sensors Sensors Sensors Sensors 1424-8220 MDPI 10.3390/s17030645 sensors-17-00645 Article Ultratrace Detection of Histamine Using a Molecularly-Imprinted Polymer-Based Voltammetric Sensor Akhoundian Maedeh Rüter Axel Shinde Sudhirkumar * Star Alexander Academic Editor Department of Biomedical Sciences, Faculty of Health and Society, Malmö University, Malmö SE-20506, Sweden; m.akhoundian@yahoo.com (M.A.); axel.ruter@fkem1.lu.se (A.R.) Correspondence: sudhirkumar.shinde@mah.se; Tel.: +46-703-463-963 21 03 2017 03 2017 17 3 645 06 02 2017 17 03 2017 © 2017 by the authors. 2017

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Rapid and cost-effective analysis of histamine, in food, environmental, and diagnostics research has been of interest recently. However, for certain applications, the already-existing biological receptor-based sensing methods have usage limits in terms of stability and costs. As a result, robust and cost-effective imprinted polymeric receptors can be the best alternative. In the present work, molecularly-imprinted polymers (MIPs) for histamine were synthesized using methacrylic acid in chloroform and acetonitrile as two different porogens. The binding affinity of the MIPs with histamine was evaluated in aqueous media. MIPs synthesized in chloroform displayed better imprinting properties for histamine. We demonstrate here histamine MIPs incorporated into a carbon paste (CP) electrode as a MIP-CP electrode sensor platforms for detection of histamine. This simple sensor format allows accurate determination of histamine in the sub-nanomolar range using an electrochemical method. The sensor exhibited two distinct linear response ranges of 1 × 10−10–7 × 10−9 M and 7 × 10−9–4 × 10−7 M. The detection limit of the sensor was calculated equal to 7.4 × 10−11 M. The specificity of the proposed electrode for histamine is demonstrated by using the analogous molecules and other neurotransmitters such as serotonin, dopamine, etc. The MIP sensor was investigated with success on spiked serum samples. The easy preparation, simple procedure, and low production cost make the MIP sensor attractive for selective and sensitive detection of analytes, even in less-equipped laboratories with minimal training.

 histamine imprinted polymers Ultratraces sensor 1. Introduction

Histamine (β-imidazolylethylamine) is a biogenic amine. It is an important mediator involved in various physiological and pathological processes, including neurotransmission and numerous brain functions, secretion of some hormones, regulation of gastrointestinal, circulatory functions, and inflammatory reactions [1]. However, a high level of histamine in the human body causes an allergy-like syndrome called histamine intolerance [2] or histamine poisoning (toxic level 50 mg per 100 g of product) [3,4]. The source of elevated histamine level is due to fermented foods, such as fish, cheese, sauerkraut, beer, wine, processed meat [2], and spoilage of the foodstuff, in particular seafood, due to uncontrolled microbial growth [5]. Therefore, monitoring of histamine is a critical task for the food industry and food safety.

A number of methods for the determination of histamine have been reported including thin-layer chromatography [6,7], gas chromatography [8,9], capillary zone electrophoresis [10], and high-performance liquid chromatography [11,12,13,14], as well as fluorimetric [15] and colorimetric assays [16]. These methods require extensive sample processing such as pretreatment of samples. In addition, it involves qualified analysts. These tedious and time-consuming methods result in expensive and slow sample throughput. In this regard, enzyme-based methods [e.g., enzyme-linked immunosorbent assay (ELISA)] [17,18] offer rapid means of detection, but necessitate the use of unstable enzymes, expensive test kits, and tend to overestimate histamine [19].

Different types of electrochemical sensors with chemical modifications [20,21,22] or with immobilized amine oxidases and dehydrogenases [23,24,25,26,27,28] have been described in several reports of histamine determination.

The development of stable histamine receptor with a capacity to detect low histamine concentrations (nM range) is an urgent need in the biomedical and diagnostics research [29,30,31,32,33,34]. In this direction, MIP-based sensors have attracted much interest due to easy preparation, good stability, and robustness. In the literature, histamine-imprinted polymers and MIP-based sensors have already been reported for histamine recognition [35,36,37] in surface enhanced Raman spectroscopy (SER) [38], thermal [39], quartz crystal microbalance (QCM) [40], amperometric [41], and impedimetric [34,42] sensors.

In the current work, a histamine MIP has been developed and used for fabrication of voltammetric sensor. The developed sensor has been successfully applied for histamine determination in serum samples. The developed methodology offers advantages such as simplicity, precision, short analysis time, low cost of analysis and instrumentation, with comparable selectivity and sensitivity with advanced instruments.

