Fluorescent-based biodegradable microneedle sensor array for tether-free continuous glucose monitoring with smartphone application

Continuous glucose monitoring (CGM) allows patients with diabetes to manage critical disease effectively and autonomously and prevent exacerbation. A painless, wireless, compact, and minimally invasive device that can provide CGM is essential for monitoring the health conditions of freely moving patients with diabetes. Here, we propose a glucose-responsive fluorescence-based highly sensitive biodegradable microneedle CGM system. These ultrathin and ultralight microneedle sensor arrays continuously and precisely monitored glucose concentration in the interstitial fluid with minimally invasive, pain-free, wound-free, and skin inflammation-free outcomes at various locations and thicknesses of the skin. Bioresorbability in the body without a need for device removal after use was a key characteristic of the microneedle glucose sensor. We demonstrated the potential long-term use of the bioresorbable device by applying the tether-free CGM system, thus confirming the successful detection of glucose levels based on changes in fluorescence intensity. In addition, this microneedle glucose sensor with a user-friendly designed home diagnosis system using mobile applications and portable accessories offers an advance in CGM and its applicability to other bioresorbable, wearable, and implantable monitoring device technology.

[1]  Youngmee Jung,et al.  Foldable three dimensional neural electrode arrays for simultaneous brain interfacing of cortical surface and intracortical multilayers , 2022, npj Flexible Electronics.

[2]  Hong-Goo Kang,et al.  Ultrathin crystalline-silicon-based strain gauges with deep learning algorithms for silent speech interfaces , 2022, Nature Communications.

[3]  Ki Jun Yu,et al.  Ultra‐Thin Flexible Encapsulating Materials for Soft Bio‐Integrated Electronics , 2022, Advanced science.

[4]  Corey M. Rountree,et al.  Ecoresorbable and bioresorbable microelectromechanical systems , 2022, Nature Electronics.

[5]  Siddharth R. Krishnan,et al.  Soft, bioresorbable coolers for reversible conduction block of peripheral nerves , 2022, Science.

[6]  Kuldeep Mahato,et al.  An integrated wearable microneedle array for the continuous monitoring of multiple biomarkers in interstitial fluid , 2022, Nature Biomedical Engineering.

[7]  W. Yeo,et al.  VR-enabled portable brain-computer interfaces via wireless soft bioelectronics. , 2022, Biosensors & bioelectronics.

[8]  Youngmee Jung,et al.  Hetero‐Integration of Silicon Nanomembranes with 2D Materials for Bioresorbable, Wireless Neurochemical System , 2022, Advanced materials.

[9]  B. Duncan,et al.  IDF diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045 , 2021, Diabetes Research and Clinical Practice.

[10]  Jung Woo Lee,et al.  Ultrahigh Sensitive Au‐Doped Silicon Nanomembrane Based Wearable Sensor Arrays for Continuous Skin Temperature Monitoring with High Precision , 2021, Advanced materials.

[11]  Yeon Sik Choi,et al.  Fully implantable and bioresorbable cardiac pacemakers without leads or batteries , 2021, Nature Biotechnology.

[12]  Yonggang Huang,et al.  Biocompatible Light Guide‐Assisted Wearable Devices for Enhanced UV Light Delivery in Deep Skin , 2021, Advanced Functional Materials.

[13]  Kuldeep Mahato,et al.  Lab under the Skin: Microneedle Based Wearable Devices , 2021, Advanced healthcare materials.

[14]  Y. Heo,et al.  Biosensing Technologies for Chronic Diseases , 2021, BioChip Journal.

[15]  Xiao-fei Zhu,et al.  Nonenzymatic Electrochemical Sensor for Wearable Interstitial Fluid Glucose Monitoring , 2021 .

[16]  S. Takeuchi,et al.  Long‐Term Continuous Glucose Monitoring Using a Fluorescence‐Based Biocompatible Hydrogel Glucose Sensor , 2020, Advanced healthcare materials.

[17]  Jae-Yoon Sim,et al.  Wireless smart contact lens for diabetic diagnosis and therapy , 2020, Science Advances.

[18]  Zhenan Bao,et al.  Multifunctional materials for implantable and wearable photonic healthcare devices , 2020, Nature Reviews Materials.

[19]  Zhaoping Li,et al.  A laser-engraved wearable sensor for sensitive detection of uric acid and tyrosine in sweat , 2019, Nature Biotechnology.

[20]  Tuomas Happonen,et al.  Porous Enzymatic Membrane for Nanotextured Glucose Sweat Sensors with High Stability toward Reliable Noninvasive Health Monitoring , 2019, ECS Meeting Abstracts.

[21]  Yun Jung Heo,et al.  Toward Long-Term Implantable Glucose Biosensors for Clinical Use , 2019, Applied Sciences.

[22]  Suyong Kim,et al.  Tissue Interlocking Dissolving Microneedles for Accurate and Efficient Transdermal Delivery of Biomolecules , 2019, Scientific Reports.

[23]  S. Sankaranarayanan,et al.  Factory-Calibrated Continuous Glucose Monitoring: How and Why It Works, and the Dangers of Reuse Beyond Approved Duration of Wear. , 2019, Diabetes technology & therapeutics.

[24]  Timothy Bretl,et al.  Large-area MRI-compatible epidermal electronic interfaces for prosthetic control and cognitive monitoring , 2019, Nature Biomedical Engineering.

[25]  M. Prausnitz,et al.  Rapidly separable microneedle patch for the sustained release of a contraceptive , 2019, Nature Biomedical Engineering.

