Detection Of Lactate Research Articles

Cellular Lactate Spectroscopy Using 1.5 Tesla Clinical Apparatus.

Cellular lactate is a key cellular metabolite and marker of anaerobic glycolysis. Cellular lactate uptake, release, production from glucose and glycogen, and interconversion with pyruvate are important determinants of cellular energy. It is known that lactate is present in the spectrum of neoplasms and low malignancy (without necrotic lesions). Also, the appearance of lactate signals is associated with anaerobic glucose, mitochondrial dysfunction, and other inflammatory responses. The aim of this study was the detection of lactate in cell cultures with the use of proton magnetic resonance (1H MRS) and a 1.5 Tesla clinical apparatus (MR OPTIMA 360), characterized as a medium-field system. In this study, selected metabolites, together with cellular lactate, were identified with the use of an appropriate protocol and management algorithm. This paper describes the results obtained for cancer cell cultures. This medium-field system has proven the possibility of detecting small molecules, such as lactate, with clinical instruments. 1H MRS performed using clinical MR apparatus is a useful tool for clinical analysis.

A green route for lignin-derived graphene electrodes: A disposable platform for electrochemical biosensors

The tremendous growth of disposable electrode-based portable devices for point-of-care testing requires mass production of disposable electrodes in a low-cost and sustainable manner. Here, we demonstrate a green route for the conversion of biomass lignin, patterning, and reduction of the lignin-derived graphene electrodes by sequential laser lithography, water lift-off and sodium borohydride (NaBH4) treatment, and their use for electrochemical lactate biosensors. Energy-saving and localized laser lithography converted the aromatic ring-rich lignin into porous laser-induced graphene (LIG). The conductivity and attachment of the LIG to the substrate were optimized in a factorial experiment with laser power and scan speed as variables. Characterization results revealed the conversion of partial heteroatoms (e.g., Na, S, O) into granular inorganic compounds on the LIG surface under laser treatment. Water was used as an eco-friendly solvent for the patterning of the LIG (P-LIG) by a lift-off process, where the inorganic residues and un-reacted lignin were dissolved, exposing the macro-/micro-pores in the P-LIG. NaBH4 induced a reduction of the P-LIG (P-rLIG) resulting in improved electrochemical kinetics with lower charge transfer resistance (27.3 Ω) compared to the LIG (248.1 Ω) and the P-LIG (61.4 Ω). The porous P-rLIG served as a 3D electrode for the deposition of Prussian blue and lactate oxidase for disposable electrochemical lactate biosensors, delivering a good analytical performance towards lactate detection with a linear range up to 16 mM and a high sensitivity (1.21 μA mM−1). These lignin-derived disposable electrodes, utilizing renewable resources together with low-energy consumption fabrication and patterning, may contribute to the sustainable manufacturing of biosensors for point-of-care and point-of-use applications.

In-phase simultaneous spectral editing of lactate and alanine with suppression of J-coupled lipids by the modified selective multiple quantum coherence sequences

1H magnetic resonance spectroscopy (MRS) with the multiple quantum coherence (MQC) technique allows for the detection of lactate, an end product of glycolysis, in the environment of lipids. The method can also be used to detect alanine, a byproduct of glutaminolysis. An issue is that when both lactate and alanine are detected together by the MQC technique, a phase mismatch arises between lactate and alanine signals due to off-resonance rotations and the difference in double quantum coherence frequencies between the two molecules. Such phase mismatch can cause errors in spectral fitting and metabolite quantification. In this study, we designed two pulse sequences that eliminate such phase differences of lactate and alanine while suppressing lipid signals by modifications of the Selective Multiple Quantum Coherence (Sel-MQC) sequence, a well-known MQC technique. Using the product operator formalism and the off-resonance rotation matrices, the phase evolutions of lactate and alanine during the spectrally selective pulses and the free precession times of the sequence at the single quantum, double quantum and zero quantum coherence states of these molecules were calculated. The multiple quantum (MQ) evolution time t1 that can remove the phase difference of lactate and alanine at the echo was calculated and fine-tuned with experiments. The lactate and alanine signal intensities and the editing efficiencies from the two modified Sel-MQC sequences were theoretically predicted by using the product operator evolutions and compared with the experimental data. The J-coupled lipid signals were successfully suppressed by both sequences. One of the two developed sequences was applied to a human body with a phantom of lactate and alanine, which resulted in successful in-phase editing of lactate and alanine and suppression of the lipid signals from the body. The study sets an important foundation for the noninvasive detection of lactate and alanine from tumors of cancer patients.

Overexpressing the hydroxycarboxylic acid receptor 1 in mouse brown adipose tissue restores glucose tolerance and insulin sensitivity in diet-induced obese mice.

