Lactate Monitoring Research Articles

Effect of milrinone versus placebo on hemodynamic in patients with septic shock: A randomize control trial

Background: Sepsis is one of the most serious healthcare problems worldwide, which is associated with high mortality and financial burdens. The common causes of death are refractory shock and multi-organ failure. Myocardial dysfunction, a relatively common complication of septic shock, causes a significantly decrease in stroke volume and cardiac output. This results in insufficient blood supply to the organs, creates multi-organ failure and finally, leading to death. The Surviving Sepsis Campaign Guidelines 2016 also recommended using dobutamine in septic shock patients who had been resuscitated until achieving normal blood pressure target of mean arterial pressure 65 mmHg or more, but still had evidence of inadequate tissue perfusion. Milrinone action via an alternative pathway from the sympathetic inotropic agents, makes the milrinone to be used as an option for improve cardiac function among sepsis patients. However, there are few studies of milrinone in patients with septic shock. Methods: We plan to conduct a double blind randomized controlled trial, enrolling patients at Siriraj hospital and Hat-Yai hospital. The adults with the diagnosis of septic shock according to definition of SEPSIS III will be screened. Patients who receive fluid resuscitation at least 30 mL/kg, mean arterial pressure (MAP) ≥ 65 mmHg, with a clinical sign of poor tissue perfusion, or evidence of impaired left ventricular systolic function (left ventricular ejection fraction (LVEF) < 40%) will be enrolled. The patients were randomly assigned in a 1:1 ratio by their sequential number to receive either milrinone (intervention group) or placebo (control group). The physician performs an echocardiogram for assessing cardiac function, before the starting of the study drug and after the 6 and 24 hours. The monitoring of vital signs, urine output, and lactate at 6 and 24 hours after milrinone or placebo commencement is recorded. Conclusion: This study will evaluate the efficacy of milrinone in improving cardiac output among adult patients with septic shock who is resuscitated to achieve target blood pressure but still have signs of poor tissue perfusion.

Fetal heart block: Vaginal delivery an option.

Fetal heart block (FHB) occurs in approximately 1:20 000 births and is associated with significant morbidity and mortality. Vaginal delivery with intrapartum fetal scalp lactate monitoring is offered as an option at our centre for selected cases, in contrast with the published literature advocating caesarean birth. To review perinatal outcomes at delivery for FHB at a tertiary referral hospital. Ours was a retrospective cohort study from 1 January, 2007 to 30 June, 2020. The infant outcomes are summarised in three delivery groups: vaginal delivery, planned caesarean section (CS) and unplanned CS. There were 23 newborns in the study period, with a median gestation at birth of 37.2 weeks and there was one antepartum fetal death in this cohort. Vaginal delivery was planned in 12 women: eight had normal births, three of these women progressed to an intrapartum (unplanned) CS and one woman had a planned CS. All live babies in the vaginal delivery cohort had an Apgar score greater than seven at five minutes. Of the 22 newborns, six required intubation, of which five had been delivered by a planned CS. Our data suggest that planned vaginal delivery is a safe option for selected women carrying a fetus with FHB. Managing labour with serial fetal scalp lactates, and the involvement of senior clinicians are important factors in achieving a successful outcome.

Resettable sweat-powered wearable electrochromic biosensor

Wearable biofuel cells (BFCs) are being widely studied as self-powered sensors to monitor one's physiological status non-invasively. However, the energy generated by such devices is often insufficient to power accompanying measurement read-out systems and communication protocols. Here, we report a reversible fully printed electrochromic self-powered sensor (ESPS) toward on-body sweat lactate monitoring. The device was realized by integrating a lactate-oxidizable BFC anode, oxygen-reducible BFC cathode, and a reversible Prussian blue (PB) electrochromic display on a single wearable patch. Through modification of the BFC electrodes, the formal potential of the PB display (0.14 V) could be positioned in between the potentials of the lactate oxidation (−0.05 V) and oxygen reduction (0.35 V). Based on this system, the ESPS enables reversible and robust color changes with distinct time- and concentration-dependent profiles. The results demonstrate that the self-powered device has practical on-body applications for continual lactate monitoring with several advantages, including facile reversibility, ease of fabrication, and naked-eye colorimetric read-out.

