Lactate Sensor Research Articles

Real‐Time Lactate Detection in A Dynamic Environment Using Micrsensing Needles

AbstractThis study introduces a novel microneedle‐based lactate sensor with SU‐8 micropillar enhancement, designed for real‐time monitoring in dynamic environments. Utilizing inkjet‐printing technology, the sensor demonstrates enhanced sensitivity and a reduced limit of detection (LoD), addressing critical challenges in clinical applications like hemodialysis and patient monitoring in ICU. Design enhancements in the medical steel needle improve stress resistance during insertion, contributing to the sensor's reliability. The experimental findings demonstrate that the microneedle is capable of achieving a high level of linearity at 0.99, with a sensitivity of 3.38 µA mM−1/mm−2–0.5 µA mM−1/mm−2 observed within the range of 0.1–0.5 mM and 1–10 mM, respectively. Meanwhile, the microneedle exhibits a low limit of detection (LoD) of 0.01 mM when tested in phosphate‐buffered saline (PBS) with varying lactate concentrations. Moreover, it demonstrates a linearity of 0.98, sensitivity of 1.13 µA mM−1 mm−2, and the same LoD of 0.01 mM in urine. The sensor maintains its performance at flow rates up to 500 mL min−1. Overall, this flexible and inkjet‐printed lactate sensor represents a significant advancement in real‐time clinical monitoring technology.

LIG-Based High-Sensitivity Multiplexed Sensing System for Simultaneous Monitoring of Metabolites and Electrolytes.

With improvements in medical environments and the widespread use of smartphones, interest in wearable biosensors for continuous body monitoring is growing. We developed a wearable multiplexed bio-sensing system that non-invasively monitors body fluids and integrates with a smartphone application. The system includes sensors, readout circuits, and a microcontroller unit (MCU) for signal processing and wireless communication. Potentiometric and amperometric measurement methods were used, with calibration capabilities added to ensure accurate readings of analyte concentrations and temperature. Laser-induced graphene (LIG)-based sensors for glucose, lactate, Na+, K+, and temperature were developed for fast, cost-effective production. The LIG electrode's 3D porous structure provided an active surface area 16 times larger than its apparent area, resulting in enhanced sensor performance. The glucose and lactate sensors exhibited high sensitivity (168.15 and 872.08 μAmM-1cm-2, respectively) and low detection limits (0.191 and 0.167 μM, respectively). The Na+ and K+ sensors demonstrated sensitivities of 65.26 and 62.19 mVdec-1, respectively, in a concentration range of 0.01-100 mM. Temperature sensors showed an average rate of resistance change per °C of 0.25%/°C, within a temperature range of 20-40 °C, providing accurate body temperature monitoring.

Scalable enzymatic lactate sensor for continuous monitoring in interstitial fluid