Interscapular brown adipose tissue (BAT) plays an important role in controlling glucose homeostasis. Increased glucose entry and glycolysis in BAT result in lactate production and release. The adipose tissue expresses the lactate receptor hydrocarboxylic acid receptor 1 (HCAR1), markedly downregulated in male diet-induced obese (DIO) and ob/ob mice. In this study, we examined the role of HCAR1 in BAT in controlling glucose homeostasis in male DIO mice. We overexpressed HCAR1 in BAT by injecting adeno-associated viruses (AAVs) expressing HCAR1 into the BAT pads of male DIO C57BL/6J mice. Overexpressing HCAR1 in BAT resulted in augmented glucose uptake by BAT in response to treatment with the HCAR1 agonist. HCAR1 overexpression elevated BAT temperature associated with increased thermogenic gene expression in BAT. HCAR1 overexpression prevented body weight gain in male DIO mice. Importantly, mice overexpressing HCAR1 in BAT exhibited improved glucose tolerance and insulin sensitivity. HCAR1 overexpression upregulated the Slc2a4 gene expression and promoted GLUT4 trafficking to the plasma membrane. In addition, mice overexpressing HCAR1 displayed a decrease in hormone-sensitive lipase (HSL) phosphorylation and increased lipogenic enzyme gene expression in BAT. Unlike DIO mice, overexpressing HCAR1 in BAT of mice fed a low-fat diet did not change body weight gain and glucose homeostasis. Taken together, our results support the interpretation that HCAR1 expressed in BAT promotes glucose entry and reduces lipolysis in BAT of male DIO mice. As activation of HCAR1 in BAT restores body weight, glucose tolerance, and insulin sensitivity in male DIO mice, our study suggests that interoceptive lactate detection via HCAR1 in BAT can regulate glucose and lipid substrate utilization and/or availability to promote healthy metabolism.NEW & NOTEWORTHY HCAR1 expressed in BAT can promote glucose entry and reduce lipolysis, resulting in body weight loss and increased insulin sensitivity. Hence, targeting HCAR1 in BAT would provide an alternative way to control body weight and euglycemia in individuals with obesity.

The development of micro–sized enzyme sensor based on direct electron transfer type open circuit potential sensing principle

One long term goal for biosensor development is towards implantable, long–term sensing for diagnostics, and monitoring of chronic health. The most common electrochemical sensors employ amperometric principles, although there is a fundamental challenge when trying to minimize the sensor size since the measurement current is directly proportional to the size of the working electrode. An alternative principle to amperometry for enzyme sensor is potentiometry, measuring open circuit potential (OCP). In this study, we demonstrate the size independency of an OCP based enzyme sensor focusing on direct electron transfer (DET) type– and quasi–DET–type oxidoreductases for, glucose and L–lactate, respectively. For glucose detection, we employed DET type flavin adenine dinucleotide glucose dehydrogenase, and the engineered L–lactate oxidase derived from Aerococcus viridans (AvLOx) conjugated with amine–reactive phenazine ethosulfate (arPES) was used as the quasi–DET type enzyme for the L–lactate detection. First, both enzymes were immobilized on 3 mm diameter gold disc electrode (GDE), and glucose and L–lactate were monitored based on OCP and transient potentiometric measurement, dOCP/dt. Then, L–lactate and glucose sensors were constructed using 10 µm GDEs, showing L–lactate and glucose concentration dependent OCP and dOCP/dt changes. The sensitivity was nearly equivalent for ΔOCP and dOCP/dt between the sensor using 3 mm and 10 µm GDE even though amperometric signal was entirely lost when measuring the arPES modified AvLOx on the 10 µm electrode. These results clearly demonstrate the size independency of an OCP based enzyme sensor which will be applied for the implantable and continuous monitoring system for metabolites in vivo.

Flexible bioelectronic device fabricated by conductive polymer-based living material.

Living materials are worked as an inside collaborative system that could naturally respond to changing environmental conditions. The regulation of bioelectronic processes in living materials could be effective for collecting biological signals and detecting biomarkers. Here, we constructed a living material with conjugated polymers poly[3-(3′-N,N,N-triethylamino-1′-propyloxy)-4-methyl-2,5-thiophene chloride] (PMNT) and Shewanella oneidensis MR-1 biofilm. In addition, the living material was integrated as a flexible bioelectronic device for lactate detection in physiological fluids (sweat, urine, and plasma). Owing to the electroconductivity of conjugated polymers, PMNT could optimize the bioelectronic process in the living material. The collected electrical signal could be wirelessly transferred to a portable smartphone for reading and analyzing. Because lactate is also a biomarker for cancer treatment, the flexible bioelectronic device was further used to detect and count the cancer cells. The proof of the bioelectronic device using conductive polymer–based living material exhibits promising applications in the next-generation personal health monitoring systems.