Wireless Wearable Electrochemical Sensing Platform with Zero-Power Osmotic Sweat Extraction for Continuous Lactate Monitoring.

Wearable and wireless monitoring of biomarkers such as lactate in sweat can provide a deeper understanding of a subject's metabolic stressors, cardiovascular health, and physiological response to exercise. However, the state-of-the-art wearable and wireless electrochemical systems rely on active sweat released either via high-exertion exercise, electrical stimulation (such as iontophoresis requiring electrical power), or chemical stimulation (such as by delivering pilocarpine or carbachol inside skin), to extract sweat under low-perspiring conditions such as at rest. Here, we present a continuous sweat lactate monitoring platform combining a hydrogel for osmotic sweat extraction, with a paper microfluidic channel for facilitating sweat transport and management, a screen-printed electrochemical lactate sensor, and a custom-built wireless wearable potentiostat system. Osmosis enables zero-electrical power sweat extraction at rest, while continuous evaporation at the end of a paper channel allows long-term sensing from fresh sweat. The positioning of the lactate sensors provides near-instantaneous sensing at low sweat volume, and the custom-designed potentiostat supports continuous monitoring with ultra-low power consumption. For a proof of concept, the prototype system was evaluated for continuous measurement of sweat lactate across a range of physiological activities with changing lactate concentrations and sweat rates: for 2 h at the resting state, 1 h during medium-intensity exercise, and 30 min during high-intensity exercise. Overall, this wearable system holds the potential of providing comprehensive and long-term continuous analysis of sweat lactate trends in the human body during rest and under exercising conditions.

(Invited) Nanomaterials-Based Electrochemical Enzyme Biosensors for Real Time Monitoring of Neurotransmitters

Measurements of neurotransmitter levels are of great physiological and pathological importance and help understanding the state and progression of a variety of neurological diseases. Such studies require the availability of effective methods to probe biochemical processes in real time and allow accurate detection and quantification in vivo. These studies are also important to develop therapies and assess pharmacological effects. However, the presence of neurotransmitters at very low concentrations and variable levels and the complexity of the biological environment pose a great challenge for detection. Electrochemical methods provide real-time measurements in vitro and in vivo. In this presentation, we will discuss design and development of nanomaterials based microbiosensing platforms for the detection of neurotransmitters in vivo, with focus on the monitoring of dopamine, lactate and glutamate. The influence of the electrode design parameters including surface coatings and electrode configurations, and the ability to obtain quantitative spatial and temporal analytical data of the release and distribution of neurotransmitters will be provided with examples of applications. Advantages and limitations of these systems for measurements in real biological environments and the use of oxygen-releasing nanomaterials to address issues related to oxygen limitations and increase sensitivity of measurements in biological environments will be discussed. Our results demonstrate the potential of electrochemical techniques to measure neurotransmitters release in real time and obtain fundamental biochemical-relevant information on physiology, metabolism and disease states in living systems.

Clinical features of severe meconium aspiration syndrome (MAS) and early predicting factors for severe MAS in neonates with meconium-stained amniotic fluid

To study the clinical features of severe meconium aspiration syndrome (MAS) and early predicting factors for the development of severe MAS in neonates with meconium-stained amniotic fluid (MSAF). A total of 295 neonates who were hospitalized due to Ⅲ° MSAF from January 2018 to December 2019 were enrolled as subjects. The neonates were classified to a non-MAS group (n=199), a mild/moderate MAS group (n=77), and a severe MAS group (n=19). A retrospective analysis was performed for general clinical data, blood gas parameters, infection indicators, and perinatal clinical data of the mother. The respiratory support regimens after birth were compared among the three groups. The receiver operating characteristic (ROC) curve and multivariate logistic regression analysis were used to investigate predicting factors for the development of severe MAS in neonates with MSAF. Among the 295 neonates with MSAF, 32.5% (96/295) experienced MAS, among whom 20% (19/96) had severe MAS. Compared with the mild/moderate MAS group and the non-MAS group, the severe MAS group had a significantly lower 5-minute Apgar score (P<0.05) and a significantly higher blood lactate level in the umbilical artery (P<0.05). Compared with the non-MAS group, the severe MAS group had a significantly higher level of interleukin-6 (IL-6) in peripheral blood at 1 hour after birth (P<0.017). In the severe MAS group, 79% (15/19) of the neonates were born inactive, among whom 13 underwent meconium suctioning, and 100% of the neonates started to receive mechanical ventilation within 24 hours. Peripheral blood IL-6 >39.02 pg/mL and white blood cell count (WBC) >30.345×109/L at 1 hour after birth were early predicting indicators for severe MAS in neonates with MSAF (P<0.05). Meconium suctioning cannot completely prevent the onset of severe MAS in neonates with MSAF. The neonates with severe MAS may develop severe respiratory distress and require mechanical ventilation early after birth. Close monitoring of blood lactate in the umbilical artery and peripheral blood IL-6 and WBC at 1 hour after birth may help with early prediction of the development and severity of MAS.

