Microneedle based electrochemical (Bio)Sensing: Towards decentralized and continuous health status monitoring

Abstract Microneedle (MN) based electrochemical (bio)sensing has become a growing field within the discipline of analytical chemistry as a result of its unique capacity for continuous, decentralized health status monitoring. There are two significant advantages to this exclusive feature: i) the ability to directly analyze interstitial fluid (ISF), a body fluid with a similar enough composition to plasma (and blood) to be considered a plentiful source of information related to biologically relevant molecules and biomarkers; and ii) the capacity to overcome some of the major limitations of blood analysis including painful extraction, high interferant concentrations, and incompatibility with diagnosis of infants (and especially newborns). Recent publications have demonstrated important advancements in electrochemical MN sensor technology, among which are included new MN fabrication methods and various modification strategies, providing different architectures and allowing for the integration of electronics. This versatility highlights the undeniable need for interdisciplinary efforts towards tangible progress in the field. In a context evidently dominated by glucose sensing, which is slowly being expanded towards other analytes, the following crucial questions arise: to what extent are electrochemical MN (bio)sensors a reliable analytical tool for continuous ISF monitoring? Which is the best calibration protocol to be followed for in vivo assays? Which strategies can be employed to protect the sensing element during skin penetration? Is there an appropriate validation methodology to assess the accuracy of electrochemical MN (bio)sensors? How significant is the distinction between successful achievements in the laboratory and the real commercial feasibility of products? This paper aims to reflect on those previous questions while reviewing the progress of electrochemical MN (bio)sensors in the last decade with a focus on the analytical aspects. Overall, we describe the current state of electrochemical MN (bio)sensors, the benefits and challenges associated to ISF monitoring, as well as key features (and bottlenecks) regarding its implementation for in vivo assays.

[1]  A. Cass,et al.  Microneedle Enzyme Sensor Arrays for Continuous In Vivo Monitoring. , 2017, Methods in enzymology.

[2]  Michelle L Rogers,et al.  Evaluation of a minimally invasive glucose biosensor for continuous tissue monitoring , 2016, Analytical and Bioanalytical Chemistry.

[3]  Pantelis Georgiou,et al.  Towards a minimally invasive device for beta-lactam monitoring in humans. , 2017, Electrochemistry communications.

[4]  A. Karyakin,et al.  Relationship Between Sweat and Blood Lactate Levels During Exhaustive Physical Exercise , 2020 .

[5]  N. Madias,et al.  Metabolic acidosis: pathophysiology, diagnosis and management , 2010, Nature Reviews Nephrology.

[6]  W. Huckabee,et al.  Control of concentration gradients of pyruvate and lactate across cell membranes in blood. , 1956, Journal of applied physiology.

[7]  Alberto Salleo,et al.  Molecularly selective nanoporous membrane-based wearable organic electrochemical device for noninvasive cortisol sensing , 2018, Science Advances.

[8]  A. Levin,et al.  Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. , 2007, Kidney international.

[9]  Wendell K. T. Coltro,et al.  Wearable electrochemical sensors for forensic and clinical applications , 2019, TrAC Trends in Analytical Chemistry.

[10]  Jong-Hoon Kim,et al.  A Microneedle Functionalized with Polyethyleneimine and Nanotubes for Highly Sensitive, Label-Free Quantification of DNA , 2017, Sensors.

[11]  A. Cass,et al.  Minimally Invasive Glucose Monitoring Using a Highly Porous Gold Microneedles-Based Biosensor: Characterization and Application in Artificial Interstitial Fluid , 2019, Catalysts.

[12]  M. Visscher,et al.  Effect of dermal thickness, tissue composition, and body site on skin biomechanical properties , 2006, Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging.

[13]  Mark R. Prausnitz,et al.  Effect of Microneedle Design on Pain in Human Volunteers , 2008, The Clinical journal of pain.

[14]  Roger Narayan,et al.  Wearable Electrochemical Microneedle Sensor for Continuous Monitoring of Levodopa: Toward Parkinson Management. , 2019, ACS sensors.

[15]  Paolo Bollella,et al.  Microneedle-based biosensor for minimally-invasive lactate detection. , 2019, Biosensors & bioelectronics.