 2. Materials and Methods

Dopamine hydrochloride, histamine, and serotonin hydrochloride was received from Sigma, (Steinheim, Germany). H-His-OH (99%) was received from Bachem Biochemica GmBH (Heidelberg, Germany) and Boc-His-OH was received from Calbiochem-Novabiochem AG (Läufelfingen, Switzerland). Methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) were purchased from Sigma-Aldrich Chemie GmbH (Taufkirchen, Germany). EGDMA was washed consecutively with 10% NaOH, water, and brine and then dried over MgSO4, and filtered prior to distillation under reduced pressure. MAA was also distilled under reduced pressure. The initiator azo-N,N’-bisdivaleronitrile (ABDV) was purchased from Wako Chemicals and used without further purification. Chloroform (CHCl3), extra dry, and acetonitrile (MeCN), extra dry, were received from Acros Organics (Geel, Belgium). The porogens were kept under nitrogen atmosphere over molecular sieves and were used without further purification. Graphite flake powder (325 mesh) was received from Alfa Aesar and carbon (mesoporous nanopowder, ˂500 nm particle size) was received from Aldrich (Steinheim, Germany). Paraffin oil was received from Kebo AB (Stockholm, Sweden).

2.1. Polymer Synthesis

Imprinted polymers were prepared using bulk polymerization (Table 1) in the following manner: Template histamine (0.24 mmol), functional monomer MAA (1.2 mmol), and EDGMA (6 mmol) were dissolved in 1.5 mL dry chloroform (MIP1) and 1.5 mL dry acetonitrile (MIP2). The initiator ABDV (1% w/w of total monomers) was added to the solution which was transferred to screw-capped glass vials, cooled to 0 °C, and purged with a flow of dry nitrogen for 10 min. The glass vials were sealed with silicone tape while still under cooling and the polymerization was initiated by placing the vials at 50 °C for 48 h. The polymers were lightly crushed and the template was extracted with methanol: acetic acid/90:10 for 24 h. This was followed by further lightly crushing the particles without fractionation to evaluate their binding properties. Corresponding non-imprinted polymers (NIP1/NIP2) were prepared in the same manner described above, but with the omission of the template molecule from the pre-polymerization solution.

 2.2. Binding Analysis

Increasing amount of histamine (0 to 1 mM) 1 mL solution was suspended in the 10 mg MIP and NIP particles. Rebinding tests of the polymeric materials were all performed in a 50 mM PBS solution (pH 7.4) with an equilibration time of 4 h followed by analysis with UV-VIS spectroscopy measuring absorbance at 208 nm. Measurements were performed on a BIOTEK POW-ERWAVE XS plate reader in a 96-well quartz plate.

 2.3. Preparation of the Sensors

In order to fabricate the sensor, 11 mg of nano-carbon (NC) and 0.2 g of graphite was dispersed in 2 mL of dimethylformamide (DMF) and sonicated for 30 min, and allowed to dry in an oven at 80 °C overnight. This mixture was then added to the 11 mg of MIP1/NIP1 and homogenized in a mortar. Subsequently, 57.6 mg of paraffin oil was added to the mixture to form a homogeneous paste. This paste was used to fill a hole (4.00 mm in diameter, 3 mm in depth) at the end of the electrode body. The excess material from the surface of the electrode was removed by polishing on a paper sheet, thus devising the MIP-CP electrode. For the normal mixing electrode, all of the steps were repeated except the dispersion and sonication steps otherwise described.

 2.4. General Method for Electrochemical Measurements

Electrochemical data was obtained with a system using an Ivium-stat potentiostat/galvanostat. The measurements were performed in a three-electrode system: working electrode (MIP/NIP-based CP electrodes), a counter electrode (platinum), and a reference electrode (Ag/AgCl). Electrochemical measurement of histamine concentration was performed according to the following procedure: The solution containing 20 mL of potassium hexacyanoferrate (0.1 M K3[Fe(CN)6]) and potassium chloride (0.1 M KCl) was added to the cell as a blank. Before each determination, histamine stock solution was prepared in PBS (0.1 M, pH = 7), spiked to the blank solution and stirred for 15 s. The MIP-CP electrode was immediately placed into the electrochemical cell and the cyclic voltammetry technique was applied using scan rate = 50 mV/s, Estep = 10 mV, and equilibration time = 5 s. The modified electrode was rinsed with milliQ water and polished on the paper sheet after each measurement.

 2.5. The Measurement of Histamine in Real Samples

In order to determine the histamine in real sample, a certain amount of histamine stock solution was spiked in to the serum sample and it was diluted with milliQ water in a 1:20 ratio. The prepared sensor was then immersed in to the spiked serum sample and solution was stirred for 15 s. Cyclic voltammetry responses were recorded immediately after equilibration time of the program, which was 5 s.