A three-dimensional electrochemical biosensor integrated with hydrogel for cells culture and lactate release monitoring

Three-dimensional (3D) cell culture has attracted increasing interest in many fields with the significant advantages in reproducing in vivo cell environment. For the characterization of biochemical information, electrochemical sensing has stood out from other techniques in real-time monitoring of living cells, and made an attempt to integrate with hydrogel for investigating the biological processes in 3D cell culture. However, it is still a challenge for real-time monitoring of cellular metabolites therein for the lack of electrochemical activity, and lactate (the product of aerobic glycolysis) is a typical example of such a predicament. Herein, we developed a 3D enzymatic electrochemical sensor that could be integrated with collagen hydrogel to monitor the lactate levels of cells cultured therein. Specifically, lactate oxidase immobilized on the outer surface of 3D sensor could oxidize lactate with H2O2 as a product, and Prussian blue nanoparticles electrodeposited on carbon nanotubes adsorbed electrode conferred the excellent and stable electrocatalytic performance to H2O2 for lactate detection. Further, the 3D sensor was integrated with collagen hydrogel with C6 glioma cells seeded therein and allowed the successful real-time monitoring of lactate released from C6 glioma cells, providing an effective detection platform for exploring the biochemical response in 3D cell culture systems.

Study of Early Lactate Clearance as an Independent Predictor of Survival in Patients with Presumed Sepsis

&#x0D; Aim: Measurement of serial serum lactate levels in patients presenting with sepsis and correlating with 1. early lactate clearance with mortality. 2. Early lactate clearance vs. first (baseline) lactate level in mortality prediction. 3. Early lactate clearance vs. ACUTE PHYSIOLOGY AND CHRONIC HEALTH EVALUATION II score in mortality prediction. 4. Early lactate clearance vs. non lactate clearance in mortality prediction.&#x0D; Place and Duration of Study: Department of General Medicine, SMIMER, Surat, Gujarat between December 1st 2017 and November 25th 2019.&#x0D; Methodology: 50 patients (36 male, 14 females; age more than 18 years) Patient with sepsis were selected from Medicine ICU by using ACUTE PHYSIOLOGY AND CHRONIC HEALTH EVALUATION II score ≥ 12 points. Lactate levels at 0, 6, 12, 24 and 48 hours were measured by using ABG done by ABL 800 basic analyzer. ACUTE PHYSIOLOGY AND CHRONIC HEALTH EVALUATION II score was calculated on admission. Lactate clearance was calculated (&lt;10% OR &gt;10%) and was correlated with mortality (&lt; 7 days or &gt; 7 days).&#x0D; Results: Among 50 patients studied, 39 patients were in lactate clearance group and 11 patients were in lactate non-clearance group. In lactate clearance group 35 (89%) patients survived and 4 (11%) patients expired. In lactate non-clearance group 9 (81%) patients expired and 2 (19%) patients survived. On observing the lactate trend, Serial serum lactate levels were decreasing in survived patients while serial serum lactate levels were static or increasing in expired patients. There was no correlation between serum lactate at 0 hour and mortality in the study group (p value &gt; 0.05). There was correlation between serum lactate at 6, 12, and 24 hours with mortality (p value &lt;0.05). There was strong correlation between serum lactate clearance and mortality (p value &lt; 0.01).&#x0D; Conclusion: Study confirmed the prognostic value of serial serum lactate monitoring and its clearance for prediction of mortality. We concluded that early lactate clearance could be used as an independent predictor of survival in patients with presumed sepsis.&#x0D; &#x0D;

