research article a covalently imprinted photonic crystal for glucose...

Hindawi Publishing CorporationJournal of NanomaterialsVolume 2013 Article ID 530701 6 pageshttpdxdoiorg1011552013530701

Research ArticleA Covalently Imprinted Photonic Crystal for Glucose Sensing

Fei Xue Ting-rui Duan Shu-yue Huang Qiu-hong Wang Min Xue and Zi-hui Meng

School of Chemical Engineering and Environment Beijing Institute of Technology Beijing 100081 China

Correspondence should be addressed to Zi-hui Meng m zihuiyahoocom

Received 27 April 2013 Revised 9 June 2013 Accepted 9 June 2013

Academic Editor Amir Kajbafvala

Copyright copy 2013 Fei Xue et al This is an open access article distributed under the Creative Commons Attribution License whichpermits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

We demonstrate a glucose-sensing material based on the combination of photonic crystal templating and a molecular-imprintingtechnique In the presence of the target molecule glucose poly(N-isopropylacrylamide-co-2-hydroxyethyl methacrylate) hydrogelwith pendent phenylboronic acid groups was synthesized in the void of a poly(methyl methacrylate) (PMMA) colloidal crystalAfter removing the PMMA photonic crystal template and glucose molecules a 3D-ordered porous covalently imprinted photoniccrystal (CIPC) hydrogel was created The unique 3D-ordered porous hydrogel revealed optical changes in response to glucoseconcentration At pH = 11 and 37∘C the diffraction of CIPC redshifted from 725 nm to 880 nm in response to 20mmol Lminus1 glucoseDue to the covalently imprinted recognizer boronic acid group the selectivity of the CIPC towards glucose over D-ribose andL-rhamnose was improved significantly

1 Introduction

Theprevalence of type 1 diabetes continues to increase world-wide Real-time continuous glucose monitoring (RT-CGM)is crucial for diabetic care which can lead to better treatmentdecisions improve metabolic control and decrease the inci-dence and progression of diabetic complications [1ndash6] Forthis reason many different analytical methods for RT-CGMhave been developed which are mainly electrochemical [7ndash9] and optical [3 10 11] Photonic crystals are highly orderedmaterials with periods on the scale of visible light and exhibitunique structural color on the basis of Bragg diffraction andlattice spacing It is found that the diffraction wavelengthof photonic crystals is dependent on their lattices Variousapproaches have been explored for making bioresponsivephotonic crystal hydrogels for glucose sensing Honda et aldeveloped a totally synthetic colorimetric glucose-sensingsystem composed of glucose-responsive hydrogel particlesin an inverse opal polymer membrane [12] The volume ofthe hydrogel particles can change reversibly as the glucoseconcentration varies and exhibits a reversible change inthe color and the peak intensity of the reflection spectraAsherrsquos group has also made remarkable contributions toglucose-responsive photonic crystals They incorporated acrystalline colloidal array (CCA) into a polyacrylamide [13]

or poly(vinyl alcohol) [14] hydrogel with pendent boronicacid groups and the polymerized crystalline colloidal array(PCCA) diffraction wavelength was dependent on the hydro-gel volume [15] Bazin and Zhu prepared core-shell micro-spheres and assembled them into a crystalline colloidal array(CCA) [3] The core-shell microspheres were functionalizedwith 3-aminophenylboronic acid to make them responsiveto glucose More recently Ayyub et al investigated one-dimensional photonic crystals as a sensitive carbohydratesensor by modifying polystyrene-b-poly(2-vinyl pyridine)films with 2-(bromomethyl)phenylboronic acid [11] Besidesboronic acid glucose oxidase (GOx) was also attached to thePCCA and glucose caused the PCCA to swell and redshiftthe diffraction wavelength [16] Although photonic crystalsnow attract more and more attention their selectivity is notpromising Immobilization of enzymes might improve theselectivity but natural receptors usually deteriorate quicklydue to the variation of temperature pH humidity and toxicchemicals

Molecular imprinting is a state-of-the-art technique toartificially mimic natural and biological receptors [17 18]Molecularly imprinted polymers (MIPs) have several advan-tages including stability under harsh physical and chemicalconditions easy preparation and more importantly theability to be ldquotailoredrdquo recognition materials for the target

