Analytical Performance of the FreeStyle Libre 2 Glucose Sensor in Healthy Male Adults.

Continuous Glucose Monitoring (CGM) not only can be used for glycemic control in chronic diseases (e.g., diabetes), but is increasingly being utilized by individuals and athletes to monitor fluctuations in training and everyday life. However, it is not clear how accurately CGM reflects plasma glucose concentration in a healthy population in the absence of chronic diseases. In an oral glucose tolerance test (OGTT) with forty-four healthy male subjects (25.5 ± 4.5 years), the interstitial fluid glucose (ISFG) concentration obtained by a CGM sensor was compared against finger-prick capillary plasma glucose (CPG) concentration at fasting baseline (T0) and 30 (T30), 60 (T60), 90 (T90), and 120 (T120) min post OGTT to investigate differences in measurement accuracy. The overall mean absolute relative difference (MARD) was 12.9% (95%-CI: 11.8-14.0%). Approximately 100% of the ISFG values were within zones A and B in the Consensus Error Grid, indicating clinical accuracy. A paired t-test revealed statistically significant differences between CPG and ISFG at all time points (T0: 97.3 mg/dL vs. 89.7 mg/dL, T30: 159.9 mg/dL vs. 144.3 mg/dL, T60: 134.8 mg/dL vs. 126.2 mg/dL, T90: 113.7 mg/dL vs. 99.3 mg/dL, and T120: 91.8 mg/dL vs. 82.6 mg/dL; p < 0.001) with medium to large effect sizes (d = 0.57-1.02) and with ISFG systematically under-reporting the reference system CPG. CGM sensors provide a convenient and reliable method for monitoring blood glucose in the everyday lives of healthy adults. Nonetheless, their use in clinical settings wherein implications are drawn from CGM readings should be handled carefully.

Defining the Spatial Resolution of Analyte Recovery during Microperfusion-Based Sampling of Brain Parenchyma.

The unique architecture of the brain and the blood-brain barrier imposes challenges for the measurement of parenchyma-derived biomarkers that prevent sufficient understanding of transient neuropathogenic processes. One solution to this challenge is direct sampling of brain interstitial fluid via implanted microperfusion probes. Seeking to understand spatial limitations to microperfusion in the brain, we employed computational fluid dynamics modeling and empirical recovery of fluorescently labeled dextrans in an animal model. We found that dextrans were successfully recovered via microperfusion over a 6 h sampling period, especially at probes implanted 2 mm from the dextran infusion point relative to probes implanted 5 mm from the injection site. Experimental recovery was consistently around 1% of simulated, suggesting that this parameter can be used to set practical limits on the maximal tissue concentration of proteins measured in microperfusates and on the spatial domain sampled by our multimodal microperfusion probe.

Development of an electrochemical biosensor for non-invasive cholesterol monitoring via microneedle-based interstitial fluid extraction.

In this study, we present the development of an innovative electrochemical biosensor integrated into a microneedle-based system for non-invasive and sensitive quantification of cholesterol levels in interstitial fluid (ISF). The biosensor employs a graphene-based electrode with a polyelectrolyte interlayer to immobilize cholesterol oxidase (ChOx), enabling selective cholesterol detection. Graphene oxide is electrochemically reduced to form a conductive layer, and PANI is chosen as the optimal polyelectrolyte for ChOx immobilization. The biosensor's performance is thoroughly evaluated, demonstrating excellent sensitivity, stability, and selectivity. Furthermore, the biosensor is successfully applied to skin-mimicking agarose gel and porcine skin, showcasing its potential for real-world interstitial fluid extraction and cholesterol monitoring. The integrated microneedle-based system offers a promising approach for non-invasive monitoring of cholesterol levels, with implications for personalized healthcare diagnostics.

Sliding Microneedle - Lateral flow immunoassay strip device for highly sensitive biomarker detection in interstitial fluid.

