基于离子载体和水凝胶的二氧化碳及钾离子传感技术研究

自然界和生物体内存在各种阴阳离子和小分子，对它们浓度的检测在环境检测、临床医学、食品加工等领域具有重要的意义。与目前常见的离子检测法不同的是，基于离子载体和水凝胶的光学传感方法成本低廉、方便携带、信号读取方式多样，逐渐成为科研人员研究的热点。本论文通过对基于离子载体的离子选择性光极和基于水凝胶的传感平台的研究，制备得到选择性高、响应灵敏、性能稳定的钾离子和二氧化碳光学化学传感器，提供具有低成本轻便高灵敏度的新方法。 本论文的主要研究内容和结果如下：

我们设计了一种基于色度变化实现二氧化碳检测的聚氨酯水凝胶传感器。水凝胶中负载pH指示剂生色离子载体Ⅰ、离子交换剂NaTFPB及阳离子胺溶液，随CO₂浓度的升高，其与胺溶液反应产生H⁺，从而改变生色离子载体的质子化程度，使水凝胶的颜色由紫色转变为蓝色。水凝胶膜厚度为30 μm，对CO₂的响应时间为5 min，检测限低至0.014% atm；改变水凝胶中离子交换剂的浓度，可以实现CO₂响应范围和灵敏度的调节。用该传感器成功监测了面粉发酵过程中的CO₂释放。这种传感器携带方便，成本低，灵敏度高，且响应区间可调，在环境监测、食品加工、医疗健康领域都具有广阔的应用前景。

通过改良 Stöber 法制备了具有良好单分散性的有机硅纳米颗粒，平均粒径为45.5 nm。通过点击反应将带正电的溶致变色染料共价连接至纳米颗粒表面，初始状态下吸附在有机硅纳米颗粒内部同时颗粒内负载离子交换剂NaTFPB，钾离子载体缬氨霉素和参比染料BODIPY。随钾离子浓度升高，其由水相进入颗粒内，使溶致变色染料交换进入水相，使该染料的荧光减弱，同时BODIPY 和溶致变色染料之间的荧光共振能量转移现象使得体系的荧光强度改变更加灵敏。点击反应策略有效抑制了染料泄漏现象，传感颗粒对钾离子的响应区间为10^-5-10^-2 M， 且具有良好的钾离子选择性。将纳米颗粒掺杂入琼脂糖凝胶，并负载在尼龙滤纸上，得到低成本、便携度高的纸基钾离子水凝胶传感膜（线性范围 0.1-10 mM），展示了这种水凝胶传感膜在临床快检及环境检测等领域作为一次性传感器的应用潜力。

Various cations, anions and small molecules exist in nature and organisms, and the detection of their concentration is critical in environmental detection, clinical medicine, food processing, and many other fields. Unlike conventional ion detection methods, ionic or molecular sensing based on ionophores and hydrogels has advantages such as low cost, portability, and diverse signal output modes, which has become a research hotspot for researchers. The potassium ion and carbon dioxide optical chemical sensors with high selectivity, sensitivity, and stability were developed in this work through the research of ion-selective optode based on ionophores and hydrogel sensing platform, which provides new approaches with low cost, portability, and high sensitivity. The following are the primary contents of this work:

We designed a colorimetric carbon dioxide (CO₂) optode sensor with a polypropylene microporous membrane on top of a thin layer (30 μm) of polyurethane hydrogel, and the CO₂ response time was 5 min with a detection limit of 0.014% atm. The hydrogel was loaded with pH indicator Chromoionophore Ⅰ, ion exchanger NaTFPB and a cationic amine solution. H⁺ concentration increases when CO₂ reacted with the amine solution, thus changing the protonation degree of Chromoionophore Ⅰ and changing the color of the hydrogel from purple to blue. The response range and sensitivity of carbon dioxide can be adjusted by changing the concentration of ion exchanger in the hydrogel. This sensor successfully detected the production of carbon dioxide during flour fermentation. The sensor is portable, low cost, highly sensitive, and has an adjustable response range. It has a wide range of potential applications in environmental monitoring, food processing, and health care in the future.

