Noninvasive Glucose Monitoring with a Contact Lens and Smartphone

Diabetes has become a chronic metabolic disorder, and the growing diabetes population makes medical care more important. We investigated using a portable and noninvasive contact lens as an ideal sensor for diabetes patients whose tear fluid contains glucose. The key feature is the reversible covalent interaction between boronic acid and glucose, which can provide a noninvasive glucose sensor for diabetes patients. We present a phenylboronic acid (PBA)-based HEMA contact lens that exhibits a reversible swelling/shrinking effect to change its thickness. The difference in thickness can be detected in a picture taken with a smartphone and analyzed using software. Our novel technique offers the following capabilities: (i) non-enzymatic and continuous glucose detection with the contact lens; (ii) no need for an embedded circuit and power source for the glucose sensor; and (iii) the use of a smartphone to detect the change in thickness of the contact lens with no need for additional photo-sensors. This technique is promising for a noninvasive measurement of the glucose level and simple implementation of glucose sensing with a smartphone.

[1]  I Gryczynski,et al.  Glucose sensor for low-cost lifetime-based sensing using a genetically engineered protein. , 1999, Analytical biochemistry.

[2]  A. Afanasiev,et al.  A soft hydrogel contact lens with an encapsulated sensor for tear glucose monitoring , 2012, 2012 IEEE 25th International Conference on Micro Electro Mechanical Systems (MEMS).

[3]  Binghe Wang,et al.  Boronolectins and fluorescent boronolectins: An examination of the detailed chemistry issues important for the design , 2005, Medicinal research reviews.

[4]  Amay J Bandodkar,et al.  Non-invasive wearable electrochemical sensors: a review. , 2014, Trends in biotechnology.

[5]  Takashi Miyata,et al.  Preparation of smart soft materials using molecular complexes , 2010 .

[6]  Francis J. Doyle,et al.  Dynamic Behavior of Glucose-Responsive Poly(methacrylic acid-g-ethylene glycol) Hydrogels , 1997 .

[7]  R. Urban,et al.  Management of blood glucose in type 2 diabetes mellitus. , 2009, American family physician.

[8]  Joseph Wang,et al.  Re-usable electrochemical glucose sensors integrated into a smartphone platform. , 2018, Biosensors & bioelectronics.

[9]  Guozhen Chen,et al.  Capacitive contact lens sensor for continuous non-invasive intraocular pressure monitoring , 2013 .

[10]  K. Varahramyan,et al.  Glucose sensor based on organic thin film transistor using glucose oxidase and conducting polymer , 2008 .

[11]  C Albarrán,et al.  Influence of the tear film on optical quality of the eye. , 1997, Contact lens & anterior eye : the journal of the British Contact Lens Association.

[12]  P Kabasakalian,et al.  Enzymatic blood glucose determination by colorimetry of N,N-diethylaniline-4-aminoantipyrine. , 1974, Clinical chemistry.

[13]  Kup-Sze Choi,et al.  Recent advances in noninvasive glucose monitoring , 2012, Medical devices.

[14]  A. Turner,et al.  Glucose oxidase: an ideal enzyme , 1992 .

[15]  H. Abelman,et al.  Components of Lens Power That Regulate Surface Principal Powers and Relative Meridians Independently , 2016 .

[16]  R. Sack,et al.  Tear Glucose Dynamics in Diabetes Mellitus , 2006, Current eye research.

[17]  Bidyut Baran Chaudhuri,et al.  A survey of Hough Transform , 2015, Pattern Recognit..

[18]  Andrea Cherrington,et al.  Standards of Medical Care in Diabetes—2017 Abridged for Primary Care Providers , 2017, Clinical Diabetes.

[19]  Joseph R. Lakowicz,et al.  A Glucose Sensing Contact Lens: A Non-Invasive Technique for Continuous Physiological Glucose Monitoring , 2003, Journal of Fluorescence.

[20]  M. M. Rahman,et al.  Worldwide trends in diabetes since 1980 : pooled analysis of 751 population-based measurement studies with over 4 . 4 million participants , 2016 .

[21]  Jeng-Tzong Sheu,et al.  Detection of an uncharged steroid with a silicon nanowire field-effect transistor , 2009 .

[22]  Yihua Zhu,et al.  2D Photonic Crystal Hydrogel Sensor for Tear Glucose Monitoring , 2018, ACS omega.

[23]  Binghe Wang,et al.  Progress in Boronic Acid-Based Fluorescent Glucose Sensors , 2004, Journal of Fluorescence.

[24]  Changhuei Yang,et al.  A smartphone-based chip-scale microscope using ambient illumination. , 2014, Lab on a chip.