Abstract Elevated lactate levels have been shown to be an indicator of poor outcome in cardiovascular patients [1]. Moreover, continuous monitoring of lactate may be more clinically valuable than the absolute value of lactate for risk stratification [2]. A promising approach involves the implementation of a lactate monitoring system inspired by advanced continuous glucose monitoring [3] to provide real-time measurements of lactate in interstitial fluid (ISF) based on miniaturized lactate sensors with submillimeter dimensions. The proposed amperometric lactate sensor employs Pt electrodes (WE = 0.785 mm²) on which the enzyme lactate oxidase is immobilized to selectively detect lactate. The sensing mechanism, shown in Fig. 1a, is based on the conversion of lactate to hydrogen peroxide, which then undergoes oxidation at the electrode surface, generating a current proportional to the concentration of lactate. Amperometric measurements are performed with an applied potential of 0.5 V, a sample volume of 2 µL and a flow rate of 1 µL/min, respecting real-life conditions. The response of the sensor towards lactate is shown in Fig. 1c, demonstrating excellent reversibility, long-term stability over 8 hours and negligible cross sensitivity to glucose (G), ascorbic acid (AA) and uric acid (UA). In addition, the sensor linear range can be extended by 10x by incorporating an outer Nafion layer, acting as a diffusion-limiter. As shown in Fig. 1d, by adjusting the thickness of Nafion layer, the linear range increases up to 20 mM lactate, as per ICU specifications. The physiological challenges associated with ISF extraction prompted us to develop a minimally invasive, submillimeter-sized sensor for direct placement inside the body. To address the most critical step of miniaturization, we have successfully fabricated a three-electrode platform on a Si ribbon measuring 300x1500 µm² and a thickness of 100 µm (Fig. 2a). The sensor is also drastically scaled down, with smallest design having a total sensing area of 200x500 µm² (WE = 0.026 mm², Fig. 2b). Its response to lactate is displayed in Fig. 2c, confirming a reliable functionality. Fig. 2d presents the calibration curves obtained from sensors with different sizes, indicating that the reduction in size does not affect the sensitivity. The developed lactate sensor demonstrates excellent performance: high sensitivity, excellent reversibility, and high stability. In addition, the linear range of the sensor is tunable by integrating an outer Nafion membrane. Finally, we demonstrate the successful fabrication and characterization of submillimeter-sized sensors, opening up their potential for minimally invasive in-vivo measurements.Working principle and characterizationCharacterization miniaturized sensors

Novel bioelectrode for sweat lactate sensor based on platinum nanoparticles/reduced graphene oxide modified carbonized silk cocoon

Silk cocoons were used as a bioelectrode for the wearable electrochemical sensors of sweat lactate via carbonization and the in situ electrodeposition of platinum nanoparticles (PtNPs) and reduced graphene oxide (rGO), followed by lactate oxidase immobilization. Scanning electron microscopy, atomic force microscopy, and x-ray photoelectron microscopy confirmed that PtNPs/rGO were deposited on the carbonized silk cocoon surfaces, characterized via the physical and chemical alterations of silk cocoons. The electrocatalytic activity of PtNPs and the high surface area and functionality of rGO enhanced the electrochemical sensitivity of the sensor in lactate detection. This biosensor detected sweat lactate selectively in a range of 0–25 mM with a limit of detection of 0.07 mM, which is sufficient to distinguish between normal individuals and muscle fatigue-prone patients at a cut-off sweat lactate level of 12.5 mM. This biosensor was applied for sweat lactate detection and validated through laser desorption–ionization mass spectrometry with satisfactory results. This bioelectrode exhibits cytocompatibility with non-irritation and non-allergy to human skin, highlighting its application as a wearable lactate biosensor for self-monitoring of muscle fatigue.

Enzymatic and Enzyme‐Free Electrochemical Lactate Sensors: A Review of the Recent Developments

ABSTRACTLactate is a useful analytical indicator in various fields. The lactate monitoring benefits from evaluating the body's condition, as excessive muscle use or fatigue can result in injury. Further, it is useful for alerting to emergencies like haemorrhage, hypoxia, respiratory distress, and sepsis. Additionally, the determination of the food's lactate level is very important in examining freshness, storage stability, and fermentation degree. Given such benefits, the determination of lactate in various samples has been widely explored, especially using electrochemical sensor technology. Despite enzymatic sensors being the focus of numerous studies, enzyme‐free platforms have gained focus over the last few years to address the matter of enzyme stability. This review article respectfully offers an overview of the concepts, applications, and recent advances of electrochemical lactate detection platforms. A comparison of hot research for enzymatic and enzyme‐free lactate sensors in terms of electrode surface engineering, enzymes and their immobilisation matrices, and several analytical parameters, including linear dynamic range, the limit of detection, sensitivity, and stability, have been discussed. In addition, future perspectives have been highlighted in this review.

The Inhibitory Effects of the Natural Stilbene Piceatannol on Lactate Transport In Vitro Mediated by Monocarboxylate Transporters.

