilot study we initially evaluated the LOD of our system by evaluating known concentrations of AFP in human serum samples. We then evaluated serum levels of AFP in HCC patient samples (n = 5) with our device and compared with values obtained using a standard ELISA. Results: The LOD of our system for the detection of AFP in spiked serum samples was 1 ng/mL. Our quantitative lateral flow assay measured AFP within 10% of the values of obtained by standard ELISA, with serum values ranging from 10-900 ng/mL. The quantitative vertical flow assay was able to provide results within 5 minutes at a cost of approximately $2/sample. Conclusions: Our inexpensive, portable and rapid test was able to measure serum levels of AFP at values comparable to standard clinical methods. Importantly, one blood marker would be insufficient to identify high risk patients, so further research will be required to expand the number of markers within the panel. The end goal will be to evaluate the ability of our point of care system to screen high risk population in LMICs, thereby identifying at risk patients earlier in disease progression.

Security Framework for Managing Data Security within Point of Care Tests

Point of Care (PoC) devices and systems can be categorized into three broad classes (CAT 1, CAT 2, and CAT 3) based on the context of operation and usage. In this paper, the categories are defined to address certain usage models of the PoC device. PoC devices that are used for PoC testing and diagnostic applications are defined CAT 1 devices; PoC devices that are used for patient monitoring are defined as CAT 2 devices (PoCM); PoC devices that are used for as interfacing with other devices are defined as CAT 3 devices (PoCI). The PoCI devices provide an interface gateway for collecting and aggregating data from other medical devices. In all categories, data security is an important aspect. This paper presents a security framework concept, which is applicable for all of the classes of PoC operation. It outlines the concepts and security framework for preventing security challenges in unauthorized access to data, unintended data flow, and data tampering during communication between system entities, the user, and the PoC system. The security framework includes secure layering of basic PoC system architecture, protection of PoC devices in the context of application and network. Developing the security framework is taken into account of a thread model of the PoC system. A proposal for a low-level protocol is discussed. This protocol is independent of communications technologies, and it is elaborated in relation to providing security. An algorithm that can be used to overcome the threat challenges has been shown using the elements in the protocol. The paper further discusses the vulnerability scanning process for the PoC system interconnected network. The paper also presents a four-step process of authentication and authorization framework for providing the security for the PoC system. Finally, the paper concludes with the machine to machine (M2M) security viewpoint and discusses the key stakeholders within an actual deployment of the PoC system and its security challenges.

Hand-held Ultrasound Scanners in Medical Education: A Systematic Review.

BackgroundUltrasound imaging devices are becoming popular in clinical and teaching settings, but there is no systematic information on their use in medical education. We conducted a systematic review of hand-held ultrasound (HHU) devices in undergraduate medical education to delineate their role, significance, and limitations.MethodsWe searched Cochrane, PubMed, Embase, and Medline using the strategy: [(Hand-held OR Portable OR Pocket OR “Point of Care Systems”) AND Ultrasound] AND (Education OR Training OR Undergraduate OR “Medical Students” OR “Medical School”). We retained 12 articles focusing on undergraduate medical education. We summarised the patterns of HHU use, pooled and estimated sensitivity, and specificity of HHU for detection of left ventricular dysfunction.ResultsFeatures reported were heterogeneous: training time (1–25 hours), number of students involved (1-an entire cohort), number of subjects scanned (27–211), and type of learning (self-directed vs. traditional lectures + hands-on sessions). Most studies reported cardiac HHU examinations, but other anatomical areas were examined, e.g. abdomen and thyroid. Pooled sensitivity 0.88 [95% confidence interval (CI) 0.83–0.92] and specificity 0.86 (95% CI 0.81–0.90) were high for the detection of left ventricular systolic dysfunction by students.ConclusionData on HHU devices in medical education are scarce and incomplete, but following training students can achieve high diagnostic accuracy, albeit in a limited number of (mainly cardiac) pathologies. There is no consensus on protocols best-suited to the educational needs of medical students, nor data on long-term impact, decay in proficiency or on the financial implications of deploying HHU in this setting.

Point-of-care PT and aPTT in patients with suspected deficiencies of coagulation factors.