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.

Ultrastable Lactate Biosensor Linearly Responding in Whole Sweat for Noninvasive Monitoring of Hypoxia.

We report on the lactate biosensor with linear calibration range from 0.5 to 100 mM, which encircles possible levels of this metabolite concentration in both human sweat and blood. The linear calibration range at high analyte concentrations, which exceeds the Michaelis constant of lactate oxidase by several orders of magnitude, is provided by an additional perfluorosulfonated ionomer diffusion membrane. In contrast to the known lactate biosensors, which retain their response within less than a couple of hours, the reported system displays 100% response for dozens of hours even upon high analyte concentrations. The biosensors with an additional diffusion-limiting membrane have been validated for lactate detection both in human blood serum and in undiluted human sweat shortly after its secretion. Both linear response in the entire range of blood and sweat lactate concentrations and ultrahigh operational stability would provide the use of the elaborated biosensor in wearable devices for the monitoring of hypoxia.

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.

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.

Multienzyme System in Amorphous Metal-Organic Frameworks for Intracellular Lactate Detection.

Lactate is an important downstream product of glycolysis in living cells, and its level is highly related with diseases. On the basis of amorphous metal-organic frameworks (aMOFs), a multienzyme system consisting of lactate oxidase (LOx) and horseradish peroxidase (HRP) was established for intracellular lactate detection. By coencapsulation in aMOFs with proximity, LOx and HRP were delivered into cells, serving as artificially constructed organelles, exhibiting high activity and selectivity for the intracellular detection of the important metabolite lactate, which improved the signal to noise ratio by ∼650-fold. As demonstrated by both experimental and simulation results, the high efficiency was attributed to the short distance between the two types of enzymes coencapsulated in aMOFs. The concept of constructing multienzyme systems in this study shows promise for the detection of various intracellular metabolites.

Chemical Exchange Saturation Transfer for Lactate-Weighted Imaging at 3 T MRI: Comprehensive In Silico, In Vitro, In Situ, and In Vivo Evaluations.

Based on in silico, in vitro, in situ, and in vivo evaluations, this study aims to establish and optimize the chemical exchange saturation transfer (CEST) imaging of lactate (Lactate-CEST—LATEST). To this end, we optimized LATEST sequences using Bloch–McConnell simulations for optimal detection of lactate with a clinical 3 T MRI scanner. The optimized sequences were used to image variable lactate concentrations in vitro (using phantom measurements), in situ (using nine human cadaveric lower leg specimens), and in vivo (using four healthy volunteers after exertional exercise) that were then statistically analyzed using the non-parametric Friedman test and Kendall Tau-b rank correlation. Within the simulated Bloch–McConnell equations framework, the magnetization transfer ratio asymmetry (MTRasym) value was quantified as 0.4% in the lactate-specific range of 0.5–1 ppm, both in vitro and in situ, and served as the imaging surrogate of the lactate level. In situ, significant differences (p < 0.001) and strong correlations (τ = 0.67) were observed between the MTRasym values and standardized intra-muscular lactate concentrations. In vivo, a temporary increase in the MTRasym values was detected after exertional exercise. In this bench-to-bedside comprehensive feasibility study, different lactate concentrations were detected using an optimized LATEST imaging protocol in vitro, in situ, and in vivo at 3 T, which prospectively paves the way towards non-invasive quantification and monitoring of lactate levels across a broad spectrum of diseases.

A dual-functional polyaniline film-based flexible electrochemical sensor for the detection of pH and lactate in sweat of the human body.

A flexible dual functional electrochemical sensor based on macroscopic polyaniline (PANI) film is reported. The PANI film is prepared by interfacial synthesis without any additional templates and surfactants, and is easily transferred from the water surface to any substrate. The surface of PANI film is flat and has a certain degree of crystallization. The PANI film exhibits good electrochemical properties, which is attributed to the order structure of PANI. The flexible sensor based on PANI film exhibits good electrochemical performances to pH and lactate. And the flexible PANI sensor has good reproducibility, selectivity and long-term stability. Meanwhile, the PANI sensor is also applied to detect the actual sample (such as food and human sweat), and the results are in accordance with the commercial pH meter, indicating the reliability of the PANI sensor.