[26]  Siddaramaiah,et al.  Photosensitization of optical band gap modified polyvinyl alcohol films with hybrid AgAlO2 nanoparticles , 2018, Journal of Materials Science: Materials in Electronics.

[27]  I. Hirsch,et al.  Clinical Implications of Real-time and Intermittently Scanned Continuous Glucose Monitoring , 2018, Diabetes Care.

[28]  John A Rogers,et al.  Bioresorbable pressure sensors protected with thermally grown silicon dioxide for the monitoring of chronic diseases and healing processes , 2018, Nature Biomedical Engineering.

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

[30]  Chuanbin Wu,et al.  Intradermal delivery of STAT3 siRNA to treat melanoma via dissolving microneedles , 2018, Scientific Reports.

[31]  N. Jain,et al.  A review on mechanical and water absorption properties of polyvinyl alcohol based composites/films , 2017 .

[32]  Ran Liu,et al.  Multilayered pyramidal dissolving microneedle patches with flexible pedestals for improving effective drug delivery , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[33]  Peng Chen,et al.  A Swellable Microneedle Patch to Rapidly Extract Skin Interstitial Fluid for Timely Metabolic Analysis , 2017, Advanced materials.

[34]  Min Zhang,et al.  Prevalence and causes of low vision and blindness in a Chinese population with type 2 diabetes: the Dongguan Eye Study , 2017, Scientific Reports.

[35]  John A Rogers,et al.  Erratum: Capacitively coupled arrays of multiplexed flexible silicon transistors for long-term cardiac electrophysiology , 2017, Nature Biomedical Engineering.

[36]  Dachao Li,et al.  A flexible electrochemical glucose sensor with composite nanostructured surface of the working electrode , 2016 .

[37]  Hongwei Zhou,et al.  A highly selective electrochemical sensor for nifedipine based on layer‐by‐layer assembly films from polyaniline and multiwalled carbon nanotube , 2016 .

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

[39]  N. Pugno,et al.  The effect of ageing on the mechanical properties of the silk of the bridge spider Larinioides cornutus (Clerck, 1757) , 2016, Scientific Reports.

[40]  Kyung Jin Seo,et al.  Bioresorbable Silicon Electronics for Transient Spatio-temporal Mapping of Electrical Activity from the Cerebral Cortex , 2016, Nature materials.

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

[42]  Mohammad Ali Shokrgozar,et al.  Silk fibroin nanoparticle as a novel drug delivery system. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[43]  Benjamin C. Tang,et al.  Managing diabetes with nanomedicine: challenges and opportunities , 2014, Nature Reviews Drug Discovery.

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

[45]  David L Kaplan,et al.  Silk-based biomaterials for sustained drug delivery. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[46]  Lifeng Kang,et al.  Effect of microneedle geometry and supporting substrate on microneedle array penetration into skin. , 2013, Journal of pharmaceutical sciences.

[47]  Robert Langer,et al.  Materials for Diabetes Therapeutics , 2012, Advanced healthcare materials.

[48]  David L. Kaplan,et al.  Fabrication of Silk Microneedles for Controlled‐Release Drug Delivery , 2012 .

[49]  Shoji Takeuchi,et al.  Long-term in vivo glucose monitoring using fluorescent hydrogel fibers , 2011, Proceedings of the National Academy of Sciences.

[50]  D. Kaplan,et al.  Degradation mechanism and control of silk fibroin. , 2011, Biomacromolecules.

[51]  Shoji Takeuchi,et al.  Injectable hydrogel microbeads for fluorescence-based in vivo continuous glucose monitoring , 2010, Proceedings of the National Academy of Sciences.

[52]  Hyungil Jung,et al.  Drawing Lithography: Three‐Dimensional Fabrication of an Ultrahigh‐Aspect‐Ratio Microneedle , 2010, Advanced materials.

[53]  S. Nayar,et al.  Composition dependent structural modulations in transparent poly(vinyl alcohol) hydrogels. , 2009, Colloids and surfaces. B, Biointerfaces.

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

[55]  Robert Langer,et al.  Transdermal drug delivery , 2008, Nature Biotechnology.

[56]  Kabseog Kim,et al.  High aspect ratio tapered hollow metallic microneedle arrays with microfluidic interconnector , 2006 .

[57]  W. Golde,et al.  A rapid, simple, and humane method for submandibular bleeding of mice using a lancet , 2005, Lab Animal.

[58]  Oliver A. Shergold,et al.  Experimental investigation into the deep penetration of soft solids by sharp and blunt punches, with application to the piercing of skin. , 2005, Journal of biomechanical engineering.

[59]  Mark R Prausnitz,et al.  Minimally invasive extraction of dermal interstitial fluid for glucose monitoring using microneedles. , 2005, Diabetes technology & therapeutics.

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

[61]  Dennis E. Discher,et al.  Polymer Vesicles , 2022 .

[62]  G L Coté,et al.  A fluorescence-based glucose biosensor using concanavalin A and dextran encapsulated in a poly(ethylene glycol) hydrogel. , 1999, Analytical chemistry.

[63]  S. Shinkai,et al.  Chiral discrimination of monosaccharides using a fluorescent molecular sensor , 1995, Nature.

[64]  R. A. Ilyas,et al.  Highly transparent and antimicrobial PVA based bionanocomposites reinforced by ginger nanofiber , 2020 .

[65]  Vamsi K Yadavalli,et al.  Swellable silk fibroin microneedles for transdermal drug delivery. , 2018, International journal of biological macromolecules.