Lactate, a signaling molecule and energy source, crosses membranes through monocarboxylate transporters (MCTs). MCT1 and MCT4 are potential cancer drug targets due to their role in metabolic reprogramming of cancer cells. Stilbenes, plant secondary metabolites found in several food sources, have anticancer effects, though their mechanisms of action are not well understood. This study links the anticancer activity of natural stilbenes to tumor cell lactate metabolism. The impact of resveratrol, pinostilbene, pterostilbene, rhapontigenin, and piceatannol on lactate transport is studied using a fluorescence resonance energy transfer (FRET)-based lactate sensor. The viability and migration of cells expressing MCT1 or MCT4 are also evaluated. Piceatannol inhibits MCT1 effectively at low micromolar concentrations, with less effect on MCT4. All stilbenes significantly reduce cell viability and migration. These findings indicate that both MCTs are stilbene targets, with piceatannol highlighted as a cost-effective, low-toxicity compound for studying MCTs in cancer, providing a new mechanism of action of the therapeutic and nutraceutical effects of natural polyphenols. This enriches the understanding of dietary polyphenols in cancer prevention and therapy.

Stretchable Sweat Lactate Sensor with Dual-Signal Read-Outs.

Innovations in wearable sweat sensors hold great promise to provide deeper insights into molecular level health information non-invasively. Lactate, a key metabolite present in sweat, holds immense significance in assessing physiological conditions and performance in sports physiology and health sensing. This paper presents the development and characterization of stretchable electrodes with ultrahigh active surface area of 648 % for lactate sensing. The as-printed stretchable electrodes were functionalized with an electron transfer layer comprising Toluidine Blue O and multi-walled carbon nanotubes (MWCNTs), and an enzymatic layer consisting of lactate dehydrogenase with β-Nicotinamide adenine dinucleotide as the cofactor for lactate selectivity. This sensor achieves a dual-signal read-out in which both electrochemical and fluorescence signals were obtained during lactate detection, demonstrating promising sensor performance in terms of sensitivity and reliability. We demonstrate the robustness of the dual-signal sensor under simulated conditions of physical deformation and shifted excitation. Under these compromised conditions, the performance of the stretchable electrodes remained largely unaffected, showcasing their potential for robust and adaptable sensing platforms in wearable health monitoring applications.

Calibration-Free and Highly Sensitive Potentiometric Enzyme-Based Biosensors.

Enzyme-based amperometric biosensors have become popular for healthcare applications. However, they have been under constant pressure for technological innovation to improve their sensitivity and usability. An ideal biosensor has high sensitivity and calibration-free characteristics. This study aims to report enzyme-based glucose and lactate sensors that utilize a proposed "time-derivative of potential (dOCP/dt)" method, with a further aim being to prove theoretically and experimentally that dOCP/dt values are proportional to substrate concentration. High sensitivity is obtained regardless of the electrode size because the electrode potential is independent of the electrode area in the biosensor. Importantly, because the substrate diffusion determines the enzyme reaction rate on the sensors, the dOCP/dt biosensors can essentially eliminate external influences such as temperature and pH. The result is the successful realization of a biosensor that is calibration-free, making it a much more practical option.

Sweat lactate sensor for detecting anaerobic threshold in heart failure: a prospective clinical trial (LacS-001)

A simple method for determining the anaerobic threshold in patients with heart failure (HF) is needed. This prospective clinical trial (LacS-001) aimed to investigate the safety of a sweat lactate-monitoring sensor and the correlation between lactate threshold in sweat (sLT) and ventilatory threshold (VT). To this end, we recruited 50 patients with HF and New York Heart Association functional classification I–II (mean age: 63.5 years, interquartile range: 58.0–72.0). Incremental exercise tests were conducted while monitoring sweat lactate levels using our sensor. sLT was defined as the first steep increase in lactate levels from baseline. Primary outcome measures were a correlation coefficient of ≥ 0.6 between sLT and VT, similarities as assessed by the Bland–Altman analysis, and standard deviation of the difference within 15 W. A correlation coefficient of 0.651 (95% confidence interval, 0.391–0.815) was achieved in 32/50 cases. The difference between sLT and VT was −4.9 ± 15.0 W. No comparative error was noted in the Bland–Altman plot. No device-related adverse events were reported among the registered patients. Our sweat lactate sensor is safe and accurate for detecting VT in patients with HF in clinical settings, thereby offering valuable additional information for treatment.

