This journal is c The Royal Society of Chemistry 2011 Chem. Soc. Rev., 2011, 40, 4805–4839 4805 Cite this: Chem. Soc. Rev., 2011, 40, 4805–4839 Optical methods for sensing glucose Mark-Steven Steiner, Axel Duerkop and Otto S. Wolfbeis* Received 5th March 2011 DOI: 10.1039/c1cs15063d This critical review covers the present state of the art in optical sensing of glucose. Following an introduction into the significance of (continuous) sensing of glucose and a brief look back, we discuss methods based on (a) monitoring the optical properties of intrinsically fluorescent or labeled enzymes, their co-enzymes and co-substrates; (b) the measurement of the products of enzymatic oxidation of glucose by glucose oxidase; (c) the use of synthetic boronic acids; (d) the use of Concanavalin A; and (e) the application of other glucose-binding proteins. We finally present an assessment in terms of the advantages and disadvantages of the various methods (237 references). 1. The significance of sensing glucose The quantitation of glucose is among the most important analytical tasks. It has been estimated that about 40% of all blood tests are related to it. In addition, there are numerous other situations where glucose is to be determined, for example in biotechnology, in the production and processing of various kinds of feed and food, in biochemistry in general, and in numerous other areas. The continuous interest in sensing glucose, mainly in blood, is one result of the increasing age and (meanwhile alarming) size of the world’s population and the fact that about 4–5% of its (Caucasian) population suffer from diabetes. The significance of sensing glucose is best documented by the numbers of hits that can be found when consulting (06 May 2011) Google (B4 750 000 hits) or Scholar Google (B324 000 hits). MedLine/SciFinder combined yields B4000 references on ‘‘glucose sensor’’ as entered, and B14 800 references containing the concept ‘‘glucose sensor’’ (search performed on 6 May 2011). Wikipedia has a most readable article on blood glucose monitoring. 1 Obviously, there is substantial public concern about diabetes and sensing glucose. Given the significance of sensing glucose, it comes as a kind of surprise that few books are available that cover the subject in depth. Cunningham and Stenken 2 probably have authored the most authoritative survey. The book by Bartlett 3 covers electrochemical sensors only, and the one by Pickup et al. 4 fluorescent sensors only. The special issue on glucose sensing as published by Geddes and Lakowicz 5 contains selected aspects of fluorescent sensors also. Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, D-93040 Regensburg, Germany. E-mail: [email protected]Mark-Steven Steiner Mark-Steven Steiner, born 1983, studied chemistry at the University of Regensburg from 2002–2007. He obtained his PhD in Analytical Chemistry in 2010 at the University of Regensburg under the super- vision of Prof. Wolfbeis. His current research is focused on fluorescent methods for use in bio-targeting and bio-imaging using luminescent upconverting nanoparticles, also in combina- tion with RGB-based signal readout using digital cameras. Axel Duerkop Axel Duerkop, born 1973, graduated in chemistry at the University of Regensburg and earned a PhD in 2001 under the supervision of Prof. Wolfbeis. He is an ‘‘Akademischer Rat’’ (Senior Researcher) and presently working at his habilitation. His research interests cover optical sensors, test strips and micro- plate assays, luminescent probes for hydrogen peroxide, for metabolites of cancer cells, and for cations and anions. Lanthanide complexes and transition metal complexes are preferred probes to be used as labels, in immunoassays (based on anisotropy and decay time), for chemosensing of thiols, DNA and saccharides. Chem Soc Rev Dynamic Article Links www.rsc.org/csr CRITICAL REVIEW Downloaded by University College London on 11 January 2013 Published on 14 June 2011 on http://pubs.rsc.org | doi:10.1039/C1CS15063D View Article Online / Journal Homepage / Table of Contents for this issue
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This journal is c The Royal Society of Chemistry 2011 Chem. Soc. Rev., 2011, 40, 4805–4839 4805
Cite this: Chem. Soc. Rev., 2011, 40, 4805–4839
Optical methods for sensing glucose
Mark-Steven Steiner, Axel Duerkop and Otto S. Wolfbeis*
Received 5th March 2011
DOI: 10.1039/c1cs15063d
This critical review covers the present state of the art in optical sensing of glucose. Following
an introduction into the significance of (continuous) sensing of glucose and a brief look back,
we discuss methods based on (a) monitoring the optical properties of intrinsically fluorescent or
labeled enzymes, their co-enzymes and co-substrates; (b) the measurement of the products of
enzymatic oxidation of glucose by glucose oxidase; (c) the use of synthetic boronic acids;
(d) the use of Concanavalin A; and (e) the application of other glucose-binding proteins.
We finally present an assessment in terms of the advantages and disadvantages of the various
methods (237 references).
1. The significance of sensing glucose
The quantitation of glucose is among the most important
analytical tasks. It has been estimated that about 40% of all
blood tests are related to it. In addition, there are numerous
other situations where glucose is to be determined, for example
in biotechnology, in the production and processing of various
kinds of feed and food, in biochemistry in general, and in
numerous other areas. The continuous interest in sensing
glucose, mainly in blood, is one result of the increasing age
and (meanwhile alarming) size of the world’s population and
the fact that about 4–5% of its (Caucasian) population suffer
from diabetes. The significance of sensing glucose is best
documented by the numbers of hits that can be found when
consulting (06 May 2011) Google (B4750000 hits) or Scholar
Google (B324000 hits). MedLine/SciFinder combined yields
B4000 references on ‘‘glucose sensor’’ as entered, and B14 800
references containing the concept ‘‘glucose sensor’’ (search
performed on 6 May 2011). Wikipedia has a most readable
article on blood glucose monitoring.1 Obviously, there is
substantial public concern about diabetes and sensing glucose.
Given the significance of sensing glucose, it comes as a kind
of surprise that few books are available that cover the subject
in depth. Cunningham and Stenken2 probably have authored
the most authoritative survey. The book by Bartlett3 covers
electrochemical sensors only, and the one by Pickup et al.4
fluorescent sensors only. The special issue on glucose sensing
as published by Geddes and Lakowicz5 contains selected
aspects of fluorescent sensors also.
Institute of Analytical Chemistry, Chemo- and Biosensors, Universityof Regensburg, D-93040 Regensburg, Germany.E-mail: [email protected]
Mark-Steven Steiner
Mark-Steven Steiner, born1983, studied chemistry at theUniversity of Regensburgfrom 2002–2007. He obtainedhis PhD in Analytical Chemistryin 2010 at the University ofRegensburg under the super-vision of Prof. Wolfbeis. Hiscurrent research is focused onfluorescent methods for use inbio-targeting and bio-imagingusing luminescent upconvertingnanoparticles, also in combina-tion with RGB-based signalreadout using digital cameras. Axel Duerkop
Axel Duerkop, born 1973,graduated in chemistry at theUniversity of Regensburg andearned a PhD in 2001under the supervision ofProf. Wolfbeis. He is an‘‘Akademischer Rat’’ (SeniorResearcher) and presentlyworking at his habilitation. Hisresearch interests cover opticalsensors, test strips and micro-plate assays, luminescent probesfor hydrogen peroxide, formetabolites of cancer cells,and for cations and anions.Lanthanide complexes and
transition metal complexes are preferred probes to be used aslabels, in immunoassays (based on anisotropy and decay time), forchemosensing of thiols, DNA and saccharides.
Chem Soc Rev Dynamic Article Links
www.rsc.org/csr CRITICAL REVIEW
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View Article Online / Journal Homepage / Table of Contents for this issue
is in widespread use, for example, for sensing glucose along
with other blood parameters including pO2, pH, Na+, K+,
Cl�, lactate or urea. The respective sensors are of the re-usable
type in a sense that a blood sample is inserted into the
instrument, a reading is made, the surface of the sensors is
washed, and the sensors are recalibrated before the next
sample is being introduced. Such instrumentation obviously
needs true (fully reversible) sensors for proper operation, or
the sensors can be regenerated by chemical means which is less
elegant and compromises the frequency of assays. A sensor
that would be applicable to all the situations where glucose is
to be determined does not exist yet. Sensing glucose in the beer
brewing industry is less of a challenge than sensing glucose in
the blood of the critically ill after a cardiac infarct.
Electrochemical methods are most established, mainly in the
form of stand-alone instruments in clinical labs and in near
patient testing. Millions of disposable electrochemical
(mediator-based) blood glucose meters are used in homecare
devices7 that enable glucose to be determined within less than
30 s in blood samples as small as 1 mL. The work of Heller and
Feldman6 on electrical wiring of enzymes has led to a new
generation of glucose sensors (that have had a tremendous
commercial success so far, first at TheraSense Inc., later at
Abbott Diabetes Care Inc.). These sensors have (sub)micro
dimensions and require even smaller quantities of blood to be
taken, thus leading to almost painless sampling which represents
a big relief to diabetics.
Optical methods are based on the measurement of photons
rather than of electrons. This has certain advantages, for
example, in the case of patients with heart pacemakers or
when sensing glucose under the action of strong electromagnetic
fields as used in cancer therapy. Fiber optic sensors, in turn,
enable glucose to be sensed in the deeper lying or less-
accessible regions of the body. Optical sensors also do not
require a reference electrode, can sense through optically
transparent walls (thus enabling sterile remote sensing), and
are capable of multiplexing.
Optical schemes for sensing glucose have not had, however,
the success of electrochemical schemes, but still are a matter of
highly active research. Among the optical methods,
absorptiometry (and reflectometry) and fluorescence and surface
plasmon resonance (SPR) have had the biggest success.
Almost all optical sensors for continuous monitoring rely on
either fluorescence or SPR. No reflectometric or interferometric
method is known that would enable continuous sensing of
glucose in blood, even though such methods have been
Otto S. Wolfbeis
Otto S. Wolfbeis, born 1947,is a Professor of AnalyticalChemistry. He has authoredmore than 500 articles ontopics such as optical (fiber)chemical sensors, analyticalfluorescence spectroscopy,and fluorescent probes, editeda (widely used) book on FiberOptic Chemical Sensors andBiosensors, acts as the editorof the Springer Series on-Fluorescence, is the Editor-in-Chief of Microchimica Acta,and one of the ten curators ofAngewandte Chemie. His
h-index is 52, and his articles have been cited >11 000 times.Several sensors developed in his group have been commercia-lized. His present research interests include fluorescent bio-sensing, the design of novel spectroscopic schemes, newfluorescent probes, beads, and labels, new methods of interfacechemistry, and analytical uses of advanced materials such asupconverting luminescent nanoparticles and graphenes. Also see:www.wolfbeis.de.
This journal is c The Royal Society of Chemistry 2011 Chem. Soc. Rev., 2011, 40, 4805–4839 4809
fluorescent transitions of the emission of FAD. The analytical
range of their sensor is from 0.4 to 5 mM. Also see ref. 27.
Sanz et al.28 reported on a detection scheme that is based on
the combined use of GOx and horseradish peroxidase. The
absorbance of HRP at 424 nm changes on exposure to
glucose, and this is attributed to changes in the absorption
of the heme group of HRP due to oxidation. The sensor was
prepared by entrapping HRP and GOx in a polyacrylamide
(PAA) gel. HRP is oxidized by the H2O2 generated in the GOx
reaction to form the so-called HRPI, in which the heme group
is in a virtual 5+ oxidation state. Tyrosine separately added
regenerated the HRP. The sensor covers the 1.5 to 300 mMconcentration range and has a long-term stability of at least
6 months. More sophisticated variations also were reported.29,30
The sensors work in whole blood (after dilution), and display a
long term stability of over 30 months and more than 200
measurements. Response times range from 10 s to 5 min. The
dynamic range can be increased to 2 mM by bubbling oxygen
through the solution.
An example of the few assays based on the use of glucose
dehydrogenase (GDH) was reported by Narayanaswamy and
Sevilla.31 GDH was immobilized on a nylon mesh cartridge
mounted on an optical fiber. The intrinsic blue fluorescence of
the cosubstrate NADH increases linearly on addition of
glucose in the range from 1.1 to 11 mM. The limit of detection
(LOD) is 0.6 mM. In fact, dehydrogenases play a much more
important role in electrochemical sensing32 than in optical
sensing. A GDH-based glucose sensor with an expanded
dynamic range was constructed33 using an engineered enzyme
which allows for an expanded and higher dynamic range than
that of the wild type protein. The His775 of a GDH from
E. coli was substituted for Asp and then showed an increased
Michaelis–Menten constant as demonstrated in a conventional
colorimetric assay which has a dynamic range from 0.5 to 30 mM
of glucose and with less than �5% error.
4.2 Labeled enzymes
Aside from the use of the intrinsic optical properties of
glucose-specific enzymes, the optical properties of labeled
enzymes also have been studied (Table 1). GOx immobilized
on poly(amidoamine) dendrimers on microscope slides reversibly
binds meso-tetra(4-carboxyphenyl)porphine (CTPP4) which has
an absorption maximum at 427 nm. Exposure of the complex to
glucose causes a linear decrease in absorbance in the range from
1.1 to 11 mM glucose34 due to dissociation of the complex.
A thermostable glucose kinase from a thermophilic microorganism
was applied35 in a competitive FRET assay in which glucose
derivatized with o-nitrophenyl-b-D-glucopyranoside serves as
a quencher of the intrinsic tryptophan fluorescence of GOx.
Addition of glucose decreases the quenching efficiency.
Compared to a more simple assay where the emission of
GOx labeled with an anilino-naphthalenesulfonate derivative
is quenched, the first system displays a larger signal change.
GOx was also labeled with a coumarin derivative.36 Its blue
fluorescence increases by up to 10% in the presence of glucose
in the 0.5–6 mM concentration range. The same group also
used fluorescein-labeled GOx (entrapped in a sol–gel) which
has a more red-shifted excitation and emission along with
Table 1 Sensing glucose via the optical properties of oxidative or reductive enzymes. AR: analytical range; BSGK: Bacillus stearothermophilusglucokinase; FLU: fluorescence; GLU: glucose; GOx: glucose oxidase; GDH: glucose dehydrogenase; RT: response time
Enzyme Method AR/mM Ref.