Diabetes is a chronic disease with significant complications, necessitating regular treatment and checkups, which can be costly and time-consuming for patients. To address this, we developed the Sliding Microneedle (MN)-Lateral flow immunoassay strip (LFIAs) device that combines the advantages of MNs and LFIAs to detect IL-6, an independent biomarker for diabetes complications. This device offers rapid and highly sensitive detection of IL-6 by extracting interstitial fluid (ISF) through MNs and transferring it to LFIAs. The stainless MN, embedded in the 3D-printed Sliding MN-LFIAs device, was inserted into the skin at a 20° angle, minimizing blood contamination risk. With a filter paper attached to the MN surface, the device collected 4.65 ± 0.05 µL of ISF containing IL-6 within 90 s. The ISF was then transferred to the LFIAs using a running buffer. After a 15-min reaction, silver enhancement (SE) treatment was applied, allowing for the highly sensitive and specific detection of IL-6 at 102 pg/mL concentrations. The Sliding MN-LFIAs device successfully distinguished between normal and diabetic rat models, demonstrating its potential as an effective tool for detecting diabetes complications quickly and affordably.

An immunosensor for the near real-time and site of inflammation detections of multiple proinflammatory cytokines.

Diseases mediated by cytokine storms are often characterized by an overexuberant pace of pathogenesis accompanied by significant morbidity and mortality. Thus, near real-time (NRT) detections via a site-of-inflammation (SOI) sampling of proinflammatory cytokines are essential to ensure a timely and effective treatment of acute inflammations, which up to now, has not been fully possible. In this work, we proposed a novel NRT and SOI immunosensor using ZIF-8 signal amplification together with an off-on strategy. To achieve NRT detections via a SOI sampling, the body fluid of choice is the dermal interstitial fluid (ISF). The significant merits of ISF over blood are the quality, quantity and diversity of ISF-based biomarkers; the fluid is non-coagulating, making it feasible to perform multiple or continuous samplings and the sampling is minimally invasive. Our immunosensor requires only 5 µL of ISF to achieve a simultaneous detection of five highly potent proinflammatory cytokines: IL-6, IFN-γ, IL-1ß, TNF-α, IP-10. We employed a microneedle array patch (MAP) together with a trifurcated nozzle pump to extract a mean volume of between 30 and 60 µL of ISF in 20 min. Under optimal conditions, the biosensor is capable of high-quality performance that exhibits a lower limit of detection (LOD) of 5.761 pg/mL over a wide linear range of 5.761-3 ‒ 20.00 ng/mL. We believe our immunosensor for NRT detections via a SOI sampling of ISF-biomarkers offers new theranostic opportunities that may not be possible with blood-based biomarkers.

Evaluation of cerebrospinal fluid (CSF) and interstitial fluid (ISF) mouse proteomes for the validation and description of Alzheimer's disease biomarkers.

BACKGROUND: Mass spectrometry (MS)-based cerebrospinal fluid (CSF) proteomics is an important method for discovering biomarkers of neurodegenerative diseases. CSF serves as a reservoir for interstitial fluid (ISF), and extensive communication between the two fluid compartments helps to remove waste products from the brain. NEW METHOD: We performed proteomic analyses of both CSF and ISF fluid compartments using intracerebral microdialysis to validate and detect novel biomarkers of Alzheimer's disease (AD) in APPtg and C57Bl/6J control mice. RESULTS: We identified up to 625 proteins in ISF and 4483 proteins in CSF samples. By comparing the biofluid profiles of APPtg and C57Bl/6J mice, we detected 37 and 108 significantly up- and downregulated candidates, respectively. In ISF, 7 highly regulated proteins, such as Gfap, Aldh1l1, Gstm1, and Txn, have already been implicated in AD progression, whereas in CSF, 9 out of 14 highly regulated proteins, such as Apba2, Syt12, Pgs1 and Vsnl1, have also been validated to be involved in AD pathogenesis. In addition, we also detected new interesting regulated proteins related to the control of synapses and neurotransmission (Kcna2, Cacng3, and Clcn6) whose roles as AD biomarkers should be further investigated. COMPARISON WITH EXISTING METHODS: This newly established combined protocol provides better insight into the mutual communication between ISF and CSF as an analysis of tissue or CSF compartments alone. CONCLUSIONS: The use of multiple fluid compartments, ISF and CSF, for the detection of their biological communication enables better detection of new promising AD biomarkers.

