Lactate Sensor Research Articles

Electrochemical sensing monitoring of blood lactic acid levels in sweat during exhaustive exercise

Carbohydrate anaerobic metabolism in the human body produces lactic acid, which is of great importance in the diagnosis and treatment of diseases and the scientific management of sports. Consequently, the development of a rapid, low-cost, and disposable lactate sensor is essential. To this end, a graphene-modified lactate sensor was created. This work concluded with the optimization of the sensor's operating parameters and the evaluation of its performance under the optimal conditions. Following the testing, the proposed lactic acid sensor demonstrated high sensitivity, excellent consistency and linearity, with a linear detection range of 3–32 mM. The detection limit was determined to be 1.4 mM, the lowest value achieved. The current performance of the biosensor is reaching its peak when presented with physiological sweat lactate concentration. To monitor sweat lactate concentration, wearable electronic devices with high precision were incorporated to provide real-time remote monitoring. By engaging in exhaustive physical exercise, the amount of sweat lactate can be determined.

Textile-based dual-mode organic electrochemical transistors for lactate biosensing

The dual-mode organic electrochemical transistors (OECT) were successfully assembled on fabric. The property of different devices has been compared. In the depletion mode, the PEDOT: PSS/textile-based OECT exhibit high transconductance of 75 mS, and the switching ratio of 8 × 102. In accumulation mode, the PEDOT: PSS/DETA/textile-based OECT exhibit transconductance of 0.55 mS, switching ratio can reach 31.7. Both modes have good cycle stability. A lactate (LA) sensor was prepared by modifying the gate electrode with lactate oxidase. The sensitivity of the sensor is 69.97 mV/decade and 47.8 mV/decade in the depletion and accumulation mode, respectively. The LA sensor in both modes has good linear response in a wide concentration range of 100 pM-10 mM. The sensor has been successfully applied to the detection of LA in sweat sample. It has the advantages of simple preparation, good performance, and convenient integration into clothes, which provides a feasible platform for intelligent wearable and portable medical detection.

Assessment of Drug Susceptibility for Patient-Derived Tumor Models through Lactate Biosensing and Machine Learning.

A patient-derived tumor model (PDM) is a practical tool to rapidly screen chemotherapeutics for individual patients. The evaluation method of cell viability directly determines the application of PDMs for drug susceptibility testing. As one of the metabolites of "glycosis", the lactate content was used to evaluate cell viability, but these assays were not specific for tumor cells. Based on the "Warburg effect", wherein tumor cells preferentially rely on "aerobic glycolysis" to produce lactate instead of pyruvate in "anaerobic glycolysis" of normal cells, we reported a gold lactate sensor (GLS) to estimate the cell viability of PDMs in drug susceptibility testing. It demonstrated high consistency between the GLS and commercial cell viability assay. Unlike either imaging or cell viability assay, the GLS characterizes the cell viability, enables dynamic monitoring, and distinguishes tumor cells from other cells. Moreover, machine learning (ML) was employed to perform a multi-index assessment for drug susceptibility of PDMs, which proved to be accurate and practical for clinical application. Therefore, the GLS provides an ideal drug susceptibility testing tool for individualized medicine.

Wearable Electrodes for Lactate: Applications in Enzyme‐Based Sensors and Energy Biodevices

AbstractWearable bioelectronics is a promising next‐generation technology for its versatility in personalized applications. Measuring lactate is one of the growing trends in wearable biosensing research. To achieve this goal, enzymes capable of catalyzing reactions involving lactate must be coupled with bioelectrode components, creating a variety of biodevices such as biosensors, biofuel cells, and other devices harvesting energy from wearers. This review provides a brief history of noninvasive and minimally invasive enzyme‐based lactate biosensors and energy biodevices. We introduce key principles of lactate oxidase and lactate dehydrogenase, together with immobilization strategies for efficient electrical contacts between redox enzymes and electrode supports. Additionally, we discuss recent examples of advanced wearable enzymatic lactate sensors and elaborate on a collection of self‐powered wearable energy biodevices (e. g., biofuel cells, triboelectric nanogenerators, and piezoelectric devices). Lastly, we finish this review with discussions on challenges in developing lactate bioelectronics and provide our outlook on the prospects and future directions of this compelling technology.