Using a modified Stöber method, we fabricated organosilica nanospheres with good monodispersity, the average hydrodynamic diameter of the nanospheres was 45.5 nm. Positively charged solvatochromic dyes were covalently attached to the surface of the nanospheres through a click reaction, which adsorbed inside the nanoparticles in the initial state. Meanwhile, the particles are loaded with ion exchanger NaTFPB, potassium ion carrier valinomycin and reference dye BODIPY. The solvatochromic dyes exchange into the aqueous phase after K⁺ enter the nanoparticles, and the fluorescence of the dye decrease. Besides, there is the fluorescence resonance energy transfer between BODIPY and solvatochromic dye, which makes the nanosensors more sensitive to potassium ion concentration. The click reaction strategy effectively suppressed the dye leakage. The response range of the nanosensors was 10^-5-10^-2 M, with excellent potassium ion selectivity. By doping nanospheres into agarose gel and loading them on nylon filter paper, a low-cost and portable potassium ion hydrogel sensing film was developed (linear range 0.1-10 mM), demonstrating the potential of the sensing film as a disposable sensor in clinical diagnostic and environmental detection.

[1] BURGUES J, MARCO S. Environmental chemical sensing using small drones: A review [J]. Science of the Total Environment, 2020, 748: 141172.
[2] MISTLBERGER G, CRESPO G A, BAKKER E. Ionophore-based optical sensors [J]. Annual Review of Analytical Chemistry, 2014, 7: 483-512.
[3] XIE X, BAKKER E. Ion selective optodes: from the bulk to the nanoscale [J]. Analytical and Bioanalytical Chemistry, 2015, 407(14): 3899-910.
[4] ZHU J, JIA P, LI N, et al. Small-molecule fluorescent probes for the detection of carbon dioxide [J]. Chinese Chemical Letters, 2018, 29(10): 1445-50.
[5] ZOSEL J, OELßNER W, DECKER M, et al. The measurement of dissolved and gaseous carbon dioxide concentration [J]. Measurement Science and Technology, 2011, 22(7).
[6] BAKKER E, BüHLMANN P, PRETSCH E. Carrier-based ion-selective electrodes and bulk optodes. 1. General characteristics [J]. Chemical Reviews, 1997, 97(8): 3083-132.
[7] BAKKER E, QIN Y. Electrochemical sensors [J]. Analytical Chemistry, 2006, 78(12): 3965-84.
[8] LIU Y, XUE Y, TANG H, et al. Click-immobilized K+-selective ionophore for potentiometric and optical sensors [J]. Sensors and Actuators B: Chemical, 2012, 171-172: 556-62.
[9] THAJEE K, WANG L, GRUDPAN K, et al. Colorimetric ionophore-based coextraction titrimetry of potassium ions [J]. Analytica Chimica Acta, 2018, 1029: 37-43.
[10] DU X, WANG R, ZHAI J, et al. Ionophore-based ion-selective nanosensors from brush block copolymer nanodots [J]. ACS Applied Nano Materials, 2020, 3(1): 782-8.
[11] LEE C H, FOLZ J, ZHANG W, et al. Ion-selective nanosensor for photoacoustic and fluorescence imaging of potassium [J]. Analytical Chemistry, 2017, 89(15): 7943-9.
[12] XIE X, MISTLBERGER G, BAKKER E. Ultrasmall fluorescent ion-exchanging nanospheres containing selective ionophores [J]. Analytical Chemistry, 2013, 85(20): 9932-8.
[13] XIE X, SZILAGYI I, ZHAI J, et al. Ion-selective optical nanosensors based on solvatochromic dyes of different lipophilicity: from bulk partitioning to interfacial accumulation [J]. ACS Sensors, 2016, 1(5): 516-20.
[14] DU X, XIE X. Ion-selective optodes: alternative approaches for simplified fabrication and signaling [J]. Sensors and Actuators B: Chemical, 2021, 335.
[15] SUN X, AGATE S, SALEM K S, et al. Hydrogel-based sensor networks: compositions, properties, and applications-a review [J]. ACS Applied Bio Materials, 2021, 4(1): 140-62.