Early detection of hypo/hyperglycemia using a microneedle electrode array-based biosensor for glucose ultrasensitive monitoring in interstitial fluid.

Diabetes is a common chronic metabolic disease with a wide range of clinical symptoms and consequences and one of the main causes of death. For the management of diabetes, painless and continuous interstitial fluid (ISF) glucose monitoring is ideal. Here, we demonstrate continuous diabetes monitoring using an integrated microneedle (MN) biosensor with an emergency alert system. MNs are a novel technique in the field of biomedical engineering because of their ability to analyze bioinformation with minimal invasion. In this work we developed a poly(methyl methacrylate) (PMMA) based MN glucose sensor. The device was produced by the 3D printing technique, microfabrication, electrodeposition, and enzyme immobilization step. The in vitro test for the glucose MN sensor showed a linear range from 1.5 to 14 mM with a sensitivity of 1.51 µA mM-1, limit of detection (LOD) of 0.35 mM and good selectivity. Highly repeatable sensing is observed with good reproducibility. The interference-free detection of glucose in the presence of physiologically relevant concentrations of ascorbic acid, uric acid, and mannose is demonstrated, along with the operational stability of the array. After resolving the biofouling consequences linked to on-body sensing, this MN platform would be appealing for minimally invasive electrochemical glucose monitoring. An alert is sent to confidants via email or SMS when the values are abnormal. The application is also able to display the recorded values in the form of a graph to help determine the state of health of the user over a period of time. It can be concluded that continuous monitoring and an emergency alert system are important for keeping an eye on diabetic patients and can send alert in case of an abnormal situation of the patient.

Wireless and Battery-Free Sensor for Interstitial Fluid Pressure Monitoring.

Congestive heart failure (CHF) is a fatal disease with progressive severity and no cure; the heart's inability to adequately pump blood leads to fluid accumulation and frequent hospital readmissions after initial treatments. Therefore, it is imperative to continuously monitor CHF patients during its early stages to slow its progression and enable timely medical interventions for optimal treatment. An increase in interstitial fluid pressure (IFP) is indicative of acute CHF exacerbation, making IFP a viable biomarker for predicting upcoming CHF if continuously monitored. In this paper, we present an inductor-capacitor (LC) sensor for subcutaneous wireless and continuous IFP monitoring. The sensor is composed of inexpensive planar copper coils defined by a simple craft cutter, which serves as both the inductor and capacitor. Because of its sensing mechanism, the sensor does not require batteries and can wirelessly transmit pressure information. The sensor has a low-profile form factor for subcutaneous implantation and can communicate with a readout device through 4 layers of skin (12.7 mm thick in total). With a soft silicone rubber as the dielectric material between the copper coils, the sensor demonstrates an average sensitivity as high as -8.03 MHz/mmHg during in vitro simulations.

Penetration of Antibiotics into Subcutaneous and Intramuscular Interstitial Fluid: A Meta-Analysis of Microdialysis Studies in Adults.