Aptamer-based lactate sensor can monitor metabolism

Aptamer-based lactate sensor can monitor metabolism

A review on the recent advancements in nanomaterials for nonenzymatic lactate sensing

AbstractLactate is one of the major biomarkers to assess the physical fitness of human in clinical or sports medicine. The proper and well‐timed lactate determination can avoid some exigent conditions including hemorrhage, respiratory distress, sepsis, and hypoxia. Therefore, rapid, facile, selective, and reliable detection of lactate have gained appreciation lately. Among the various lactate detection methods, electrochemical method is the most rapid, convenient, and sensitive technique. Specifically, nanomaterial‐based nonenzymatic electrochemical lactate sensors are much desirable to solve the demerits and stability issues of enzymatic lactate sensors. Numerous materials including metal and metal oxide nanoparticles, metal–organic frameworks, molecularly imprinted polymers, and carbons were used as electrocatalysts to achieve highly sensitive lactate sensors. This present review mainly focuses on the recent developments of these materials for enzyme‐free lactate oxidation and the future prospective of electrode modification catalysts for lactate sensors.

NIR Luminescent Oxygen-Sensing Nanoparticles for Continuous Glucose and Lactate Monitoring.

A highly sensitive, biocompatible, and scalable phosphorescent oxygen sensor formulation is designed and evaluated for use in continuous metabolite sensors for biological systems. Ethyl cellulose (EC) and polystyrene (PS) nanoparticles (NPs) stabilized with Pluronic F68 (PF 68), Polydimethylsiloxane-b-polyethyleneglycol methyl ether (PDMS-PEG), sodium dodecylsulfate (SDS), and cetyltimethylammonium bromide (CTAB) were prepared and studied. The resulting NPs with eight different surfactant−polymer matrix combinations were evaluated for physical properties, oxygen sensitivity, effect of changes in dispersion matrix, and cytotoxicity. The EC NPs exhibited a narrower size distribution and 40% higher sensitivity than PS, with Stern−Volmer constants (Ksv) 0.041−0.052 µM−1 for EC, compared to 0.029−0.034 µM−1 for PS. Notably, ethyl cellulose NPs protected with PF68 were selected as the preferred formulation, as they were not cytotoxic towards 3T3 fibroblasts and exhibited a wide phosphorescence lifetime response of >211.1 µs over 258−0 µM and ~100 µs over 2.58−0 µM oxygen, with a limit of detection (LoD) of oxygen in aqueous phase of 0.0016 µM. The EC-PF68 NPs were then efficiently encapsulated in alginate microparticles along with glucose oxidase (GOx) and catalase (CAT) to form phosphorescent nanoparticles-in-microparticle (NIMs) glucose sensing microdomains. The fabricated glucose sensors showed a sensitivity of 0.40 µs dL mg−1 with a dynamic phosphorescence lifetime range of 46.6−197.1 µs over 0−150 mg dL−1 glucose, with a glucose LoD of 18.3 mg dL−1 and maximum distinguishable concentration of 111.1 mg dL−1. Similarly, lactate sensors were prepared with NIMs microdomains containing lactate oxidase (LOx) and found to have a detection range of 0−14 mg dL−1 with LoD of 1.8 mg dL−1 and maximum concentration of 13.7 mg dL−1 with lactate sensitivity of 10.7 µs dL mg−1. Owing to its versatility, the proposed NIMs-based design can be extended to a wide range of metabolites and different oxygen-sensing dyes with different excitation wavelengths based on specific application.

Application of Non-Enzymatic Lactate Sensor Modified by Graphitic Carbon Nitride/Iron–Platinum Nanoparticles and Combined With the Low Power Consumption Instrumentation Amplifier and Calibration Readout Circuit

In a previous study, this laboratory produced and tested a lactic acid biosensor using a copper-doped zinc oxide (CZO) sensing film modified with graphite carbon nitride (g-C <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> ) and iron platinum nanoparticles (FePt NPs). The previous sensor exhibited two non-ideal effects during persistent use and when alternating between high and low lactose concentrations. Using a low unity-gain frequency and low power consumption instrumentation amplifier (UGFPCIA) in conjunction with a calibration readout circuit, it was possible to reduce the previously observed drift and hysteresis effects. The UGFPCIA and calibration readout circuit were connected to a voltage-time (V-T) measurement system so the effects could be accurately quantified. The influence of the UGFPCIA on the measurement characteristics of the lactate biosensor were recorded and compared to a similar device using a commercial LT1167. Results showed that the UGFPCIA produced a more stable measurement, where linearity increased from 0.985 to 0.998. When measuring interference effects, the fluctuation in response voltage became smaller, and the time drift effect was successfully reduced by 89.7%. The hysteresis effect reduced the forward period by 0.13 mV, and the reverse period by 4.37 mV.