2 Journal of Nanomaterials

analytes MIPs have attracted considerable attention as arecognition element with high selectivity for glucose sensorsChen et al reported an MIP that could be used to measureglucose concentrations in complex biological media At alka-line pH themetal-complexing polymer ldquocatchesrdquo glucose andinstantly releases protons in proportion to the glucose con-centration over a clinically relevant range (0 to 25mmol Lminus1)[19] Malitesta et al electropolymerized a glucose-imprintedpoly(O-phenylenediamine) polymer which was employed asthe recognition element of a QCM biomimetic sensor forglucose [20] Wursquos group designed a kind of molecularlyimprinted hybrid microgels that can optically monitor glu-cose levels with high sensitivity and selectivity in complexmedia at physiological pH [21] Recently Lirsquos group coupledmolecular imprinting with photonic crystal to create self-reporting specific sensors to detect protein medicines andsome biomarkers [22ndash25] However specificity cannot beguaranteed by traditional noncovalent imprinting protocoland in most cases the diffraction shifts are not remarkableWe here report on a covalently imprinted photonic crystal(CIPC) for glucose sensing The use of boronic acid deriva-tives to sense diol-containing substances has been exploitedfor a long time Boronic acid can bind cis diol-containing sub-stances through covalent bonds Our CIPC glucose-sensinghydrogel also utilized boronic acid groups as recognitionelements In order to improve the selectivity of photoniccrystal sensor covalently imprinting was introduced into thephotonic crystal hydrogel Boronic acid derivatives have beenpolymerized in the presence of glucose to create imprintedglucose-binding sites Polymer hydrogel volume changescould be actuated by boronic acid-glucose complexationTheCIPC volume changes alter the photonic crystal spacingwhich alters the Bragg diffraction condition

2 Materials and Methods

21 Materials Acrylamide (AM) acrylic acid (AA) 221015840-azobisisoheptonitrile (ABVN) 2-hydroxyethyl methacrylate(HEMA) N-isopropylacrylamide (NIPA) 22-diethoxyac-etophenone (DEAP) 4-ethylene phenylboronic acid (4-EPBA) and NN1015840-methylenebisacrylamide (BIS) were allpurchased from Tokyo Chemical Industry (Tokyo Japan)Methyl methacrylate (MMA) glycine glucose D-riboseL-rhamnose acetonitrile dimethyl sulfoxide (DMSO) andacetonitrile were all from local suppliers and were useddirectly

22 Instruments The diffraction spectra were detected usingan Avaspec-2048TEC optical fiber spectrometer (AvantesNetherlands) UV polymerization was carried out in aSCIENTZ D3-IIUV cross-linker (Ning Bo China) Theassembling of PMMA colloidal crystal was carried out ina Safe HWS-150 incubator (Ning Bo China) SEM imageswere taken using a HITACHI S4800 field emission scanningelectron microscope (Tokyo Japan) with an acceleratingvoltage of 15 kV A Shimadzu LC-20AT HPLC system on aPromosil silica column (46 times 250mm Agela TechnologiesTianjing China) with an evaporative light-scattering detector

500 nm

Figure 1 SEM image of the PMMA colloidal crystal

(ELSD)was used to quantitatively characterize the imprintingeffect of MIPs The mobile phase was acetonitrilewater (21vv) with a flow rate of 1mLminminus1 and the injection volumewas 20120583L

23 Preparation of PMMA Colloidal Crystal Poly(methylmethacrylate) (PMMA) monodispersed colloidal particles(280 nm) were synthesized using a modification of pub-lished methods [26 27] MMA (30mL) and deionized water(250mL) were mixed in a 4-neck flask at 80∘C stirred at300 rminminus1 and bubbledwith nitrogenAfter equilibrating to80∘C 15mL water containing 06 g potassium persulfate wasadded to the flask to initiate polymerization MonodispersePMMA particles with a diameter of approximately 280 nmwere obtained after 40 minutes (Figure 1) The resultingparticles were washed by centrifugation and rinsed at leastthree times with deionized water