Lactate threshold evaluation in swimming using a sweat lactate sensor: A prospective study.

Since assessing aerobic capacity is key to enhancing swimming performance, a simple and widely applicable technology should be developed. Therefore, we aimed to noninvasively visualize real-time changes in sweat lactate (sLA) levels during swimming and investigate the relationship between lactate thresholds in sweat (sLT) and blood (bLT). This prospective study included 24 university swimmers (age: 20.7s±1.8years, 58% male) who underwent exercise tests at incremental speeds with or without breaks in a swimming flume to measure heart rate (HR), bLT, and sLT based on sLA levels using a waterproof wearable lactate sensor attached to the dorsal upper arm on two different days. The correlation coefficient and Bland-Altman methods were used to verify the similarities of the sLT with bLT and personal performance. In all tests, dynamic changes in sLA levels were continuously measured and projected onto the wearable device without delay, artifacts, or contamination. Following an initial minimal current response, with increasing speed the sLA levels increased substantially, coinciding with a continuous rise in HR. The speed at sLT strongly correlated with that at bLT (p<0.01 and r=0.824). The Bland-Altman plot showed a strong agreement (mean difference: 0.08±0.1m/s). This prospective study achieved real-time sLA monitoring during swimming, even with vigorous movement. The sLT closely approximated bLT; both were subsequently validated for their relevance to performance.

Accuracy and Feasibility of a Novel Glucose/Lactate Continuous Multi-Analyte Sensing Platform in Humans.

Continuous glucose monitoring systems (CGMs) have been commercially available since 1999. However, automated insulin delivery systems may benefit from real-time inputs in addition to glucose. Continuous multi-analyte sensing platforms will meet this area of potential growth without increasing the burden of additional devices. We aimed to generate pilot data regarding the safety and function of a first-in-human, single-probe glucose/lactate multi-analyte continuous sensor. The investigational glucose/lactate continuous multi-analyte sensor (PercuSense Inc, Valencia, California) was inserted to the upper arms of 16 adults with diabetes, and data were available for analysis from 11 of these participants (seven female; mean [SD] = age 43 years [16]; body mass index [BMI] = 27 kg/m2 [5]). A commercially available Guardian 3 CGM (Medtronic, Northridge, California) was also inserted into the abdomen for comparison. All participants underwent a meal-test followed by an exercise challenge on day 1 and day 4 of wear. Performance was benchmarked against venous blood YSI glucose and lactate values. The investigational glucose sensor had an overall mean absolute relative difference (MARD) of 14.5% (median = 11.2%) which improved on day 4 compared with day 1 (13.9% vs 15.2%). The Guardian 3 CGM had an overall MARD of 13.9% (median = 9.4%). The lactate sensor readings within 20/20% and 40/40% of YSI values were 59.7% and 83.1%, respectively. Our initial data support safety and functionality of a novel glucose/lactate continuous multi-analyte sensor. Further sensor refinement will improve run-in performance and accuracy.

Alanyl‐tRNA synthetase AARS1: A novel lactate sensor and lactyltransferase mediating p53 lactylation and tumorigenesis

Alanyl‐tRNA synthetase AARS1: A novel lactate sensor and lactyltransferase mediating p53 lactylation and tumorigenesis

A new colorimetric lactate biosensor based on CUPRAC reagent using binary enzyme (lactate-pyruvate oxidases)-immobilized silanized magnetite nanoparticles