Hexokinase Intrinsic UV fluorescence (exc./em. 295/330 nm) of Trp decreases on addition of GLU due toconformational change; enzyme entrapped in sol–gel; no phosphorylation, no glucose consumption
1–120 20
GOx Intrinsic UV fluorescence (exc./em. 278/335 nm) of Trp in GOx and of coenzyme FAD increaseson addition of GLU due to conformational change; silica gel entrapped
0.2–20 21
GOx Intrinsic UV fluorescence (exc./em. 278/340 nm) of Trp in GOx increases on addition of GLUdue to conformational change; GOx entrapped in a gelatine membrane; time course studied
2.5–20 22
GOx Intrinsic UV fluorescence (exc./em. 278/335 nm) of Trp in GOx and of coenzyme FAD increaseson addition of GLU due to conformational change; sol–gel entrapped
0.5–20 23
GOx Intrinsic green fluorescence (exc./em. 450/500 nm) of the coenzyme FAD increases on addition ofGLU due to conformational change; entrapped in a semipermeable membrane
1.5–2 24
GOx Intrinsic green fluorescence (exc./em. 450/520 nm) of the coenzyme FAD increases on addition ofGLU; entrapped in sol–gel
— 25
GOx HRP and GOx entrapped in PAA gel; absorbance of the heme-group of HRP changes when HP(produced by GOx and GLU) oxidizes HRP (424 nm)
0.001–0.3 28
GOx HRP and GOx entrapped in PAA gel; absorbance of the heme-group of HRP changes when HP(produced by GOx and GLU) oxidizes HRP (424 nm), continuous mode
0.001–0.05 29
GOx Absorbance at 490 nm (FAD)(chosen because of properties of optical system) decreases onaddition of GLU; covalently attached to nylon net
2–10 30
GDH GDH immobilized on nylon mesh cartridge mounted on optical fiber; intrinsic blue fluorescence(NADH) (exc./em. 340/460 nm) increases on addition of GLU; RT: 5 min
1.1–11 31
GOx Absorbance at 427 nm decreases on addition of GLU due to dissociation of a meso-tetraphenyl-porphine–GOx complex; immobilized to poly(amidoamine) on microscope slides
1.1–11.1 34
BSGK Quenchometric FRET, donor: Trp emission (exc./em. 290/340 nm), acceptor: o-nitrophenyl-b-D-glucopyranoside. Increase of donor emission at 340 nm on addition of GLU; demonstrated forsolutions only
1–6 35
Labeled GOx Enzyme labeled with 7-hydroxycoumarin-4-acetic acid, fluorescence emission (exc./em. 327/452 nm)increases on addition of GLU; demonstrated for solutions only
0.5–6 36
Labeled GOx Labeled with fluorescein derivative, fluorescence emission (exc./em. 492/515 nm) increases onaddition of GLU; GOx immobilized in sol–gel
0.6–5.6 370.5–8.3 38
Labeled GOx Labeled with fluorescein, fluorescence (exc./em. 489/520 nm) increases on addition of GLU; GOximmobilized on polyacrylamide; flow injection method
4814 Chem. Soc. Rev., 2011, 40, 4805–4839 This journal is c The Royal Society of Chemistry 2011
an HP-based detection scheme.87 GOx was incorporated in a
montmorillonite clay placed on an electrode. This mineral
contains Fe(II) and Fe(III) species that catalyze the conversion
of O2 and HP to form the superoxide anion radical. The iron
species are continuously regenerated by the electrode. The O2�
radical, in turn, reacts with Amplex Red to give fluorescent
resorufin. Glucose in concentrations between 1 and 150 mMcaused an increased emission at 583 nm (Table 4).
An absorbance based glucose sensor using Prussian Blue as
a probe for HP was presented by Koncki et al.88,89 Prussian
Blue incorporated in a film of poly(pyrrolyl benzoic acid)
reacts with HP to give Prussian White. The reaction can be
Table 2 Sensing glucose via fluorometric measurement of the consumption of oxygen caused by the action of GOx. AR: analytical range; CPG:controlled pore glass; FI: fluorescence intensity; GLU: glucose; OEPK: octaethylporphyrin ketone; PVA: polyvinyl acetate; RT: response time;Ru(bpy): ruthenium tris(bipyridyl); Ru(dpp): ruthenium tris(diphenyl-phenanthroline; Ru(phen): ruthenium tris(phenanthroline))
Oxygen probe and polymer (sensor) matrix Comments AR/mM Ref.
Decacyclene contained in a silicone membrane GOx incorporated in a nylon membrane; measurement of FI(exc./em. 410/450 nm); RT: 1–6 min
0.1–20 40
Decacyclene contained in a silicone membrane GOx absorbed on carbon black and crosslinked withglutardialdehyde; measurement of FI (exc./em. 400/500 nm);RT: 8–60 s
0.01–2 41
Decacyclene contained in a silicone membrane GOx absorbed on CPG; measurement of FI (exc./em. 410/495 nm);RT: 50–80 s
0–30 42
Al/ferron complex immobilized on ananion-exchange resin
GOx immobilized in a nylon membrane; measurement of FI(exc./em. 390/600 nm); RT: 20–60 s
0.5–2.5 43
Pt-OEPK dissolved in polystyrene;microporous fiber support (PTFE, celluloseacetate, nylon, fiber glass, filter paper)
GOx crosslinked with glutardialdehyde or immobilized onCPG; measurement of FI and of phase shift (lifetime);RT: 5–90 s
0.2–20 44–46
Pt or Pd porphyrin dissolved in polystyrene Patent; GOx in polyacrylamide; measurement of FI — 47Ru(phen) contained in a silicone membrane GOx absorbed on carbon black and crosslinked with
glutardialdehyde;measurement of FI (exc./em. 460/570 nm); RT 6 min
0.06–1 49
Ru(dpp) in polyurethane film Patent; GOx immobilized on polystyrene NPs; measurement of FI;NPs incorporated in polyurethane film
— 50
GOx and probe Ru(phen) in polyacrylamide Measurement of FI (exc./em. 488/610 nm); RT: 2 s;micrometre-sized sensor
0.7–10 51
Ru(phen) incorporated in ormosil–PVA film GOx immobilized in ormosil sol–gel; measurement offluorescence phase shift (exc./em. 468/589 nm); RT: 6 s;kinetic curve simulation
0–0.5 and 0.5–3 52
Ru(ddp) dissolved in polystyrene GOx monolayer on the surface layer (ultrafiltration membrane);measurement of FI (exc./em. 465/610 nm); RT: 100 s
1–80 53
Ru(dpp) immobilized on silica particles insilicone
GOx immobilized on an eggshell membrane or swim bladder;measurement of FI (exc./em. 468/602 nm); RT: 5 min
0–1.5 5455
GOx and Ru(phen) in nanoporous sol–gel Measurement of fluorescence phase shift (exc./em. 468/570 nm) 0.5–15 57Ru(dpp) and GOx in xerogel Measurement of FI (exc./em. 460/602 nm); RT: 6–9 min 0.6–100 58GOx and probe Ru(dpp) immobilized in asol–gel composite
Measurement of fluorescence lifetime; RT: 20 s 0–30 61
Ru(dpp) immobilized in sol–gel GOx in the second sol–gel layer; measurement of FI(exc./em. 458/535 nm); RT: 30–300 s; immobilized on thewell-bottom of a microtiter plate
0–28 62
Ru(dpp) and GOx in ormosil measurement of FI (exc./em. 400/620 nm); RT: 6 min;immobilized on the well-bottom of a microtiter plate
0.1–5 63
Ru complex dissolved in a sol–gel matrix GOx in photosensitive polymer; measurement of FI(exc./em. 475/600 nm); RT: 1–3 min; needle type sensor
0.2–1 65
Ru(dpp) contained in a sol–gel matrix GOx in sol–gel; measurement of FI (exc./em. 465/610 nm);RT: 50–250 s
0.1–15 66
Ru(phen) on silica particles in silicone film GOx immobilized in sol–gel; measurement of FI(exc./em. 460/602 nm); RT: 5–8 min
0.06–30 66
Ru(bpy) contained in a poly(dimethylsiloxane)matrix
GOx entrapped in poly-HEMA hydrogel; self-referencedscheme: 2-sensor technique; one sensor measures oxygenbackground, the other the quantity of oxygen consumed;FI measured (exc./em. 470/600 nm); RT: 9–28 s
0–20 68
Commercial fiber optic oxygen sensor Sensor surface covered with immobilized GOx; measurement ofphase shift; self-referenced; RT: 9 min; used in combinationwith a microdialysis membrane
0–10 6970
Oxygen sensor and GOx-modified oxygensensor
Patent; dual sensor; measurement of FI; fluoresceinisothiocyanate, perylene dibutyrate
— 7172
Oxygen sensor in combination with GOxapoenzyme
Patent; dual sensor; measurement of FI; perylene dibutyrate orfluoranthene
This journal is c The Royal Society of Chemistry 2011 Chem. Soc. Rev., 2011, 40, 4805–4839 4815
reversed with ascorbic acid. The sensor film was implemented in
a flow injection system and enabled glucose to be determined in
the range from 0.05–2 mM. The method was further optimized
to provide a double channel FIA system, and pharmaceutical,
food and clinical samples were successfully analysed.90
An SPR glucose biosensor was reported that consists of
silver nanoparticles (NPs) and GOx embedded in a stimuli-
responsive hydrogel. The HP generated in the enzymatic
reaction induced degradation of the highly clustered silver
NPs by the decomposition of hydrogen peroxide. As a
result, the distance between the silver NPs in the hydrogel
matrix is increased. This, in turn, results in an enlarged
distance between the silver NPs and a decreased localized
surface plasmon resonance. A schematic of the detection
principle is shown in Fig. 9. Glucose concentrations as low
than 10 pM were detectable owing to an increased osmotic
pressure.91
Another sensing approach based on the swelling of a GOx
modified hydrogel was demonstrated by Ye et al.92 Gratings
were photochemically produced in this hydrogel, irradiated
with a He–Ne laser, and the light intensities of the first- and
second-order diffracted beams were recorded. The system
covers the concentration range from 0.1 to 1.0 mM of glucose.
GOx was conjugated to Mn-doped zinc sulfide QDs. The HP
produced in the presence of glucose quenches the emission of
the dots. The nanosensors were successfully applied to sense
glucose in serum samples.93 A similar embodiment is making
Table 3 Nanoparticle (NP) or microparticle (mP) based sensing of glucose via fluorometric measurement of the consumption of oxygen caused byGOx. AR: analytical range; ET: electron transfer; HRP horseradish peroxidase; LI: luminescence intensity; QD: quantum dot; Ru(dpp):ruthenium-tris(diphenylphenanthroline); Ru(phen): ruthenium-tris-phenanthroline; RT: response time
Ru(dpp) GOx, probe and referencedye entrapped inpolyacrylamide NPs
Measurement of LI (exc./em. 488/610 nm); RT: 150–200 s;ratiometric sensor; implantable; 45 nm; scheme referred to asPEBBLE
0.3–5 80
CdSe/ZnScore–shell QDs
GOx and HRP immobilizedon the surface of QD
Measurement of LI; ET from QD (exc./em. 485/525 nm) toGOx and HRP decreases intensity on addition of GLU;RT: 30 min
0–28 81
Ru(phen) Solution assay GOx immobilized on Fe3O4 magnetic NPs; measurement ofLI (exc./em. 460/610 nm); RT: 2 min
1–20 82
Fig. 8 Europium tetracycline (EuTc) based HP sensor. Absorbance
spectra (left) and emission spectra (right) of the EuTc/GOx system in
the absence (A) and presence (B), respectively, of glucose. With kind
permission from Springer Science + Business Media from ref. 86.
Table 4 Sensing glucose via fluorometric measurement of the formation of hydrogen peroxide (HP) caused by the action of GOx. AR: analyticalrange; EuTC: europium(III) tetracycline complex; FI: fluorescence intensity; FRET: fluorescence resonance energy transfer; LR: linear range; NPs:nanoparticles; P4S: poly-(4-styrenesulfonate); PF: polyfluorene; PFP: poly(fluorene phenylene); PLL: poly-L-lysine; PAA: polyacryl amide; QD:quantum dot
Probe Sensor matrix Comments AR/mM Ref.
EuTC Hypan GOx absorbed on the surface of a sensor placed in a microtiter plate;fluorescence lifetime imaging; exc./em. 400/616 nm; response time:10 min; increase in FI and lifetime on addition of GLU due to formationof a EuTC-HP complex
0.3–10 850.1–2 86
Amplex Red GOx inmontmorilloniteclay
GLU and Amplex Red injected in clay on an electrode; HP catalyticallyconverted to a superoxide anion radical by clay; superoxide convertsAmplex red into a fluorescent resorufin (exc./em. 563/583 nm);FI increases on addition of GLU; regeneration of clay (Fe2+/Fe3+)by the electrode; non-continuous
0.001–0.15 87
Prussian Blue (PB) PB incorporatedinto a film ofpolypyrrole
GOx immobilized on surface; Prussian White (PW) first generated withascorbic acid; HP then oxidizes PW to blue PB; absorbance at 720 nm;flow injection system
0.05–2 888990
Ag-NPs Ag-NPs and GOxin a stimuli-responsivehydrogel
HP degenerates clustered Ag-NPs and swells hydrogel; decrease inlocalized surface plasmon resonance on addition of GLU (400 nm)
10�9–1 91
Hydrogel GOx in hydrogel HP causes swelling of hydrogel; decrease in diffraction efficiency;sensing at neutral pH; response time: 1–2 min
0.1–1 92
Mn-doped ZnS QD GOx covalently labelled to Mn-doped ZnS QD; HP quenches emissionof the dots; applied to serum samples
0.01–0.1 93
CdTe QD GOx covalently labelled to CdTe QD; HP quenches emission of the dots 0.005–1 94Hemoglobin (Hb) GOx in PAA HP released by GOx oxidizes Hb 1.1–66.6 95
4816 Chem. Soc. Rev., 2011, 40, 4805–4839 This journal is c The Royal Society of Chemistry 2011
use of GOx conjugated to CdTe quantum dots.94 Quenching
of the fluorescence of the QDs is again caused by the HP
produced during the oxidation of glucose.
In a flow cell based setup for the determination of glucose in
blood, GOx was incorporated in a film of polyacrylamide to
produce HP which is capable of oxidizing hemoglobin.95
This results in measurable changes in its absorbance. Glucose
can be determined in the 1–67 mM concentration range. The
quenching effect exerted by H2O2 on the luminescence of CdTe
quantum dots was exploited96 in a (solution) assay for glucose
over the 1.7 to 6.7 mM concentration range. Conceivably, it
can be extended to sensing membranes if an appropriate
polymer is found.
5.3. Glucose sensing via measurement of changes in pH
Changes of pH may also serve as the analytical information in
glucose sensing schemes (Table 5). Protons are produced as a
result of the reaction of gluconolactone with water (eqn (1)).
However, this approach is limited because often the initial pH
of the sample and its buffer capacity are unknown. Therefore,
optical glucose biosensors based on pH transduction are rarely
used in practice.
Trettnak et al.97 were the first to present such a type of
glucose sensor, with an enzymatic reaction coupled to a fibre
optic pH transducer. They used HPTS as a pH-sensitive dye
that was immobilized in hydrogel along with GOx and placed
at the tip of an optical fiber. The sensor has a response time of
8–12 min within an analytical range of 0.1 to 2 mM of glucose.