[16] DU X, ZHAI J, LI X, et al. Hydrogel-based optical ion sensors: principles and challenges for point-of-care testing and environmental monitoring [J]. ACS Sensors, 2021, 6(6): 1990-2001.
[17] DU X, ZHAI J, ZENG D, et al. Distance-based detection of calcium ions with hydrogels entrapping exhaustive ion-selective nanoparticles [J]. Sensors and Actuators B: Chemical, 2020, 319.
[18] MAIERHOFER M, RIEGER V, MAYR T. Optical ammonia sensors based on fluorescent aza-BODIPY dyes- a flexible toolbox [J]. Analytical and Bioanalytical Chemistry, 2020, 412(27): 7559-67.
[19] MüLLER B J, BORISOV S M, KLIMANT I. Red- to NIR-emitting, BODIPY-based, K+-selective fluoroionophores and sensing materials [J]. Advanced Functional Materials, 2016, 26(42): 7697-707.
[20] DERVIEUX E, THERON M, UHRING W. Carbon dioxide sensing-biomedical applications to human subjects [J]. Sensors (Basel), 2021, 22(1).
[21] REYES F, GRUTTER M, JAZCILEVICH A, et al. Tecnical Note: Analysis of non-regulated vehicular emissions by extractive FTIR spectrometry: tests on a hybrid car in Mexico City [J]. Atmospheric Chemistry and Physics, 2006, 6(12): 5339-46.
[22] MCDONAGH C, BURKE C S, MACCRAITH B D. Optical chemical sensors [J]. Chemical Reviews, 2008, 108(2): 400-22.
[23] WOLFBEIS O S, WEIDGANS B M. FIBER OPTIC CHEMICAL SENSORS AND BIOSENSORS: A VIEW BACK; proceedings of the Optical Chemical Sensors, Dordrecht, F 2006//, 2006 [C]. Springer Netherlands.
[24] NEURAUTER G, KLIMANT I, WOLFBEIS O S. Fiber-optic microsensor for high resolution pCO2 sensing in marine environment [J]. Fresenius' Journal of Analytical Chemistry, 2000, 366(5): 481-7.
[25] STAUDINGER C, BREININGER J, KLIMANT I, et al. Near-infrared fluorescent aza-BODIPY dyes for sensing and imaging of pH from the neutral to highly alkaline range [J]. Analyst, 2019, 144(7): 2393-402.
[26] MULLER B J, RAPPITSCH T, STAUDINGER C, et al. Sodium-selective fluoroionophorebased optodes for seawater salinity measurement [J]. Analytical Chemistry, 2017, 89(13): 7195-202.
[27] LI X, GAO X, SHI W, et al. Design strategies for water-soluble small molecular chromogenic and fluorogenic probes [J]. Chemical Reviews, 2014, 114(1): 590-659.
[28] HAN Z-X, ZHANG X-B, LI Z, et al. Efficient Fluorescence Resonance Energy Transfer-Based Ratiometric Fluorescent Cellular Imaging Probe for Zn2+ using a rhodamine spirolactam as a trigger [J]. Analytical Chemistry, 2010, 82(8): 3108-13.
[29] HUANG S, WU Y, ZENG F, et al. Handy ratiometric detection of gaseous nerve agents with AIE-fluorophore-based solid test strips [J]. Journal of Materials Chemistry C, 2016, 4(42): 10105-10.
[30] XIE X, GUTIERREZ A, TROFIMOV V, et al. Charged solvatochromic dyes as signal transducers in pH independent fluorescent and colorimetric ion selective nanosensors [J]. Analytical Chemistry, 2015, 87(19): 9954-9.
[31] WANG L, XIE X, ZHAI J, et al. Reversible pH-independent optical potassium sensor with lipophilic solvatochromic dye transducer on surface modified microporous nylon [J]. Chemical Communications (Camb), 2016, 52(99): 14254-7.