A novel optical lactate biosensor is presented that utilizes a colorimetric interaction between H2O2 liberated by a binary enzymatic reaction and bis(neocuproine)copper(II) complex ([Cu(Nc)2]2+) known as CUPRAC (cupric reducing antioxidant capacity) reagent. In the first step, lactate oxidase (LOx) and pyruvate oxidase (POx) were separately immobilized on silanized magnetite nanoparticles (SiO2@Fe3O4 NPs), and thus, 2 mol of H2O2 was released per 1 mol of the substrate due to a sequential enzymatic reaction of the mixture of LOx-SiO2@Fe3O4 and POx-SiO2@Fe3O4 NPs with lactate and pyruvate, respectively. In the second step, the absorbance at 450 nm of the yellow-orange [Cu(Nc)2]+ complex formed through the color reaction of enzymatically produced H2O2 with [Cu(Nc)2]2+ was recorded. The results indicate that the developed colorimetric binary enzymatic biosensor exhibits a broad linear range of response between 0.5 and 50.0 µM for lactate under optimal conditions with a detection limit of 0.17 µM. The fabricated biosensor did not respond to other saccharides, while the positive interferences of certain reducing compounds such as dopamine, ascorbic acid, and uric acid were minimized through their oxidative removal with a pre-oxidant (NaBiO3) before enzymatic and colorimetric reactions. The fabricated optical biosensor was applied to various samples such as artificial blood, artificial/real sweat, and cow milk. The high recovery values (close to 100%) achieved for lactate-spiked samples indicate an acceptable accuracy of this colorimetric biosensor in the determination of lactate in real samples. Due to the increase in H2O2 production with the bienzymatic lactate sensor, the proposed method displays double-fold sensitivity relative to monoenzymatic biosensors and involves a neat color reaction with cupric-neocuproine having a clear stoichiometry as opposed to the rather indefinite stoichiometry of analogous redox dye methods.Graphical

Engineering of Lactate Oxidase and Dehydrogenase for Development of Direct Electron Transfer Type Lactate Sensor and Application for Multiplexed Biosensor System

Engineering of Lactate Oxidase and Dehydrogenase for Development of Direct Electron Transfer Type Lactate Sensor and Application for Multiplexed Biosensor System

Early feasibility study with an implantable near-infrared spectroscopy sensor for glucose, ketones, lactate and ethanol.

To evaluate the safety and performance of an implantable near-infrared (NIR) spectroscopy sensor for multi-metabolite monitoring of glucose, ketones, lactate, and ethanol. This is an early feasibility study (GLOW, NCT04782934) including 7 participants (4 with type 1 diabetes (T1D), 3 healthy volunteers) in whom the YANG NIR spectroscopy sensor (Indigo) was implanted for 28 days. Metabolic challenges were used to vary glucose levels (40-400 mg/dL, 2.2-22.2 mmol/L) and/or induce increases in ketones (ketone drink, up to 3.5 mM), lactate (exercise bike, up to 13 mM) and ethanol (4-8 alcoholic beverages, 40-80g). NIR spectra for glucose, ketones, lactate, and ethanol levels analyzed with partial least squares regression were compared with blood values for glucose (Biosen EKF), ketones and lactate (GlucoMen LX Plus), and breath ethanol levels (ACE II Breathalyzer). The effect of potential confounders on glucose measurements (paracetamol, aspartame, acetylsalicylic acid, ibuprofen, sorbitol, caffeine, fructose, vitamin C) was investigated in T1D participants. The implanted YANG sensor was safe and well tolerated and did not cause any infectious or wound healing complications. Six out 7 sensors remained fully operational over the entire study period. Glucose measurements were sufficiently accurate (overall mean absolute (relative) difference MARD of 7.4%, MAD 8.8 mg/dl) without significant impact of confounders. MAD values were 0.12 mM for ketones, 0.16 mM for lactate, and 0.18 mM for ethanol. The first implantable multi-biomarker sensor was shown to be well tolerated and produce accurate measurements of glucose, ketones, lactate, and ethanol. Clinical trial identifier: NCT04782934.