Effect of Coordinated Solvent Molecules in Cu-MOF on Enzyme Free Sensing of Glucose and Lactate in Physiological pH

Developing a nonenzymatic sweat sensor for selective determination of glucose and lactate holds great significance in clinical diagnostics. Among various catalysts, transition metal-based metal-organic frameworks (MOF) have recently drawn more attention due to their tunable porosity and enhanced electrocatalytic activity. The presence of the solvent molecule in the framework can influence both structural and electrochemical properties. In the present work, Copper-terephthalate (CuBDC) MOF was synthesized in a solvothermal method with different time durations. The effect of the coordinated solvent molecules on the metal centre on structural and electrocatalytic properties was systematically investigated using various characterization techniques. As most of the copper-based composites reported so far showed performance in an alkaline medium, we demonstrate the detection of glucose and lactate in a neutral medium that enables direct analyte measurement from the body fluid. Electrochemical studies indicate that the solvated structure shows superior sensitivity to the desolvated MOF for glucose and lactate. The high sensitivity of the solvated MOF is attributed to the favourable solvent exchange mechanism and ion diffusion through the channels of the MOF. Furthermore, CuBDC12E and CuBDC48E show negligible interference toward competing analytes. The proposed sensor also exhibits good sensing performance in artificial sweat, making it suitable for a non-invasive, practical sweat sensor.

Multicommutation flow analysis system for non-enzymatic lactate determination based on light-driven photometric assay

A fully-mechanized bioanalytical system for the photometric light-driven lactate determination is presented. The system is based on highly integrated four diode flow-through cell in which two UV-LEDs are used for the photochemical reduction of Fe(III) in the presence of lactate whereas LED-photodiode system allows the photometric detection of Fe(II)-Ferrozine complex to be registered. The developed multicommutation flow analysis system consisting of bifunctional optoelectronic device (photodegradation of Fe(III)-lactate complex and detection), solenoid micropumps and microvalves, is fully controlled and powered by the Arduino-compatible electronics. In consequence, independent and precise control of crucial parameters of the assay, including irradiation time and current supplying UV-LEDs is possible. Under optimized condition the system is useful for the lactate determination in the sub-milimolar range of concentration (6.0–300.0 μmol/L) with satisfactory sensitivity (597.1 AU·L/μmol) and detection limit (3.4 μmol/L), significant reduction of sample and reagents consumption (1.25 μL or 0.5 μL for 40- and 100-fold dilution of human serum samples, respectively) and high sample flow throughput (24 detections per hour). As the system offers the monitoring of detection process, the kinetic discrimination of effects from potential interferents is possible, improving the assay selectivity. The practical utility of the designed system was confirmed by its used for analysis of human serum standards. The recovery values were in the range of 92.1–104.2%. As the limit of quantitation offered by the system is significantly lower than physiological lactate levels, the serum samples have to be diluted what results in further decrease of both sample volume required for analysis and nonselective effects from matrix.

Electrochemical sensor for enzymatic lactate detection based on laser-scribed graphitic carbon modified with platinum, chitosan and lactate oxidase

We developed a flexible laser scribed graphitic carbon based lactate biosensor fabricated using a low cost 450 nm laser. We demonstrated a facile fabrication method involving electrodeposition of platinum followed by two casting steps for modification with chitosan and lactate oxidase. The biosensor demonstrated chronoamperometric lactate detection within a linear range from 0.2 mM to 3 mM, (R2 > 0.99), with a limit of detection of 0.11 mM and a sensitivity of 35.8 μA/mM/cm2. The biosensor was successful in performing up to 10 consecutive measurements (one after the other) indicating good working stability (RSD <5%). Concerning storage stability, there was no decrease in signal response after 30 days of storage at 4 °C. Additionally, we demonstrate enzymatic lactate detection whilst the flexible polyimide substrates were fixed at a curvature (K) of 0.14 mm−1. No noticeable change in signal response was observed in comparison to calibrations obtained at a curvature of 0 mm−1, signifying potential opportunities for sensor attachment or integration with oral-care products such as mouth swabs. Both laser scribed graphitic carbon and Ag/AgCl modified-laser scribed graphitic carbon were successful as reference electrodes for chronoamperometric lactate measurements. Furthermore, using a three-electrode configuration on polyimide, lactate detection in both artificial saliva and sterile human serum samples was achieved for two spiked concentrations (0.5 mM and 1 mM).