Automated online monitoring of lactate and pyruvate in tamoxifen resistant MCF-7 cells using sequential-injection capillary electrophoresis with contactless conductivity detection (SI-CE-C4D) and correlation with MCT1 and MCT4 genes expression

Breast cancer is among the most common cancer types worldwide. The first and second line treatment protocols for various stages of breast cancer in females rely on tamoxifen. Until now, the development of tamoxifen resistance is not entirely understood. In this study, an automated sequential injection capillary electrophoresis with capacitively coupled contactless conductivity detector was developed for online levels monitoring of both lactate and pyruvate from the supernatant media of MCF-7 cells developing tamoxifen resistance. Changes in concentration of the two metabolites were simultaneously monitored from three model cell cultures and two control untreated cells. The electrophoretic separation was performed under reversed electroosmotic flow conditions. The system delivers high sample throughput at low sample consumption of 20 µL per analysis. The method is robust and achieved high sensitivity and resolution. Limits of detection were 8.0 and 17.0 nM and linear ranges were 0.15–5 and 0.01–1 mM with a correlation coefficient of 0.9951 and 0.9963 for lactate and pyruvate, respectively. Inter-run and intra-run accuracy were in the range of 95.37–107.02% with precision (RSD, %) of ≤9.84%. The method was completely validated and the data obtained were in agreement with results achieved using the lactate and pyruvate assay kits. The highly informative generated data revealed a significant increase in lactate and pyruvate production in the three tamoxifen resistant MCF-7 cells models compared to the two control cells starting from 5.8 hours and 6.8 hours culturing times, respectively. The increase in concentrations of both lactate and pyruvate were correlated with an increase in MCT1 and MCT4 genes expression.

Continuous Lactate Monitoring System Based on Percutaneous Microneedle Array.

Lactate measurement is important in the fields of sports and medicine. Lactate accumulation can seriously affect an athlete’s performance. The most common problem caused by lactate accumulation in athletes is muscle soreness due to excessive exercise. Moreover, from a medical viewpoint, lactate is one of the main prognostic factors of sepsis. Currently, blood sampling is the most common approach to lactate measurement for lactate sensing, and continuous measurement is not available. In this study, a low-cost continuous lactate monitoring system (CLMS) is developed based on a percutaneous microneedle array that uses a three-electrode lactate sensor. The working electrode has an area of 10 mm × 6 mm, including a 3 × 3 array of stainless-steel microneedles. The length, width, and thickness of each needle are 1 mm, 0.44 mm, and 0.03 mm, respectively. The working electrode is then plated with gold, polyaniline, lactate enzyme, Nafion, and Poly(2-hydroxyethyl methacrylate) (poly HEMA). The reference electrode is a 2 × 1 array covered with AgCl, and the counter electrode is a 2 × 1 array plated with gold. The sensor is incorporated into the CLMS and connected to a smartphone application and the cloud. The CLMS was tested on 40 human subjects who rode indoor bicycles, starting at 100 W and increasing in steps of 25 W at intervals of 5 min until exhaustion. The data acquired from the app connected to the CLMS were analyzed to determine the subjects’ lactate response to exercise and the feasibility of assessing exercise performance and training exercise intensity by using the proposed system.

Hyperlactatemia as a prognostic indicator for contemporary left ventricular assist device implantation.

This study evaluates the impact of early post-operative hyperlactatemia on outcomes after left ventricular assist device (LVAD) implantation. Adults undergoing contemporary LVAD implantation between 2009 to 2018 were included. Peak post-operative (within 24-h) lactate level was analyzed. The cohort was stratified into patients with and without post-operative hyperlactatemia, which was defined as peak > 3.5 mMol/L. The primary outcome was survival, and secondary outcomes included post-implant adverse events. Sub-analysis was performed to evaluate the impact of time for lactate normalization, define as lactate < 2 mMol/L. Multivariable cox regression was used for risk-adjustment. A total of 190 patients were included. 49.5% experienced early post-operative hyperlactatemia. Patients with post-operative hyperlactatemia had significantly higher rates of post-implant complications including re-operation, renal failure, and hepatic dysfunction (all, p ≤ 0.05). The post-operative hyperlactatemia group also had significantly higher 90-day and 1-year mortality rates following LVAD implantation (both, p ≤ 0.05). In multivariable analysis, post-operative hyperlactatemia (HR 1.69, 95% CI 1.09-2.60, p = 0.02) was an independent predictor of overall mortality following LVAD implantation. Increased time for normalization of lactate also adversely impacted risk-adjusted overall mortality following implantation as a continuous variable (HR 1.02, 95% CI 1.01-1.03, p < .001). This study demonstrates early post-operative hyperlactatemia is associated with increased morbidity and mortality following LVAD implantation. Even early post-operative lactate trends within the first 24 post-operative hours appear to have a useful role in predicting longitudinal survival following implantation. Careful monitoring of post-operative lactate with measures to normalize levels should be considered in the early care of LVAD patients.