There are several clinical settings and patient conditions especially in intensive care units, emergency departments, and operating theaters, where the coagulation status of a patient must be known immediately and point-of-care (POC) systems are beneficial due to low time to result. This noninterventional, single-blinded, multicenter study with prospectively collected whole blood samples was performed to evaluate the diagnostic accuracy of the CoaguChek PT Test (POC PT) and CoaguChek aPTT Test (POC aPTT) compared to standard laboratory testing in patients with suspected deficiencies of coagulation factors. In total, 390 subjects were included. Both POC PT and POC aPTT showed concordance with the laboratory PT and aPTT. Lot-to-lot variation was below 2% both for POC PT and for POC aPTT. The mean relative difference of capillary blood compared to venous blood was 0.2 % with POC PT and 8.4% with POC aPTT. The coefficients of variation for repeatability of POC PT using whole blood were found to be between 2% and 3.6%. Our findings suggest reliable quantitative results with this POC system to support on-site decision-making for patients with suspected deficiencies of coagulation factors in acute and intensive care.

Solar-thermal complex sample processing for nucleic acid based diagnostics in limited resource settings.

The use of point-of-care (POC) devices in limited resource settings where access to commonly used infrastructure, such as water and electricity, can be restricted represents simultaneously one of the best application fits for POC systems as well as one of the most challenging places to deploy them. Of the many challenges involved in these systems, the preparation and processing of complex samples like stool, vomit, and biopsies are particularly difficult due to the high number and varied nature of mechanical and chemical interferents present in the sample. Previously we have demonstrated the ability to use solar-thermal energy to perform PCR based nucleic acid amplifications. In this work demonstrate how the technique, using similar infrastructure, can also be used to perform solar-thermal based sample processing system for extracting and isolating Vibrio Cholerae nucleic acids from fecal samples. The use of opto-thermal energy enables the use of sunlight to drive thermal lysing reactions in large volumes without the need for external electrical power. Using the system demonstrate the ability to reach a 95°C threshold in less than 5 minutes and maintain a stable sample temperature of +/− 2°C following the ramp up. The system is demonstrated to provide linear results between 104 and 108 CFU/mL when the released nucleic acids were quantified via traditional means. Additionally, we couple the sample processing unit with our previously demonstrated solar-thermal PCR and tablet based detection system to demonstrate very low power sample-in-answer-out detection.

Assessment of a new point-of-care system for detection of prostate specific antigen.

BackgroundMeasurement of the prostate specific antigen (PSA) remains an important tool in prostate cancer (PC) diagnosis. Due to limited availability of laboratory devices in an outpatient setting, compact and easy-to-handle point-of-care (POC) systems are desirable. Recently, a chip for PSA measurement on the concile® Ω100 POC reader platform was introduced. To investigate the clinical applicability, we evaluated the system in a consecutive cohort of patients undergoing PSA measurement in our outpatient clinic.MethodsBetween 07/2014 and 01/2015, PSA was analyzed in a total of 198 patients by the POC reader system and in parallel by an Immulite 2000® and Centaur® standard laboratory system, respectively. By standard (Immulite®) measurement, 67 (34,2 %) had PSA > 4 ng/ml and 131 (65,8 %) had PSA ≤ 4 ng/ml. Results were correlated by linear regression analyses for all patients and within PSA subgroups. For patients with available prostate histology after PSA measurement (n = 68), receiver-operating characteristic curves were created and area under the curve (AUC), sensitivity and specificity for the prediction of PC at best cut-off value were calculated.ResultsThe coefficients of determination (r2) for the POC device compared to laboratory testing were 0.72 (Immulite®) and 0.63 (Centaur®), respectively (both p < 0.0001). In the PSA range of ≤4 ng/ml, the observed correlations were 0.75 and 0.70, respectively. For the POC test system, AUC for detection of PC was calculated with 0.745 while the standard laboratory tests showed 0.778 (Immulite®) and 0.771 (Centaur®). At best cut-off of 3.64 ng/ml, PSA analysis by the POC system showed a sensitivity of 85.7 % and a specificity of 66.7 %.ConclusionsThe POC system obtained good concordance to elaborate laboratory measurement. In a screening scenario, the system provides quick and reliable PSA measurement, especially in the PSA range up to 4 ng/ml.