BACKGROUND AND OBJECTIVE: The interstitial fluid of tissues is the effect site for antibiotics targeting extracellular pathogens. Microdialysis studies investigating these concentrations in muscle and subcutaneous tissue have reported notable variability in tissue penetration. This study aimed to comprehensively summarise the existing data on interstitial fluid penetration in these tissues and to identify potential factors influencing antibiotic distribution. METHODS: A literature review was conducted, focusing on subcutaneous and intramuscular microdialysis studies of antibiotics in both adult healthy volunteers and patients. Random-effect meta-analyses were used to aggregate effect size estimates of tissue penetration. The primary parameter of interest was the unbound penetration ratio, which represents the ratio of the area under the concentration-time curve in interstitial fluid relative to the area under the concentration-time curve in plasma, using unbound concentrations. RESULTS: In total, 52 reports were incorporated into this analysis. The unbound antibiotic exposure in the interstitial fluid of healthy volunteers was, on average, 22% lower than in plasma. The unbound penetration ratio values were higher after multiple dosing but did not significantly differ between muscle and subcutaneous tissue. Unbound penetration ratio values were lower for acids and bases compared with neutral antibiotics. Neither the molecular weight nor the logP of the antibiotics accounted for the variations in the unbound penetration ratio. Obesity was associated with lower interstitial fluid penetration. Conditions such as sepsis, tissue inflammation and tissue ischaemia were not significantly associated with altered interstitial fluid penetration. CONCLUSIONS: This study highlights the variability and generally lower exposure of unbound antibiotics in the subcutaneous and intramuscular interstitial fluid compared with exposure in plasma. Future research should focus on understanding the therapeutic relevance of these differences and identify key covariates that may influence them.

Integration of Hollow Microneedle Arrays with Jellyfish-Shaped Electrochemical Sensor for the Detection of Biomarkers in Interstitial Fluid.

This study integrates hollow microneedle arrays (HMNA) with a novel jellyfish-shaped electrochemical sensor for the detection of key biomarkers, including uric acid (UA), glucose, and pH, in artificial interstitial fluid. The jellyfish-shaped sensor displayed linear responses in detecting UA and glucose via differential pulse voltammetry (DPV) and chronoamperometry, respectively. Notably, the open circuit potential (OCP) of the system showed a linear variation with pH changes, validating its pH-sensing capability. The sensor system demonstrates exceptional electrochemical responsiveness within the physiological concentration ranges of these biomarkers in simulated epidermis sensing applications. The detection linear ranges of UA, glucose, and pH were 0~0.8 mM, 0~7 mM, and 4.0~8.0, respectively. These findings highlight the potential of the HMNA-integrated jellyfish-shaped sensors in real-world epidermal applications for comprehensive disease diagnosis and health monitoring.

Calibration algorithms for continuous glucose monitoring systems based on interstitial fluid sensing.

Continuous glucose monitoring (CGM) is of great importance to the treatment and prevention of diabetes. As a proven commercial technology, electrochemical glucose sensor based on interstitial fluid (ISF) sensing has high sensitivity and wide detection range. Therefore, it has good promotion prospects in noninvasive or minimally-invasive CGM system. However, since there are concentration differences and time lag between glucose in plasma and ISF, the accuracy of this type of sensors are still limited. Typical calibration algorithms rely on simple linear regression which do not account for the variability of the sensitivity of sensors. To enhance the accuracy and stability of CGM based on ISF, optimization of calibration algorithm for sensors is indispensable. While there have been considerable researches on improving calibration algorithms for CGM, they have still received less attention. This article reviews the problem of typical calibration and presents the outstanding calibration algorithms in recent years. Finally, combined with existing research and emerging sensing technologies, this paper makes an outlook on the future calibration algorithms for CGM sensors.

Wearable Aptalyzer Integrates Microneedle and Electrochemical Sensing for In Vivo Monitoring of Glucose and Lactate in Live Animals.

Continuous monitoring of clinically relevant biomarkers within the interstitial fluid (ISF) using microneedle (MN)-based assays, has the potential to transform healthcare. This study introduces the Wearable Aptalyzer, an integrated system fabricated by combining biocompatible hydrogel MN arrays for ISF extraction with an electrochemical aptamer-based biosensor for in situ monitoring of blood analytes. The use of aptamers enables continuous monitoring of a wide range of analytes, beyond what is possible with enzymatic monitoring. The Wearable Aptalyzer is used for real-time and multiplexed monitoring of glucose and lactate in ISF. Validation experiments using live mice and rat models of type 1 diabetes demonstrate strong correlation between the measurements collected from the Wearable Aptalyzer in ISF and those obtained from gold-standard techniques for blood glucose and lactate, for each analyte alone and in combination. The Wearable Aptalyzer effectively addresses the limitations inherent in enzymatic detection methods as well as solid MN biosensors and the need for reliable and multiplexed bioanalytical monitoring in vivo.