Illuminating lactate in cells, mice, and patient samples

Lactate has emerged as a central metabolic fuel and an important signaling molecule. In this issue of Cell Metabolism, Li etal. develop a high-quality lactate sensor, allowing them to monitor lactate levels in cells, subcellular organelles, live mice, and human body fluids.

Lactate sensing by neuroepithelial cells isolated from the gills of killifish (Fundulus heteroclitus).

Lactate is produced in most vertebrate cells as a by-product of anaerobic metabolism. In addition to its role as a fuel for many tissues, circulating lactate can act as a signalling molecule and stimulates ventilation in air- and water-breathing vertebrates. Recent evidence suggests lactate acts on O2- and CO2/H+-sensitive chemoreceptors located in the mammalian carotid body. While analogous receptors (neuroepithelial cells or NECs) in fish gills are presumed to also function as lactate sensors, direct evidence is lacking. Here, using ratiometric Fura-2 Ca2+ imaging, we show that chemosensitive NECs isolated from killifish gills respond to lactate (5-10 mmol l-1; pHe ∼7.8) with intracellular Ca2+ elevations. These responses were inhibited by an L-type Ca2+ channel blocker (nifedipine; 0.5 µmoll-1), a monocarboxylic acid transporter (MCT) blocker (α-cyano-4-hydroxycinnamate; 300 µmoll-1) or a competitive MCT substrate (pyruvate; 5 mmol l-1). These data provide the first direct evidence that gill NECs act as lactate sensors.

Dual-gate thin film transistor lactate sensors operating in the subthreshold regime

Organic thin-film transistors (TFTs) with an electrochemically functionalized sensing gate are promising platforms for wearable health-monitoring technologies because they are light, flexible, and cheap. Achieving both high sensitivity and low power is highly demanding for portable or wearable devices. In this work, we present flexible printed dual-gate (DG) organic TFTs operating in the subthreshold regime with ultralow power and high sensitivity. The subthreshold operation of the gate-modulated TFT-based sensors not only increases the sensitivity but also reduces the power consumption. The DG configuration has deeper depletion and stronger accumulation, thereby further making the subthreshold slope sharper. We integrate an enzymatic lactate-sensing extended-gate electrode into the printed DG TFT and achieve exceptionally high sensitivity (0.77) and ultralow static power consumption (10 nW). Our sensors are successfully demonstrated in physiological lactate monitoring with human saliva. The accuracy of the DG TFT sensing system is as good as that of a high-cost conventional assay. The developed platform can be readily extended to various materials and technologies for high performance wearable sensing applications.

Ultrasensitive sensors reveal the spatiotemporal landscape of lactate metabolism in physiology and disease

Despite its central importance in cellular metabolism, many details remain to be determined regarding subcellular lactate metabolism and its regulation in physiology and disease, as there is sensitive spatiotemporal resolution of lactate distribution, and dynamics remains a technical challenge. Here, we develop and characterize an ultrasensitive, highly responsive, ratiometric lactate sensor, named FiLa, enabling the monitoring of subtle lactate fluctuations in living cells and animals. Utilizing FiLa, we demonstrate that lactate is highly enriched in mammalian mitochondria and compile an atlas of subcellular lactate metabolism that reveals lactate as a key hub sensing various metabolic activities. In addition, FiLa sensors also enable direct imaging of elevated lactate levels in diabetic mice and facilitate the establishment of a simple, rapid, and sensitive lactate assay for point-of-care clinical screening. Thus, FiLa sensors provide powerful, broadly applicable tools for defining the spatiotemporal landscape of lactate metabolism in health and disease.

What Is Left for Real-Life Lactate Monitoring? Current Advances in Electrochemical Lactate (Bio)Sensors for Agrifood and Biomedical Applications.