 3. Results 3.1. Molecularly- Imprinted Polymers for Histamine 3.1.1. Polymer Synthesis

The preparation of histamine MIPs was done following established procedure with slight modifications (Table 1) starting from prepolymerization mixtures containing histamine as the template, methacrylic acid (MAA) as functional monomers, and ethylenglycol dimethacrylate (EGDMA) as a crosslinking monomer. In order to study the effect of porogen on histamine imprinting, we chose CHCl3 and MeCN over highly-hygroscopic polar dimethyl sulfoxide (DMSO) among mostly used porogens reported earlier. After free radical polymerization, the resulting polymers were freed from the template by washing with acidic methanol, leaving binding sites complementary to a relatively narrow group of histamine.

 3.1.2. Optical Batch Rebinding Experiment

At this stage, we were interested in measuring histamine in biological fluids at neutral pH and aqueous environment. The functional monomer MAA [43] (the pKa 6.5), which was used by Bongaers et al. [42], Horemans et al. [40], and Trikka et al. [35], is a deprotonated form (COO−) at neutral pH, which binds to histamine. The MIP synthesized from MAA is suitable for rebinding of histamine at pH 7.4 [34,35]. Therefore, we performed rebinding experiments for synthesized MIPs at pH 7.4 using PBS buffer followed by analysis with UV spectrophotometer. For the rebinding experiment, 10 mg of MIP and NIP powder were added to 1 mL of histamine between 0 to 1 mM concentration ranges. The resulting suspensions were shaken for 4 h at room temperature. The supernatant was collected after centrifugation and the free concentration of histamine was determined by UV-VIS spectroscopy. Hereby, the amount of bound histamine per gram of MIP or NIP was calculated and the binding isotherms were constructed. The binding isotherms for the MIP and NIP were prepared in CHCl3 and MeCN are demonstrated in Figure 1a,b. The polymer prepared in CHCl3 displayed better imprinting performance compared to those in MeCN. This is due to the difference in polarity (chloroform is less polar than acetonitrile) a large concentration of prepolymer complex would be expected using chloroform as a porogen [44]. Further, Trikka et al. [35] has confirmed by 1H NMR spectroscopy that interaction between histamine and MAA are mainly hydrogen bonding when chloroform is used as a solvent. The best performing MIP and NIP prepared in CHCl3 was further used for MIP-modified carbon paste (CP) electrodes.

 3.2. MIP-CP Electrode 3.2.1. Fabrication of MIP-CP Electrode

In the first steps of the fabrication process for optimization of composite, we have tested different sequences of mixing of nano carbon (NC), graphite and MIP/NIP as follows: (1) graphite + NC + MIP/NIP normal mix, these powders were physically mixed together as a dry powder; (2) graphite + NC + MIP/NIP (dispersed) powders were mixed together and dispersed in DMF, sonicated, and dried; (3) graphite + NC (dispersed) + MIP/NIP, graphite, and NC was dispersed in DMF, sonicated, and dried followed by mixing of MIP/NIP powder as described in material and methods. Paraffin oil was added to prepare the paste in all the composites. Subsequently, electrochemical responses of hexacyanoferrate solution with different concentrations of histamine were investigated for all electrodes (Figure 2). The MIP-CP electrode prepared by the graphite + NC (dispersed) + MIP/NIP method gave a linear electrochemical signal in cyclic voltammetric measurement (Figure 3). This is most likely related to accessibility of MIP for recognition of histamine in the composite materials.

 3.2.2. Selectivity of the Modified CP Electrode

The MIP-CP electrode was evaluated using structurally-similar compounds and neurotransmitters. In order to accomplish these experiments, the MIP-CP electrode was immersed in individual solution (concentration = 7 × 10−9 M) and the electrochemical detection process was carried out according to the above mentioned procedure. Figure 4 illustrates the responses of histamine and other histamine-like compounds, including the neurotransmitters serotonin and dopamine, in the histamine MIP-CP electrode under the exact same conditions. As can be seen, the responses of histamine to the MIP-CP electrode is the highest compared to other analytes, followed by H-His-OH amino acid having a similar structure. It is interesting to note that when the MIP-CP electrode was tested for Boc-His-OH, a lower response was observed. This may suggest that primary amine of histamine and MAA is important for interaction involved in molecular recognition.

 3.3. Analytical Characterization 3.3.1. Calibration of the MIP-CP Electrode

The developed sensor was used for calibration curve plotting. It is worth noting that the values of the current response used for the calibration curve are actually the absolute values of the oxidative peak current observed for blank solution and after spiking of different concentrations of histamine solutions. The calibration graph obtained for histamine determination of the prepared sensor is shown in Figure 5 that exhibited two distinct linear response ranges of 1 × 10−10–7 × 10−9 and 7 × 10−9–4 × 10−7 M with the detection limit of 7.4 × 10−11 M (S/N = 3).

 3.3.2. Histamine Determination in Human Plasma

The analytical utility of the method was assessed by applying it to the determination of histamine in human serum samples. Percent recovery of histamine was obtained demonstrating that the proposed sensor is a promising approach in sensor preparation and histamine analysis. The results for the determination of histamine in different samples are summarized in Table 2.

