To evaluate the feasibility of an implantable subconjunctival glucose monitoring system (SGMS) for glucose monitoring in humans, we investigated the in vivo performance of the sensor in a clinical trial with five patients.
Methods:
The new SGMS consists of an implantable ocular mini implant (OMI) and a hand-held fluorescence photometer. The implantable subconjunctival glucose sensor is composed of a fluorescence resonance energy transfer system based on Concanavalin A chemistry, embedded in a nelfilcon polymer hydrogel disk. Blood glucose changes in humans were induced by oral glucose intake and insulin injections.
Results:
The in vivo response of the new SGMS was tested in a first human clinical study with five diabetes patients. The OMI was well tolerated in the eyes of the patients. The SGMS exhibited high correlation coefficients (>0.88) with blood glucose changes and a good stability of the sensor response to glucose for the study period of 2 weeks. Lag times were in the range of 5–10 min. A total of 98% of all data pairs was in the clinical acceptable ranges A and B of the consensus error grid.
Conclusions:
For the first time, the possibility to measure glucose in vivo in the subconjunctival interstitial fluid for a period of 2 weeks was demonstrated in a human clinical trial.
International Diabetes Federation. IDF Diabetes Atlas4th edition [CD-ROM]. Brussels, Belgium: International Diabetes Federation; 2009.
2.
KlonoffDC. The increasing incidence of diabetes in the 21st century. J. Diabetes Sci Technol.2009;3 (1): 1–2.
3.
The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med.1993;329 (14): 977–86.
4.
RawerRStorkWKreinerCF. Non-invasive polarimetric measurement of glucose concentration in the anterior chamber of the eye. Graefes Arch Clin Exp Ophthalmol.2004;242 (12): 1017–23. Epub 2004 Nov 19.
5.
MalikBHCotéGL. Characterizing dual wavelength polarimetry through the eye for monitoring glucose. Biomed Opt Express.2010;1 (5): 1247–58.
AlexeevVLDasSFinegoldDNAsherSA. Photonic crystal glucose-sensing material for noninvasive monitoring of glucose in tear fluid. Clin Chem.2004;50 (12): 2353–60. Epub 2004 Sep 30.
12.
TaorminaCRBacaJTAsherSAGrabowskiJJFinegoldDN. Analysis of tear glucose concentration with electrospray ionization mass spectrometry. J Am Soc Mass Spectrom.2007;18 (2): 332–6. Epub 2006 Nov 2.
KlonoffDC. Continuous glucose monitoring: Roadmap for 21st century diabetes therapy. Diabetes Care.2005;28 (5): 1231–9.
15.
OliverNSToumazouCCassAEJohnstonDG. Glucose sensors: A review of current and emerging technology. Diabetic Med.2009;26 (3): 197–210.
16.
WankoTLloydBJJrMatthewsJ. The fine structure of human conjunctiva in the perilimbal zone. Invest Ophthalmol.1964;3: 285–301.
17.
SumnerJBHowellSF. Identification of Hemagglutinin of Jack Bean with Concanavalin A. J. Bacteriol.1936;32 (2): 227–37.
18.
GoldsteinIJHollermanCESmithEE. Protein-carbohydrate interaction. II. Inhibition studies on the interaction of Concanavalin A with polysaccharides. Biochemistry.1965;4: 876–83.
19.
GoldsteinIJReichertCMMisakiA. Interaction of concanavalin A with model substrates. Ann N Y Acad Sci.1974;234 (0): 283–96.
20.
SchultzJSMansouriSGoldsteinIJ. Affinity sensor: A new technique for developing implantable sensors for glucose and other metabolites. Diabetes Care.1982;5 (3): 245–53.
21.
MansouriSSchultzJS. A Miniature Optical Glucose Sensor Based on Affinity Binding. Biotechnology.1984;2: 885–90.
22.
MeadowsDSchultzJS. Fiber-optic biosensors based on fluorescence energy transfer. Talanta.1988;35 (2): 145–50.
23.
MeadowsDLSchultzJS. Design, manufacture and characterization of an optical fiber glucose affinity sensor based on a homogeneous fluorescence energy transfer assay system. Anal Chim Acta.1993;280 (1): 21–30.
24.
BallerstadtRSchultzJS. Competitive-binding assay method based on fluorescence quenching of ligands held in close proximity by a multivalent receptor. Anal Chim Acta.1997;345 (1): 203–12.
RussellRJPishkoMVGefridesCCMcShaneMJCotéGL. A fluorescence-based glucose biosensor using concanavalin A and dextran encapsulated in a poly(ethylene glycol) hydrogel. Anal Chem.1999;71 (15): 3126–32.
27.
BallerstadtRSchultzJS. A fluorescence affinity hollow fiber sensor for continuous transdermal glucose monitoring. Anal Chem.2000;72 (17): 4184–92.
28.
BallerstadtRPolakABeuhlerAFryeJ. In vitro long-term performance study of a near-infrared fluorescence affinity sensor for glucose monitoring. Biosens Bioelectron.2004;19 (8): 905–14.
29.
BallerstadtREvansCGowdaAMcNicholsR. In vivo performance evaluation of a transdermal near- infrared fluorescence resonance energy transfer affinity sensor for continuous glucose monitoring. Diabetes Technol Ther.2006;8 (3): 296–311.
30.
BallerstadtREvansCGowdaAMcNicholsR. Fiber-coupled fluorescence affinity sensor for 3-day in vivo glucose sensing. J Diabetes Sci Technol.2007;1 (3): 384–93.
ParkesJLSlatinSLPardoSGinsbergBH. A new consensus error grid to evaluate the clinical significance of inaccuracies in the measurement of blood glucose. Diabetes Care.2000;23 (8): 1143–8.
33.
BallerstadtREvansCMcNicholsRGowdaA. Concanavalin A for in vivo glucose sensing: A biotoxicity review. Biosens Bioelectron.2006;22 (2): 275–84. Epub 2006 Feb 20.
34.
BoyneMSSilverDMKaplanJSaudekCD. Timing of changes in interstitial and venous blood glucose measured with a continuous subcutaneous glucose sensor. Diabetes.2003;52 (11): 2790–4.