Monitoring of lactate is spreading from the evident clinical environment, where its role as a biomarker is notorious, to the agrifood ambit as well. In the former, lactate concentration can serve as a useful indicator of several diseases (e.g., tumour development and lactic acidosis) and a relevant value in sports performance for athletes, among others. In the latter, the spotlight is placed on the food control, bringing to the table meaningful information such as decaying product detection and stress monitoring of species. No matter what purpose is involved, electrochemical (bio)sensors stand as a solid and suitable choice. However, for the time being, this statement seems to be true only for discrete measurements. The reality exposes that real and continuous lactate monitoring is still a troublesome goal. In this review, a critical overview of electrochemical lactate (bio)sensors for clinical and agrifood situations is performed. Additionally, the transduction possibilities and different sensor designs approaches are also discussed. The main aim is to reflect the current state of the art and to indicate relevant advances (and bottlenecks) to keep in mind for further development and the final achievement of this highly worthy objective.

Non-Invasive Lactate Monitoring System Using Wearable Chipless Microwave Sensors With Enhanced Sensitivity and Zero Power Consumption.

Monitoring lactate levels is an established method for determining hyperlactatemia in critically ill patients and assessing aerobic fitness. It is a widely used gold-standard technique in both professional and serious amateur sports. Non-invasive real-time lactate monitoring offers significant advantages over the current technology of finger-prick blood sampling. Possible candidate technology for developing non-invasive real-time lactate monitoring should be highly sensitive, flexible, and capable of real-time monitoring of lactate levels in interstitial fluid or within specific working muscle groups depending on the type of sport. Herein we describe a planar, flexible, passive, chipless tag resonator that is electromagnetically coupled to a reader placed in proximity to the lactate sensor tag. The tag resonator is a thin metallic tracing that can be taped on the skin. The resonance frequency of the tag fluctuates proportionately with changing lactate concentrations in a solution mimicking human interstitial fluid with very high sensitivity. The spectrum of the tag is reflected in the spectrum of the reader, which is a planar microwave resonator designed at a different frequency. The reader could be embedded in a cellphone or an application-specific wearable device for data communication and processing. The tag can accurately and reproducibly measure lactate concentrations in the range of 1 to 10 mM, which is in the physiological range of lactate observed at rest and during intense physical activity. Furthermore, the chrematistics of this technology will allow monitoring of lactate in specific working muscle groups.

A performance improvement of enzyme-based electrochemical lactate sensor fabricated by electroplating novel PdCu mediator on a laser induced graphene electrode

A lactate sensor for lactate sensing using porous laser-induced graphene (LIG) electrodes with an electrodeposited PdCu catalyst was developed in this study. CO2 laser was used to convert the polyimide film surface to multilayered LIG. The morphology and composition of LIG were analyzed through field-emission scanning electron microscopy and Raman spectroscopy, respectively, to confirm that the fabricated LIG electrode was composed of porous and stacked graphene layers. PdCu was electrodeposited on the LIG electrode and lactate oxidase (LOx) was immobilized on the LIG surface to create a LOx/PdCu/LIG structure. According to the Randles–Ševčík equation, the calculated active surface area of the fabricated PdCu/LIG electrode was ∼12.8 mm2, which was larger than the apparent area of PdCu/LIG (1.766 mm2) by a factor of 7.25. The measured sensitivities of the fabricated lactate sensors with the LOx/PdCu/LIG electrode were −51.91 μA/mM·cm2 (0.1–5 mM) and −17.18 μA/mM·cm2 (5–30 mM). The calculated limit of detection was 0.28 μM. The selectivity of the fabricated lactate sensor is excellent toward various potentially interfering materials such as ascorbic acid, uric acid, lactose, sucrose, K+ and Na+.

A dual-lactate sensor for milk spoilage based on modified recycled UHT milk carton cellulose surface

Cellulose waste from UHT milk carton is readily transformed into a novel substrate for colorimetric and electrochemical lactate sensor as milk spoilage indication for the first time. For colorimetric sensor, the cellulose is prepared by using alkali and bleach treatment, followed by enzymatic immobilization on its surface. For electrochemical sensor, the cellulose is immersed into extracted aluminum solution to create conductive working electrode with increased surface roughness compared with recycle cellulose verified by atomic force microscopy. Scanning electron micrographs illustrate 3D fibrous network of cellulose with air interstices in between and X-ray photoelectron spectroscopy shows a binding energy of 73.456 eV confirming the presence of Al–O bond after immersing cellulose into aluminum solution. The colorimetric sensor shows the intense purpleness upon the increase of lactate concentration, while the aluminum coated cellulose electrode exhibits the enhanced current response towards the increased lactate concentration. This dual-lactate sensor offers a linearity of 0.125–2 M, covering a cut-off lactate level (1.0 M) for milk spoilage. Ultimately, this sensor is successfully applied for lactate determination in real milk samples, validated by a standard HPLC.