The PMMA colloids were self-assembled into colloidalcrystals via a vertical deposition method as a template ofthe opal structure Typically glass slides were immergedin H2SO4H2O2mixture (7 3 VV) for 12 h then rinsed

with deionized water in ultrasonic bath three times anddried before use Mono-disperse PMMA particles were fullydispersed in deionized water (025ndash035 ww) whichwere added to a clean Petri dish for the colloidal crystalformation Clean glass slides were placed vertically intothe Petri dish for colloidal crystal growth After completevolatilization of the deionized water a colloidal crystal ofPMMAparticles was formed on both sides of each glass slide

24 Preparation of CIPC Films Three MIPs pre-polym-erization solutions each with different recipes (see Table 1)were prepared Take MIPs recipe (B) for instance glu-cose (017mmol) covalent functional monomer 4-APBA(017mmol) backbone monomers HEMA (15mmol) andNIPA (15mmol) were dissolved into a mixture of 15mLDMSO Then crosslinker BIS (0254mmol) and initiatorABVN (1268 120583mol) were added and the mixture was fullydeoxygenated by nitrogen purging for 10min The prepoly-merization solution was layered carefully on the PMMAphotonic crystal template so that it can infiltrate into the CCAand then polymerize at 60∘C to form hydrogel film The filmwas immersed into acetone to remove the PMMA photoniccrystal template followed by the removal of glucose by acidic

Journal of Nanomaterials 3

Table 1 Composition of different MIPs prepolymerization solutions

MIPs Template(mmol)

Monomers(mmol)

Crosslinker(mmol)

Initiator(mmol)

Solvent(mL) Polymerization

A Glucose (07) 4-EPBA (07) + AM(14) + HEMA (14) BIS (00162) DEAP (005) Acetonitrile (2) UV irradiation 4∘C

B Glucose (017) 4-EPBA (017) + NIPA(15) + HEMA (15) BIS (0254) ABVN (001) DMSO (1) 60∘C

C Glucose (017) 4-EPBA (017) +HEMA (15) BIS (0317) DEAP (05) Acetonitrile (3) UV irradiation 4∘C

500 nm

Figure 2 SEM image of the macroporous structure of the CIPCfilm

solution to give the CIPChydrogel A nonimprinted photoniccrystal (NIPC) was prepared in the same procedure in theabsence of glucose

The three CIPC films were dried in a vacuum oven overnight and then were exposed to glucose to evaluate theiradsorption capability and selectivity Typically glucose solu-tions (20mmol Lminus1) prepared in 1mL methanoldeionizedwater (6 4 vv) were incubated with 10mg CIPC filmfor 1 h at room temperature After incubation the residualconcentration of glucose in the solution was determined byHPLC

3 Results and Discussion

Figure 1 shows the SEM images of the used PMMA colloidalcrystal in which the PMMA particle size is about 280 nmFrom Figure 1 we can see that the PMMA colloidal crystalhas high ordering After removing the PMMA photoniccrystal template highly orderedmacroporous structure couldbe observed using SEM (Figure 2) More importantly theordering of themacroporous structure was kept well In orderto optimize the recipe of covalently imprinted molecules wetried three different recipesThe adsorption rates of the threekinds of MIPs in 20mmol Lminus1 glucose were measured viaHPLC It was revealed in Figure 3 that even though recipeMIPs(A) and MIPs(C) had better adsorption rates recipeMIPs(B) had better imprinting effect among the three MIPsAs a result we chose recipe MIPs(B) to study the followingabsorption and sensing properties of the CIPC

Boronic acid is a classic saccharide receptor [28 29]which can form reversible covalent bonds with glucoseHerein 4-EPBA which contains a boronic acid functional

100

MIPs

80

NIPs

60

Adso

rptio

n ra

te (

)

40

20

0A B C

Figure 3 Adsorptivity of the MIPs of different recipes

Adso

rptio

n ra

te (

)