A device with immobilized GOx and FITC (acting as a pH
probe in a polymer at the end of an optical fiber) was patented
by Applied Research Systems.98 A similar fiber optic setup was
presented by McCurley.99 A cadaverine unit was linked to a
rhodamine fluorophore and incorporated in a hydrogel along
with GOx and catalase. The material was placed at the distal
end of an optical fiber. The cadaverine moiety becomes
protonated as a result of enzymatic oxidation of glucose,
and this causes swelling of the hydrogel. This, in turn,
decreases the fluorescence intensity of the rhodamine due to its
decreased concentration in the higher sample volume. Glucose
was determined in the 0 to 1.6 mM concentration range.
Polyaniline displays a pH sensitive spectrum and thus can be
used as a pH sensor probe. It turns green on formation of
acids by enzymatic reactions and was used in a microplate
glucose assay.100 The absorbance at 600 nm decreases with pH,
but increases at 840 nm. Micro- to millimolar concentrations of
glucose were determined.
A miniature optical sensor array was reported that uses
GOx covalently immobilized on cellulose acetate microscopic
beads.101 A phenoxazine derivative was incorporated into
other polymer microbeads that serve as pH sensitive probes
(see Fig. 10). Both kinds of beads, along with white reference
beads, were evenly arranged in a microarray. The reversible
color response caused by pH changes was quantified by
Fig. 9 Schematic of the detection principle of an LSPR-based optical
enzyme biosensor using a stimuli-responsive hydrogel–silver nano-
particles composite. Reprinted from ref. 91, with permission from
Elsevier.
Table 5 Enzymatic sensing of glucose via changes of pH. AR: analytical range; FI: fluorescence intensity; HPTS: hydroxypyrenetrisulfonate;MTP: microtiter plate; PANI: polyaniline; RT: response time
Probe Sensor matrix Comments AR/mM Ref.
FITC Glass tip of opticalfiber
Patent; GOx and FITC coated to glass by glutardialdehyde report changes ofpH in a polymer at the end of optical fiber
— 98
Rhodamine Hydrogel Cadaverine unit linked to rhodamine with GOx and catalase placed at the tip ofoptical fiber; enzymatically released protonation of cadaverine causes swelling ofthe hydrogel and decreases FI of rhodamine
0–1.6 99
Polyaniline PANI PANI displays a pH sensitive absorbance at 600 nm (decrease) and at 840 nm(increases) and is used itself as pH transducer; membrane becomes green fromprotons released by GOx action; calibration dependent on concentration ofphosphate buffer
1–30 100
Phenoxazinederivative
Micro array GOx on cellulose acetate microbeads and phenoxazine in polymer microbeads andadditionally white reference beads cause reversible reflectometric color responsedue to pH change in red, green and blue channel of CCD image; RT: 12 min
0–16 101
HPTS Cationic chargedbiocompatiblecapsules
pH changes cause ratiometric variation of emission spectra of capsulescontaining HPTS and adsorbed GOx
0–30 102
Azlactone Sol–gel pH sensitive azlactone and GOx embedded in hydrogel in a single layer or duallayer sensor; one layer shows faster (20 s) response but higher leaching; duallayer sensor has 40 s response time
0.1–15 103
Rhodamine Hydrogel GOx and Rhodamine derivative immobilized in a film of poly(vinyl acetate) 0.002–0.3 104NIR pH-sensitivecyanine dye
Aqueous solution Glu changes pKa of o-hydroxymethyl arylboronic acid monitored by changes inabsorbance and fluorescence of NIR pH-sensitive dye; ratiometric (640 nm/484 nm)absorbance or fluorescence (666 nm); pH 7.0; higher response to fructose over glucose
4818 Chem. Soc. Rev., 2011, 40, 4805–4839 This journal is c The Royal Society of Chemistry 2011
Table 6 Sensing glucose via synthetic boronic acids. Note that most methods are reported for solutions only and cannot be readily extended tocontinuous sensing. (ABS: absorbance; AR: analytical range; BA: boronic acid; BBV: boronic acid-based bipyridinium appended bis-viologen; FI:fluorescence intensity; FLU: fluorescence; FRET: fluorescence resonance energy transfer; HOLO: holography; HPTS: hydroxypyrene trisulfonate;LU: luminescence; NP: nanoparticles; PhBA: phenylboronic acid; SPR: surface plasmon resonance; SR-B: sulforhodamine-B)
Boronate Method and comments AR/mM Ref.
Anthracene based bis-PhBA FLU; increase in fluorescence on addition of GLU (exc./em. 370/423 nm); ditopicrecognition enhances sensitivity and selectivity for GLU; tested in 33% methanolicsolution; pH 7.77
0.3–1 106
PhBA FLU; computer guided design; sensor shows 400 fold greater affinity to GLU thanto other saccharides; also highest fluorescence response to GLU; up to 50%quenching on addition of GLU
— 107
Anthracene based bis-PhBA FLU; increase in fluorescence (exc./em. 377/427 nm) on addition of GLU; selectivefor GLU in the gluco-furanoidic form over fructose and galactose
— 108
3-Amino-PhBA (on naphthalicanhydride fluorophore)
FLU; quenching (exc./em. 354/400 nm) on addition of saccharide; pH 7.7; moreselective for fructose than for GLU
— 109
3-Amino-PhBA FLU; nitro-naphthalic anhydride fluorophore displays dual emission (430/550 nm)at pH 8 which is quenched on addition of saccharide; selectivity: GLU > galactose> fructose
— 110
PhBA (on naphthalicanhydride fluorophore)
FLU; sulfo-naphthalic anhydride fluorophore displays dual emission (400/474 nm)at pH 7.4 which is enhanced on addition of saccharide; selectivity: GLU> galactose> fructose
— 111
PhBA with 6-quinoliniumnucleus
FLU; quenching of fluorescence on addition of GLU (exc./em. 345/450 nm); moreselective for fructose than for GLU; AR: submillimolar; ‘‘contact lens sensor’’;works at pH 7
0.1–1 112113
BA based on stilbene, chalconeand polyene
FLU; quenching of fluorescence (em. 400–550 nm) on addition of GLU; strongresponse to fructose and GLU; ‘‘contact lens sensor’’; pH 7
0–50 114
PhBA on ruthenium complex FLU; quenching of fluorescence (em. 620 nm) on addition of GLU; pH 11; alsoresponds to fructose
0.01–0.1 115
Aryl-BA FLU; competitive assay; binding of BA to Ru(bpy)2(5,6-dihydroxy-1,10-phenan-throline) at pH 8 increases fluorescence and lifetime of the complex; addition ofGLU leads to decrease of both; patent
0–40 116
117PhBA Patent; FLU; fluorophore is selected from transition metal–ligand complexes and
thiazine, oxazine, oxazone, or oxazinone are anthracene compounds; fluorophoreimmobilized in a GLU permeable biocompatible polymer matrix that is implantablebelow the skin
— 118119
3-Amino-PhBA ABS; copolymer of aniline and 3-amino-PhBA; addition of saccharide shifts theabsorption peak at 600 nm to the shortwave; absorbance between 650 and 800 nmincreases. Response: sorbitol > fructose > mannitol > glycerol > glucose
1–30 120
Di-PhBA FLU; competitive assay; reaction of Alizarin Red S with BA leads to fluorescentproduct (exc./em. 495/570 nm); fluorescence decreases on addition of GLU;Di-PhBA shows higher stability constant for GLU than for fructose
— 121
Octylboronic acid FLU; competitive assay; reaction of Alizarin with BA leads to fluorescent product(exc./em. 460/570 nm); fluorescence decreases on addition of GLU; incorporation ofBA and Alizarin in PVC polymer; in vivo application
1–50 123
PhBA FLU; saccharide-induced conformational changes in copolymers containingBA and fluorescent units; changes detected by monitoring the excimer band(em. 430–600 nm) to monomer band (360–430 nm) ratio of intensities measured;comparable response to GLU and to fructose
— 124
PhBA (based on azo dye) ABS; color change from orange to purple on addition of saccharide; higherselectivity for fructose over GLU
5–10 126
PhBA SPR; coating of a sensor chip (gold layer) with vinylpolymer with pending BAgroups; shift of angle on addition of saccharide; higher response to fructose than toGLU
— 127
BBV FLU; study of 11 fluorescent dyes (all with negative charges) quenched by BBV(exc./em. 460/510 nm); increase of fluorescence on addition of GLU; pH 7.4;stronger fluorescence response to GLU with higher negative charge of the indicatordye
Physiologicalrange
128
BBV FLU of HPTS; study of 6 BBV receptors (all with positive charges); quench HPTS inthe presence of saccharides; best quencher: 3,30-o-BBV (followed by fructose andgalactose); apparent binding constant for GLU higher than for galactose andfructose but magnitude of fluorescence enhancement greater for fructose; fructosecauses higher fluorescence recovery
0–5 130
BBV FLU; sensor array of 6 BBV; quenching of HPTS; increase in FI on addition ofsaccharides; data evaluation with linear discriminant analysis statistics
— 131
BBV FLU; a dye and BBV covalently incorporated in hydrogel; fluorescence ofindicator dye (exc./em. 470/540 nm) is quenched by BBV; increase of fluorescenceon addition of GLU; flow cell; higher binding constant for glucose than forfructose
2.5–20 132
BBV FLU; HPTS derivative and BBV derivative covalently incorporated in hydrogel;fluorescence of indicator dye (exc./em. 470/540 nm) is quenched by BBV; increase offluorescence on addition of GLU; response time: 1–11 min; only GLU tested; fiberoptic setup
This journal is c The Royal Society of Chemistry 2011 Chem. Soc. Rev., 2011, 40, 4805–4839 4819
modulated by the strength of this interaction. Increased
fluorescence through suppression of PET is observed on
binding of glucose. The cleft-like structure makes the
system particularly selective and sensitive for glucose due to
formation of an intramolecular 1 : 1 complex between the two
boronic acids and the 1,2- and 4,6-hydroxy groups of glucose.
Response therefore is much more selective to glucose than to
fructose, galactose, allose and ethylene glycol due to ditopic
recognition and formation of a 1 : 1 complex. Fluorescence
was detected at 423 nm at an excitation wavelength of 370 nm,
and glucose determined in the concentration range from
0.3 mM to 7 mM.
Table 6 (continued )
Boronate Method and comments AR/mM Ref.
BBV FLU; evaluation of different HPTS derivatives and BBV derivatives covalentlyincorporated in hydrogel; fluorescence of indicator dye (exc./em. 470/540 nm) isquenched by BBV; increase of fluorescence on addition of GLU; fiber optic sensingsetup
2.5–20 134
BBV FLU; HPTS derivative and BBV covalently incorporated in hydrogel; fluorescenceof indicator dye (exc./em. 470/540 nm) is quenched by BBV; increase of fluorescenceon addition of GLU; sensitivity fructose > galactose> GLU; fiber optic sensingsetup; patent
2.5–20 135137
BBV FLU; dye (HPTS) (exc./em. 460/510 nm) and TSPP (exc./em. 414/644 nm) isquenched by BBV; reference dye SR-B (exc./em. 565/586 nm) not quenched by BBV;increase of fluorescence on addition of GLU; ratiometric measurement; GLU testedonly
2.5–20 138
BBV FLU; fluorescence of CdSe/ZnS QDs (exc./em. 460/604 nm) is quenched by BBV;increase of FI on addition of GLU; only GLU tested
2–20 139
PhBA FLU; fluorescence of CdS QDs (exc./em. 390/604 nm) is quenched in the presence ofGLU due to shrinking of hydrogel; only GLU tested
2–25 140
PhBA on QD LU; LU of CdTe/ZnTe/ZnS QDs (exc./em. 390/604 nm) is quenched and red shiftedin the presence of GLU due to agglomerates; only GLU tested; application towardsmouse melanoma cells
0.4–20 141
PhBA in hydrogel aroundAg-NP
FLU; fluorescence of Ag NPs (exc./em. 390/600 nm) is quenched in the presence ofGLU due to agglomerats; only GLU tested
1–30 142
Anthracene based bis-PhBA FLU; increase in fluorescence and lifetime on addition of GLU(exc./em. 380/425 nm); interference studies with BSA and SDS
Physiologicalrange
144
Bis-anthracene based bis-PhBA FLU; increase in fluorescence (exc./em. 370/425 nm) on addition of GLU;‘‘selective for GLU’’; measured in 50% methanol
Physiologicalrange
145
Anthracene based bis-PhBA Patent; FLU; probe covalently immobilized on cellulose support; increase inFI on addition of GLU
— 147
Pyrene based bis-PhBA FLU; pyrene units with varying lengths of the spacer; incorporation in GLUimprinted polymer; fluorescence increase (exc./em. 343/378 nm) on additionof GLU (and other saccharides) in 33% methanolic solution only
— 148
Pyrene–phenanthrene basedbis-PhBA
FRET between phenanthrene (donor, exc./em. 299/369 nm) and pyrene(acceptor, exc./em. 342/397 nm) on addition of GLU plus decrease in excimeremission (460 nm); higher selectivity (higher binding constant and FI) for GLU;pH 8.21
— 149
Pyrene based bis-PhBA FLU; evaluation of different pyrene probes; effect of linker length, kind of fluoro-phore between two PhBA units on GLU selectivity; single pyrene fluorophore andhexamethylene linker achieved good GLU selectivity as did the pyrene/phenan-threne based bis-PhBA (FRET and excimer, see ref. 147); tested in 52% methanolicsolution only
— 150
Pyrene based PhBA FLU; emergence of excimer emission of pyrene-PhBA (exc./em. 342/377 nm,excimer 470 nm) upon addition of GLU and cationic polymer; pH 10.2; highselectivity of excimer formation for GLU
0.1–10 151
Cyclotetrapeptide based PhBA FLU; addition of GLU causes quenching of fluorescence (exc./em. 285/480 nm) of aPhBA containing a cyclotetrapeptide; solvent: 50% methanol; pH 11.7(!); highselectivity for D-GLU over L-GLU, lactate and other saccharides (cannot formditopic 1:1 binding complexes)
0–10 152
Hemicyanine derivatives basedon PhBA
FLU; increase in fluorescence (exc./em. 460/600 nm) on addition of saccharide;pH 7; higher selectivity for fructose and galactose than for GLU
5–500 153
Acridine-based PhBA Patent; FLU; acridine-based fluorophore with PhBA; em. 500 nm — 154Chlorooxazine boronate Patent; FLU; measurement of FI and lifetime — 155Dansyl PhBA Dansyl based PhBA in a plasticized PVC membrane; FLU; quenching of FLU
(exc./em. 335/530 nm) on addition of GLU; cross-sensitivity towards pH0.1–100 156
Acrylamido/Vinyl-PhBA HOLO; PhBA in hydrogel; binding of GLU induces swelling of a gel matrix;changes in diffraction wavelength; pH 7–9; RT: > 10 min
Physiologicalrange
157158159160161
PhBA HOLO; crystalline colloidal array within polyacrylamide hydrogel with PhBAgroups; binding of GLU enhances crosslinking and shrinkage of the hydrogel; blueshift of diffraction of a photonic crystal; pH 7; higher selectivity for GLU than forgalactose, mannose and fructose
FLU; ConA immobilized on the inside of hollow dialysis fiber; FITC-labeled dextran as competitive ligand; only smallmolecules can pass in and out; increase in concentration of free dextran on addition of GLU; increase in fluorescence
Physiological range 171