[16]  Hye Rim Cho,et al.  A graphene-based electrochemical device with thermoresponsive microneedles for diabetes monitoring and therapy. , 2016, Nature nanotechnology.

[17]  Matthew W. Moorman,et al.  Towards an Integrated Microneedle Total Analysis Chip for Protein Detection , 2016 .

[18]  Robert B. Smith,et al.  Microneedle array sensors based on carbon nanoparticle composites: interfacial chemistry and electroanalytical properties , 2019, Journal of Materials Science.

[19]  Beelee Chua,et al.  Effect of microneedles shape on skin penetration and minimally invasive continuous glucose monitoring in vivo , 2013 .

[20]  Yu Chong,et al.  The mechanical properties of the skin epidermis in relation to targeted gene and drug delivery. , 2007, Biomaterials.

[21]  Marc Parrilla,et al.  Epidermal Patch with Glucose Biosensor: pH and Temperature Correction toward More Accurate Sweat Analysis during Sport Practice , 2020, Analytical chemistry.

[22]  C. Pichard,et al.  Monitoring nutrition in the ICU. , 2019, Clinical nutrition.

[23]  E. V. D. Wouden,et al.  Microfabricated solid-state ion-selective electrode probe for measuring potassium in the living rodent brain: Compatibility with DC-EEG recordings to study spreading depression , 2015 .

[24]  Beelee Chua,et al.  Design, Development, and Evaluation of a Novel Microneedle Array-based Continuous Glucose Monitor , 2014, Journal of diabetes science and technology.

[25]  Chenjie Xu,et al.  Recent advances in the design of polymeric microneedles for transdermal drug delivery and biosensing. , 2017, Lab on a chip.

[26]  W. Tamborlane,et al.  A tale of two compartments: interstitial versus blood glucose monitoring. , 2009, Diabetes technology & therapeutics.

[27]  Ryan F. Donnelly,et al.  Microneedles: A New Frontier in Nanomedicine Delivery , 2016, Pharmaceutical Research.

[28]  Michelle L Rogers,et al.  Development of a Minimally Invasive Microneedle-Based Sensor for Continuous Monitoring of β-Lactam Antibiotic Concentrations in Vivo. , 2019, ACS sensors.

[29]  Y. Lee,et al.  Skin thickness of Korean adults , 2002, Surgical and Radiologic Anatomy.

[30]  Göran Stemme,et al.  Real-time intradermal continuous glucose monitoring using a minimally invasive microneedle-based system , 2018, Biomedical microdevices.

[31]  Xi Xie,et al.  Reduced Graphene Oxide Nanohybrid-Assembled Microneedles as Mini-Invasive Electrodes for Real-Time Transdermal Biosensing. , 2019, Small.

[32]  Y. Marunaka.  Roles of interstitial fluid pH in diabetes mellitus: Glycolysis and mitochondrial function. , 2015, World journal of diabetes.

[33]  Hyungil Jung,et al.  An optimized hollow microneedle for minimally invasive blood extraction , 2013, Biomedical microdevices.

[34]  Ronen Polsky,et al.  Multiplexed microneedle-based biosensor array for characterization of metabolic acidosis. , 2012, Talanta.

[35]  Mark R. Prausnitz,et al.  Mechanisms of sampling interstitial fluid from skin using a microneedle patch , 2018, Proceedings of the National Academy of Sciences.

[36]  Jung-Hwan Park,et al.  Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[37]  Wei Chen,et al.  PVDF-Nafion nanomembranes coated microneedles for in vivo transcutaneous implantable glucose sensing. , 2015, Biosensors & bioelectronics.

[38]  Paolo Bollella,et al.  Minimally-invasive Microneedle-based Biosensor Array for Simultaneous Lactate and Glucose Monitoring in Artificial Interstitial Fluid , 2019, Electroanalysis.

[39]  P. Kalfon,et al.  Continuous glucose monitoring in the ICU: clinical considerations and consensus , 2017, Critical Care.

[40]  S. Gopi,et al.  Current advances in the detection of neurotransmitters by nanomaterials: An update , 2020 .