0

10

20

30

40

50

60

70

80

0 2 4 6 8 10 12 14 16t (min)

pH = 64

pH = 8

pH = 96

pH = 11

Figure 4 Adsorptivity of the CIPC towards 10mmol Lminus1 glucoseunder different pH

group was used as the covalent recognizer which formsboronate with glucose The formation of boronate is depen-dent on pH ionic strength and temperature Thus a glu-cose sensor should work in an optimal environment Theadsorptivity of CIPC was measured by exposure to varyingconcentrations of glucose (0 to 20mmol Lminus1) followed bythe detection of glucose in the residual solution using HPLC

4 Journal of NanomaterialsAd

sorp

tion

rate

()

60

70

80

90

100

50 100 150NaCl (mM)

CMIPCNIPC

Figure 5 Adsorptivity of the CIPC towards 10mmol Lminus1 glucoseunder different ion strength

Adso

rptio

n ra

te (

)

0

5

10

15

20

25

25 37

Temperature (∘C)CMIPCNIPC

Figure 6 Adsorptivity of the CIPC towards 10mmol Lminus1 glucose atroom temperature and body temperature

Figure 4 shows that the adsorption kinetics of glucose onCIPC in different pH condition As shown in Figure 4 withinabout 3 minutes soaking in a solution of 10mmol Lminus1 glucosethe adsorption already reaches the adsorption equilibriumThe presence of macropores provides high specific surfacearea more interaction sites and can also offer increasedmass transport In addition the response of the sensor toglucose decreases as the pH increases The adsorptivity of10mmol Lminus1 glucose at pH 11 is 5 times higher than that ofat pH 64 An alkaline environment is favorable for boronateformation between glucose and 4-EPBA

The adsorptivity of glucose to the CIPC also increaseswith increasing ionic strength (Figure 5) The effects oftemperature on glucose sensing were also investigated bymeasuring the adsorptivity at room temperature and bodytemperature The result in Figure 6 revealed that the CIPChad better selectivity at 37∘C than at 25∘C The sensitivity is

considerably better at body temperature which is beneficialfor the detection of glucose in bodily fluid In short the CIPCcan characteristically detect glucose under alkaline condi-tions at high ionic strength and human body temperatureWith regard to the imprinting effect even though the NIPCalso contains substantial amount of 4-EPBA that enables theNIPC to absorb significant amount of glucose the imprintingprocess gave molecular ldquomemoryrdquo to the hydrogel matrixThis gives the CIPC not only the 4-EPBA covalent recognizerbut also the imprinted pockets that possess molecular ldquomem-oryrdquo for glucose Therefore the CIPC absorbs more glucosethanNIPC For 10mmol Lminus1 glucose at pH 11 the absorptivityof theCIPC ismore than 3 times higher than that of theNIPC

The CIPC swelled upon glucose adsorption at physiolog-ical ionic strengths As seen in Figure 7(a) in the absence ofglucose the CIPC diffracts visible light at 725 nm and thediffraction redshifted gradually upon the addition of glucoseWhen the glucose concentration reached 20mmol Lminus1 whichis clinically indicative of serious diabetes the CIPC diffractsvisible light at 880 nm giving a redshift of 155 nm In thecase of NIPC a redshift of less than 60 nm was observed(Figure 7(b)) After adsorption of glucose a charged complexforms between phenylboronic acid and the 12-cis-diol groupof glucose and the lattice of the CIPC hydrogel swells whichresults in the diffraction redshift This swelling of the CIPCis reversible In addition to adsorptivity the specificity of thehydrogel towards glucose was also improved significantly byimprinting Compared with the NIPC which had ratios ofredshift of glucoseribose and glucoserhamnose of 16 thecorresponding ratios for CIPCwere 30 (Figure 8) suggestingthat a higher selectivity towards glucose was achieved due toimprinting

4 Conclusion

In summary a glucose-responsive photonic crystal hydrogelwas produced by synthesized hydrogel in the void of PMMAphotonic crystal template followed by removing the tem-plate Molecular imprinting improved the selectivity of thephotonic crystal-responsive hydrogel towards glucose Thediffraction of the CIPC red-shifted from 725 nm to 880 nm inresponse to 20mmol Lminus1 glucose Improvement of the currentCIPC technology is still underway which aims to optimizethe CIPC composition to make the diffraction visible thusallowing promising clinical application in noninvasive real-time glucose monitoring