Reagent-Free Lactate Detection Using Prussian Blue and Electropolymerized-Molecularly Imprinted Polymers-Based Electrochemical Biosensors.

Sweat lactate, a promising biomarker for assessing physical performance and health conditions, calls for noninvasive, convenient, and affordable detection methods. This study leverages molecularly imprinted polymers (MIPs) as a synthetic biorecognition element for lactate detection due to their affordability and high stability. Traditional MIPs-based electrochemical sensors often require external redox probes such as ferricyanide/ferrocyanide in the solution to signal the binding between analytes and MIPs, which restricts their applicability. To address this, our study introduces an innovative approach utilizing a layer of Prussian blue (PB) nanoparticles as the internal redox probe on screen-printed carbon electrodes (SPCE), followed by a layer of electropolymerized MIP (eMIP) for molecular recognition, enabling reagent-free lactate detection. The real-time growth of eMIP and the processes of template elution and lactate rebinding were examined and validated using electrochemical surface plasmon resonance (EC-SPR) spectroscopy. The sensor's performance was thoroughly investigated using Differential Pulsed Voltammetry (DPV) and Electrochemical Impedance Spectroscopy (EIS) with samples spiked in 0.1 M KCl solution and artificial sweat. The developed sensors demonstrated a fast and selective response to lactate, detecting concentrations from 1 to 35 mM with a Limit of Detection (LOD) of 0.20 mM, defined by a signal-to-noise ratio of 3 in the DPV measurements. They also exhibited excellent reproducibility, reusability, and a shelf life of up to 10 months under ambient conditions. These eMIP/PB/SPCE-based lactate sensors show considerable potential as point-of-care (POC) devices for sweat lactate detection, and the technology could be adapted for reagent-free detection of a broad spectrum of molecules.

Alanyl-tRNA synthetase, AARS1, is a lactate sensor and lactyltransferase that lactylates p53 and contributes to tumorigenesis

Lysine lactylation is a post-translational modification that links cellular metabolism to protein function. Here, we find that AARS1 functions as a lactate sensor that mediates global lysine lacylation in tumor cells. AARS1 binds to lactate and catalyzes the formation of lactate-AMP, followed by transfer of lactate to the lysince acceptor residue. Proteomics studies reveal a large number of AARS1 targets, including p53 where lysine 120 and lysine 139 in the DNA binding domain are lactylated. Generation and utilization of p53 variants carrying constitutively lactylated lysine residues revealed that AARS1 lactylation of p53 hinders its liquid-liquid phase separation, DNA binding, and transcriptional activation. AARS1 expression and p53 lacylation correlate with poor prognosis among cancer patients carrying wild type p53. β-alanine disrupts lactate binding to AARS1, reduces p53 lacylation, and mitigates tumorigenesis in animal models. We propose that AARS1 contributes to tumorigenesis by coupling tumor cell metabolism to proteome alteration.

GO@ZnO/CuO sensitive selective detection of lactic acid photoelectrochemistry design of sensors

The photoelectrochemical lactate sensor is a sensor that integrates electrochemical and optoelectronic principles for detecting lactate concentration. Lactic acid is a metabolic product in organisms, and its concentration changes are closely related to the health status of the body. The development of highly sensitive and selective lactic acid sensors is of great significance for fields such as medical diagnosis, exercise physiology, and the food industry. This study used a simple hydrothermal method to prepare CuO and ZnO composite electrodes, with GO flake structures covering the surface of nanoparticles, providing a larger surface area and enhanced interaction. Advanced nanomaterials were used as the working electrode materials for electrochemical sensors, which generate current signals through specific reactions with lactic acid to enhance the sensitivity and stability of the sensors. The limit of detection (LOD) is 0.203 mM. Efficient monitoring of lactate concentration provides a novel and multifunctional method, which is of great significance for promoting research in the fields of medicine and life sciences.

A Self-Powered Lactate Sensor Based on the Piezoelectric Effect for Assessing Tumor Development.