[41]  Conor O'Mahony,et al.  Biosensing in dermal interstitial fluid using microneedle based electrochemical devices , 2020 .

[42]  B. Cui,et al.  Fabrication of sharp silicon hollow microneedles by deep-reactive ion etching towards minimally invasive diagnostics , 2019, Microsystems & Nanoengineering.

[43]  D. Barbier,et al.  Silicon/SU8 multi-electrode micro-needle for in vivo neurochemical monitoring. , 2015, Biosensors & bioelectronics.

[44]  Roger Narayan,et al.  Microneedle array-based carbon paste amperometric sensors and biosensors. , 2011, The Analyst.

[45]  P. Georgiou,et al.  Microneedle biosensors for real-time, minimally invasive drug monitoring of phenoxymethylpenicillin: a first-in-human evaluation in healthy volunteers. , 2019, The Lancet. Digital health.

[46]  Kaushalkumar Dave,et al.  Microneedles in the clinic. , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[47]  P. R. Miller,et al.  Nitrogen-incorporated ultrananocrystalline diamond microneedle arrays for electrochemical biosensing , 2015 .

[48]  A. Caliò,et al.  Polymeric microneedles based enzymatic electrodes for electrochemical biosensing of glucose and lactic acid , 2016 .

[49]  Sanjiv Sharma,et al.  Rapid, low cost prototyping of transdermal devices for personal healthcare monitoring , 2017, Sensing and Bio-Sensing Research.

[50]  Mehdi Javanmard,et al.  Microneedle Biosensor: A Method for Direct Label-free Real Time Protein Detection. , 2013, Sensors and actuators. B, Chemical.

[51]  L Tian,et al.  Wearable sensors: modalities, challenges, and prospects. , 2018, Lab on a chip.

[52]  Pantelis Georgiou,et al.  A pilot study in humans of microneedle sensor arrays for continuous glucose monitoring , 2018 .

[53]  C. O’Mahony,et al.  Development of Low Cost Rapid Fabrication of Sharp Polymer Microneedles for In Vivo Glucose Biosensing Applications , 2015 .

[54]  Roger Narayan,et al.  Microneedle‐Based Transdermal Sensor for On‐Chip Potentiometric Determination of K+ , 2014, Advanced healthcare materials.

[55]  F. Rius,et al.  A reference electrode based on polyvinyl butyral (PVB) polymer for decentralized chemical measurements. , 2014, Analytica chimica acta.

[56]  R. Mazze,et al.  Evaluating the accuracy, reliability, and clinical applicability of continuous glucose monitoring (CGM): Is CGM ready for real time? , 2009, Diabetes technology & therapeutics.

[57]  Saram Lee,et al.  Recent advances in electrochemical non-enzymatic glucose sensors - A review. , 2018, Analytica chimica acta.

[58]  Seong J. Cho,et al.  Continuous glucose monitoring using a microneedle array sensor coupled with a wireless signal transmitter , 2019, Sensors and Actuators B: Chemical.

[59]  Guojun Zhang,et al.  MoS2/Pt nanocomposite-functionalized microneedle for real-time monitoring of hydrogen peroxide release from living cells. , 2017, The Analyst.

[60]  B. Liu,et al.  Rapid fabrication of microneedles using magnetorheological drawing lithography. , 2018, Acta biomaterialia.

[61]  ViLinh Tran,et al.  Human Suction Blister Fluid Composition Determined Using High-Resolution Metabolomics , 2018, Analytical chemistry.

[62]  Marc Parrilla,et al.  Cytotoxicity Study of Ionophore-Based Membranes: Towards On-Body and In Vivo Ion Sensing. , 2019, ACS sensors.

[63]  W. Waring,et al.  Serum urea concentration and the risk of hepatotoxicity after paracetamol overdose. , 2008, QJM : monthly journal of the Association of Physicians.

[64]  G. Deuschl,et al.  MDS clinical diagnostic criteria for Parkinson's disease , 2015, Movement disorders : official journal of the Movement Disorder Society.

[65]  Rosa Villa,et al.  Profiling of oxygen in biofilms using individually addressable disk microelectrodes on a microfabricated needle , 2015, Microchimica Acta.