FLU; Sepharose-immobilized ConA as a binding agent and FITC-dextran as a competing ligand which fluoresces onillumination; dextran competes with GLU for binding sites on the immobilized ConA; patent
— 172
FLU; ConA immobilized on the inside of hollow dialysis fiber, FITC-labeled dextran as competitive ligand; only smallmolecules can pass in and out; increase in concentration of free dextran on addition of GLU; increase in fluorescence;fiber optic setup; response time: 5–7 min
Physiological range 173
FLU; Sephadex beads with GLU groups labeled with Safranin O and Pararosanilin (block exc. and em. of Alexa-488);Alexa-488 labeled ConA binds to these GLU groups; fluorescence of Alexa is quenched; fluorescence at 522 nm (exc.490 nm) is restored on addition of GLU; response time: 4–5 min; whole system in hollow dialysis fiber; fiber opticsetup
0.2–30 175
FLU; Sephadex beads with GLU groups labeled with dye (block exc. and em. of Alexa-647); Alexa-647 labeled ConAbinds to these GLU groups; fluorescence of Alexa is quenched; fluorescence (670 nm) is restored on addition of GLU;response time: 15–30 min; whole system in hollow dialysis fiber; fiber optic setup; high operational stability; works innear-IR
2.5–20 176
Patent: FLU; ConA labeled with Alexa-594 and aminodextran labeled with a Crystal Violet succinimidyl ester areplaced in a hollow fiber of regenerated cellulose; fluorescence lifetime measured with automated apparatus
— 178
FRET between TRITC-ConA and FITC-dextran; restoration of FITC emission on addition of GLU; fiber opticsetup; response time 10 min; two excitation sources for internal calibration (480 nm, 550 nm); hollow fiber setup
0–83 179
FRET; ConA labeled with Cy5, insulin labeled with MG and maltose; FRET; restoration of Cy5 fluorescence andincrease in lifetime on addition of GLU; less aggregation and better reversibility of the assay by using protein insteadof dextran; NIR emission; decay times can be measured through skin using long wavelength excitation and emission,suggesting the possibility of an implanted GLU sensor
0–60 180
FRET; ConA labeled with Ru(bpy)3, insulin labeled with MG and maltose; FRET; restoration of Ru luminescenceand increase in lifetime on addition of GLU; less aggregation and better reversibility of the assay by using proteininstead of dextran; NIR emission but short wavelength excitation; long lifetime
0–50 181
FRET; TRITC labeled ConA and FITC labeled dextran incorporated in hydrogel; FRET; decrease of FRET onaddition of GLU; response time: 10 min
0–44 182
Patent: FRET; TRITC labeled ConA and FITC labeled dextran incorporated in hydrogel; decrease of FRET onaddition of GLU
— 183
Patent: FRET between TRITC-ConA and FITC-dextran; incorporated in contact lens; apparatus to irradiate thesensor dyes and detect FRET
— 184
Patent; FRET; agarose microparticles containing TRITC-ConA and dextran-FITC are loaded onto a micromachinedpad having a 10 mm square array of 400 microneedles of 1 mm diameter; injected subcutaneously; fiber opticfluorometer used to measure the rhodamine fluorescence
— 185
FRET; ConA labeled with allophycocyanine, dextran labeled with MG; FRET, MG shields allophycocyanine;Restoration of allophycocyanine fluorescence (663 nm) on addition of GLU; lifetime measurement; inhibition ofFRET by albumin and serum; works in near-IR
2.5–30 186
FRET; layer-by-layer assembly of films in microcapsules containing TRITC-ConA and dextran-FITC in thin polymerfilms
0–100 187
Patent; REFL; hydrogel containing ConA and GLU groups; swelling of the gel on addition of GLU; change inreflected light
— 189
FLU; FRET from Alexa-647 (donor) labeled dextran to Cy7 (acceptor) labeled on agarose together with ConA;decrease of FRET on addition of GLU; fiber optical setup in vivo; response time: 5–15 min; works in near-IR
2.5–25 177
FRET; TRITC-ConA and FITC dextran incorporated in hydrogel pads contained in wells of a microtiter plate;layer-by-layer method; response time: 8 min; enables continuous sensing
0–10 190
FRET; TRITC-b-cyclodextrin and QD/ConA conjugate incorporated in hydrogel and photopolymerized at the tip ofan optical fiber; response time: 3–8 min; fiber optic setup; interstitial GLU sensor; enables continuous sensing; appliedto in vivo glucose determination
0–28 191192
FRET; ConA coupled to CdTe QDs, Au-NPs modified with cyclodextrin; FRET on aggregation; restoration ofquenched QD luminescence on addition of GLU; direct determination in serum; no interference by other saccharides(exc./em. 320 nm/530 nm)
0–0.05 193
SPR; silver-NPs bound to dextran 3000; aggregation with ConA; plasmon absorbance reduction on addition of GLU 0–0.05 194SPR; dextran coated Au-NPs aggregated by ConA; dissociation of aggregates on addition of GLU; reduction ofplasmon absorbance; thickness of NPs and ConA concentration modify the analytical range
— 195
SPR; dextran coated Au-NPs aggregated by ConA; dissociation of aggregates on addition of GLU; reduction ofplasmon absorbance; thickness of NPs and ConA concentration modify the analytical range
0–50 196
RLS; dextran coated Au-NPs aggregated by ConA; dissociation of aggregates on addition of GLU; light scatteringmeasured at 560 and 680 nm; self-referenced
1–60 197
OCT; macroporous Sephadex particles and ConA incorporated in GLU-permeable housing; light scattering decreaseson addition of GLU to render suspension transparent; response time: 23 min; enables continuous sensing
2.5–20 198
Patent; FLU; reversible change in fluorescence due to turbidity changes in a ConA/Sephadex system at various GLUconcentrations; ConA/Sephadex suspension sandwiched inside a rectangular semipermeable dialysis capsule ofmembranes of regenerated cellulose; turbidity decreased on addition of GLU, increasing fluorescence; enablescontinuous sensing
— 199
FLU; dextran-modified single wall carbon nanotubes (SWCNTs) aggregated by ConA, resulting in quenched SWCNTphotoluminescence; restoration of initial PL on addition of GLU; response time: 3–28 min (exc./em. 633/> 900 nm);PBS pH 7
apo-GOx Flu; GLU induces quenching of intensity and lifetime of apo-GOx non-covalently labeled with ANS(exc./em.=325/480 nm)
10–20 202
apo-GOx Patent; Flu; GLU induces quenching of intensity and lifetime of apo-GOx non-covalently labeled withANS in 3% acetone (exc./em.=370/510 nm)
10–20 203
apo-GDH Flu; GLU induces quenching of intensity and fluorescence polarization of apo-GDH non-covalentlylabeled with ANS
0–60 204
apo-GOx FRET; labeled apo-GOx and labeled dextran; decrease of FRET from FITC to TRITC when theapo-GOx–dextran complex dissociates as a result of the competition of glucose
0–90 205
apo-GOx FRET; microcapsules comprising labeled apo-GOx and labeled dextran multilayer films constructedusing affinity binding and the layer-by-layer self-assembly; decrease of FRET from FITC to TRITC whenthe apo-GOx–dextran complex dissociates as a result of the competition of glucose; 5 times greaterspecificity for GLU over other sugars
0–30 206
apo-GOx FRET; microcapsules comprising Cy5-apo-GOx and TRITC-dextran multilayer films constructed usingaffinity binding and the layer-by-layer self-assembly; decrease of FRET from TRITC to Cy5 when theapo-GOx–dextran complex dissociates as a result of the competition of glucose; 5 times greater specificityfor GLU over other sugars; labeled apo-GOx and labeled dextran
0–40 207208
apo-GOx LI; SWCNTs cross-linked with apo-GOx in PVA polymer; alteration of the swelling state of the hydrogelin the presence of glucose causes change in NIR emission
— 209
Fig. 25 Schematic of a resonance energy transfer glucose assay based
on competitive binding between dextran and glucose for binding sites
on apo-GOx. Reprinted with permission from ref. 205. Copyright 2004
This journal is c The Royal Society of Chemistry 2011 Chem. Soc. Rev., 2011, 40, 4805–4839 4831
mutations near the binding pocket were constructed which
allowed for site-specific covalent coupling of the fluorophores.
The fluorescence of acrylodan is quenched on conjugation to
the GBP, but enhances on addition of glucose due to changes
in the polarity of the micro-environment. A series of patents
filed by Becton Dickinson is covering this sensing
scheme.213–215 GBP or the glucose/galactose binding protein
(GGBP), respectively, were site-specifically labeled with dyes
such as IANBD, Nile red, coumarins, or benzodioxazoles. The
conjugates were then incorporated into a hydrophilic polymer
and attached to the end of an optical fiber.
A GGBP mutant labeled with a Nile Red derivative and
possessing a lower affinity to glucose was described by Pitner
and co-workers.216 Upon binding to glucose, the emission at
around 640–650 nm changes by up to 50% in the blood
glucose range. A similar approach217 uses a thermostable
glucose binding protein (tm-GBP). A series of site specific
mutated and labeled conjugates was evaluated. The fluorescence
of the label Cy5 is quenched on binding of glucose, and its
maximum is shifted from 666 nm to 700 nm. This again
enables ratiometric measurements to be performed. The
tm-GBP has also a higher affinity for glucose and enables
Table 9 Sensing of glucose via glucose-binding proteins (both native and engineered). AR: analytical range; CFP: cyan fluorescent protein; Cys:cystein; FLU: fluorescence; FRET: fluorescence resonance energy transfer; GBP: glucose-binding protein; GGBP: glucose/galactose-bindingprotein; GFP: green fluorescent protein; GLU: glucose; IANBD: 4-(N-(iodoacetoxy)ethyl-N-methyl)amino-7-nitrobenz-2-oxa-1,3-diazole; SPR:surface plasmon resonance; tm-GBP: thermostable glucose binding protein; tm-GGBP: thermostable glucose binding protein; YFP: yellowfluorescent protein
Optical method and comments AR/mM Ref.
FLU; specific mutation of GGBP to reduce GLU binding; measurement of the intrinsic protein fluorescence(exc./em. 295/350 nm); increase in fluorescence on addition of GLU; max. 10% signal change
5–10 180
FLU; site specific covalent coupling of acrylodan or IANBD to Cys near the binding pocket of GBP; quenchingof acrylodan and fluorescence enhancement of IANBD on addition of GLU due to changes in the polarity of themicroenvironment
o 0.1 212
Patent; FLU; site specific covalent coupling of IANBD to the Cys group near the binding pocket of GGBP;fluorescence enhancement of IANBD on addition of GLU due to changes in polarity in microenvironment; fibercoated with labeled protein which had been embedded in a polymer matrix
— 213214
Patent; FLU; site specific labeling of GGBP with dye containing squaraine nucleus, Nile Red nucleus, benzo-dioxazole nucleus, coumarin nucleus or aza coumarin nucleus dyes
— 215
FLU; site specific labeling of GGBP with Nile Red derivatives; enhancement of NIR fluorescence (650 nm)intensity on binding of GLU due to changes in polarity in microenvironment
Physiologicalconcentrations
216
FLU; tm-GBP labeled with labels Cy3, Cy5, acrylodan, IANBD; Cy5 conjugate shows best properties; quenchedon binding of GLU and em shift from 666 nm to 700 nm; immobilization in MTP; NIR; self-calibration(ratio of em 666 nm and 700 nm); reversible
1–30 217
Patent; FLU; tm-GGBP labeled with acrylodan; specific sensing group for GLU; reporter group undergoeschange of fluorescence intensity on GLU binding
— 218
Patent; FLU; GGBP labeled with a fluorescent dye or with another protein labeled with a fluorescent dye; specificsensing group for GLU; reporter group undergoes change of fluorescence intensity on GLU binding; fiber coatedwith labeled protein
— 219
FRET; GBP labeled with Alexa-488 (donor) and QSY7 (acceptor) (FRET system) compared with a dimethyl-aminonaphthalene-labeled GBP; max. 16% increase of fluorescence in the FRET system on addition of GLU;300% fluorescence enhancement for labeled GBP
0–0.01 220
FLU; GBP mutant labeled with Badan; 200% increase of fluorescence intensity and 70% increase of fluorescencelifetime on addition of GLU
1–100 221
FLU (lifetime); ANS labeled GBP; decrease only in fluorescence intensity on binding of GLU, no significantchange in lifetime; GBP in cuvette, Ru complex on the outside wall in PVA film; phase-modulation fluorometry
0–0.008 222
Patent; FLU; lifetime; ANS labeled GBP; decrease of fluorescence intensity on binding of GLU, change in lifetime — 223Patent; FLU; polarization; HSA labeled with ANS and GGBP labeled with ANS; self-referenced o 0.1 224FLU; GBP labeled with acrylodan and Ru label; only fluorescence of acrylodan is quenched on binding of GLU;Ru emission is stable; self-referenced probe; also a FRET occurs; phase-modulation fluorometry also possible
o 0.1 225
FRET; GGBP site specific labeled with acrylodan (a) or acrylodan and rhodamine (b); (a) decrease of fluorescenceon addition of GLU up to 10%; (b) increase in emission of rhodamine up to 10% on addition of GLU due toFRET
— 226
Patent; FLU; ratiometric (2 l); GGBP labeled with IANBD or IANBD and Texas Red; labeled protein embeddedin a polymer matrix and coating of a fiber; increase in fluorescence on addition of GLU
0.1–100 227
FLU; GGBP labeled with tetramethylrhodamine-5-iodoacetamide (TMR) and rhodamine red (RR); best resultswith GGBP mutant labeled with 2 TMR units; increase in fluorescence on addition of GLU; tested in simulatedblood serum; modest effect of physiological concentrations of fructose and galactose
0.001–12 228
FRET; GBP dual-labeled with GFPuv (GFP with several mutations to enhance the excitation by UV light)(exc./em. 395/510 nm) and YFP (exc./em. 513/527); reduction of FRET on addition of GLU; system in a dialysishollow fiber; response time: 100 s
o0.1 229
FRET; GBP dual-labeled with CFP (exc./em. 436/480 nm) and YFP (exc./em. 513/535 nm); reduction of FRETon addition of GLU; no significant decrease in FRET by other saccharides; monitors GLU distribution and levelsin living cells
0.07–5.3 231232
Patent; FRET; GBP dual-labeled with FP; implantable device — 233FLU; specific engineered glucose binding protein-like polypeptide; labeled with coumarin derivative; quenchingof fluorescence on addition of GLU; immobilized at the tip of an optical fiber
2–20 234
Patent; SPR; thiol-modified GBP immobilized on the chip surface; change of refractive index on binding of GLU — 235236237
This journal is c The Royal Society of Chemistry 2011 Chem. Soc. Rev., 2011, 40, 4805–4839 4833
at 485 nm is quenched in the presence of glucose. The response
time of the sensor is approximately 1 min, and the dynamic range
is from 2 to 20 mM. The method was applied to determine
glucose in whole porcine blood samples.