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

[26]  Chung-Yu Wu,et al.  Fabrication of a miniature CMOS-based optical biosensor. , 2007, Biosensors & bioelectronics.

[27]  Heon Hwang,et al.  Multi-Level Thresholding based on Non-Parametric Approaches for Fast Segmentation , 2013 .

[28]  Hongying Zhu,et al.  Optical imaging techniques for point-of-care diagnostics. , 2013, Lab on a chip.

[29]  Gonzalo Pajares,et al.  Multilevel Thresholding Segmentation Based on Harmony Search Optimization , 2013, J. Appl. Math..

[30]  Jeffrey T La Belle,et al.  Self-monitoring of tear glucose: the development of a tear based glucose sensor as an alternative to self-monitoring of blood glucose. , 2016, Chemical communications.

[31]  M. Weibel,et al.  The glucose oxidase mechanism. Interpretation of the pH dependence. , 1971, The Journal of biological chemistry.

[32]  Aydogan Ozcan,et al.  Integrated rapid-diagnostic-test reader platform on a cellphone. , 2012, Lab on a chip.

[33]  Yu-Te Liao,et al.  A 3-$\mu\hbox{W}$ CMOS Glucose Sensor for Wireless Contact-Lens Tear Glucose Monitoring , 2012, IEEE Journal of Solid-State Circuits.

[34]  Joseph R Lakowicz,et al.  A glucose-sensing contact lens: from bench top to patient. , 2005, Current opinion in biotechnology.

[35]  Y. Jang,et al.  Standards of Medical Care in Diabetes-2010 by the American Diabetes Association: Prevention and Management of Cardiovascular Disease , 2010 .

[36]  Yusuf Yagci,et al.  Fullerene-Attached Polymeric Homogeneous/Heterogeneous Photoactivators for Visible-Light-Induced CuAAC Click Reactions , 2016 .

[37]  Salim Chikhi,et al.  Artificial bees for multilevel thresholding of iris images , 2015, Swarm Evol. Comput..

[38]  W. Cefalu,et al.  Standards of Medical Care in Diabetes—2018 Abridged for Primary Care Providers , 2018, Clinical Diabetes.

[39]  D K Sen,et al.  Tear glucose levels in normal people and in diabetic patients. , 1980, The British journal of ophthalmology.

[40]  Daniel Piso,et al.  Modern Monitoring Intraocular Pressure Sensing Devices Based on Application Specific Integrated Circuits , 2012 .

[41]  조남욱.  전자/제조업의 Collaboration 전략 , 2003 .

[42]  Frank A. Gomez,et al.  Paper-based Microfluidic Point-of-care Diagnostic Devices for Monitoring Drug Metabolism , 2013 .

[43]  Akira Matsumoto,et al.  Swelling and Shrinking Kinetics of Totally Synthetic, Glucose-Responsive Polymer Gel Bearing Phenylborate Derivative as a Glucose-Sensing Moiety , 2004 .

[44]  Heather A Clark,et al.  Fluorescent sensors for the basic metabolic panel enable measurement with a smart phone device over the physiological range. , 2014, The Analyst.

[45]  Aydogan Ozcan,et al.  Cellphone-based devices for bioanalytical sciences , 2014, Analytical and Bioanalytical Chemistry.

[46]  Franklin Bien,et al.  Soft, smart contact lenses with integrations of wireless circuits, glucose sensors, and displays , 2018, Science Advances.

[47]  William Hodge,et al.  Noninvasive Diagnostic Devices for Diabetes through Measuring Tear Glucose , 2011, Journal of diabetes science and technology.

[48]  R. Villa,et al.  Non-invasive intraocular pressure monitoring with a contact lens engineered with a nanostructured polymeric sensing film , 2011 .

[49]  H Hoshino,et al.  Glucose-sensing electrode coated with polymer complex gel containing phenylboronic Acid. , 1996, Analytical chemistry.

[50]  Donald C. Cooper,et al.  Mobile Image Ratiometry: A New Method for Instantaneous Analysis of Rapid Test Strips , 2012 .

[51]  Yu-Chieh Huang,et al.  A Wirelessly Powered Smart Contact Lens with Reconfigurable Wide Range and Tunable Sensitivity Sensor Readout Circuitry , 2017, Sensors.

[52]  Hiroyuki Kudo,et al.  Soft contact lens biosensor for in situ monitoring of tear glucose as non-invasive blood sugar assessment. , 2011, Talanta.

[53]  Derek Tseng,et al.  Fluorescent imaging of single nanoparticles and viruses on a smart phone. , 2013, ACS nano.

[54]  Jeehyun Kim,et al.  Handheld Optical Coherence Tomography Scanner for Primary Care Diagnostics , 2011, IEEE Transactions on Biomedical Engineering.