Smartphone‐based Electrochemical On‐site Quantitative Detection Device for Nonenzyme Lactate Detection

AbstractOn‐site quantitative detection provides the opportunity for accurate and timely health care, clinical diagnosis, environmental monitoring, and food analysis. A variety of portable electrochemical detection instruments have been developed at present for on‐site quantitative detection use, including commercially available portable potentiostats, but the reality is that these electrochemical detection devices still have the problem of narrow output voltage range and detection current range, and their performance of output voltage resolution and detection current resolution is still unsatisfactory. The narrow voltage or current range makes it difficult for some chemical reactions with peaks outside the range to proceed, and the insufficiency of voltage resolution and detection current resolution are key parameters restricting the detection accuracy of existing devices. In this regard, it is urgent to carry out partial transformation of the existing device to increase the use range and detection accuracy of the device. In the current work, a smartphone‐based electrochemical on‐site quantitative detection device was developed. The device comprises a portable small potentiostat, a smartphone equipped with a specially designed Android electrochemical detection application, and a disposable sensor (NiONP modified screen‐printed electrode [SPE]). The potentiostat can realize electrochemical detection methods, including cyclic voltammetry, chronoamperometry, and differential pulse voltammetry. In addition, the potentiostat can output a potential range −2.047∼+2.047 V with a current detection sensitivity scale 1×10−8∼1×10−3 A, and the current detection range could reach ±10 nA∼±10 mA. Most importantly, the current detection resolution of the potentiostat can reach 0.003 % (3.125 pA on ±10 nA range). The smartphone was used for communicating with the potentiostat, setting detection parameters, and mapping voltammograms in real time. The SPE was modified with nickel oxide nanoparticles and perfluorinated resin solution, which were employed as sensors to convert and amplify the electrochemical current response during the on‐site quantitative detection. Results indicated that the device features excellent performance for the lactate detection. The device covered a linear range 0.1∼30 mM on lactate detection with the correlation coefficient (R2) reaching 0.997.

A Flexible Dual-Analyte Electrochemical Biosensor for Salivary Glucose and Lactate Detection.

Electrochemical biosensors have been widely applied in the development of metabolite detection systems for disease management. However, conventional intravenous and fingertip blood tests are invasive and cannot track dynamic trends of multiple metabolites. Among various body fluids, saliva can be easily accessed and is regarded as a promising candidate for non-invasive metabolite detection. Recent works on the development of electrochemical biosensors for monitoring salivary metabolites have demonstrated high sensitivity and wide linear range. However, most of this research has been focused on salivary detection of a single metabolite. Here, we present a dual-channel electrochemical biosensor for simultaneous detection of lactate and glucose in saliva based on a flexible screen-printed electrode with two working electrodes. The sensitivities of glucose and lactate channels were 18.7 μA/(mM·cm2) and 21.8 μA/(mM·cm2), respectively. The dual-channel biosensor exhibited wide linear ranges of 0–1500 μM for the glucose channel and 0–2000 μM for the lactate channel and the cross-talk between the two detection channels was negligible, which made it adequately suitable for sensing low-level salivary metabolites. Such attractive characteristics demonstrate the potential of this dual-analyte biosensor in the development of wearable devices for monitoring disease progression and fitness.

Coherence pathway analysis of J-coupled lipids and lactate and effective suppression of lipids upon the selective multiple quantum coherence lactate editing sequence

Objective. The selective multiple quantum coherence (Sel-MQC) sequence is a magnetic resonance spectroscopy (MRS) technique used to detect lactate and suppress co-resonant lipid signals in vivo. The coherence pathways of J-coupled lipids upon the sequence, however, have not been studied, hindering a logical design of the sequence to fully attenuate lipid signals. The objective of this study is to elucidate the coherence pathways of J-coupled lipids upon the Sel-MQC sequence and find a strategy to effectively suppress lipid signals from these pathways while keeping the lactate signal. Approach. The product operator formalism was used to express the evolutions of the J-coupled spins of lipids and lactate. The transformations of the product operators by the spectrally selective pulses of the sequence were calculated by using the off-resonance rotation matrices. The coherence pathways and the conversion rates of the individual pathways were derived from them. Experiments were performed on phantoms and two human subjects at 3 T. Main results. The coherence pathways contributing to the various lipid resonance signals by the Sel-MQC sequence depending on the gradient ratios and RF pulse lengths were identified. Theoretical calculations of the signals from the determined coherence pathways and signal attenuations by gradients matched the experimental data very well. Lipid signals from fatty tissues of the subjects were successfully suppressed to the noise level by using the gradient ratio −0.8:−1:2 or 1:0.8:2. The new gradient ratios kept the lactate signal the same as with the previously used gradient ratio 0:−1:2. Significance. The study has elucidated the coherence pathways of J-coupled lipids upon the Sel-MQC sequence and demonstrated how lipid signals can be effectively suppressed while keeping lactate signals by using information from the coherence pathway analysis. The findings enable applying the Sel-MQC sequence to lactate detection in an environment of high concentrations of lipids.