Becton Dickinson has patented235–237 a surface plasmon
resonance-based sensor family. Thiol-modified GBP was
immobilized on the surface of a gold chip. Glucose binding
was interpreted in terms of a conformational change of the
GBP which eventually results in a decrease in the resonance
angle. It was also concluded that the change from an open to a
closed state results in a decrease in the hydrodynamic volume
which is greater than the increase in mass upon binding.
9. Final assessment
It is obvious from the wealth of literature on sensors for
glucose that there is a substantial need for such sensors. It is
difficult, on the other side, to identify the most suitable sensor
for a specific problem. The sensing schemes treated here differ
in their mode of recognition, the method of transduction, their
analytical ranges and the limits of detection. Each of them
therefore will have a specific application.
Continuous sensing of glucose in context with the artificial
pancreas is generally considered as being the Holy Grail in
biosensor technology. Sensors based on GOx, while used in
commercial clinical instrumentation for discontinuous but
repeated assays, are not well suited for continuous monitoring
for various reasons as outlined in Table 10. Affinity binding
assays using the intrinsic fluorescence of enzymes or oxidized or
reduced cofactors suffer from narrow analytical ranges.
Approaches based on boronic esters hold more promise provided
that a selectivity of >100 for glucose over fructose is warranted
and that effects of pH can be kept under control. Despite
numerous approaches based on the use of concanavalin A, no
system yet has been brought to a state of technology that would
enable its application in vivo. Aggregation is but one of the issues.
In our opinion, the glucose binding proteins provide the best
perspective. Both apo-GOx and GBPs from various sources
may be used. Protein engineering has resulted in modified
proteins so that the physiological range of glucose concentrations
also can be covered. While the intrinsic fluorescence of such
proteins yields a less suitable analytical information,
labelled—and in particular doubly-labelled—GBPs and others
seem to hold the largest promise.
Table 10 Pros and cons of the various schemes reported for sensing glucose
Method Pros Cons
Kinetic enzymatic assaysusing GOx
Kinetic, fully reversible; 2-wavelength andfluorescence lifetime measurements possible; range1–20 mM; works at pH 6–8
Enzyme activity decays with time; critically timedependent, signal change small at low pO2;pH-dependent
Affinity binding of glucose toapo-GOx (FAD removed)
Affinity based, fully reversible; can be calibrated;works at pH 6–8; apo-enzyme fairly stable; signal nottime-dependent; pO2 has no effect; ratiometric andlifetime-based sensing possible
Range 0.1–200 mM; site-specific labeling of enzymeneeded; pH-dependent; apo-enzyme moderatelystable
Chemical binding of glucoseto synthetic boronic acid
Stable system, fully (but slowly) reversible; works atpH 7–8 (but strongly pH-dependent); no effect ofvarying pO2; ratiometric and lifetime-based sensingpossible
Range 1–200 mM; rarely specific for glucose(with 2 exceptions); pH-dependent
Affinity binding to Con A Slow system, fully (but slowly) reversible;calibration possible (very slow); works at pH 7–8(hardly pH-dependent); no effect of varying pO2; 2lFRET, and lifetime measurement possible, range:1–200 mM
Only fairly specific for glucose; ConA tends toaggregate within a few hours; slow; complex; intendedfor in vivo use and continuous monitoring; complexlabeling protocols; ConA is toxic
Affinity binding to glucose-binding proteins
Fully reversible; calibration possible; works atpH 7–8; fairly simple; hardly pH-dependent; pO2 hasno effect; ratiometric (2l) readout possible, FRET,and lifetime measurements possible: range 1–100 mM
Fairly specific for glucose; covers low concentrationrange only unless genetically engineered; partiallycomplex labeling; 1-pt calibration conceivable
Fig. 26 Design of a GIP (glucose indicator protein) for sensing
glucose based on FRET. (a) The GBP adopts an ‘‘open’’ form in the
presence of glucose, which triggers a conformation change, causing
two GFPs to depart from one another leading to the change in FRET.
The dot represents one molecule of glucose bound to the binding cleft
of GBP. (b) Domain structure of the GIP. GFPuv: green fluorescent
protein with several mutations to enhance the excitation by UV light.
2 D. D. Cunningham and J. A. Stenken, In Vivo Glucose Sensing,Wiley, 2009, pp. 450.
3 P. N. Bartlett, Bioelectrochemistry: Fundamentals, ExperimentalTechniques and Applications, Wiley, 2008, pp. 478.
4 J. C. Pickup, F. Hussain, N. D. Evans, O. J. Rolinski and D. J. S.Birch, Fluorescence-based glucose sensors, Biosens. Bioelectron.,2005, 20, 2555–2565.
5 Topics in Fluorescence Spectroscopy, ed. C. D. Geddes andJ. R. Lakowicz, Glucose Sensing, Springer, 2006, vol. 11, pp. 442.
6 A. Heller and B. Feldman, Electrochemical Glucose Sensors andTheir Applications in Diabetes Management, Chem. Rev., 2008,108, 2482–2505.
7 V. Fragkou and A. P. F. Turner, Commercial biosensors fordiabetes, in Handbook of Optical Sensing of Glucose in BiologicalFluids and Tissues, ed. V. M. Tuchin, CRC Press, Boca Raton,Fla, 2009, pp. 41–64.
8 S. H. Lee and M. M. Karim, in Topics in Fluorescence Spectro-scopy, ed. C. D. Geddes and J. R. Lakowicz, Glucose Sensing,Springer, New York, 2006, vol. 11, ch. 12, pp. 311–322.
9 O. S. Khalil, in Topics in Fluorescence Spectroscopy, ed.C. D. Geddes and J. R. Lakowicz, Glucose Sensing, Springer,New York, 2006, vol. 11, ch. 7, pp. 165–200.
10 E. A. Moshou, B. V. Sharma, S. K. Deo and S. Daunert,Fluorescence Glucose Detection: Advances Toward the IdealIn Vivo Biosensor, J. Fluoresc., 2004, 14, 535–547.
11 Y. Wickramasinghe, Y. Yang and S. A. Spencer, CurrentProblems and Potential Techniques in In Vivo Glucose Monitoring,J. Fluoresc., 2004, 14, 513–520.
12 S. M. Borisov and O. S. Wolfbeis, Optical Biosensors,Chem. Rev., 2008, 108, 423–461.
13 A. Duerkop, M. Schaeferling and O. S. Wolfbeis, in Topics inFluorescence Spectroscopy, ed. C. D. Geddes and J. R. Lakowicz,Glucose Sensing, Springer, New York, 2006, vol. 11, ch. 15,pp. 351–375.
14 M. M. F. Choi, Progress in Enzyme-Based Biosensors UsingOptical Transducers, Microchim. Acta, 2004, 148, 107–132.
15 H. S. Mader and O. S. Wolfbeis, Boronic acid based probes formicrodetermination of saccharides and glycosylated biomolecules,Microchim. Acta, 2008, 162, 1–34.
16 H. Fang, G. Kaur and B. Wang, Progress in Boronic Acid-BasedFluorescent Glucose Sensors, J. Fluoresc., 2004, 14, 481–489.
18 M. J. P. Leiner, M. R. Hubmann and O. S. Wolfbeis, The totalfluorescence of human urine, Anal. Chim. Acta, 1987, 198, 13–23.
19 O. S. Wolfbeis and M. Leiner, Mapping of the total fluorescenceof human blood serum as a new method for its characterization,Anal. Chim. Acta, 1985, 167, 203–215.
20 F. Hussain, D. J. S. Birch and J. C. Pickup, Glucose sensing basedon the intrinsic fluorescence of sol–gel immobilized yeast hexo-kinase, Anal. Biochem., 2005, 339, 137–143.
21 M. Portaccio, M. Lepore, B. Della Ventura, O. Stoilova,N. Manolova, I. Rashkov and D. G. Mita, Fiber-optic glucosebiosensor based on glucose oxidase immobilised in a silica gelmatrix, J. Sol–Gel Sci. Technol., 2009, 50, 437–448.
22 P. De Luca, M. Lepore, M. Portaccio, R. Esposito, S. Rossi,U. Bencivenga and D. G. Mita, Glucose determination by meansof steady-state and time-course UV fluorescence in free orimmobilized Glucose Oxidase, Sensors, 2007, 7, 2612–2625.
23 J. F. Sierra, J. Galban and J. R. Castillo, Determination ofglucose in blood based on the intrinsic fluorescence of glucoseoxidase, Anal. Chem., 1997, 69, 1471–1476.
24 W. Trettnak and O. S. Wolfbeis, Fully reversible fibre-opticglucose biosensor based on the intrinsic fluorescence of glucoseoxidase, Anal. Chim. Acta, 1989, 221, 195–203.
25 A. M. Hartnett, C. M. Ingersoll, G. A. Baker and F. V. Bright,Kinetics and Thermodynamics of Free Flavins and the Flavin-Based Redox Active Site within Glucose Oxidase Dissolved inSolution or Sequestered within a Sol–Gel-Derived Glass, Anal.Chem., 1999, 71, 1215–1224.
26 R. Esposito, B. Della Ventura, S. De Nicola, C. Altucci,R. Velotta, D. G. Mita and M. Lepore, Glucose sensing bytime-resolved fluorescence of sol–gel immobilized glucoseoxidase, Sensors, 2011, 11, 3483–3497.
27 M. Przybyt, E. Miller and T. Schreder, Thermostability of glucoseoxidase in silica gel obtained by sol–gel method and in solutionstudied by fluorimetric method, J. Photochem. Photobiol., 2011,103, 22–28.
28 V. Sanz, S. de Marcos and J. Galban, A reagentless opticalbiosensor based on the intrinsic absorption properties of peroxidase,Biosens. Bioelectron., 2007, 22, 956–964.
29 V. Sanz, S. de Marcos and J. Galban, Direct glucose determina-tion in blood using a reagentless optical biosensor, Biosens.Bioelectron., 2007, 22, 2876–2883.
30 I. Chudobova, E. Vrbova, M. Kodıcek, J. Janovcova and J. Kas,Fibre optic biosensor for the determination of D-glucose based onabsorption changes of immobilized glucose oxidase, Anal. Chim.Acta, 1996, 319, 103–110.
31 R. Narayanaswamy and F. Sevilla, III, An optical fibre probe forthe determination of glucose based on immobilized glucosedehydrogenase, Anal. Lett., 1988, 21, 1165–1175.
32 J. Wang, Electroanalysis, 2001, 13, 983–988.33 T. Yamazaki, K. Kojima and K. K. Sode, Extended-range
34 B. J. White and H. J. Harmon, Novel optical solid-state glucosesensor using immobilized glucose oxidase, Biochem. Biophys. Res.Commun., 2002, 296, 1069–1071.
35 S. D’Auria, N. DiCesare, M. Staiano, Z. Gryczynski, M. Rossiand J. R. Lakowicz, A Novel Fluorescence Competitive Assay forGlucose Determinations by Using a Thermostable Glucokinasefrom the Thermophilic Microorganism Bacillus stearothermophilus,Anal. Biochem., 2002, 303, 138–144.
36 J. F. Sierra, J. Galban, S. deMarcos and J. R. Castillo, Fluorimetric-enzymatic determination of glucose based on labelled glucoseoxidase, Anal. Chim. Acta, 1998, 368, 97–104.
37 S. de Marcos, J. Galindo, J. F. Sierra, J. Galban andJ. R. Castillo, An optical glucose biosensor based on derivedglucose oxidase immobilised onto a sol–gel matrix, Sens. Actuators,B, 1999, 57, 227–232.
38 J. F. Sierra, J. Galbam, S. de Marcos and J. R. Castillo, Directdetermination of glucose in serum by fluorimetry using a labeledenzyme, Anal. Chim. Acta, 2000, 414, 33–41.
39 V. Sanz, J. Galban, S. de Marcos and J. R. Castillo, Fluorometricsensors based on chemically modified enzymes: Glucosedetermination in drinks, Talanta, 2003, 60, 415–423.
40 W. Trettnak, M. J. Leiner and O. S. Wolfbeis, Optical sensors:Part 34. Fibre optic glucose biosensor with an oxygen optrode asthe transducer, Analyst, 1988, 113, 1519–1523.
41 B. P. Schaffar and O. S. Wolfbeis, A fast responding fibre opticglucose biosensor based on an oxygen optrode, Biosens. Bioelectron.,1990, 5, 137–148.
42 B. A. A. Dremel, S.-Y. Li and R. D. Schmid, On-line determinationof glucose and lactate in animal cell culture based on fibre opticdetection of oxygen in flow-injection analysis, Biosens. Bioelectron.,1992, 7, 133–139.
43 M. J. Valencia-Gonzalez, Y. M. Liu, M. E. Diaz-Garcia andA. Sanz-Medel, Optosensing of D-glucose with an immobilizedglucose oxidase minireactor and an oxygen room-temperaturephosphorescence transducer, Anal. Chim. Acta, 1993, 283, 439–446.
This journal is c The Royal Society of Chemistry 2011 Chem. Soc. Rev., 2011, 40, 4805–4839 4835
44 D. B. Papkovsky, A. N. Ovchinnikov, V. I. Ogurtsov,G. V. Ponomarev and T. Korpela, Biosensors on the basis ofluminescent oxygen sensor: the use of microporous light-scatteringsupport materials, Sens. Actuators, B, 1998, 51, 137–145.
45 A. N. Ovchinnikov, V. I. Ogurtsov, W. Trettnak andD. B. Papkovsky, Enzymatic Flow-Injection Analysis ofMetabolites Using New Type of Oxygen Sensor Membranesand Phosphorescence Phase Measurements, Anal. Lett., 1999,32, 701–716.
46 D. B. Papkovsky, Luminescent porphyrins as probes for optical(bio) sensors, Sens. Actuators, B, 1993, 11, 293–300.
47 T. C. Collins, C. Munkholm and R. E. Slovacek, BAYER Corp.,Optical oxidative enzyme-based sensors, WO Pat. 2000 011205,2000.
