Editing Blood glucose monitoring (section)

==Glucose sensing bio-implants==
Investigations on the use of test strips have shown that the required self-injury acts as a psychological barrier restraining the patients from sufficient glucose control.<ref>{{Cite journal | vauthors = Reach G |date=2015 |title=The Mental Mechanisms of Patient Adherence to Long-Term Therapies |journal=Philosophy and Medicine |series=Philosophy and Medicine 118 |volume=118 |doi=10.1007/978-3-319-12265-6 |isbn=978-3-319-12264-9 |s2cid=79106629 |issn=0376-7418}}</ref> As a result, [[Complications of diabetes mellitus|secondary diseases]] are caused by excessive glucose levels. A significant improvement of diabetes therapy might be achieved with an implantable sensor that would continuously monitor blood sugar levels within the body and transmit the measured data outside. The burden of regular blood testing would be taken from the patient, who would instead follow the course of their glucose levels on an intelligent device like a laptop or a smartphone.{{Citation needed|date=April 2022}}

Glucose concentrations do not necessarily have to be measured in blood vessels, but may also be determined in the [[interstitial fluid]], where the same levels prevail – with a time lag of a few minutes – due to its connection with the [[capillary system]]. However, the enzymatic glucose detection scheme used in single-use test strips is not directly suitable for [[implant (medicine)|implants]]. One main problem is caused by the varying supply of oxygen, by which glucose is converted to [[glucono delta-lactone|glucono lactone]] and H{{sub|2}}O{{sub|2}} by [[glucose oxidase]]. Since the implantation of a sensor into the body is accompanied by growth of encapsulation tissue,<ref name= Frost06>{{cite journal | vauthors = Frost M, Meyerhoff ME | title = In vivo chemical sensors: tackling biocompatibility | journal = Analytical Chemistry | volume = 78 | issue = 21 | pages = 7370–7 | date = November 2006 | pmid = 17128516 | doi = 10.1021/ac069475k | doi-access =  }}</ref> the diffusion of oxygen to the reaction zone is continuously diminished. This decreasing oxygen availability causes the sensor reading to drift, requiring frequent re-calibration using finger-sticks and test strips.