[66]  Fan Yang,et al.  A sensitive acupuncture needle microsensor for real-time monitoring of nitric oxide in acupoints of rats , 2017, Scientific Reports.

[67]  Tatsuo Nakagawa,et al.  Wearable Wireless Tyrosinase Bandage and Microneedle Sensors: Toward Melanoma Screening , 2018, Advanced healthcare materials.

[68]  P. Brenchley,et al.  Reverse iontophoresis of urea in health and chronic kidney disease: a potential diagnostic and monitoring tool? , 2012, European journal of clinical investigation.

[69]  Benjamin C. Tang,et al.  Microneedle Electrodes Toward an Amperometric Glucose‐Sensing Smart Patch , 2014, Advanced healthcare materials.

[70]  Joshua Ray Windmiller,et al.  Continuous minimally-invasive alcohol monitoring using microneedle sensor arrays. , 2017, Biosensors & bioelectronics.

[71]  Kuldeep Mahato,et al.  Paper based diagnostics for personalized health care: Emerging technologies and commercial aspects. , 2017, Biosensors & bioelectronics.

[72]  Marc Parrilla,et al.  Wearable Potentiometric Ion Patch for On-Body Electrolyte Monitoring in Sweat: Toward a Validation Strategy to Ensure Physiological Relevance. , 2019, Analytical chemistry.

[73]  David C Klonoff,et al.  Wearable physiological systems and technologies for metabolic monitoring. , 2018, Journal of applied physiology.

[74]  A. Levey,et al.  Glomerular filtration rate and albuminuria for detection and staging of acute and chronic kidney disease in adults: a systematic review. , 2015, JAMA.

[75]  M. Zavar,et al.  Microneedle Copper (II) Selective Electrode based on Polypyrrole Doped with 8-Hydroxyquinoline-5-Sulfonic Acid , 2015 .

[76]  Ronen Polsky,et al.  Integrated carbon fiber electrodes within hollow polymer microneedles for transdermal electrochemical sensing. , 2011, Biomicrofluidics.

[77]  Weihua Huang,et al.  Flexible Electrochemical Urea Sensor Based on Surface Molecularly Imprinted Nanotubes for Detection of Human Sweat. , 2018, Analytical chemistry.

[78]  C. Agostoni,et al.  Electrolyte abnormalities in cystic fibrosis: systematic review of the literature , 2014, Pediatric Nephrology.

[79]  Shenzhou Lu,et al.  Silk/polyols/GOD microneedle based electrochemical biosensor for continuous glucose monitoring , 2020, RSC advances.

[80]  Xiaoxuan Zhang,et al.  Encoded Microneedle Arrays for Detection of Skin Interstitial Fluid Biomarkers , 2019, Advanced materials.

[81]  Zhen Gu,et al.  Blood sampling using microneedles as a minimally invasive platform for biomedical diagnostics , 2018, Applied Materials Today.

[82]  Matsuhiko Nishizawa,et al.  An array of porous microneedles for transdermal monitoring of intercellular swelling , 2017, Biomedical microdevices.

[83]  Somasekhar R. Chinnadayyala,et al.  Editors' Choice—Review—In Vivo and In Vitro Microneedle Based Enzymatic and Non-Enzymatic Continuous Glucose Monitoring Biosensors , 2018 .

[84]  Changqing Yi,et al.  Simultaneous detection of glucose, uric acid and cholesterol using flexible microneedle electrode array-based biosensor and multi-channel portable electrochemical analyzer , 2019, Sensors and Actuators B: Chemical.

[85]  W. Zhou,et al.  A Mini Review of Microneedle Array Electrode for Bio-Signal Recording: A Review , 2020, IEEE Sensors Journal.

[86]  Marc Parrilla,et al.  Wearable Potentiometric Sensors for Medical Applications , 2019, Sensors.

[87]  J. Little,et al.  Apolipoprotein and lipoprotein concentrations in familial apolipoprotein C-II deficiency. , 1982, Atherosclerosis.

[88]  P. Jansson,et al.  Microdialysis methodology for the measurement of dermal interstitial fluid in humans , 1996, The British journal of dermatology.