48 X. Wang, H. Chen, T. Zhou, Z. Lin, J. Zeng, Z. Xie, X. Chen,K. Wong, G. Chen and X. Wang, Optical colorimetric sensorstrip for direct readout glucose measurement, Biosens. Bioelectron.,2009, 24, 3702–3705.
49 M. C. Moreno-Bondi, O. S. Wolfbeis, M. J. P. Leiner and B. P. H.Schaffar, Oxygen optrode for use in a fiber-optic glucose biosensor,Anal. Chem., 1990, 62, 2377–2380.
50 V. Desprez, N. Oranth, J. Spinke, J. Tusa and K. James, RocheDiagnostics GmbH, Nanoparticles for optical sensors, Eur. Pat.1496126, 2005.
51 Z. Rosenzweig and R. Kopelman, Analytical properties andsensor size effects of a micrometer-sized optical fiber glucosebiosensor, Anal. Chem., 1996, 68, 1408–1413.
52 X.-D. Wang, T.-Y. Zhou, X. Chen, K.-Y. Wong and X.-R.Wang, An optical biosensor for the rapid determination ofglucose in human serum, Sens. Actuators, B, 2008, 129, 866–873.
53 A. Neubauer, D. Pum, U. B. Sleytr, I. Klimant andO. S. Wolfbeis, Fibre-optic glucose biosensor using enzymemembranes with 2-D crystalline structure, Biosens. Bioelectron.,1996, 11, 317–325.
54 M. M. F. Choi, W. S. H. Pang, X. Wu and D. Xiao, An opticalglucose biosensor with eggshell membrane as an enzymeimmobilisation platform, Analyst, 2001, 126, 1558–1563.
55 Z. Zhou, L. Qiao, P. Zhang, D. Xiao and M. M. F. Choi, Anoptical glucose biosensor based on glucose oxidase immobilizedon a swim bladder membrane, Anal. Bioanal. Chem., 2005, 383,673–679.
56 O. S. Wolfbeis, M. J. P. Leiner and H. E. Posch,Microchim. Acta,1986, 90, 359–366.
57 R. M. Bukowski, V. P. Chodavarapu, A. H. Titus,A. N. Cartwright and F. V. Bright, Phase fluorometric glucosebiosensor using oxygen as transducer and enzyme-doped xerogels,Electron. Lett., 2007, 43, 202–204.
58 X. J. Wu and M. M. F. Choi, An optical glucose biosensor basedon entrapped-glucose oxidase in silicate xerogel hybridised withhydroxyethyl carboxymethyl cellulose, Anal. Chim. Acta, 2004,514, 219–226.
59 Z. Zhou, D. Xiao and M. M. F. Choi, A fluorescent glucosebiosensor based on immobilized glucose oxidase on bamboo innershell membrane, Biosens. Bioelectron., 2006, 21, 1613–1620.
60 H. Han, Y. Li, H. Yue, Z. Zhou, D. Xiao and M. M. F. Choi,Clinical determination of glucose in human serum by a tomatoskin biosensor, Clin. Chim. Acta, 2008, 395, 155–158.
61 P. J. Scully, L. Betancor, J. Bolyo, S. Dzyadevych, J. M. Guisan,R. Fernandez-Lafuente, N. Jaffrezic-Renault, G. Kuncova,V. Matejec, B. O’Kennedy, O. Podrazky, K. Rose, L. Sasekand J. S. Young, Optical fibre biosensors using enzymatic transducersto monitor glucose, Meas. Sci. Technol., 2007, 18, 3177–3186.
62 H. D. Duong and J. I. Rhee, Use of CdSe/ZnS core–shellquantum dots as energy transfer donors in sensing glucose,Talanta, 2007, 72, 1275–1282.
63 G. Chang, Y. Tatsu, T. Goto, H. Imaishi and K. Morigaki,Glucose concentration determination based on silica sol–gelencapsulated glucose oxidase optical biosensor arrays, Talanta,2010, 83, 61–65.
64 www.presens.de.65 H. Endo, Y. Yonemori, K. Musiya, M. Maita, T. Shibuya,
H. Ren, T. Hayashi and K. Mitsubayashi, A needle-type opticalenzyme sensor system for determining glucose levels in fish blood,Anal. Chim. Acta, 2006, 573, 117–124.
66 O. S. Wolfbeis, I. Oehme, N. Papkovskaya and I. Klimant,Sol–gel based glucose biosensors employing optical oxygentransducers, and a method for compensating for variable oxygenbackground, Biosens. Bioelectron., 2000, 15, 69–76.
67 X. Wu, M. M. F. Choi and D. Xiao, A glucose biosensor withenzyme-entrapped sol–gel and an oxygen-sensitive optodemembrane, Analyst, 2000, 125, 157–162.
68 L. Li and D. R. Walt, Dual-analyte fiber-optic sensor for thesimultaneous and continuous measurement of glucose andoxygen, Anal. Chem., 1995, 67, 3746–3752.
69 A. Pasic, H. Koehler, L. Schaupp, T. R. Pieber and I. Klimant,Fiber-optic flow-through sensor for online monitoring of glucose,Anal. Bioanal. Chem., 2006, 386, 1293–1302.
70 A. Pasic, H. Koehler, I. Klimant and L. Schaupp, Miniaturizedfiber-optic hybrid sensor for continuous glucose monitoring insubcutaneous tissue, Sens. Actuators, B, 2007, 122, 60–68.
71 J. B. Slate and P. C. Lord, Minimed Inc., Optical glucose sensor,Can. Pat. 2152862, 1996.
72 K. M. Curry, Baxter Int., Fiber optical probe connector forphysiologic measurement devices, Eur. Pat. 0309214, 1989.
73 D. B. Wagner, Becton Dickinson & Co., Method and apparatusfor monitoring glucose, Eur. Pat. 0251475, 1988.
74 J. Q. Brown, R. Srivastava and M. J. McShane, Encapsulation ofglucose oxidase and an oxygen-quenched fluorophore in poly-electrolyte-coated calcium alginate microspheres as opticalglucose sensor systems, Biosens. Bioelectron., 2005, 21, 212–216.
75 J. Q. Brown, R. Srivastava, H. Zhu and M. J. McShane, Enzy-matic Fluorescent Microsphere Glucose Sensors: Evaluation ofResponse Under Dynamic Conditions, Diabetes Technol. Ther.,2006, 8, 288–295.
76 J. Q. Brown and M. J. McShane, Modeling of sphericalfluorescent glucose microsensor systems: Design of enzymaticsmart tattoos, Biosens. Bioelectron., 2006, 21, 1760–1769.
77 S. Nagl, M. I. J. Stich, M. Schaferling and O. S. Wolfbeis,Method for simultaneous luminescence sensing of two speciesusing optical probes of different decay time, and its application toan enzymatic reaction at varying temperature, Anal. Bioanal.Chem., 2009, 393, 1199–1207.
78 M. I. J. Stich, L. H. Fischer and O. S. Wolfbeis, MultipleFluorescent Chemical Sensing and Imaging, Chem. Soc. Rev.,2010, 39, 3102–3114.
79 K. J. Casha and H. A. Clark, Nanosensors and nanomaterials formonitoring glucose in diabetes, Trends Mol. Med., 2010, 16,584–593.
80 H. Xu, J. W. Aylott and R. Kopelman, Fluorescent nano-PEBBLE sensors designed for intracellular glucose imaging,Analyst, 2002, 127, 1471–1477.
81 H. D. Duong and J. I. Rhee, Use of CdSe/ZnS core–shellquantum dots as energy transfer donors in sensing glucose,Talanta, 2007, 73, 899–905.
82 L. M. Rossi, A. D. Quach and Z. Rosenzweig, Glucose oxida-se–magnetite nanoparticle bioconjugate for glucose sensing,Anal. Bioanal. Chem., 2004, 380, 606–613.
83 M. Schaeferling, D. B. M. Groegel and S. Schreml, LuminescentProbes and Nanoparticles for Detection and Imaging of Hydro-gen Peroxide, Microchim. Acta, 2011, DOI: 10.1007/s00604-011-0606-3, in press.
84 M. Wu, Z. Lin, A. Duerkop and O. S. Wolfbeis, Time-resolvedenzymatic determination of glucose using a fluorescent Europiumprobe for hydrogen peroxide, Anal. Bioanal. Chem., 2004, 380,619–626.
85 O. S. Wolfbeis, M. Schaeferling and A. Duerkop, Reversibleoptical sensor membrane for hydrogen peroxide using animmobilized fluorescent probe, and its application to a glucosebiosensor, Microchim. Acta, 2003, 143, 221–227.
86 M. Schaferling, M. Wu and O. S. Wolfbeis, Time-resolvedfluorescent imaging of glucose, J. Fluoresc., 2004, 5, 561–568.
87 T. Chih, H.-J. Jao and C. M. Wang, Glucose sensing based on aneffective conversion of O2 and H2O2 into superoxide anion radicalwith clay minerals, J. Electroanal. Chem., 2005, 581, 159–166.
88 R. Koncki and O. S. Wolfbeis, Composite films of Prussian blueand N-substituted polypyrroles: covalent immobilization ofenzymes and application to near infrared optical biosensing,Biosens. Bioelectron., 1999, 14, 87–92.
4836 Chem. Soc. Rev., 2011, 40, 4805–4839 This journal is c The Royal Society of Chemistry 2011
89 R. Koncki, T. Lenarczuk, A. Radomska and S. Glab, Opticalbiosensors based on Prussian Blue films, Analyst, 2001, 126,1080–1085.
90 T. Lenarczuk, D. Wencel, S. Glab and R. Koncki, Prussian blue-based optical glucose biosensor in flow-injection analysis, Anal.Chim. Acta, 2001, 447, 23–32.
91 T. Endo, R. Ikeda, Y. Yanagida and T. Hatsuzawa, Stimuli-responsive hydrogel–silver nanoparticles composite for develop-ment of localized surface plasmon resonance-based opticalbiosensor, Anal. Chim. Acta, 2008, 611, 205–211.
92 G. Ye, X. Li and X. Wang, Diffraction grating of hydrogelfunctionalized with glucose oxidase for glucose detection,Chem. Commun., 2010, 46, 3872–3874.
93 P. Wu, Y. He, H.-F. Wang and X.-P. Yan, Conjugation ofGlucose Oxidase onto Mn-Doped ZnS Quantum Dots forPhosphorescent Sensing of Glucose in Biological Fluids,Anal. Chem., 2010, 82, 1427–1433.
94 L. Cao, J. Ye, L. Tong and B. Tang, A New Route to theConsiderable Enhancement of Glucose Oxidase (GOx) Activity:The Simple Assembly of a Complex from CdTe Quantum Dotsand GOx, and Its Glucose Sensing, Chem.–Eur. J., 2008, 14,9633–9640.
95 V. Sanz, S. de Marcos and J. Galban, A blood-assisted opticalbiosensor for automatic glucose determination, Talanta, 2009, 78,846–851.
96 L. Yang, X. Ren, X. Meng, H. Li and F. Tang, Optical analysis oflactate dehydrogenase and glucose by CdTe quantum dots andtheir dual simultaneous detection, Biosens. Bioelectron., 2011, 26,3488–3493.
97 W. Trettnak, M. J. P. Leiner and O. S. Wolfbeis, Fibre-opticglucose sensor with a pH optrode as the transducer, Biosensors,1989, 4, 15–26.
98 J. W. Attridge and G. A. Robinson, ARS Holding N. V., Sensorfor optical assay, WO Pat. 9325892, 1993.
99 M. F. McCurley, An optical biosensor using a fluorescent,swelling sensing element, Biosens. Bioelectron., 1994, 9, 527–533.
100 S. A. Piletsky, T. L. Panasyuk, E. V. Piletskaya, T. A. Sergeeva,A. V. El’skaya, E. Pringsheim and O. S. Wolfbeis, Polyaniline-coated microtiter plates for use in longwave optical bioassays,Fresenius’ J. Anal. Chem., 2000, 366, 807–810.
101 K. Tohda and M. Gratzl, Micro-miniature Autonomous OpticalSensor Array for Monitoring Ions and Metabolites 2: ColorResponses to pH, K+ and Glucose, Anal. Sci., 2006, 22, 383–388.
102 S. R. Nayak and M. J. McShane, Fluorescence glucose monitoringbased on transduction of enzymatically-driven pH changes withinmicrocapsules, Sens. Lett., 2006, 4, 433–439.
103 K. Ertekin, S. Cinar, T. Aydemir and S. Alp, Glucose sensingemploying fluorescent pH indicator: 4-[(p-NN-dimethylamino)-benzylidene]-2-phenyloxazole-5-one, Dyes Pigm., 2005, 67, 133–138.
104 R. Doong and H. Shih, Array-based titanium dioxide biosensorsfor ratiometric determination of glucose, glutamate and urea,Biosens. Bioelectron., 2010, 25, 1439–1446.
105 Y. Kim, S. A. Hilderbrand, R. Weissleder and C.-H. Tung, Sugarsensing based on induced pH changes, Chem. Commun., 2007,2299–2301.
106 T. D. James, K. R. A. S. Sandanayake, R. S. Iguchi andS. Shinkai, Novel saccharide-photoinduced electron transfer sen-sors based on the interaction of boronic acid and amine, J. Am.Chem. Soc., 1995, 117, 8982–8987.
107 W. Yang, H. He and D. G. Drueckhammer, Computer-guideddesign in molecular recognition: design and synthesis of a gluco-pyranose receptor, Angew. Chem., Int. Ed., 2001, 40, 1714–1718.
108 H. Eggert, J. Frederiksen, C. Morin and J. C. Norrild, A newglucose selective fluorescent bisboronic acid. First report ofstrong a-furanose complexation in aqueous solution at physio-logical pH, J. Org. Chem., 1999, 64, 3846–3852.
109 D. P. Adhikiri and M. D. Heagy MD, Fluorescent chemosensorsfor carbohydrates which shows large change in chelation-enhanced quenching, Tetrahedron Lett., 1999, 40, 7893–7896.
110 H. Cao, D. I. Diaz, N. DiCesare, J. R. Lakowicz andM. D. Heagy, Monoboronic acid sensor that displays anomalousfluorescence sensitivity to glucose, Org. Lett., 2002, 4, 1503–1505.
111 Z. Cao, P. Nandhikonda and M. D. Heagy, Highly Water-Soluble Monoboronic Acid Probes That Show Optical Sensitivity
to Glucose Based on 4-Sulfo-1,8-naphthalic Anhydride, J. Org.Chem., 2009, 74, 3544–3546.
112 R. Badugu, J. R. Lakowicz and C. D. Geddes, Boronic acidfluorescent sensors for monosaccharide signalling based on the6-methoxyquinolinium heterocyclic nucleus: progress towardnoninvasive and continuous glucose monitoring, Bioorg. Med.Chem., 2005, 13, 113–119.