Microdialysis and CO2 sensors detect pancreatic ischemia in a porcine model.

Pancreatic transplantation is associated with a high rate of early postoperative graft thrombosis. If a thrombosis is detected in time, a potentially graft-saving intervention can be initiated. Current postoperative monitoring lacks tools for early detection of ischemia. The aim of this study was to investigate if microdialysis and tissue pCO2 sensors detect pancreatic ischemia and whether intraparenchymal and organ surface measurements are comparable. In 8 anaesthetized pigs, pairs of lactate monitoring microdialysis catheters and tissue pCO2 sensors were simultaneously inserted into the parenchyma and attached to the surface of the pancreas. Ischemia was induced by sequential arterial and venous occlusions of 45-minute duration, with two-hour reperfusion after each occlusion. Microdialysate was analyzed every 15 minutes. Tissue pCO2 was measured continuously. We investigated how surface and parenchymal measurements correlated and the capability of lactate and pCO2 to discriminate ischemic from non-ischemic periods. Ischemia was successfully induced by arterial occlusion in 8 animals and by venous occlusion in 5. During all ischemic episodes, lactate increased with a fold change of 3.2-9.5 (range) in the parenchyma and 1.7-7.6 on the surface. Tissue pCO2 increased with a fold change of 1.6-3.5 in the parenchyma and 1.3-3.0 on the surface. Systemic lactate and pCO2 remained unchanged. The area under curve (AUC) for lactate was 0.97 (95% confidence interval (CI) 0.93-1.00) for parenchymal and 0.90 (0.83-0.97) for surface (p<0.001 for both). For pCO2 the AUC was 0.93 (0.89-0.96) for parenchymal and 0.85 (0.81-0.90) for surface (p<0.001 for both). The median correlation coefficients between parenchyma and surface were 0.90 (interquartile range (IQR) 0.77-0.95) for lactate and 0.93 (0.89-0.97) for pCO2. Local organ monitoring with microdialysis and tissue pCO2 sensors detect pancreatic ischemia with adequate correlation between surface and parenchymal measurements. Both techniques and locations seem feasible for further development of clinical pancreas monitoring.

Fabrication of porous nickel (II)-based MOF@carbon nanofiber hybrid mat for high-performance non-enzymatic glucose sensing

Nickel (pyridine-2,6-dicarboxylic acid)-MOFs supported on the flexible carbon nanofiber mat (Ni(PDA)MOF@CNF) have been prepared via facile in-situ self-assembly of Ni(PDA)MOFs in the presence of CNF mat and then used as a binder-free electrode for non-enzymatic glucose detection. The porous structure of the Ni(PDA)MOF promotes the intimate contact between active centers and glucose molecules, leading to enhanced electrocatalytic performance toward anodic glucose oxidation reaction. The Ni(PDA)MOF@CNF offers a high sensitivity of 9457.5 μA mM−1 cm−2, a low detection limit of 0.053 μM, a wide linear range of 10–3000 μM, and a short response time (2 s). The selectivity of the hybrid sensor was evaluated against various bio-compounds such as ascorbic acid, dopamine, lactose, fructose, sucrose, and uric acid (UA), and found its satisfactory anti-inference activities even at their higher concentrations than normal physiologic levels. The as-fabricated Ni(PDA)MOF@CNF sensor was explored to measure the glucose content of human serum samples with reasonable performances. Furthermore, the hybrid sensor electrode showed excellent storage stability at room temperature. Hence, the flexible cost-effective Ni(PDA)MOF@CNF sensor mat could be used as a promising glucose sensing electrode for glucose and human sweat lactate monitoring in practice.

Osmotically Enabled Wearable Patch for Sweat Harvesting and Lactate Quantification.