Intradermal Lactate Monitoring Based on a Microneedle Sensor Patch for Enhanced In Vivo Accuracy.

Lactate is an important diagnostic and prognostic biomarker of several human pathological conditions, such as sepsis, malaria, and dengue fever. Unfortunately, due to the lack of reliable analytical decentralized platforms, the determination of lactate yet relies on discrete blood-based assays, which are invasive and inefficient and may cause tension and pain in the patient. Herein, we demonstrate the potential of a fully integrated microneedle (MN) sensing system for the minimally invasive transdermal detection of lactate in an interstitial fluid (ISF). The originality of this analytical technology relies on: (i) a strategy to provide a uniform coating of a doped polymer-based membrane as a diffusion-limiting layer on the MN structure, optimized to perform full-range lactate detection in the ISF (linear range of response: 0.25-35 mM, 30 s assay time, 8 h operation), (ii) double validation of ex vivo and in vivo results based on ISF and blood measurements in rats, (iii) monitoring of lactate level fluctuations under the administration of anesthesia to mimic bedside clinical scenarios, and (iv) in-house design and fabrication of a fully integrated and portable sensing device in the form of a wearable patch including a custom application and user-friendly interface in a smartphone for the rapid, routine, continuous, and real-time lactate monitoring. The main analytical merits of the lactate MN sensor include appropriate selectivity, reversibility, stability, and durability by using a two-electrode amperometric readout. The ex-vivo testing of the MN patch of preconditioned rat skin pieces and euthanized rats successfully demonstrated the accuracy in measuring lactate levels. The in vivo measurements suggested the existence of a positive correlation between ISF and blood lactate when a lag time of 10 min is considered (Pearson's coefficient = 0.85, mean difference = 0.08 mM). The developed MN-based platform offers distinct advantages over noncontinuous blood sampling in a wide range of contexts, especially where access to laboratory services is limited or blood sampling is not suitable. Implementation of the wearable patch in healthcare could envision personalized medicine in a variety of clinical settings.

Plasma and interstitial fluid antibiotic levels of subcutaneously implanted compounded florfenicol calcium sulfate beads in New Zealand White rabbits (Oryctolagus cuniculus).

OBJECTIVE: To determine antibiotic levels in plasma and interstitial fluid (ISF) after SC placement of compounded florfenicol (FF) calcium sulfate beads (CSBs) in New Zealand White rabbits (Oryctolagus cuniculus). ANIMALS: 6 juvenile female rabbits (n = 5 treatment and 1 control). METHODS: An ultrafiltration probe and CSBs were placed SC in 6 rabbits (n = 5 for FF CSBs and 1 for control CSBs). Plasma (3, 6, 12, 24, and 48 hours and 7, 14, and 21 days) and ISF (daily for 21 days) samples were collected, and FF was measured by HPLC for pharmacokinetic analysis. Hematology, biochemistry, and histopathology were assessed. RESULTS: Means ± SD for the area under the curve, maximum concentration, time of maximum concentration, terminal half-life, and mean residence time to the last data point for plasma and ISF were 16.63 ± 8.16 and 17,902 ± 7,564 h·µg/mL, 0.79 ± 0.38 and 245 ± 223 µg/mL, 2.90 ± 0.3 and 59 ± 40 hours, 30.81 ± 16.9 and 27.3 ± 9.39 hours, 23.4 ± 10 and 73.7 ± 13 hours, respectively. Plasma FF was < 2 µg/mL at all time points. The ISF FF remained > 8 µg/mL for 109.98 to 231.58 hours. One rabbit death occurred during treatment, but the cause of death was undetermined. Local tissue inflammation was present, but no clinically significant systemic adverse effects were found on hematology, biochemistry, or histopathology in the remaining rabbits. CLINICAL RELEVANCE: Florfenicol CSBs maintained antibiotic concentrations in ISF at levels likely to be effective against bacteria sensitive to > 8 µg/mL for 5 to 10 days while maintaining low (< 2 µg/mL) plasma levels. Florfenicol CSBs may be effective for local antibiotic treatment in rabbit abscesses.