113 R. Badugu, J. R. Lakowicz and C. D. Geddes, A glucose sensingcontact lens: a non-invasive technique for continuous physio-logical glucose monitoring, J. Fluoresc., 2003, 13, 371–374.
114 R. Badugu, J. R. Lakowicz and C. D. Geddes, Noninvasivecontinuous monitoring of physiological glucose using a mono-saccharide-sensing contact lens, Anal. Chem., 2004, 76, 610–618.
115 O. S. Wolfbeis, I. Klimant, T. Werner, C. Huber, U. Kosch,C. Krause, G. Neurauter and A. Durkop, Set of luminescencedecay time based chemical sensors for clinical applications,Sens. Actuators, B, 1998, 51, 17–24.
116 Z. Murtaza, L. Tolosa, P. Harms and J. R. Lakowicz, On thePossibility of Glucose Sensing Using Boronic Acid and aLuminescent Ruthenium Metal–Ligand Complex, J. Fluoresc.,2002, 12, 187–192.
117 J. R. Lakowicz and Z. Murtaza, Regents of the University ofMaryland, Glucose sensing using metal–ligand complexes,WO Pat. 2000 043536, 2000.
118 J. H. Satcher, A. M. Lane, C. B. Darrow, D. R. Cary andJ. A. Tran, The Regents of the University of California,Medtronic Minimed Inc., Glucose sensing molecules havingselected fluorescent properties, WO Pat. 2001 020334, 2001.
119 J. H. Satcher, A. M. Lane, C. B. Darrow, D. R. Cary andJ. A. Tran, The Regents of the University of California, MinimedInc., Saccharide sensing molecules having enhanced fluorescentproperties, US Pat. 6,673,625, 2004.
120 E. Pringsheim, E. Terpetschnig, S. A. Piletsky and O. S. Wolfbeis,A polyaniline with near-infrared optical response to saccharides,Adv. Mater., 1999, 11, 865–868.
121 S. Arimori, C. Ward and T. D. James, A D-glucose selectivefluorescent assay, Tetrahedron Lett., 2002, 43, 303–305.
122 Q. Wang, G. Li, W. Xiao, H. Qi and G. Li, Glucose-responsivevesicular sensor based on boronic acid-glucose recognition in theARS/PBA/DBBTAB covesicles, Sens. Actuators, B, 2006, 119,695–700.
123 K. Billingsley, M. K. Balaconis, J. M. Dubach, N. Zhang, E. Lim,K. P. Francis and H. A. Clark, Fluorescent Nano-Optodes forGlucose Detection, Anal. Chem., 2010, 82, 3707–3713.
124 Y. Kanekiyo, H. Sato and H. Tao, Saccharide sensing based onsaccharide-induced conformational changes in fluorescent boronicacid polymers, Macromol. Rapid Commun., 2005, 26, 1542–1546.
125 O. S. Wolfbeis, H. Offenbacher, H. Kroneis and H. Marsoner,A Fast Responding Fluorescence Sensor for Oxygen, Mikrochim.Acta, 1984, 82, 153–158.
126 N. DiCesare and J. R. Lakowicz, New Color Chemosensors forMonosaccharides Based on Azo Dyes, Org. Lett., 2001, 3,3891–3893.
127 N. Soh, M. Sonezaki and T. Imato, Modification of a thingold film with boronic acid membrane and its application to asaccharide sensor based on surface plasmon resonance,Electroanalysis, 2003, 15, 1281–1290.
128 D. B. Cordes, A. Miller, S. Gamsey, Z. Sharrett, P. Thoniyot,R. Wessling and B. Singaram, Optical glucose detection acrossthe visible spectrum using anionic fluorescent dyes and a viologenquencher in a two-component saccharide sensing system,Org. Biomol. Chem., 2005, 3, 1708–1713.
129 O. S. Wolfbeis, E. Fuerlinger, H. Kroneis and H. Marsener,A Study on Fluorescent Indicators for Measuring Near Neutral(‘‘Physiological’’) pH-Values, Fresenius’ Z. Anal. Chem., 1983,314, 119–124.
130 S. Gamsey, A. Miller, M. M. Olmstead, C. M. Beavers,L. C. Hirayama, S. Pradhan, R. A. Wessling and B. Singaram,Boronic acid-based bipyridinium salts as tunable receptors formonosaccharides and a-hydroxycarboxylates, J. Am. Chem. Soc.,2007, 129, 1278–1286.
131 A. Schiller, R. A. Wessling and B. Singaram, A fluorescent sensorarray for saccharides based on boronic acid appended bipyridiniumsalts, Angew. Chem., Int. Ed., 2007, 46, 6457–6459.
This journal is c The Royal Society of Chemistry 2011 Chem. Soc. Rev., 2011, 40, 4805–4839 4837
132 J. T. Suri, D. B. Cordes, F. E. Cappuccio, R. A. Wessling andB. Singaram, Continuous glucose sensing with a fluorescent thin-film hydrogel, Angew. Chem., Int. Ed., 2003, 42, 5857–5859.
133 P. Thoniyot, F. E. Cappuccio, S. Gamsey, D. B. Cordes,R. A. Wessling and B. Singaram, Continuous Glucose Sensingwith Fluorescent Thin-Film Hydrogels. 2. Fiber Optic SensorFabrication and In Vitro Testing, Diabetes Technol. Ther., 2006,8, 279–287.
134 F. E. Cappuccio, J. T. Suri, D. B. Cordes, R. A. Wessling andB. Singaram, Evaluation of pyranine derivatives in boronic acidbased saccharide sensing: significance of charge interactionbetween dye and quencher in solution and hydrogel,J. Fluoresc., 2004, 14, 521–533.
135 S. Gamsey, J. T. Suri, R. A. Wessling and B. Singaram,Continuous glucose detection using boronic acid-substitutedviologens in fluorescent hydrogels: linker effects and extensionto fiber optics, Langmuir, 2006, 22, 9067–9074.
136 B. Vilozny, A. Schiller, R. A. Wessling and B. Singaram, Multi-well plates loaded with fluorescent hydrogel sensor for measuringpH and glucose concentration, J. Mater. Chem., 2011, 21,7589–7595.
137 D. R. Markle, J. T. Suri, R. A. Wessling and M. A. Romey,Glumetrics Inc., Optical determination of pH and glucose,WO Pat. 2008 097747, 2008.
138 D. B. Cordes, A. Miller, S. Gamsey and B. Singaram, Simultaneoususe of multiple fluorescent reporter dyes for glucose sensing inaqueous solution, Anal. Bioanal. Chem., 2007, 387, 2767–2773.
139 D. B. Cordes, S. Gamsey and B. Singaram, Fluorescent QuantumDots with Boronic Acid Substituted Viologens To SenseGlucose in Aqueous Solution, Angew. Chem., Int. Ed., 2006, 45,3829–3832.
140 W. Wu, T. Zhou, M. Aiello and S. Zhou, Construction of opticalglucose nanobiosensor with high sensitivity and selectivity atphysiological pH on the basis of organic–inorganic hybrid micro-gels, Biosens. Bioelectron., 2010, 25, 2603–2610.
141 W. Wu, T. Zhou, A. Berliner, P. Banerjee and S. Zhou, Glucose-Mediated Assembly of Phenylboronic Acid Modified CdTe/ZnTe/ZnS Quantum Dots for Intercellular Glucose Probing,Angew. Chem., Int. Ed., 2010, 122, 6704–6708.
142 W. Wu, N. Mitra, E. C. Y. Yan and S. Zhou, MultifunctionalHybrid Nanogel for Integration of Optical Glucose Sensing andSelf-Regulated Insulin Release at Physiological pH, ACS Nano,2010, 4, 4831–4839.
143 L. Wang and Y. Li, Luminescent nanocrystals for nonenzymaticglucose concentration determination, Chem.–Eur. J., 2007, 13,4203–4207.
144 N. DiCesare and J. R. Lakowicz, Evaluation of Two SyntheticGlucose Probes for Fluorescence-Lifetime-Based Sensing,Anal. Biochem., 2001, 294, 154–160.
145 V. V. Karnati, X. Gao, S. Gao, W. Yang, W. Ni, S. Sankar andB. Wang, A glucose-selective fluorescence sensor based on boronicacid–diol interaction, Bioorg. Med. Chem. Lett., 2002, 12, 3373–3377.
146 T. Kawanishi, M. A. Romey, P. C. Zhu, M. Z. Holody andS. Shinkai, A study of boronic acid based fluorescent glucosesensors, J. Fluoresc., 2004, 14, 499–512.
147 T. Kawanishi, Terumo Kabushiki Kaisha, Intracorporealsubstance measuring assembly and application for measuring bloodglucose with a fluorescent indicator, US Pat. 2005 221277, 2005.
148 B. Appleton and T. D. Gibson, Detection of total sugarconcentration using photoinduced electron transfer materials:Development of operationally stable, reusable optical sensors,Sens. Actuators, B, 2000, 65, 302–304.
149 S. Arimori, M. L. Bell, C. S. Oh and T. D. James, A modularfluorescence intramolecular energy transfer saccharide sensor,Org. Lett., 2002, 4, 4249–4251.
150 M. D. Phillips and T. D. James, Boronic acid based modularfluorescent sensors for glucose, J. Fluoresc., 2004, 14, 549–559.
151 Y. Kanekiyo and H. Tao, Selective glucose sensing utilizingcomplexation with fluorescent boronic acid on polycation,Chem. Lett., 2005, 196–197.
152 G. Heinrichs, M. Schellentrager and S. Kubik, An enantio-selective fluorescence sensor for glucose based on a cyclictetrapeptide containing two boronic acid binding sites, Eur. J.Org. Chem., 2006, 18, 4177–4186.
153 S. Trupp, A. Schweitzer and G. J. Mohr, Fluororeactants for thedetection of saccharides based on hemicyanine dyes with aboronic acid receptor, Microchim. Acta, 2006, 153, 127–131.
154 A. M. Heiss, Medtronic Minimed Inc., Analyte sensing viaacridine-based boronate biosensors, US Pat. 2005 0191761, 2005.
155 C. B. Darrow, J. H. Satcher, S. M. Lane and H. J. Gable, TheRegents of the University of California, Fluorescent lifetimeassays for non-invasive quantification of analytes such as glucose,WO Pat. 2001 075450, 2001.
156 B. Peng and Y. Qin, Lipophilic polymer membrane optical sensorwith a synthetic receptor for saccharide detection, Anal. Chem.,2008, 80, 6137–6141.
157 X. Yang, M.-C. Lee, F. Sartain, X. Pan and C. R. Lowe,Designed Boronate Ligands for Glucose-Selective HolographicSensors, Chem.–Eur. J., 2006, 12, 8491–8497.
158 G. J. Worsley, G. A. Tourniaire, K. E. S. Medlock, F. K. Sartain,H. E. Harmer, M. Thatcher, A. M. Horgan and J. Pritchard,Continuous blood glucose monitoring with a thin-film opticalsensor, Clin. Chem., 2007, 53, 1820–1826.
159 X. Yang, X. Pan, J. Blyth and C. R. Lowe, Towards the real-timemonitoring of glucose in tear fluid: Holographic glucose sensorswith reduced interference from lactate and pH, Biosens. Bioelectron.,2008, 23, 899–905.
160 S. Kabilan, A. J. Marshall, F. K. Sartain, M.-C. Lee, A. Hussain,X. Yang, J. Blyth, N. Karangu, K. James, J. Zeng, D. Smith,A. Domschke and C. R. Lowe, Holographic glucose sensors,Biosens. Bioelectron., 2005, 20, 1602–1610.
161 S. Kabilan, J. Blyth, M. C. Lee, A. J. Marshall, A. Hussain,X.-P. Yang and C. R. Lowe, Glucose-sensitive holographicsensors, J. Mol. Recognit., 2004, 17, 162–166.
162 S. A. Asher, V. L. Alexeev, A. V. Goponenko, A. C. Sharma,I. K. Lednev, C. S. Wilcox and D. N. Finegold, Photonic CrystalCarbohydrate Sensors: Low Ionic Strength Sugar Sensing, J. Am.Chem. Soc., 2003, 125, 3322.
163 J. H. Holtz and S. A. Asher, Nature, 1997, 389, 829.164 V. L. Alexeev, A. C. Sharma, A. V. Goponenko, S. Das,
I. K. Lednev, C. S. Wilcox, D. N. Finegold and S. A. Asher,High Ionic Strength Glucose-Sensing Photonic Crystal,Anal. Chem., 2003, 75, 2316–2323.
165 M. Ben-Moshe, V. L. Alexeev and S. A. Asher, Anal. Chem.,2006, 78, 5149.
166 M. M. Ward Muscatello, L. E. Stunja and S. A. Asher,Polymerized Crystalline Colloidal Array Sensing of High GlucoseConcentrations, Anal. Chem., 2009, 81, 4978–4986.
167 Y. J. Lee, S. A. Pruzinsky and P. V. Braun, Langmuir, 2004,20, 3096.
168 S. Tierney, B. M. H. Falch, D. R. Hjelme and B. T. Stokke,Determination of Glucose Levels Using a FunctionalizedHydrogel-Optical Fiber Biosensor: Toward Continuous Monitoringof Blood Glucose in vivo, Anal. Chem., 2009, 81, 3630–3636.
169 S. Tierney, S. Volden and B. T. Stokke, Glucose sensors based ona responsive gel incorporated as a Fabry–Perot cavity on a fiber-optic readout platform, Biosens. Bioelectron., 2009, 24,2034–2039.
170 D. Meadows and J. S. Schultz, Fiber-optic biosensors based onfluorescence energy transfer, Talanta, 1988, 35, 145–150.
171 J. S. Schultz, The United States of America represented by theDept of Health, Optical sensor for blood plasma constituents,US Pat. 4344438, 1980.
172 J. S. Schultz, S. Mansouri and I. J. Goldstein, Affinity sensor: anew technique for developing implantable sensors for glucose andother metabolites, Diabetes Care, 1982, 5, 245–253.
173 S. Mansouri and J. S. Schultz, A Miniature Optical GlucoseSensor Based on Affinity Binding, Nat. Biotechnol., 1984, 2,885–890.
174 R. Ballerstadt, C. Evans, R. McNichols and A. Gowda,Concanavalin A for in vivo glucose sensing: A biotoxicity review,Biosens. Bioelectron., 2006, 22, 275–284.
175 R. Ballerstadt and J. S. Schultz, A Fluorescence Affinity HollowFiber Sensor for Continuous Transdermal Glucose Monitoring,Anal. Chem., 2000, 72, 4185–4192.
176 R. Ballerstadt, A. Polak, A. Beuhler and J. Frye, In vitro long-term performance study of a near-infrared fluorescence affinitysensor for glucose monitoring, Biosens. Bioelectron., 2004, 19,905–914.