Lactate is an essential biomarker for determining the health of the muscles and oxidative stress levels in the human body. However, most of the currently available sweat lactate monitoring devices require external power, cannot measure lactate under low sweat rates (such as in humans at rest), and do not provide adequate information about the relationship between sweat and blood lactate levels. Here, we discuss the on-skin operation of our recently developed wearable sweat sampling patch. The patch combines osmosis (using hydrogel discs) and capillary action (using paper microfluidic channel) for long-term sweat withdrawal and management. When subjects are at rest, the hydrogel disc can withdraw fluid from the skin via osmosis and deliver it to the paper. The lactate amount in the fluid is determined using a colorimetric assay. During active sweating (e.g., exercise), the paper can harvest sweat even in the absence of the hydrogel patch. The captured fluid contains lactate, which we quantify using a colorimetric assay. The measurements show the that the total number of moles of lactate in sweat is correlated to sweat rate. Lactate concentrations in sweat and blood correlate well only during high-intensity exercise. Hence, sweat appears to be a suitable biofluid for lactate quantification. Overall, this wearable patch holds the potential of providing a comprehensive analysis of sweat lactate trends in the human body.

Blood lactate concentration in COVID-19: a systematic literature review.

Coronavirus disease 2019 (COVID-19) is an infectious respiratory condition sustained by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which manifests prevalently as mild to moderate respiratory tract infection. Nevertheless, in a number of cases the clinical course may deteriorate, with onset of end organ injury, systemic dysfunction, thrombosis and ischemia. Given the clinical picture, baseline assessment and serial monitoring of blood lactate concentration may be conceivably useful inCOVID-19. We hence performed a systematic literature review to explore the possible association between increased blood lactate levels, disease severity and mortality in COVID-19 patients, including comparison of lactate values between COVID-19 and non-COVID-19 patients. We carried out an electronic search in Medline and Scopus, using the keywords "COVID-19" OR "SARS-CoV-2" AND "lactate" OR "lactic acid" OR "hyperlactatemia", between 2019 and present time (i.e. October 10, 2021), which allowed to identify 19studies, totalling 6,459 patients. Overall, we found that COVID-19 patients with worse outcome tend to display higher lactate values than those with better outcome, although most COVID-19 patients in the studies included in our analysis did not have sustained baseline hyperlactatemia. Substantially elevated lactate values were neither consistently present in all COVID-19 patients who developed unfavourable clinical outcomes. These findings suggest that blood lactate monitoring upon admission and throughout hospitalization may be useful for early identification of higher risk of unfavourable COVID-19 illness progression, though therapeutic decisions based on using conventional hyperlactatemia cut-off values (i.e.,2.0mmol/L) upon first evaluation may be inappropriate in patients with SARS-CoV-2 infection.

Synthesis and Application of Ag NPs@graphene Oxide Nanocomposite as an Electrochemical Sensor for Sweat Lactate Monitoring in Sports Medicine

Synthesis and Application of Ag NPs@graphene Oxide Nanocomposite as an Electrochemical Sensor for Sweat Lactate Monitoring in Sports Medicine

A movable type bioelectronics printing technology for modular fabrication of biosensors

Biosensors have been widely used in various fields such as food industry, environmental testing and medical testing for their high sensitivity. However, current fabrication methods of biosensors, such as screen printing, micro fabrication and 3D printing suffer from complex procedures, requirement of cleanroom facility and limited fabrication materials, which significantly restrict the development and utilization of biosensors. Here, we propose a movable type bioelectronics printing method for the fabrication of biosensors by directly transferring bioelectronic materials onto various substrates using pre-fabricated molds. This simple, low-cost, yet robust method facilitates on-demand printing of master molds of partial or complete circuits on both rigid or flexible substrates. With this method, bioactive materials such as enzymes can be directly transferred onto substrates together with other electronic components, without complex modification after electrode fabrication using conventional methods. For demonstration, a dual-channel flexible electrochemical biosensor was fabricated by the movable type bioelectronics printing method for continuous monitoring of glucose and lactate. The movable type bioelectronics printing technology holds advantages of repeatability, flexibility and low cost for fabrication of biosensors on rigid and flexible substrates, as well as direct transfer printing of bioactive materials, which greatly promotes small-scale production of biosensors.