[32] PHICHI M, IMYIM A, TUNTULANI T, et al. Paper-based cation-selective optode sensor containing benzothiazole calix
[4]arene for dual colorimetric Ag+ and Hg2+ detection [J]. Analytica Chimica Acta, 2020, 1104: 147-55.
[33] CHEN Q, LI X, WANG R, et al. Rapid equilibrated colorimetric detection of protamine and heparin: Recognition at the nanoscale liquid-liquid interface [J]. Analytical Chemistry, 2019, 91(16): 10390-4.
[34] DU X, WANG Y, ZHAI J, et al. One-pot synthesized organosilica nanospheres for multiplexed fluorescent nanobarcoding and subcellular tracking [J]. Nanoscale, 2022, 14(5): 1787-95.
[35] CICCIONE J, JIA T, COLL J-L, et al. Unambiguous and controlled one-pot synthesis of multifunctional silica nanoparticles [J]. Chemistry of Materials, 2016, 28(3): 885-9.
[36] XIE X, ZHAI J, CRESPO G A, et al. Ionophore-based ion-selective optical nanosensors operating in exhaustive sensing mode [J]. Analytical Chemistry, 2014, 86(17): 8770-5.
[37] WANG L, BAKKER E. A tunable detection range of ion-selective nano-optodes by controlling solvatochromic dye transducer lipophilicity [J]. Chemical Communications (Camb), 2019, 55(83): 12539-42.
[38] GE Y, ZHU J, ZHAO W, et al. Ion-selective optodes based on near infrared fluorescent chromoionophores for pH and metal ion measurements [J]. Sensors and Actuators B: Chemical, 2012, 166-167: 480-4.
[39] XIE X, LI X, GE Y, et al. Rhodamine-based ratiometric fluorescent ion-selective bulk optodes [J]. Sensors and Actuators B: Chemical, 2010, 151(1): 71-6.
[40] JOKIC T, BORISOV S M, SAF R, et al. Highly photostable near-infrared fluorescent ph indicators and sensors based on BF2-chelated tetraarylazadipyrromethene dyes [J]. Analytical Chemistry, 2012, 84(15): 6723-30.
[41] XIE X, CRESPO G A, BAKKER E. Oxazinoindolines as fluorescent H+turn-on chromoionophores for optical and electrochemical ion sensors [J]. Analytical Chemistry, 2013, 85(15): 7434-40.
[42] TENJIMBAYASHI M, KOMATSU H, AKAMATSU M, et al. Determination of blood potassium using a fouling-resistant PVDF–HFP-based optode [J]. RSC Advances, 2016, 6(17): 14261-5.
[43] WANG X, QIN Y, MEYERHOFF M E. Paper-based plasticizer-free sodium ion-selective sensor with camera phone as a detector [J]. Chemical Communications, 2015, 51(82): 15176-9.
[44] SHIBATA H, IKEDA Y, HIRUTA Y, et al. Inkjet-printed pH-independent paper-based calcium sensor with fluorescence signal readout relying on a solvatochromic dye [J]. Analytical and Bioanalytical Chemistry, 2020, 412(14): 3489-97.
[45] RUCKH T T, SKIPWITH C G, CHANG W, et al. Ion-switchable quantum dot förster resonance energy transfer rates in ratiometric potassium sensors [J]. ACS Nano, 2016, 10(4): 4020-30.
[46] DUBACH J M, LIM E, ZHANG N, et al. In vivo sodium concentration continuously monitored with fluorescent sensors [J]. Integrative Biology, 2011, 3(2): 142-8.
[47] LI Y, DENG C, YANG M. A novel surface acoustic wave-impedance humidity sensor based on the composite of polyaniline and poly(vinyl alcohol) with a capability of detecting low humidity [J]. Sensors and Actuators B: Chemical, 2012, 165(1): 7-12.
[48] CAJLAKOVIC M, LOBNIK A, WERNER T. Stability of new optical pH sensing material based on cross-linked poly(vinyl alcohol) copolymer [J]. Analytica Chimica Acta, 2002, 455(2): 207-13.
[49] JIANG H, ZHU Y, CHEN C, et al. Photonic crystal pH and metal cation sensors based on poly(vinyl alcohol) hydrogel [J]. New Journal of Chemistry, 2012, 36(4): 1051-6.