Sensing patches for biomarker identification in skin-derived biofluids.

In conventional clinical disease diagnosis and screening based on biomarker detection, most analysis samples are collected from serum, blood. However, these invasive collection methods require specific instruments, professionals, and may lead to infection risks. Additionally, the diagnosis process suffers from untimely results. The identification of skin-related biomarkers plays an unprecedented role in early disease diagnosis. More importantly, these skin-mediated approaches for collecting biomarker-containing biofluid samples are noninvasive or minimally invasive, which is more preferable for point-of-care testing (POCT). Therefore, skin-based biomarker detection patches have been promoted, owing to their unique advantages, such as simple fabrication, desirable transdermal properties and no requirements for professional medical staff. Currently, the skin biomarkers extracted from sweat, interstitial fluid (ISF) and wound exudate, are achieved with wearable sweat patches, transdermal MN patches, and wound patches, respectively. In this review, we detail these three types of skin patches in biofluids collection and diseases-related biomarkers identification. Patch classification and the corresponding manufacturing as well as detection strategies are also summarized. The remaining challenges in clinical applications and current issues in accurate detection are discussed for further advancement of this technology (Scheme 1).

Hydrogel-Coated SERS Microneedles for Drug Monitoring in Dermal Interstitial Fluid.

In vivo drug monitoring is crucial for evaluating the effectiveness and safety of drug treatment. Blood sampling and analysis is the current gold standard but needs professional skills and cannot meet the requirements of point-of-care testing. Dermal interstitial fluid (ISF) showed great potential to replace blood for in vivo drug monitoring; however, the detection was challenging, and the drug distribution behavior in ISF was still unclear until now. In this study, we proposed surface-enhanced Raman spectroscopy (SERS) microneedles (MNs) for the painless and real-time analysis of drugs in ISF after intravenous injection. Using methylene blue (MB) and mitoxantrone (MTO) as model drugs, the innovative core-satellite structured Au@Ag SERS substrate, hydrogel coating over the MNs, rendered sensitive and quantitative drug detection in ISF of mice within 10 min. Based on this technique, the pharmacokinetics of the two drugs in ISF was investigated and compared with those in blood, where the drugs were analyzed via liquid chromatography-mass spectrometry. It was found that the MB concentration in ISF and blood was comparable, whereas the concentration of MTO in ISF was 2-3 orders of magnitude lower than in blood. This work proposed an efficient tool for ISF drug monitoring. More importantly, it experimentally proved that the penetration ratio of blood to ISF was drug-dependent, providing insightful information into the potential of ISF as a blood alternative for in vivo drug detection.

Metabolome analyses of skin dialysate: Insights into skin interstitial fluid biomarkers.

BACKGROUND: Metabolites in biofluids can serve as biomarkers for diagnosing diseases and monitoring body conditions. Among the available biofluids, interstitial fluid (ISF) in the skin has garnered considerable attention owing to its advantages, which include inability to clot, easy access to the skin, and possibility of incorporating wearable devices. However, the scientific understanding of skin ISF composition is limited. OBJECTIVE: In this study, we aimed to compare metabolites between skin dialysate containing metabolites from the skin ISF and venous blood (plasma) samples, both collected under resting states. METHODS: We collected forearm skin dialysate using intradermal microdialysis alongside venous blood (plasma) samples from 12 healthy young adults. We analyzed these samples using capillary electrophoresis-fourier transform mass spectrometry-based metabolomics (CE-FTMS). RESULTS: Significant positive correlations were observed in 39 metabolites between the skin dialysate and plasma, including creatine (a mitochondrial disease biomarker), 1-methyladenosine (an early detection of cancer biomarker), and trimethylamine N-oxide (a posterior predictor of heart failure biomarker). Based on the Human Metabolome Technologies database, we identified 12 metabolites unique to forearm skin dialysate including nucleic acids, benzoate acids, fatty acids, amino acids, ascorbic acid, 3-methoxy-4-hydroxyphenylethyleneglycol (an Alzheimer's disease biomarker), and cysteic acid (an acute myocardial infarction biomarker). CONCLUSION: We show that some venous blood biomarkers may be predicted from skin dialysate or skin ISF, and that these fluids may serve as diagnostic and monitoring tools for health and clinical conditions.