Conducting Polymer-Reinforced Laser-Irradiated Graphene as a Heterostructured 3D Transducer for Flexible Skin Patch Biosensors.

Flexible skin patch biosensors are promising for the noninvasive determination of physiological parameters in perspiration for fitness and health monitoring. However, various prerequisites need to be met for the development of such biosensors, including the creation of a flexible conductive platform, bending/contact stability, fast electrochemical kinetics, and immobilization of biomolecules. Here, we describe a conducting polymer-reinforced laser-irradiated graphene (LIG) network as a heterostructured three-dimensional (3D) transducer for flexible skin patch biosensors. LIG with a hierarchically interconnected graphene structure is geometrically patterned on polyimide via localized laser irradiation as a flexible conductive platform, which is then reinforced by poly(3,4-ethylenedioxythiophene) (PEDOT) as a conductive binder (PEDOT/LIG) with improved structural/contact stability and electrochemical kinetics. The interconnected pores of the reinforced PEDOT/LIG function as a 3D host matrix for high loading of “artificial” (Prussian blue, PB) and natural enzymes (lactate oxidase, LOx), forming a compact and heterostructured 3D transducer (LOx/PB-PEDOT/LIG) for lactate biosensing with excellent sensitivity (11.83 μA mM–1). We demonstrated the fabrication of flexible skin patch biosensors comprising a custom-built integrated three-electrode system achieve amperometric detection of lactate in artificial sweat over a wide physiological linear range of 0–18 mM. The advantage of this facile and versatile transducer is further illustrated by the development of a folded 3D wristband lactate biosensor and a dual channel biosensors for simultaneous monitoring of lactate and glucose. This innovative design concept of a heterostructured transducer for flexible biosensors combined with a versatile fabrication approach could potentially drive the development of new wearable and skin-mountable biosensors for monitoring various physiological parameters in biofluids for noninvasive fitness and health management.

In-vivo quantification of lactate using Near Infrared reflectance spectroscopy.

Elevated lactate levels in blood (hyperlactatemia) are indications of hypoperfusion or sepsis in critical care conditions. Quantification and monitoring of this important marker is performed using intermittent blood sampling, which fails to provide a complete scenario to aid clinicians in diagnosis. The feasibility of Near Infrared (NIR) Spectroscopy as an alternative to state-of-the-art techniques in critical care environments for non-invasive and continuous monitoring of lactate has previously been established. Nevertheless, the challenge lies in translating this research from bench to bedside monitoring. For this reason, a pilot investigation was carried out with a portable NIR spectrometer, where spectra in the range of 900-1300 nm were collected from 8 healthy human volunteers undertaking a high intensity incremental exercise protocol for lactate monitoring. This paper reports on the measurement set-up, spectra acquisition and analysis of diffuse NIR reflectance spectra of varying concentrations of lactate. The results obtained by 2D correlation analysis and linear regression are promising and show that the wavelengths 923 nm, 1047 nm, 1142 nm, 1233 nm, 1280 nm and 1330 nm are significant for lactate concentration determination in the NIR region. This provides the necessary confidence for using NIR sensor technology for lactate detection in critical care.

In-situ monitoring of cell-secreted lactate by electrochemiluminescence sensing under biomimetic microfluidic confinement

Cell migration proceeds in 3D matrices in vivo, which can naturally switch to distinct phenotypes for better invasion in confined microenvironments. The studies of important metabolites under confinement are extremely meaningful for comprehensive insights into cancer metastasis. The integration of cell confinement device and analytical techniques is a key point for in-situ analysis of significant metabolites in vitro. Herein, an electrochemiluminescence (ECL) sensing platform was designed for in-situ monitoring of cell-secreted lactate in highly confined microenvironments. The 3-µm confiner was exactly fabricated via microfabrication and microfluidics technique, and cells in high confinement and low adhesion tended to be round with contractile blebs on cell margins. Significantly, in-situ monitoring of lactate was successfully achieved on the ECL platform with the catalysis of lactate oxidase, in which the levels in different time intervals were acquired in the luminol-hydrogen peroxide system. Furthermore, the results were verified by the liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology, which showed similar fluctuations with the ECL platform. This system offered an available avenue for metabolites analysis in highly confined microenvironments, which may advance deeper insights into metabolic mechanisms of cancer metastasis