4838 Chem. Soc. Rev., 2011, 40, 4805–4839 This journal is c The Royal Society of Chemistry 2011
177 R. Ballerstadt, C. Evans, A. Gowda and R. McNichols, In VivoPerformance Evaluation of a Transdermal Near-InfraredFluorescence Resonance Energy Transfer Affinity Sensor forContinuous Glucose Monitoring, Diabetes Technol. Ther., 2006,8, 296–311.
178 J. S. Kristensen, K. Gregorius, C. Struve, J. M. Frederiksen andY. Yu, Precisense, Sensor for detection of carbohydrate,WO Pat.2006 061207, 2006.
179 D. Meadows and J. S. Schultz, Design, manufacture andcharacterization of an optical fiber glucose affinity sensor basedon an homogeneous fluorescence energy transfer assay system,Anal. Chim. Acta, 1993, 280, 21–30.
180 L. Tolosa, H. Malak, G. Rao and J. R. Lakowicz, Optical assayfor glucose based on the luminescence decay time of the longwavelength dye Cy5, Sens. Actuators, B, 1997, 45, 93–99.
181 L. Tolosa, H. Szmacinski, G. Rao and J. R. Lakowicz, Lifetime-Based Sensing of Glucose Using Energy Transfer with a LongLifetime Donor, Anal. Biochem., 1997, 250, 102–108.
182 R. J. Russell, M. V. Pishko, C. C. Gefrides, M. J. McShane andG. L. Cote, A Fluorescence-Based Glucose Biosensor UsingConcanavalin A and Dextran Encapsulated in a Poly(ethyleneglycol) Hydrogel, Anal. Chem., 1999, 71, 3126–3132.
183 G. L. Cote, M. V. Pishko, K. Sirkar, R. Russell andR. R. Anderson, The Texas A&M University System, TheGeneral Hospital Corporation, Compositions and methods foranalyte detection, US Pat. 6485703, 2002.
184 W. March, Novartis AG, Apparatus for measuring blood glucoseconcentrations, WO Pat. 2002 087429, 2002.
185 B. Petersson and A. Weber, Precisense, Optical sensor for in situmeasurement of analytes, WO Pat. 2002 030275, 2002.
186 L. J. McCartney, J. C. Pickup, O. J. Rolinski and D. J. S. Birch,Near-infrared fluorescence lifetime assay for serum glucose basedon allophycocyanin labelled concanavalin A, Anal. Biochem.,2001, 292, 216–221.
187 S. Chinnayelka and M. J. McShane, Glucose-Sensitive Nano-assemblies Comprising Affinity-Binding Complexes Trapped inFuzzy Microshells, J. Fluoresc., 2004, 14, 585–595.
188 B. M. Cummins, J. Lim, E. E. Simanek, M. V. Pishko andG. L. Cote, Encapsulation of a concanavalin A/dendrimerglucose sensing assay within microporated poly(ethylene glycol)microspheres, Biomed. Opt. Express, 2011, 2, 1243–1257.
189 I. S. Han, S. Lew and M. H. Han, M-Biotech Inc., Photometricglucose measurement system using glucose-sensitive hydrogel,US Pat. 6,835,553 B2, 2004.
190 K. Y. Cheung, W. C. Mak and D. Trau, Reusable optical bioassayplatform with permeability-controlled hydrogel pads for selectivesaccharide detection, Anal. Chim. Acta, 2008, 607, 204–210.
191 K.-C. Liao, T. Hogen-Esch, F. J. Richmond, L. Marcu,W. Clifton and G. E. Loeb, Percutaneous fiber-optic sensor forchronic glucose monitoring in vivo, Biosens. Bioelectron., 2008, 23,1458–1465.
192 K.-C. Liao, S.-C. Chang, C.-Y. Chiu and Y.-H. Chou, AcuteResponse in vivo of a Fiber-Optic Sensor for Continuous GlucoseMonitoring from Canine Studies on Point Accuracy, Sensors,2010, 10, 7789–7802.
193 B. Tang, L. Cao, K. Xu, L. Zhuo, J. Ge, Q. Li and L. Yu, A NewNanobiosensor for Glucose with High Sensitivity and Selectivityin Serum Based on Fluorescence Resonance Energy Transfer(FRET) between CdTe Quantum Dots and Au Nanoparticles,Chem.–Eur. J., 2008, 14, 3637–3644.
194 J. Zhang, D. Roll, C. D. Geddes and J. R. Lakowicz, Aggregationof Silver Nanoparticle–Dextran Adducts with Concanavalin Aand Competitive Complexation with Glucose, J. Phys. Chem. B,2004, 108, 12210–12214.
195 K. Aslana, J. R. Lakowicz and C. D. Geddes, Tunable plasmonicglucose sensing based on the dissociation of Con A-aggregateddextran-coated gold colloids, Anal. Chim. Acta, 2004, 517,139–144.
196 K. Aslana, J. R. Lakowicz and C. D. Geddes, Nanogold-plasmon-resonance-based glucose sensing, Anal. Biochem., 2004,330, 145–155.
197 K. Aslan, J. R. Lakowicz and C. D. Geddes, Nanogold PlasmonResonance-Based Glucose Sensing. 2. Wavelength-RatiometricResonance Light Scattering, Anal. Chem., 2005, 77, 2007–2014.
198 R. Ballerstadt, A. Kholodnykh, C. Evans, A. Boretsky,M. Motamedi, A. Gowda and R. McNichols, Affinity-BasedTurbidity Sensor for Glucose Monitoring by Optical CoherenceTomography: Toward the Development of an ImplantableSensor, Anal. Chem., 2007, 79, 6965–6974.
199 R. Ballerstadt, R. McNichols and A. Gowda, BioTex Inc.,System, device and method for determining the concentrationof an analyte, US Pat. 7236812, 2007.
200 P. W. Barone and M. S. Strano, Reversible Control of CarbonNanotube Aggregation for a Glucose Affinity Sensor, Angew.Chem., Int. Ed., 2006, 108, 8318–8321.
201 P. W. Barone and M. S. Strano, The use of single-walled carbonnanotubes for optical glucose detection, Chem. Anal., 2010, 174,317–329.
202 S. D’Auria, P. Herman, M. Rossi and J. R. Lakowicz, TheFluorescence Emission of the Apo-glucose Oxidase fromAspergillus niger as Probe to Estimate Glucose Concentrations,Biochem. Biophys. Res. Commun., 1999, 263, 550–553.
203 J. R. Lakowitz and S. D’auria, Regents of the University ofMaryland, Baltimore, Inactive enzymes as non-consumingsensors, WO Pat. 2001 018237, 2001.
204 S. D’Auria, N. Di Cesare, Z. Gryczynski, I. Gryczynski, M. Rossiand J. R. Lakowicz, A Thermophilic Apoglucose Dehydrogenaseas Nonconsuming Glucose Sensor, Biochem. Biophys. Res.Commun., 2000, 274, 727–731.
205 S. Chinnayelka and M. J. McShane, Resonance Energy TransferNanobiosensors Based on Affinity Binding between Apo-GOxand Its Substrate, Biomacromolecules, 2004, 5, 1657–1661.
206 S. Chinnayelka and M. J. McShane, Microcapsule BiosensorsUsing Competitive Binding Resonance Energy Transfer AssaysBased on Apoenzymes, Anal. Chem., 2005, 77, 5501–5511.
207 S. Chinnayelka and M. J. McShane, Glucose Sensors Based onMicrocapsules Containing an Orange/Red Competitive BindingResonance Energy Transfer Assay, Diabetes Technol. Ther., 2006,8, 269–278.
208 S. Chinnayelka, H. Zhu and M. J. McShane, Near-InfraredResonance Energy Transfer Glucose Biosensors in HybridMicrocapsule Carriers, J. Sensors, 2008, 2008, 1–11.
209 P. W. Barone, H. Yoon, R. Ortiz-Garcia, J. Zhang, J.-H. Ahn,J.-H. Kim and M. S. Strano, Modulation of Single-WalledCarbon Nanotube Photoluminescence by Hydrogel Swelling,ACS Nano, 2009, 3, 3869–3877.
210 M. de Champdore, M. Staiano, V. Aurilia, O. V. Stepanenko,A. Parracino, M. Rossi and S. D’Auria, Thermostable Proteins asProbe for the Design of Advanced Fluorescence Biosensors, Rev.Environ. Sci. Biotechnol., 2006, 5, 233–242.
211 A. Sakaguchi-Mikami, A. Taneoka, R. Yamoto, S. Ferri andK. Sode, Engineering of ligand specificity of periplasmicbinding protein for glucose sensing, Biotechnol. Lett., 2008, 30,1453–1460.
212 J. S. Marvin and H. W. Hellinga, Engineering Biosensors byIntroducing Fluorescent Allosteric Signal Transducers: Constructionof a Novel Glucose Sensor, J. Am. Chem. Soc., 1998, 120, 7–11.
213 H. W. Hellinga, Duke University, Biosensor, US Pat. 6277627,1998.
214 R. W. Jacobson, K. Weidemaier, J. Alarcon, C. Herdman andS. Keith, Becton Dickinson and Co., Fiber optic device for sensinganalytes and method of making same, US Pat. 2005/0113658 A1,2005.
215 J. B. Pitner, Becton Dickinson and Co., Long wavelength thiol-reactive fluorophores, US Pat. 2006/0280652 A1, 2006.
216 K. J. Thomas, D. B. Sherman, T. J. Amiss, S. A. Andaluz andJ. B. Pitner, A Long-Wavelength Fluorescent Glucose BiosensorBased on Bioconjugates of Galactose/Glucose Binding Proteinand Nile Red Derivatives, Diabetes Technol. Ther., 2006, 8,261–268.
217 Y. Tian, M. J. Cuneo, A. Changela, B. Hocker, L. S. Beese andH. W. Hellinga, Structure-based design of robust glucose biosen-sors using a Thermotoga maritima periplasmic glucose-bindingprotein, Protein Sci., 2007, 16, 2240–2250.
218 T. J. Amiss, E. M. Gill and D. B. Sherman, Becton Dickinson andCo., Thermostable proteins and methods of making and usingthereof, US Pat. 2008/0044856 A1, 2008.
This journal is c The Royal Society of Chemistry 2011 Chem. Soc. Rev., 2011, 40, 4805–4839 4839
219 A. Lastovich, J. Hartsell, J. Alarcon, G. Vonk and B. C. Roberts,Becton Dickinson and Co., Biosensors for measuring analytes inthe interstitial fluid, US Pat. 2008/0275318 A1, 2008.
220 F. Khan, L. Gnudi and J. C. Pickup, Fluorescence-based sensingof glucose using engineered glucose/galactose-binding protein:A comparison of fluorescence resonance energy transfer andenvironmentally sensitive dye labelling strategies, Biochem. Biophys.Res. Commun., 2008, 365, 102–106.
221 F. Khan, T. E. Saxl and J. C. Pickup, Fluorescence intensity- andlifetime-based glucose sensing using an engineered high-Kd
mutant of glucose/galactose-binding protein, Anal. Biochem.,2010, 399, 39–43.
222 L. Tolosa, I. Gryczynski, L. R. Eichhorn, J. D. Dattelbaum,F. N. Castellano, G. Rao and J. R. Lakowicz, Glucose Sensorfor Low-Cost Lifetime-Based Sensing Using a GeneticallyEngineered Protein, Anal. Biochem., 1999, 267, 114–120.
223 J. R. Lakowicz, L. Tolosa, L. Eichhorn and R. Govind,Engineered proteins for analyte sensing, US Pat. 6197534, 1999.
224 J. R. Lakowicz, I. Gryczynski, Z. Gryczynski and J. D.Dattelbaum, Regents of the University of Maryland, Baltimore,Anisotropy based sensing, WO Pat. 2000 028327, 2000.
225 X. Ge, L. Tolosa and G. Rao, Dual-Labeled Glucose BindingProtein for Ratiometric Measurements of Glucose, Anal. Chem.,2004, 76, 1403–1410.
226 V. Scognamiglio, V. Aurilia, N. Cennamo, P. Ringhieri, L. Iozzino,M. Tartaglia, M. Staiano, G. Ruggiero, P. Orlando, T. Labella,L. Zeni, A. Vitale and S. D’Auria, D-galactose/D-glucose-bindingProtein from Escherichia coli as Probe for a Non-consuming GlucoseImplantable Fluorescence Biosensor, Sensors, 2007, 10, 2484–2491.
227 H. V. Hsieh, J. B. Pitner, T. J. Amiss, C. M. Nyez, D. B. Shermanand D. J. Wright, Binding proteins as biosensors, US Pat. 2007/0281368 A1, 2007.
228 B. S. Der and J. D. Dattelbaum, Construction of a reagentlessglucose biosensor using molecular exciton luminescence,Anal. Biochem., 2008, 375, 132–140.
229 K. Ye and J. S. Schultz, Genetic Engineering of an AllostericallyBased Glucose Indicator Protein for Continuous GlucoseMonitoring by Fluorescence Resonance Energy Transfer,Anal. Chem., 2003, 75, 3451–3459.
230 S. Jin, J. V. Veetil, J. R. Garrett and K. Ye, Construction of apanel of glucose indicator proteins for continuous glucosemonitoring, Biosens. Bioelectron., 2011, 26, 3427–3431.
231 M. Fehr, S. Lalonde, I. Lager, M. W. Wolff and W. B. Frommer,In vivo imaging of the dynamics of glucose uptake in the cytosol ofCOS-7 cells by fluorescent nanosensors, J. Biol. Chem., 2003, 278,19127–19133.
232 S. A. John, M. Ottolia, J. N. Weiss and B. Ribalet, Dynamicmodulation of intracellular glucose imaged in single cells usingFRET-based glucose nanosensor, Pfluegers Arch.–Eur. J. Physiol.,2008, 456, 307–322.
233 Y. Gross and T. Hyman, Glusense Ltd., Implantable Sensor,WO Pat. 2007 110867, 2007.
234 J. Siegrist, T. Kazarian, C. Ensor, S. Joel, M. Madou, P. Wangand S. Daunert, Continuous glucose sensor using novelgenetically engineered binding polypeptides towards in vivoapplications, Sens. Actuators, B, 2010, 149, 51–58.
235 J. B. Pitner, Becton Dickinson and Co., Binding protein asbiosensors, US Pat. 7,064,103 B2, 2006.
236 J. B. Pitner, Becton Dickinson and Co., Binding protein asbiosensors, US Pat. 7,316,909 B2, 2008.
237 J. B. Pitner, H. V. Hsieh and J. E. Gestwicki, Becton Dickinsonand Co., Detection of ligands by refractive surface methods,Eur. Pat. 1 209 468 B1, 2006.