Microfluidic emulation of mechanical circulatory support device shear-mediated platelet activation.

Thrombosis of ventricular assist devices (VADs) compromises their performance, with associated risks of systemic embolization, stroke, pump stop and possible death. Anti-thrombotic (AT) drugs, utilized to limit thrombosis, are largely dosed empirically, with limited testing of their efficacy. Further, such testing, if performed, typically examines efficacy under static conditions, which is not reflective of actual shear-mediated flow. Here we adopted our previously developed Device Thrombogenicity Emulation methodology to design microfluidic platforms able to emulate representative shear stress profiles of mechanical circulatory support (MCS) devices. Our long-term goal is to utilize these systems for point-of-care (POC) personalized testing of AT efficacy under specific, individual shear profiles. First, we designed different types of microfluidic channels able to replicate sample shear stress patterns observed in MCS devices. Second, we explored the flexibility of microfluidic technology in generating dynamic shear stress profiles by modulating the geometrical features of the channels. Finally, we designed microfluidic channel systems able to emulate the shear stress profiles of two commercial VADs. From CFD analyses, the VAD-emulating microfluidic systems were able to replicate the main characteristics of the shear stress waveforms of the macroscale VADs (i.e., shear stress peaks and duration). Our results establish the basis for development of a lab-on-chip POC system able to perform device-specific and patient-specific platelet activation state assays.

Near patient CD4 count in a hospitalized HIV patient population.

Point-of-care (POC) CD4 T-cell counting is increasingly recognized as providing improved linkage-to-care during management of HIV infection, particularly in resource-limited settings where disease burden is highest. This study evaluated prototype POC CD4 T-cell counters from MBio Diagnostics in the context of low CD4 count, hospitalized patients in Mozambique. This study measured system performance when presented with challenging, low count samples from HIV/AIDS patients with acute illnesses resulting in hospitalization. Forty whole blood samples were collected from donors on the medical service at Maputo Central Hospital and absolute CD4 counts were generated on the MBio CD4 system and a reference laboratory using flow cytometry. The mean and median CD4 counts by the flow cytometry reference were 173 and 80 cells/µL, respectively. Correlation between the MBio CD4 System and the reference was good. Bland-Altman analysis showed a mean bias of +15 cells/µL (+9 to +21 cells/µL, 95% CI), and limits of agreement of -47 to 77 cells/µL. For samples with counts >100 cells/µL (N = 14), the mean coefficient of variation was 7.3%. For samples with counts <50 cells/µL, mean absolute bias of replicate samples was 4.8 cells/µL. When two MBio readers were compared, Bland-Altman bias was -4 cells/µL (-13 to +6 cells/µL, 95% CI), and limits of agreement of -63 and +55 cells/µL. The MBio System holds promise as a POC system for quantitation of CD4 T cells in resource-limited settings given system throughput (80-100 cartridges/day), design simplicity, and ease-of-use. © 2015 International Clinical Cytometry Society.

Mach-Zehnder interferometer (MZI) point-of-care system for rapid multiplexed detection of microRNAs in human urine specimens.

MicroRNAs have been identified as promising biomarkers for human diseases. The development of a point-of-care (POC) test for the disease-associated miRNAs would be especially beneficial, since miRNAs are unexpectedly well preserved in various human specimens, including urine. Here, we present the Mach-Zehnder interferometer-miRNA detection system capable of detecting multiple miRNAs in clinical urine samples rapidly and simultaneously in a label-free and real-time manner. Through measurement of the light phase change, the MZI sensor provides an optical platform for fast profiling of small molecules with improved accuracy. We demonstrate that this system could specifically detect target miRNAs (miR-21, and let-7a), and even identify the single nucleotide polymorphism of the let-7 family of miRNAs from synthetic and cell line samples. The clinical applicability of this system is confirmed by simultaneously detecting two types of miRNAs in urine samples of bladder cancer patients in a single reaction, with a detection time of 15 min. The POC system can be expanded to detect a number of miRNAs of different species and should be useful for a variety of clinical applications requiring at or near the site of patient care.