Conflict of Interests

None of the authors has ever had direct or indirect financialrelations with the commercial identities mentioned in thepaper nor do they declare any other conflict of interests

Acknowledgments

This research was supported by NSFC project (20775007)The authors thank Gregory Morgan from Department of


1 mM 5 mM 10 mM20 mM

0 mM

Refle

ctan

ce (

)

650 700 750 800 850 900 950 1000Wavelength (nm)

(a)

200

CIPC

150

NIPC

100

Red

shift

(nm

)

50

00 5 10 15 20

Glucose (mM)

(b)

Figure 7 Redshift of CIPC (a) and the difference in redshift of CIPC and NIPC (b) in response to glucose CIPC and NIPC were immersedin glucose solution of different concentration at pH 11 150mmol Lminus1 ion strength and 37∘C

4

CIPCNIPC

3

2

1

0Glucoseribose GlucoseL-rhamnose

Figure 8 Ratio of the redshift between glucose and other saccha-rides for the CIPC and the NIPC

Chemistry University of Pittsburgh for his useful commentsand language editing which have greatly improved the paper

References

[1] S L Ellis R G Naik K Gemperline and S K Garg ldquoUse ofcontinuous glucosemonitoring in patients with type 1 diabetesrdquoCurrent Diabetes Reviews vol 4 no 3 pp 207ndash217 2008

[2] C M Girardin C Huot M Gonthier and E Delvin ldquoContin-uous glucose monitoring a review of biochemical perspectivesand clinical use in type 1 diabetesrdquoClinical Biochemistry vol 42no 3 pp 136ndash142 2009

[3] G Bazin and J X Zhu ldquoGlucose-sensitivity of core-shellmicrospheres and their crystalline colloidal arraysrdquo ScienceChina Chemistry vol 56 no 1 pp 65ndash70 2013

[4] A L Secher L Ringholm H U Andersen P Damm andE R Mathiesen ldquoThe effect of real-time continuous glucosemonitoring in diabetic pregnancy a randomized controlledtrialrdquo Diabetes Technology ampTherapeutics vol 15 pp A21ndashA222013

[5] N Mauras L Fox K Englert and R W Beck ldquoContinuousglucose monitoring in type 1 diabetesrdquo Endocrine vol 43 no1 pp 41ndash50 2013

[6] S Cordua A L Secher L Ringholm P Damm and E RMathiesen ldquoReal-time continuous glucose monitoring duringdelivery in women with type 1 diabetesrdquo Diabetes Technology ampTherapeutics vol 15 pp A73ndashA73 2013

[7] L Qu S Xia C Bian J Sun and J Han ldquoA micro-poten-tiometric hemoglobin immunosensor based on electropoly-merized polypyrrole-gold nanoparticles compositerdquo Biosensorsamp Bioelectronics vol 24 no 12 pp 3419ndash3424 2009

[8] P Scodeller V Flexer R Szamocki et al ldquoWired-enzymecore-shell Au nanoparticle biosensorrdquo Journal of the AmericanChemical Society vol 130 no 38 pp 12690ndash12697 2008

[9] N Quoc Dung D Patil H Jung and D Kim ldquoA high-performance nonenzymatic glucose sensor made of CuO-SWCNT nanocompositesrdquo Biosensors and Bioelectronics vol42 pp 280ndash286 2013

[10] B S Der and J D Dattelbaum ldquoConstruction of a reagentlessglucose biosensor using molecular exciton luminescencerdquoAna-lytical Biochemistry vol 375 no 1 pp 132ndash140 2008

[11] O B Ayyub M B Ibrahim R M Briber and P KofinasldquoSelf-assembled block copolymer photonic crystal for selectivefructose detectionrdquo Biosensors and Bioelectronics vol 46 pp124ndash129 2013

[12] M Honda K Kataoka T Seki and Y Takeoka ldquoConfinedstimuli-responsive polymer gel in inverse opal polymer mem-brane for colorimetric glucose sensorrdquo Langmuir vol 25 no 14pp 8349ndash8356 2009

[13] S A Asher V L Alexeev A V Goponenko et al ldquoPhotoniccrystal carbohydrate sensors low ionic strength sugar sensingrdquo