The build-up of lactate in solid tumors stands as a crucial and early occurrence in malignancy development, and the concentration of lactate in the tumor microenvironment may be a more sensitive indicator for analyzing primary tumors. In this study, we designed a self-powered lactate sensor for the rapid analysis of tumor samples, utilizing the coupling between the piezoelectric effect and enzymatic reaction. This lactate sensor is fabricated using a ZnO nanowire array modified with lactate oxidase (LOx). The sensing process does not require an external power source or batteries. The device can directly output electric signals containing lactate concentration information when subjected to external forces. The lactate concentration detection upper limit of the sensor is at least 27 mM, with a limit of detection (LOD) of approximately 1.3 mM and a response time of around 10 s. This study innovatively applied self-powered technology to the in situ detection of the tumor microenvironment and used the results to estimate the growth period of the primary tumor. The availability of this application has been confirmed through biological experiments. Furthermore, the sensor data generated by the device offer valuable insights for evaluating the likelihood of remote tumor metastasis. This study may expand the research scope of self-powered technology in the field of medical diagnosis and offer a novel perspective on cancer diagnosis.

Abstract 3069: Targeting lactic acid sensing GPR132 in ccRCC

Abstract Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of kidney cancer, accounting for 70-80% of the cases. Despite the improvements in tumor therapeutics, patients with metastatic clear cell tumors still have a five-year survival rate lower than 10%. Most of the ccRCC tumors harbor loss of VHL tumor suppressor gene on chromosome 3, leading to constitutively stabilized HIF, activation of downstream pathways involved in glycolysis, angiogenesis and metastasis and a highly acidic, vascularized, and immunosuppressive tumor microenvironment (TME). Such molecular alterations lead to the buildup of lactic acid within the tumor microenvironment. Long has been considered as a byproduct of hypoxic tumor metabolism, but recent studies have demonstrated a pro-tumorigenic role of lactic acid. Therefore, elucidating the molecular mechanisms on how tumor cells take advantage of lactic acid can identify potential novel therapeutic options. To understand how ccRCC cells sense extracellular lactic acid, I explored the concept of a lactate sensor. The currently known lactate sensors are GPR81 and GPR132. By querying TCGA data, GPR81 is reduced in ccRCC tumors and does not predict patient outcome while GPR132 is elevated in ccRCC tumors compared to normal kidney and demonstrates a strong negative effect on survival. Therefore, GPR132 stands out as a potential lactate sensor in ccRCC with meaningful impact on patient survival. Previously, GPR132 has been shown to be involved in tumor associated macrophage M1 to M2 transition upon lactic acid exposure. However, GPR132 exerts a striking impact on ccRCC tumors. Depleting GPR132 significantly decreased the HIF2α level in multiple ccRCC cell lines, establishing a molecular connection between lactic acid, GPR132 and HIF2α. Furthermore, due to suppressed HIF2α signaling, GPR132 knockout led to decreased lactic acid uptake through MCT1. Such decreased lactic transporter MCT1 abrogated the elevated aggressive phenotype in ccRCC cells when exposed to lactic acid. Metabolically, GPR132 knockout led to decreased lipid deposition. In addition, such deprivation of lipid droplet is not replenished when cells are exposed to lactic acid. Furthermore, by conducting an isotype-tracing experiment, GPR132 knockout actively decreased lactic acid uptake by the tumors and limit their resources to regenerate TCA cycle intermediates and build up lipid droplets. More importantly, GPR132 knockout led to defective mitochondria activities and activation of apoptosis, both of which led to significantly suppressed ccRCC growth in vitro and in vivo. This suggested that GPR132 likely affects ccRCC fitness through multiple layers of signaling mechanisms. Overall, our study has revealed that lactate sensing GPR132 is a critical signaling pathway for ccRCC tumor development in a glycolytic feed-forward context. As a membrane bound receptor, GPR132 holds immense potential as a novel therapeutic target in ccRCC. Citation Format: Dazhi Wang. Targeting lactic acid sensing GPR132 in ccRCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3069.