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.

Highly Reliable Passive RFID-Based Inductor–Capacitor Sensory System Strengthened by Solvatochromism for Fast and Wide-Range Lactate Detection

A passive radio frequency-identification-based inductor-capacitor (LC) lactate sensory system with a specific dye-containing interdigitated capacitor (IDC) in which the sensing signal is amplified by the solvatochromic effect is proposed. When a lactate solution contacts the IDC of the LC lactate sensor, the capacitance of the IDC changes, changing the resonance frequency of the sensor. This changes the oscillation frequency of the Colpitts oscillator in the readout circuit. By analyzing the frequency changes, the concentration of the lactate solution can be measured quickly and accurately over a wide range. To our knowledge, the proposed device is the first passive, battery-free LC lactate sensor that uses solvatochromic dye-containing IDC sensing elements to detect lactate solution concentrations. Four solvatochromic dyes were tested and incorporated into a polymer as the lactate-sensitive membranes of the IDCs. The proposed LC sensor tag offers excellent sensitivity and linearity over a wide lactate concentration range of about <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$10 \mu \text{M}$ </tex-math></inline-formula> to 1 M. The response and recovery times of our LC sensory system were significantly shorter than those of previously reported lactate sensors. Our results are useful for the development of reliable wearable devices capable of real-time lactate detection at a low cost.

Self-powered molecular imprinted polymers-based triboelectric sensor for noninvasive monitoring lactate levels in human sweat

Recent progress in wearable sweat sensors had overcome numerous limitations of conventional sensors and provided methods of collecting molecular-level insight into the dynamics of human bodies. Lactate, a major metabolite in human sweat, can serve as the critical limiting factor for continuing physical activity. However, pioneering works in biosensors for lactate detection in sweat has been encountered major challenges such as noble material usage, immobile power supply, and complicated circuit connection to realize the compact sustainable sensing systems. To solve these restrictions, herein, the self-powered molecular imprinted polymers-based triboelectric sensor (MIP-TES) was designed to offer a multifunctional noninvasive approach for specific and simultaneous lactate detection. Free-standing PVDF/graphene flexible electrode modified poly(3-aminophenyl boronic acid) imprinted lactate molecule demonstrated the change of the surface properties after lactate adsorption. MIP-modified electrode revealed the selective lactate sensing over non molecular imprinted polymers (NIP) electrode through the superior and stable signal change with variation of lactate concentration in human sweat. Moreover, MIP modified lactate sensor was further introduced in the triboelectric nanogenerator system to harvest mechanical energy from contact and separation into electrical output. The more adsorbed lactate led to lower energy barriers and decreasing electrical potential when detecting higher lactate concentration. Self-power triboelectric lactate sensor could directly power the number of LED lights without an external energy supply. Eventually, it was validated the feasible application of wearable sensors on human skin. The proposed self-powered lactate has created a fascinating horizon in portability, compact, and the real-time analysis of people’s perspiration in the future.

Inkjet-printed flexible non-enzymatic lactate sensor with high sensitivity and low interference using a stacked NiOx/NiOx-Nafion nanocomposite electrode with clinical blood test verification

In this paper, we present a flexible, inkjet-printed, non-enzymatic lactate sensor with high sensitivity and specificity, using a stacked nickel oxide-Nafion nanocomposite/nickel oxide working electrode. Instead of deploying a pure Nafion film on the top of the nickel oxide particles, the nickel oxide-Nafion nanocomposite layer in the new electrode scheme functions not only as an anti-interfering layer but also a reactive layer and the bottom pure nickel oxide layer free from interfering substances mainly participates in the redox reaction to enhance the sensing current. Experimental results show that the sensor with a working electrode printed using a 30 μL NiOx ink and a mixture of 30 μL NiO and 4 μL Nafion ink can exhibit an anti-interference ability of >95%, a sensitivity of 20.56 nA/mM/mm2, and limit of detection (LoD) of 0.27 mM satisfying the criteria for human lactate detection. In clinical trial, blood plasma test results show that lactate levels detected using this sensor have a strong linear correlation coefficient square of 0.959 with those measured using the colorimetry method used in hospitals, indicating its potential for application in the management of patients with abnormal lactate values requiring intensive care.