One approach to achieving long-term glucose sensing is to measure and compensate for the changing local oxygen concentration.<ref name=Gou10>{{cite journal | vauthors = Gough DA, Kumosa LS, Routh TL, Lin JT, Lucisano JY | title = Function of an implanted tissue glucose sensor for more than 1 year in animals | journal = Science Translational Medicine | volume = 2 | issue = 42 | pages = 42ra53 | date = July 2010 | pmid = 20668297 | pmc = 4528300 | doi = 10.1126/scitranslmed.3001148 }}</ref> Other approaches replace the troublesome glucose oxidase reaction with a reversible sensing reaction, known as an [[ligand binding assay|affinity assay]]. This scheme was originally put forward by Schultz & Sims in 1978.<ref name=ScSi78>{{cite journal | vauthors = Schultz JS, Mansouri S, Goldstein IJ | title = Affinity sensor: a new technique for developing implantable sensors for glucose and other metabolites | journal = Diabetes Care | volume = 5 | issue = 3 | pages = 245–53 | year = 1979 | pmid = 6184210 | doi = 10.2337/diacare.5.3.245 | s2cid = 20186661 }}</ref><ref>{{Cite journal| vauthors = Schultz J, Sims G |year=1979|title=Affinity sensors for individual metabolites|journal=Biotechnol Bioeng Symp.|volume=9|issue=9|pages=65–71|pmid=94999}}</ref> A number of different affinity assays have been investigated,<ref name=Ball94>{{cite journal | vauthors = Ballerstädt R, Ehwald R | title = Suitability of aqueous dispersions of dextran and Concanavalin A for glucose sensing in different variants of the affinity sensor | journal =  Biosens. Bioelectron. | volume = 9 |issue=8 | pages = 557–67 | year = 1994 | doi = 10.1016/0956-5663(94)80048-0}}</ref><ref name=Zha07>{{cite journal | vauthors = Zhao Y, Li S, Davidson A, Yang B, Wang Q, Lin Q | s2cid = 17572337 | title = A MEMS viscometric sensor for continuous glucose monitoring | journal = J. Micromech. Microeng. | volume = 17 |issue=12 | pages = 2528–37 | year = 2007 | doi = 10.1088/0960-1317/17/12/020|bibcode=2007JMiMi..17.2528Z }}</ref><ref name=Ball07>{{cite journal | vauthors = Ballerstadt R, Kholodnykh A, Evans C, Boretsky A, Motamedi M, Gowda A, McNichols R | title = Affinity-based turbidity sensor for glucose monitoring by optical coherence tomography: toward the development of an implantable sensor | journal = Analytical Chemistry | volume = 79 | issue = 18 | pages = 6965–74 | date = September 2007 | pmid = 17702528 | doi = 10.1021/ac0707434 }}</ref> with [[fluorescent glucose biosensor|fluorescent assays]] proving most common.<ref name=Mead93>{{cite journal | vauthors = Meadows DL, Schultz JS | title =  Design, manufacture and characterization of an optical fiber glucose affinity sensor based on an homogeneous fluorescence energy transfer assay system | journal = Anal. Chim. Acta | volume = 280 | pages = 21–30 | year = 1993 | issue = 1 | doi = 10.1016/0003-2670(93)80236-E| bibcode = 1993AcAC..280...21M | hdl = 2027.42/30643 | url = https://deepblue.lib.umich.edu/bitstream/2027.42/30643/1/0000285.pdf | hdl-access = free }}</ref><ref name=Ball04>{{cite journal | vauthors = Ballerstadt R, Polak A, Beuhler A, Frye J | title = In vitro long-term performance study of a near-infrared fluorescence affinity sensor for glucose monitoring | journal = Biosensors & Bioelectronics | volume = 19 | issue = 8 | pages = 905–14 | date = March 2004 | pmid = 15128110 | doi = 10.1016/j.bios.2003.08.019 }}</ref><ref name=Niel09>{{cite journal | vauthors = Nielsen JK, Christiansen JS, Kristensen JS, Toft HO, Hansen LL, Aasmul S, Gregorius K | title = Clinical evaluation of a transcutaneous interrogated fluorescence lifetime-based microsensor for continuous glucose reading | journal = Journal of Diabetes Science and Technology | volume = 3 | issue = 1 | pages = 98–109 | date = January 2009 | pmid = 20046654 | pmc = 2769858 | doi = 10.1177/193229680900300111 }}</ref> [[MEMS]] technology has recently allowed for smaller and more convenient alternatives to fluorescent detection, via measurement of [[viscosity]].<ref name=JAP2013>{{cite journal | vauthors = Birkholz M, Ehwald KE, Basmer T, Kulse P, Reich C, Drews J, Genschow D, Haak U, Marschmeyer S, Matthus E, Schulz K, Wolansky D, Winkler W, Guschauski T, Ehwald R | title = Sensing glucose concentrations at GHz frequencies with a fully embedded Biomicro-electromechanical system (BioMEMS) | journal = Journal of Applied Physics | volume = 113 | issue = 24 | pages = 244904–244904–8 | date = June 2013 | pmid = 25332510 | pmc = 3977869 | doi = 10.1063/1.4811351 | bibcode = 2013JAP...113x4904B }}</ref> Investigation of affinity-based sensors has shown that encapsulation by body tissue does not cause a drift of the sensor signal, but only a time lag of the signal compared to the direct measurement in blood.<ref name=Die04>{{cite journal | vauthors = Diem P, Kalt L, Haueter U, Krinelke L, Fajfr R, Reihl B, Beyer U | title = Clinical performance of a continuous viscometric affinity sensor for glucose | journal = Diabetes Technology & Therapeutics | volume = 6 | issue = 6 | pages = 790–9 | date = December 2004 | pmid = 15684631 | doi = 10.1089/dia.2004.6.790 }}</ref> A new implantable continuous glucose monitor based on affinity principles and fluorescence detection is the Eversense device manufactured by Senseonics Inc. This device has been approved by the FDA for 90 day implantation.<ref>{{cite journal | vauthors = Kropff J, Choudhary P, Neupane S, Barnard K, Bain SC, Kapitza C, Forst T, Link M, Dehennis A, DeVries JH | display-authors = 6 | title = Accuracy and Longevity of an Implantable Continuous Glucose Sensor in the PRECISE Study: A 180-Day, Prospective, Multicenter, Pivotal Trial | journal = Diabetes Care | volume = 40 | issue = 1 | pages = 63–68 | date = January 2017 | pmid = 27815290 | doi = 10.2337/dc16-1525 | doi-access = free }}</ref><ref>{{Cite journal|date=September 1997|title=How a US Patent Protects You, and Does Your Project Qualify for a US Patent?|journal=World Patent Information|volume=19|issue=3|pages=239|doi=10.1016/s0172-2190(97)90099-5|issn=0172-2190}}</ref>