[50] CUMMINS B M, LIM J, SIMANEK E E, et al. Encapsulation of a Concanavalin A/dendrimer glucose sensing assay within microporated poly (ethylene glycol) microspheres [J]. Biomedical Optics Express, 2011, 2(5): 1243-57.
[51] WANG R, DU X, ZHAI J, et al. Distance and color change based hydrogel sensor for visual quantitative determination of buffer concentrations [J]. ACS Sensors, 2019, 4(4): 1017-22.
[52] ZHANG Y, GE J. Liquid photonic crystal detection reagent for reliable sensing of Cu2+ in water [J]. RSC Advances, 2020, 10(18): 10972-9.
[53] SAITO H, TAKEOKA Y, WATANABE M. Simple and precision design of porous gel as a visible indicator for ionic species and concentration [J]. Chemical Communications (Camb), 2003, (17): 2126-7.
[54] AIGNER D, UNGERBOCK B, MAYR T, et al. Fluorescent materials for pH sensing and imaging based on novel 1,4-diketopyrrolo-
[3,4-c]pyrrole dyesdaggerElectronic supplementary information (ESI) available: NMR and MS spectra, further sensor characteristics and sensor long-time performance. See DOI: 10.1039/c3tc31130aClick here for additional data file [J]. Journal of Materials Chemistry C: Materials for Optical and Electronic Devices, 2013, 1(36): 5685-93.
[55] AXPE E, CHAN D, OFFEDDU G S, et al. A multiscale model for solute diffusion in hydrogels [J]. Macromolecules, 2019, 52(18): 6889-97.
[56] DALFEN I, DMITRIEV R I, HOLST G, et al. Background-free fluorescence-decay-time sensing and imaging of ph with highly photostable diazaoxotriangulenium dyes [J]. Analytical Chemistry, 2019, 91(1): 808-16.
[57] GOTOR R, ASHOKKUMAR P, HECHT M, et al. Optical ph sensor covering the range from pH 0-14 compatible with mobile-device readout and based on a set of rationally designed indicator dyes [J]. Analytical Chemistry, 2017, 89(16): 8437-44.
[58] DU X, HUANG M, WANG R, et al. A rapid point-of-care optical ion sensing platform based on target-induced dye release from smart hydrogels [J]. Chemical Communications, 2019, 55(12): 1774-7.
[59] JOKIC T, BORISOV S M, SAF R, et al. Highly photostable near-infrared fluorescent pH indicators and sensors based on BF2-chelated tetraarylazadipyrromethene dyes [J]. Analytical Chemistry, 2012, 84(15): 6723-30.
[60] KENNEY R M, BOYCE M W, WHITMAN N A, et al. A pH-sensing optode for mapping spatiotemporal gradients in 3D paper-based cell cultures[J]. Analytical Chemistry, 2018, 90(3): 2376-83.
[61] MEIER R J, SIMBURGER J M, SOUKKA T, et al. Background-free referenced luminescence sensing and imaging of pH using upconverting phosphors and color camera read-out [J]. Analytical Chemistry, 2014, 86(11): 5535-40.
[62] MüLLER B J, STEINMANN N, BORISOV S M, et al. Ammonia sensing with fluoroionophores – A promising way to minimize interferences caused by volatile amines [J]. Sensors and Actuators B: Chemical, 2018, 255: 1897-901.
[63] HOLTZ J H, ASHER S A. Polymerized colloidal crystal hydrogel films as intelligent chemical sensing materials [J]. Nature, 1997, 389(6653): 829-32.
[64] ASHER S A, SHARMA A C, GOPONENKO A V, et al. Photonic crystal aqueous metal cation sensing materials [J]. Analytical Chemistry, 2003, 75(7): 1676-83.
[65] SAITO H, TAKEOKA Y, WATANABE M. Simple and precision design of porous gel as a visible indicator for ionic species and concentration [J]. Chemical Communications, 2003, (17): 2126-7.
