Nurse-led diuretic titration via a point-of-care urinary sodium sensor in patients with acute decompensated heart failure (EASY-HF): A single-centre, randomized, open-label study.

AIMS: Early evaluation of the natriuretic response is recommended to guide diuretic therapy in acute decompensated heart failure (ADHF). However, its implementation in daily practice is hampered by implementation barriers and increased time constraints. The Readily Available Urinary Sodium Analysis in Patients with Acute Decompensated Heart Failure (EASY-HF) study assessed the feasibility, efficacy and safety of a nurse-led urinary sodium-based diuretic titration protocol with the use of a point-of-care urinary sodium sensor. METHODS AND RESULTS: The EASY-HF study was a single-centre, randomized, open-label study comparing diuretic management at the treating physician's discretion as standard of care (SOC) with a nurse-led natriuresis-guided protocol in patients with ADHF. The LAQUAtwin Sodium Meter (HORIBA) was used as point-of-care sensor to measure urine sodium concentration. The primary endpoint was natriuresis after 48 h. Secondary endpoints included safety profile and user-friendliness of both the protocol and the point-of-care sensor. Sixty patients were randomized towards SOC (n = 30) versus protocolized care (n = 30). The mean age was 80 ± 8 years, 25% were women and median N-terminal pro-B-type natriuretic peptide was 4667 (2667-7709) ng/L. Natriuresis after 48 h was significantly higher in the protocolized versus SOC group (820 ± 279 vs. 657 ± 273 mmol; p = 0.027). Pre-defined safety endpoints were similar among both groups. The sensor-based protocol was evaluated as easy to use by the nursing staff, and preferred over urinary collections. CONCLUSION: A nurse-led diuretic titration protocol via a point-of-care urinary sodium sensor was feasible, safe and resulted in an increased natriuresis in ADHF compared to SOC.

LiFT (a Lithium Fiber-Based Test): An At-Home Companion Diagnostics for a Safer Lithium Therapy in Bipolar Disorder.

This work presents LiFT (a lithium fiber-based test), a low-cost electrochemical sensor that can measure lithium in human saliva and urine with FDA-required accuracy. Lithium is used for the treatment of bipolar disorder, and has a narrow therapeutic window. Close monitoring of lithium concentration in biofluids and adjustment of drug dosage can minimize the devastating side effects. LiFT is an inexpensive, yet accurate and simple-to-operate lithium sensor for frequent at-home testing for early identification of lithium toxicity. The low cost and high accuracy of LiFT are enabled through an innovative design and the use of ubiquitous materials such as yarn and carbon black for fabrication. LiFT measures Li+ through potentiometric recognition using a lithium selective sensing membrane that is deposited on the ink-coated yarn. A detection limit of 0.97 µM is obtained with a sensitivity of 59.07±1.25 mV/decade for the Li+ sensor in deionized water. Moreover, the sodium correction extended LiFT's linear range in urine and saliva to 0.5 mM. The LiFT platform sends the test results to the patient's smartphone, which subsequently can be shared with the patient's healthcare provider to expedite diagnosis and prevention of acute lithium toxicity.

Development and early testing of a simple, low cost, fast sensor for maternal and neonatal group B Streptococcus.

Streptococcus agalactiae, (Group B Streptococcus (GBS)), is a common colonizer of the female vagina. In women giving birth it can be transmitted to the baby and cause serious illness and even death to the child. We have developed a biosensor comprising of phospholipids and fatty acids vesicles encapsulating high concentration, self-quenched carboxyfluorescein, which is released by the lysis of the vesicle by virulence factors expressed by GBS, becoming diluted and fluorescent. The microbial specificity of the sensor was tested against a number of GBS strains and other microbes including Candida albicans, Enterococcus faecalis and Staphylococcus epidermidis and a statistically significant response to GBS measured over these other microbes. To test the invivo efficacy of the biosensor, a pilot study using donated lower vaginal swabs from non-pregnant women was conducted, where 58 female adults were recruited. Participants donated two swabs, one which was used for the vesicle test and one for the 'gold standard', enriched culture media (ECM) test. An overall GBS carriage rate of 17.2% was measured using the ECM test. The vesicle biosensor test took 45 min to obtain a result, and showed a sensitivity of 83.3%, specificity of 85.7% and accuracy of 85.3%. The test accuracy is in line with current novel GBS identification tests, with the advantage of being rapid, easy to use, low-cost and able to be conducted by bedside during start of labour.

Home-Based Electrochemical Rapid Sensor (HERS): A Diagnostic Tool for Bacterial Vaginosis.