Continuous evaluation of single-dose moxifloxacin concentrations in brain extracellular fluid, cerebrospinal fluid, and plasma: a novel porcine model.

BACKGROUND: Knowledge regarding CNS pharmacokinetics of moxifloxacin is limited, with unknown consequences for patients with meningitis caused by bacteria resistant to beta-lactams or caused by TB. OBJECTIVE: (i) To develop a novel porcine model for continuous investigation of moxifloxacin concentrations within brain extracellular fluid (ECF), CSF and plasma using microdialysis, and (ii) to compare these findings to the pharmacokinetic/pharmacodynamic (PK/PD) target against TB. METHODS: Six female pigs received an intravenous single dose of moxifloxacin (6 mg/kg) similar to the current oral treatment against TB. Subsequently, moxifloxacin concentrations were determined by microdialysis within five compartments: brain ECF (cortical and subcortical) and CSF (ventricular, cisternal and lumbar) for the following 8 hours. Data were compared to simultaneously obtained plasma samples. Chemical analysis was performed by high pressure liquid chromatography with mass spectrometry. The applied PK/PD target was defined as a maximum drug concentration (Cmax):MIC ratio >8. RESULTS: We present a novel porcine model for continuous in vivo CNS pharmacokinetics for moxifloxacin. Cmax and AUC0-8h within brain ECF were significantly lower compared to plasma and lumbar CSF, but insignificantly different compared to ventricular and cisternal CSF. Unbound Cmax:MIC ratio across all investigated compartments ranged from 1.9 to 4.3. CONCLUSION: A single dose of weight-adjusted moxifloxacin administered intravenously did not achieve adequate target site concentrations within the uninflamed porcine brain ECF and CSF to reach the applied TB CNS target.

An integrated wearable differential microneedle array for continuous glucose monitoring in interstitial fluids.

Monitoring biomarkers in human interstitial fluids (ISF) using microneedle sensors has been extensively studied. However, most of the previous studies were limited to simple in vitro demonstrations and lacked system integration and analytical performance. Here we report a miniaturized, high-precision, fully integrated wearable electrochemical microneedle sensing device that works with a customized smartphone application to wirelessly and in real-time monitor glucose in human ISF. A microneedle array fabrication method is proposed which enables multiple individually addressable, regionally separated sensing electrodes on a single microneedle system. As a demonstration, a glucose sensor and a differential sensor are integrated in a single sensing patch. The differential sensing electrodes can eliminate common-mode interference signals, thus significantly improving the detection accuracy. The basic mechanism of microneedle penetration into the skin was analyzed using the finite element method (FEM). By optimizing the structure of the microneedle, the puncture efficiency was improved while the puncture force was reduced. The electrochemical properties, biocompatibility, and system stability of the microneedle sensing device were characterized before human application. The test results were closely correlated with the gold standard (blood). The platform can be used not only for glucose detection, but also for various ISF biomarkers, and it expands the potential of microneedle technology in wearable sensing.

A Review of Recent Advances in Microneedle-Based Sensing within the Dermal ISF That Could Transform Medical Testing.

Interstitial fluid (ISF) has attracted extensive attention in an extremely wide range of areas due to its unique advantages, such as portability, high precision, comfortable operation, and superior stability. In recent years, the microneedle (MN) technique has been considered to be an excellent tool for extracting ISF because it is painless and noninvasive. Recent reports have shown that MN has good application prospects in ISF extraction. In this review, we provide comprehensive and in-depth insight into integrated MN devices for ISF detection, covering the basic structure as well as the fabrication of integrated MN devices and various applications in ISF extraction. Challenges and prospects are highlighted, with a discussion on how to transition such MN-integrated devices toward personalized healthcare monitoring systems.