Journal of the American Chemical Society vol 125 no 11 pp3322ndash3329 2003

[14] Q Cui M M Ward Muscatello and S A Asher ldquoPhotoniccrystal borax competitive binding carbohydrate sensing motifrdquoAnalyst vol 134 no 5 pp 875ndash880 2009

[15] V L Alexeev A C Sharma A V Goponenko et al ldquoHighionic strength glucose-sensing photonic crystalrdquo AnalyticalChemistry vol 75 no 10 pp 2316ndash2323 2003

[16] M Kamenjicki and S A Asher ldquoEpoxide functionalized poly-merized crystalline colloidal arraysrdquo Sensors and Actuators Bvol 106 no 1 pp 373ndash377 2005

[17] G Wulff ldquoMolecular imprinting in cross-linked materials withthe aid of molecular templatesmdasha way towards artificial anti-bodiesrdquo Angewandte Chemie International Edition in Englishvol 34 no 17 pp 1812ndash1832 1995

[18] C Baggiani C Giovannoli L Anfossi C Passini P Baravalleand G Giraudi ldquoA Connection between the binding propertiesof imprinted and nonimprinted polymers a change of perspec-tive inmolecular imprintingrdquo Journal of the American ChemicalSociety vol 134 no 3 pp 1513ndash1518 2012

[19] G Chen Z Guan C-T Chen L Fu V Sundaresan and F HArnold ldquoA glucose-sensing polymerrdquoNature Biotechnology vol15 no 4 pp 354ndash357 1997

[20] C Malitesta I Losito and P G Zambonin ldquoMolecularlyimprinted electrosynthesized polymers new materials forbiomimetic sensorsrdquo Analytical Chemistry vol 71 no 7 pp1366ndash1370 1999

[21] W Wu J Shen Y Li H Zhu P Banerjee and S ZhouldquoSpecific glucose-to-SPR signal transduction at physiologicalpH by molecularly imprinted responsive hybrid microgelsrdquoBiomaterials vol 33 no 29 pp 7115ndash7125 2012

[22] W Zhu S Tao C-A Tao et al ldquoHierarchically imprintedporous films for rapid and selective detection of explosivesrdquoLangmuir vol 27 no 13 pp 8451ndash8457 2011

[23] D Xu W Zhu Y Jiang et al ldquoRational design of molecularlyimprinted photonic films assisted by chemometricsrdquo Journal ofMaterials Chemistry vol 22 no 32 pp 16572ndash16581 2012

[24] X Hu G Li J Huang D Zhang and Y Qiu ldquoConstruction ofself-reporting specific chemical sensors with high sensitivityrdquoAdvanced Materials vol 19 no 24 pp 4327ndash4332 2007

[25] X Hu G Li M Li et al ldquoUltrasensitive specific stimulant assaybased onmolecularly imprinted photonic hydrogelsrdquoAdvancedFunctional Materials vol 18 no 4 pp 575ndash583 2008

[26] J C Lytle H Yan N S Ergang W H Smyrl and AStein ldquoStructural and electrochemical properties of three-dimensionally ordered macroporous tin(IV) oxide filmsrdquo Jour-nal of Materials Chemistry vol 14 no 10 pp 1616ndash1622 2004

[27] T Tanrisever O Okay and I C Sonmezoglu ldquoKinetics ofemulsifier-free emulsion polymerization of methyl methacry-laterdquo Journal of Applied Polymer Science vol 61 no 3 pp 485ndash493 1996

[28] Y-J Lee S A Pruzinsky and P V Braun ldquoGlucose-sensitiveinverse opal hydrogels analysis of optical diffraction responserdquoLangmuir vol 20 no 8 pp 3096ndash3106 2004

[29] C Ancla V Lapeyre I Gosse B Catargi and V RavaineldquoDesigned glucose-responsive microgels with selective shrink-ing behaviorrdquo Langmuir vol 27 no 20 pp 12693ndash12701 2011

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The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014


CoatingsJournal of

Advances in

Materials Science and EngineeringHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Smart Materials Research