[89]  Philip R. Miller,et al.  Microneedle-based sensors for medical diagnosis. , 2016, Journal of materials chemistry. B.

[90]  M D Luque de Castro,et al.  Sweat: a sample with limited present applications and promising future in metabolomics. , 2014, Journal of pharmaceutical and biomedical analysis.

[91]  Li Tian,et al.  Copper active sites in biology. , 2014, Chemical reviews.

[92]  Conor O'Mahony,et al.  Microscopic gel-liquid interfaces supported by hollow microneedle array for voltammetric drug detection , 2014 .

[93]  Justin T. Baca,et al.  Extraction and biomolecular analysis of dermal interstitial fluid collected with hollow microneedles , 2018, Communications Biology.

[94]  Zhigang Zhu,et al.  Current and Emerging Technology for Continuous Glucose Monitoring , 2017, Sensors.

[95]  Hazhir Teymourian,et al.  Continuous Opioid Monitoring along with Nerve Agents on a Wearable Microneedle Sensor Array. , 2020, Journal of the American Chemical Society.

[96]  D. Christiani,et al.  Serum bilirubin levels on ICU admission are associated with ARDS development and mortality in sepsis , 2009, Thorax.

[97]  M. Tabbers,et al.  ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Fluid and electrolytes. , 2018, Clinical nutrition.

[98]  Justin T. Baca,et al.  Proteomic Characterization of Dermal Interstitial Fluid Extracted Using a Novel Microneedle-Assisted Technique. , 2018, Journal of proteome research.

[99]  Taeghwan Hyeon,et al.  Enzyme‐Based Glucose Sensor: From Invasive to Wearable Device , 2018, Advanced healthcare materials.

[100]  V. Ganesan,et al.  Electrochemical sensor and biosensor platforms based on advanced nanomaterials for biological and biomedical applications. , 2018, Biosensors & bioelectronics.

[101]  Hyungil Jung,et al.  A three-dimensional and bevel-angled ultrahigh aspect ratio microneedle for minimally invasive and painless blood sampling , 2018 .

[102]  Guojun Ma,et al.  Microneedle, bio‐microneedle and bio‐inspired microneedle: A review , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[103]  Sam Emaminejad,et al.  Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis , 2016, Nature.

[104]  L. Strindberg,et al.  Validation of an endogenous reference technique for the calibration of microdialysis catheters , 2000, Scandinavian journal of clinical and laboratory investigation.

[105]  Jeong-Bong Lee,et al.  Fabrication of a Microneedle/CNT Hierarchical Micro/Nano Surface Electrochemical Sensor and Its In-Vitro Glucose Sensing Characterization , 2013, Sensors.

[106]  D. Angus,et al.  Parenteral calcium for intensive care unit patients. , 2008, The Cochrane database of systematic reviews.

[107]  O. Siggaard‐Andersen,et al.  Composition of interstitial fluid. , 1995, Clinical chemistry.

[108]  David S Jones,et al.  Hydrogel-Forming Microneedle Arrays Allow Detection of Drugs and Glucose In Vivo: Potential for Use in Diagnosis and Therapeutic Drug Monitoring , 2015, PloS one.

[109]  Sara W. Bird,et al.  A smartphone-based diagnostic platform for rapid detection of Zika, chikungunya, and dengue viruses , 2017, Scientific Reports.

[110]  Wei Zhang,et al.  Uniform sensing layer of immiscible enzyme-mediator compounds developed via a spray aerosol mixing technique towards low cost minimally invasive microneedle continuous glucose monitoring devices. , 2018, Biosensors & bioelectronics.

[111]  Youngcheol Chae,et al.  A CMOS VEGF Sensor for Cancer Diagnosis Using a Peptide Aptamer-Based Functionalized Microneedle , 2019, IEEE Transactions on Biomedical Circuits and Systems.

[112]  N. Oliver,et al.  Use of microneedle array devices for continuous glucose monitoring: a review. , 2013, Diabetes technology & therapeutics.

[113]  Ryan F. Donnelly,et al.  Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development , 2016 .

[114]  V. Shah,et al.  Acute neurological findings in a national cohort of neonates with severe neonatal hyperbilirubinemia , 2011, Journal of Perinatology.