[66] GUO J, ZHOU M, YANG C. Fluorescent hydrogel waveguide for on-site detection of heavy metal ions [J]. Scientific Reports, 2017, 7(1): 7902.
[67] HUANG Y, WU X, TIAN T, et al. Target-responsive DNAzyme hydrogel for portable colorimetric detection of lanthanide(III) ions [J]. Science China Chemistry, 2017, 60(2): 293-8.
[68] LIN H, ZOU Y, HUANG Y, et al. DNAzyme crosslinked hydrogel: a new platform for visual detection of metal ions [J]. Chemical Communications, 2011, 47(33): 9312-4.
[69] HUANG Y, MA Y, CHEN Y, et al. Target-responsive dnazyme cross-linked hydrogel for visual quantitative detection of lead [J]. Analytical Chemistry, 2014, 86(22): 11434-9.
[70] QING Z, MAO Z, QING T, et al. Visual and portable strategy for copper(Ⅱ) detection based on a striplike poly(thymine)-caged and microwell-printed hydrogel [J]. Analytical Chemistry, 2014, 86(22): 11263-8.
[71] SUN Y, LI S, CHEN R, et al. Ultrasensitive and rapid detection of T-2 toxin using a target-responsive DNA hydrogel [J]. Sensors and Actuators B: Chemical, 2020, 311: 127912.
[72] BISWAKARMA D, DEY N, BHATTACHARYA S. A thermo-responsive supramolecular hydrogel that senses cholera toxin via color-changing response [J]. Chemical Communications, 2020, 56(56): 7789-92.
[73] GE J, YIN Y. Responsive photonic crystals [J]. Angewandte Chemie, International Edition in English, 2011, 50(7): 1492-522.
[74] LEE J Y, KO K, CHUNG H. Application of colorimetric sensor in monitoring dissolved CO2 in natural waters [J]. Journal of Environmental Management, 2022, 312: 114893.
[75] CALVO-LOPEZ A, YMBERN O, IZQUIERDO D, et al. Low cost and compact analytical microsystem for carbon dioxide determination in production processes of wine and beer [J]. Analytica Chimica Acta, 2016, 931: 64-9.
[76] BEYENAL H, DAVIS C C, LEWANDOWSKI Z. An improved Severinghaus-type carbon dioxide microelectrode for use in biofilms [J]. Sensors and Actuators B: Chemical, 2004, 97(2-3): 202-10.
[77] STEININGER F, REVSBECH N P, KOREN K. Total dissolved inorganic carbon sensor based on amperometric CO2 microsensor and local acidification [J]. ACS Sensors, 2021, 6(7): 2529-33.
[78] XIE X, BAKKER E. Non-Severinghaus potentiometric dissolved CO2 sensor with improved characteristics [J]. Analytical Chemistry, 2013, 85(3): 1332-6.
[79] WANG H, VAGIN S I, RIEGER B, et al. An ultrasensitive fluorescent paper-based CO2 sensor [J]. ACS Applied Materials & Interfaces, 2020, 12(18): 20507-13.
[80] LI T, WU Y, HUANG J, et al. Gas sensors based on membrane diffusion for environmental monitoring [J]. Sensors and Actuators B: Chemical, 2017, 243: 566-78.
[81] LI X, TANG B, WU B, et al. Highly sensitive diffraction grating of hydrogels as sensors for carbon dioxide detection [J]. Industrial & Engineering Chemistry Research, 2021, 60(12): 4639-49.
[82] KONG Y, JIANG G, WU Y, et al. Amine hybrid aerogel for high-efficiency CO2 capture: Effect of amine loading and CO2 concentration [J]. Chemical Engineering Journal, 2016, 306: 362-8.
[83] XU X, HEATH C, PEJCIC B, et al. CO2 capture by amine infused hydrogels (AIHs) [J]. Journal of Materials Chemistry A, 2018, 6(11): 4829-38.
[84] MA Y, CAMETTI M, DŽOLIĆ Z, et al. AIE-active bis-cyanostilbene-based organogels for quantitative fluorescence sensing of CO2 based on molecular recognition principles [J]. Journal of Materials Chemistry C, 2018, 6(34): 9232-7.