MetallurgyJournal of


BioMed Research International

MaterialsJournal of


Nano

materials


Journal ofNanomaterials


analytes MIPs have attracted considerable attention as arecognition element with high selectivity for glucose sensorsChen et al reported an MIP that could be used to measureglucose concentrations in complex biological media At alka-line pH themetal-complexing polymer ldquocatchesrdquo glucose andinstantly releases protons in proportion to the glucose con-centration over a clinically relevant range (0 to 25mmol Lminus1)[19] Malitesta et al electropolymerized a glucose-imprintedpoly(O-phenylenediamine) polymer which was employed asthe recognition element of a QCM biomimetic sensor forglucose [20] Wursquos group designed a kind of molecularlyimprinted hybrid microgels that can optically monitor glu-cose levels with high sensitivity and selectivity in complexmedia at physiological pH [21] Recently Lirsquos group coupledmolecular imprinting with photonic crystal to create self-reporting specific sensors to detect protein medicines andsome biomarkers [22ndash25] However specificity cannot beguaranteed by traditional noncovalent imprinting protocoland in most cases the diffraction shifts are not remarkableWe here report on a covalently imprinted photonic crystal(CIPC) for glucose sensing The use of boronic acid deriva-tives to sense diol-containing substances has been exploitedfor a long time Boronic acid can bind cis diol-containing sub-stances through covalent bonds Our CIPC glucose-sensinghydrogel also utilized boronic acid groups as recognitionelements In order to improve the selectivity of photoniccrystal sensor covalently imprinting was introduced into thephotonic crystal hydrogel Boronic acid derivatives have beenpolymerized in the presence of glucose to create imprintedglucose-binding sites Polymer hydrogel volume changescould be actuated by boronic acid-glucose complexationTheCIPC volume changes alter the photonic crystal spacingwhich alters the Bragg diffraction condition

2 Materials and Methods

21 Materials Acrylamide (AM) acrylic acid (AA) 221015840-azobisisoheptonitrile (ABVN) 2-hydroxyethyl methacrylate(HEMA) N-isopropylacrylamide (NIPA) 22-diethoxyac-etophenone (DEAP) 4-ethylene phenylboronic acid (4-EPBA) and NN1015840-methylenebisacrylamide (BIS) were allpurchased from Tokyo Chemical Industry (Tokyo Japan)Methyl methacrylate (MMA) glycine glucose D-riboseL-rhamnose acetonitrile dimethyl sulfoxide (DMSO) andacetonitrile were all from local suppliers and were useddirectly

22 Instruments The diffraction spectra were detected usingan Avaspec-2048TEC optical fiber spectrometer (AvantesNetherlands) UV polymerization was carried out in aSCIENTZ D3-IIUV cross-linker (Ning Bo China) Theassembling of PMMA colloidal crystal was carried out ina Safe HWS-150 incubator (Ning Bo China) SEM imageswere taken using a HITACHI S4800 field emission scanningelectron microscope (Tokyo Japan) with an acceleratingvoltage of 15 kV A Shimadzu LC-20AT HPLC system on aPromosil silica column (46 times 250mm Agela TechnologiesTianjing China) with an evaporative light-scattering detector

500 nm

Figure 1 SEM image of the PMMA colloidal crystal

(ELSD)was used to quantitatively characterize the imprintingeffect of MIPs The mobile phase was acetonitrilewater (21vv) with a flow rate of 1mLminminus1 and the injection volumewas 20120583L

23 Preparation of PMMA Colloidal Crystal Poly(methylmethacrylate) (PMMA) monodispersed colloidal particles(280 nm) were synthesized using a modification of pub-lished methods [26 27] MMA (30mL) and deionized water(250mL) were mixed in a 4-neck flask at 80∘C stirred at300 rminminus1 and bubbledwith nitrogenAfter equilibrating to80∘C 15mL water containing 06 g potassium persulfate wasadded to the flask to initiate polymerization MonodispersePMMA particles with a diameter of approximately 280 nmwere obtained after 40 minutes (Figure 1) The resultingparticles were washed by centrifugation and rinsed at leastthree times with deionized water