Bacterial vaginosis (BV) is the most frequently occurring vaginal infection worldwide, yet it remains significantly underdiagnosed as a majority of patients are asymptomatic. Untreated BV poses a serious threat as it increases one's risk of STI acquisition, pregnancy complications, and infertility. We aim to minimize these risks by creating a low-cost disposable sensor for at-home BV diagnosis. A clinical diagnosis of BV is most commonly made according to the Amsel criteria. In this method, a fish-like odor, caused by increased levels of trimethylamine (TMA) in vaginal fluid, is used as a key diagnostic. This paper outlines the development of a Home-Based Electrochemical Rapid Sensor (HERS), capable of detecting TMA in simulated vaginal fluid (sVF). Instead of odor-based detection of volatilized TMA, we identify TMA in trimethylammonium form by utilizing HERS and a potentiometric readout. We fabricated the ion selective electrode using a carbon-black-coated cotton string and a TMA-selective membrane consisting of calix[4]arene and sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate. When paired with a standard reference electrode, our device was able to quantify TMA concentration in deionized (DI) water, as well as sVF samples at multiple pH levels with a clinically relevant limit of detection (8.66 µM, and theoretically expected Nernstian slope of 55.14 mV/decade).

Development of a Point-of-Care SPR Sensor for the Diagnosis of Acute Myocardial Infarction.

A novel point-of-care surface plasmon resonance (SPR) sensor was developed for the sensitive and real-time detection of cardiac troponin I (cTnI) using epitope-imprinted molecular receptors. The surface coverage of a nano-molecularly imprinted polymer (nanoMIP)-functionalized SPR sensor chip and the size of nanoMIPs (155.7 nm) were characterized using fluorescence microscopy and dynamic light scattering techniques, respectively. Atomic force microscopy, electrochemical impedance spectroscopy, square wave voltammetry and cyclic voltammetry techniques confirmed the successful implementation of each step of the sensor fabrication. The SPR bio-detection assay was initially established by targeting the cTnI peptide template, and the sensor allowed the detection of the peptide in the concentration range of 100-1000 nM with a correlation coefficient (R2) of 0.96 and limit of detection (LOD) of 76.47 nM. The optimum assay conditions for protein recognition were subsequently determined, and the cTnI biomarker could be detected in a wide concentration range (0.78-50 ng mL-1) with high reproducibility (R2 = 0.91) and sensitivity (LOD: 0.52 ng mL-1). The overall sensor results were subjected to three binding isotherm models, where nanoMIP-cTnI interaction followed the Langmuir binding isotherm with the dissociation constant of 2.99 × 10-11 M, indicating a very strong affinity between the cTnI biomarker and epitope-imprinted synthetic receptor. Furthermore, the selectivity of the sensor was confirmed through studying with a control nanoMIP that was prepared by imprinting a non-specific peptide template. Based on the cross-reactivity tests with non-specific molecules (i.e., glucose, p53 protein, transferrin and bovine serum albumin), the nanoMIP-SPR sensor is highly specific for the target biomarker. The developed biomimetic sensor, relying on the direct assay strategy, holds great potential not only for the early and point-of-care testing of acute myocardial infarction but also for other life-threatening diseases that can be diagnosed by determining the elevated levels of certain biomarkers.

Electrochemiluminescence sensor for point-of-care detection of pyrrolizidine alkaloids.

Pyrrolizidine alkaloids (PAs) and PA N-oxides are hepatotoxic natural products, produced by over 6000 plant species worldwide. However, an unmet need remains for confirmative measurement of PAs in routine clinical tests. Here, we develop a visual, easy-to-use, and economic mesoporous silica-electrochemiluminescence (MPS-ECL) sensor for point-of-care (POC) testing of PAs, utilizing MPS's amplification effect on positive ions. The relationship between PAs' different structures and corresponding Ru(bpy)32+ ECL activity shows that reaction mechanism, stability of intermediate, molecular geometry and alternative anodic reactivity significantly affect the ECL activity. The ECL intensity varies among different PAs: monocrotaline ˃ senecionine N-oxide ˃ retrorsine ˃ senkirkine. The POC sensors possess excellent linearity (0.9993 > R2 > 0.9944), low detection limits (0.02 µM-0.07 µM), and good recoveries (90.12%-105.93%), indicating good accuracy and practicability. The portable and low-cost sensor is user-friendly, which holds promise to be applied to POC testing of PAs in drugs, food products, and clinical samples, which is promising for initial assessments of PA-induced health risk.

Recent Advances in Surface Plasmon Resonance Imaging Sensors.

The surface plasmon resonance (SPR) sensor is an important tool widely used for studying binding kinetics between biomolecular species. The SPR approach offers unique advantages in light of its real-time and label-free sensing capabilities. Until now, nearly all established SPR instrumentation schemes are based on single- or several-channel configurations. With the emergence of drug screening and investigation of biomolecular interactions on a massive scale these days for finding more effective treatments of diseases, there is a growing demand for the development of high-throughput 2-D SPR sensor arrays based on imaging. The so-called SPR imaging (SPRi) approach has been explored intensively in recent years. This review aims to provide an up-to-date and concise summary of recent advances in SPRi. The specific focuses are on practical instrumentation designs and their respective biosensing applications in relation to molecular sensing, healthcare testing, and environmental screening.