[115]  Kai Chang,et al.  A sample-to-answer quantitative platform for point-of-care testing of biochemical markers in whole blood , 2020 .

[116]  Christofer Toumazou,et al.  An array of individually addressable micro-needles for mapping pH distributions. , 2016, The Analyst.

[117]  M. Castaño‐Álvarez,et al.  Fast and reliable urine analysis using a portable platform based on microfluidic electrophoresis chips with electrochemical detection , 2013 .

[118]  Yi Lin,et al.  Optimal design and fabrication of a microneedle arrays patch , 2020, Journal of Manufacturing Processes.

[119]  Paolo Pelosi,et al.  Respiratory monitoring in adult intensive care unit , 2017, Expert review of respiratory medicine.

[120]  Han Huang,et al.  Elastic modulus and viscoelastic properties of full thickness skin characterised at micro scales. , 2013, Biomaterials.

[121]  Sei Kwang Hahn,et al.  Microneedle Biosensor for Real‐Time Electrical Detection of Nitric Oxide for In Situ Cancer Diagnosis During Endomicroscopy , 2015, Advanced healthcare materials.

[122]  Viness Pillay,et al.  Current advances in the fabrication of microneedles for transdermal delivery. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[123]  Sam Emaminejad,et al.  Autonomous sweat extraction and analysis applied to cystic fibrosis and glucose monitoring using a fully integrated wearable platform , 2017, Proceedings of the National Academy of Sciences.

[124]  Joseph Wang,et al.  Wearable salivary uric acid mouthguard biosensor with integrated wireless electronics. , 2015, Biosensors & bioelectronics.

[125]  J. Massie,et al.  The limitations of sweat electrolyte reference intervals for the diagnosis of cystic fibrosis: a systematic review. , 2007, The Clinical biochemist. Reviews.

[126]  L. Stefano,et al.  Microneedles-based electrochemical sensors: New tools for advanced biosensing , 2019, Current Opinion in Electrochemistry.

[127]  Keyun Chen,et al.  Flexible microneedle array electrode using magnetorheological drawing lithography for bio-signal monitoring , 2017 .

[128]  Niclas Roxhed,et al.  Wearable All-Solid-State Potentiometric Microneedle Patch for Intradermal Potassium Detection. , 2018, Analytical chemistry.

[129]  Y. Skrobik,et al.  Intravenous phosphate in the intensive care unit: More aggressive repletion regimens for moderate and severe hypophosphatemia , 2003, Intensive Care Medicine.

[130]  Jianwei Zhao,et al.  The fabrication of an Ni6MnO8 nanoflake-modified acupuncture needle electrode for highly sensitive ascorbic acid detection , 2019, RSC advances.

[131]  Evgeny Katz,et al.  Bicomponent Microneedle Array Biosensor for Minimally‐Invasive Glutamate Monitoring , 2011 .

[132]  Maelíosa T. C. McCrudden,et al.  Microneedles for intradermal and transdermal drug delivery. , 2013, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[133]  H. Zahouani,et al.  In vivo measurements of the elastic mechanical properties of human skin by indentation tests. , 2008, Medical engineering & physics.

[134]  M. Moradi-Lakeh,et al.  The Value of Serum Uric Acid as a Mortality Prediction in Critically Ill Children , 2010, Iranian journal of pediatrics.

[135]  R. Garcia-Torres,et al.  Stability and Stabilization of Enzyme Biosensors: The Key to Successful Application and Commercialization. , 2018, Annual review of food science and technology.

[136]  P. Durrington,et al.  Presence of paraoxonase in human interstitial fluid , 1997, FEBS letters.

[137]  James Davis,et al.  Design of composite microneedle sensor systems for the measurement of transdermal pH , 2019, Materials Chemistry and Physics.

[138]  W Thomas,et al.  Glucose measurement in patients with diabetes mellitus with dermal interstitial fluid. , 1997, The Journal of laboratory and clinical medicine.

[139]  Keng Wooi Ng,et al.  Poly(lactic acid)/Carbon Nanotube Composite Microneedle Arrays for Dermal Biosensing. , 2019, Analytical chemistry.