The PMMA colloids were self-assembled into colloidalcrystals via a vertical deposition method as a template ofthe opal structure Typically glass slides were immergedin H2SO4H2O2mixture (7 3 VV) for 12 h then rinsed

with deionized water in ultrasonic bath three times anddried before use Mono-disperse PMMA particles were fullydispersed in deionized water (025ndash035 ww) whichwere added to a clean Petri dish for the colloidal crystalformation Clean glass slides were placed vertically intothe Petri dish for colloidal crystal growth After completevolatilization of the deionized water a colloidal crystal ofPMMAparticles was formed on both sides of each glass slide

24 Preparation of CIPC Films Three MIPs pre-polym-erization solutions each with different recipes (see Table 1)were prepared Take MIPs recipe (B) for instance glu-cose (017mmol) covalent functional monomer 4-APBA(017mmol) backbone monomers HEMA (15mmol) andNIPA (15mmol) were dissolved into a mixture of 15mLDMSO Then crosslinker BIS (0254mmol) and initiatorABVN (1268 120583mol) were added and the mixture was fullydeoxygenated by nitrogen purging for 10min The prepoly-merization solution was layered carefully on the PMMAphotonic crystal template so that it can infiltrate into the CCAand then polymerize at 60∘C to form hydrogel film The filmwas immersed into acetone to remove the PMMA photoniccrystal template followed by the removal of glucose by acidic



MIPs Template(mmol)

Monomers(mmol)

Crosslinker(mmol)

Initiator(mmol)





500 nm







100

MIPs

80

NIPs

60

Adso

rptio

n ra

te (

)

40

20

0A B C


Adso

rptio

n ra

te (

)

0

10

20

30

40

50

60

70

80

0 2 4 6 8 10 12 14 16t (min)

pH = 64

pH = 8

pH = 96

pH = 11




sorp

tion

rate

()

60

70

80

90

100

50 100 150NaCl (mM)

CMIPCNIPC


Adso

rptio

n ra

te (

)

0

5

10

15

20

25

25 37







4 Conclusion




Acknowledgments




0 mM

Refle

ctan

ce (

)

650 700 750 800 850 900 950 1000Wavelength (nm)

(a)

200

CIPC

150

NIPC

100

Red

shift

(nm

)

50

00 5 10 15 20

Glucose (mM)

(b)


4

CIPCNIPC

3

2

1




References







































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials





MIPs Template(mmol)

Monomers(mmol)

Crosslinker(mmol)

Initiator(mmol)





500 nm







100

MIPs

80

NIPs

60

Adso

rptio

n ra

te (

)

40

20

0A B C


Adso

rptio

n ra

te (

)

0

10

20

30

40

50

60

70

80

0 2 4 6 8 10 12 14 16t (min)

pH = 64

pH = 8

pH = 96

pH = 11




sorp

tion

rate

()

60

70

80

90

100

50 100 150NaCl (mM)

CMIPCNIPC


Adso

rptio

n ra

te (

)

0

5

10

15

20

25

25 37







4 Conclusion




Acknowledgments




0 mM

Refle

ctan

ce (

)

650 700 750 800 850 900 950 1000Wavelength (nm)

(a)

200

CIPC

150

NIPC

100

Red

shift

(nm

)

50

00 5 10 15 20

Glucose (mM)

(b)


4

CIPCNIPC

3

2

1




References







































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials




sorp

tion

rate

()

60

70

80

90

100

50 100 150NaCl (mM)

CMIPCNIPC


Adso

rptio

n ra

te (

)

0

5

10

15

20

25

25 37







4 Conclusion




Acknowledgments




0 mM

Refle

ctan

ce (

)

650 700 750 800 850 900 950 1000Wavelength (nm)

(a)

200

CIPC

150

NIPC

100

Red

shift

(nm

)

50

00 5 10 15 20

Glucose (mM)

(b)


4

CIPCNIPC

3

2

1




References







































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials





0 mM

Refle

ctan

ce (

)

650 700 750 800 850 900 950 1000Wavelength (nm)

(a)

200

CIPC

150

NIPC

100

Red

shift

(nm

)

50

00 5 10 15 20

Glucose (mM)

(b)


4

CIPCNIPC

3

2

1




References







































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials




























CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials



research article a covalently imprinted photonic crystal for glucose...

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