[140]  I. Kucherenko,et al.  Advances in the biosensors for lactate and pyruvate detection for medical applications: A review , 2019, TrAC Trends in Analytical Chemistry.

[141]  Guo-Jun Zhang,et al.  Monitoring of pH changes in a live rat brain with MoS2/PAN functionalized microneedles. , 2018, The Analyst.

[142]  Xi Xie,et al.  Protection of Nanostructures-Integrated Microneedle Biosensor Using Dissolvable Polymer Coating. , 2019, ACS applied materials & interfaces.

[143]  L. C. Clark,et al.  ELECTRODE SYSTEMS FOR CONTINUOUS MONITORING IN CARDIOVASCULAR SURGERY , 1962 .

[144]  Yue Xu,et al.  Quantification of lactate in synovia by microchip with contactless conductivity detection. , 2013, Analytical biochemistry.

[145]  J. Kong,et al.  Engineered Microneedles for Interstitial Fluid Cell‐Free DNA Capture and Sensing Using Iontophoretic Dual‐Extraction Wearable Patch , 2020, Advanced Functional Materials.

[146]  Giuseppe Barillaro,et al.  Microneedles for Transdermal Biosensing: Current Picture and Future Direction , 2015, Advanced healthcare materials.

[147]  B. Halliwell,et al.  Hydrogen peroxide in the human body , 2000, FEBS letters.

[148]  Gopinathan K Menon,et al.  New insights into skin structure: scratching the surface. , 2002, Advanced drug delivery reviews.

[149]  J. Samitier,et al.  Micro-needle implantable electrochemical oxygen sensor: ex-vivo and in-vivo studies. , 2020, Biosensors & bioelectronics.

[150]  Fernando Soto,et al.  A microneedle biosensor for minimally-invasive transdermal detection of nerve agents. , 2017, The Analyst.

[151]  Seong J. Cho,et al.  Mussel-inspired enzyme immobilization and dual real-time compensation algorithms for durable and accurate continuous glucose monitoring. , 2019, Biosensors & bioelectronics.

[152]  P. R. Miller,et al.  Microneedle-based self-powered glucose sensor , 2014 .

[153]  Franklin Bien,et al.  Wearable smart sensor systems integrated on soft contact lenses for wireless ocular diagnostics , 2017, Nature Communications.

[154]  H. Lieberman,et al.  Interstitial glucose concentrations and hypoglycemia during 2 days of caloric deficit and sustained exercise: a double-blind, placebo-controlled trial. , 2016, Journal of applied physiology.

[155]  F P T Baaijens,et al.  Monitoring the penetration process of single microneedles with varying tip diameters. , 2014, Journal of the mechanical behavior of biomedical materials.

[156]  N. Voelcker,et al.  Gold microneedles fabricated by casting of gold ink used for urea sensing , 2019, Materials Letters.

[157]  Ganesh Kumar Mani,et al.  Microneedle pH Sensor: Direct, Label-Free, Real-Time Detection of Cerebrospinal Fluid and Bladder pH. , 2017, ACS applied materials & interfaces.

[158]  Sam Emaminejad,et al.  A Wearable Electrochemical Platform for Noninvasive Simultaneous Monitoring of Ca(2+) and pH. , 2016, ACS nano.

[159]  Mark R Prausnitz,et al.  Insertion of microneedles into skin: measurement and prediction of insertion force and needle fracture force. , 2004, Journal of biomechanics.

[160]  Kostis Michelakis,et al.  Microfluidic device to investigate factors affecting performance in biosensors designed for transdermal applications. , 2012, Lab on a chip.

[161]  J. Bouwstra,et al.  Improved piercing of microneedle arrays in dermatomed human skin by an impact insertion method. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[162]  W. Tamborlane,et al.  Interstitial fluid concentrations of glycerol, glucose, and amino acids in human quadricep muscle and adipose tissue. Evidence for significant lipolysis in skeletal muscle. , 1995, The Journal of clinical investigation.

[163]  Marc Parrilla,et al.  Wearable potentiometric ion sensors , 2019, TrAC Trends in Analytical Chemistry.

[164]  John G. Bruno,et al.  Aptamer-based point-of-care diagnostic platforms , 2017 .