 3.4. Comparison of the Developed Method and Other Previously Reported Electrochemical Methods

In Table 3, the analytical parameter of reported electrochemical methods for quantification of histamine are summarized. Compared to most of other methods, the approach presented here shows a wide dynamic range and has a lower detection limit. The proposed procedures for making MIP-CP electrode and analytical method developed using bulk imprinted polymer is very simple and inexpensive. In this proposed sensor, the low detection limit, wide linear working range, and comparable sensitivity and selectivity to the advanced instrumentation is noteworthy.

 4. Conclusions

Histamine, a biogenic amine, is an indicator in pathophysiology, microbial infection and food safety. Routinely, faster detection of histamine is performed by time-consuming chemical methods or ELISA. Therefore, MIPs, as synthetic receptors, are a cost-effective alternative. In this study, histamine-imprinted polymers were prepared by bulk imprinted polymerization in chloroform and acetonitrile. The imprinted polymer prepared in chloroform displayed better imprinting performance in a neutral buffer. Modification of carbon paste (CP) electrode with histamine MIPs as recognition elements lead to an excellent sensor for histamine. As a proof of principle, the measurement of histamine in the human serum is demonstrated using MIP-based voltammetric sensor.

 Acknowledgments

We acknowledge Börje Sellergren and Tautgirdas Ruzgas for discussion. We thank Bo Mattiasson and Gizem Ertürk for the invitation to submit in the special issue entitled “Biosensors and Molecular Imprinting”.

 Author Contributions

S.S. designed the experiments; A.R. synthesized MIP and performed histamine rebinding study; M.A. performed the sensor construction, testing, and validation study. S.S. and M.A. analyzed data and wrote the manuscript.

 Conflicts of Interest

The authors declare no conflict of interest.

References Jutel M. Watanabe T. Akdis M. Blaser K. Akdis C.A. Immune regulation by histamine Curr. Opin. Immunol. 2002 14 735 740 10.1016/S0952-7915(02)00395-3 Maintz L. Novak N. Histamine and histamine intolerance Am. J. Clin. Nutr. 2007 85 1185 1196 17490952 Taylor S.L. Eitenmiller R.R. Histamine food poisoning: Toxicology and clinical aspects CRC Crit. Rev. Toxicol. 1986 17 91 128 10.3109/10408448609023767 3530640 Lehane L. Olley J. Histamine fish poisoning revisited Int. J. Food Microbiol. 2000 58 1 37 10.1016/S0168-1605(00)00296-8 Fernandes J.O. Judas I.C. Oliveira M.B. Ferreira I.M.P.L.V.O. Ferreira M.A. A GC-MS method for quantitation of histamine and other biogenic amines in beer Chromatographia 2001 53 S327 S331 10.1007/BF02490351 Tao Z. Sato M. Han Y. Tan Z. Yamaguchi T. Nakano T. A simple and rapid method for histamine analysis in fish and fishery products by tlc determination Food Control 2011 22 1154 1157 10.1016/j.foodcont.2010.12.014 Lieber E.R. Taylor S.L. Thin-layer chromatographic screening methods for histamine in tuna fish J. Chromatogr. A 1978 153 143 152 10.1016/S0021-9673(00)89865-9 Antoine F.R. Wei C.I. Otwell W.S. Sims C.A. Littell R.C. Hogle A.D. Marshall M.R. Gas chromatographic analysis of histamine in mahi-mahi (coryphaena hippurus) J. Agric. Food Chem. 2002 50 4754 4759 10.1021/jf020148x 12166956 Hwang B.-S. Wang J.-T. Choong Y.-M. A rapid gas chromatographic method for the determination of histamine in fish and fish products Food Chem. 2003 82 329 334 10.1016/S0308-8146(03)00005-0 Zhang L.-Y. Sun M.-X. Determination of histamine and histidine by capillary zone electrophoresis with pre-column naphthalene-2,3-dicarboxaldehyde derivatization and fluorescence detection J. Chromatogr. A 2004 1040 133 140 10.1016/j.chroma.2004.03.051 15248433 Bauza T. Blaise A. Daumas F. Cabanis J.C. Determination of biogenic amines and their precursor amino acids in wines of the vallée du rhône by high-performance liquid chromatography with precolumn derivatization and fluorimetric detection J. Chromatogr. A 1995 707 373 379 10.1016/0021-9673(95)00318-H Jensen T.B. Marley P.D. Development of an assay for histamine using automated high-performance liquid chromatography with electrochemical detection J. Chromatogr. B: Biomed. Sci. Appl. 1995 670 199 207 10.1016/0378-4347(95)00131-X Önal A. A review: Current analytical methods for the determination of biogenic amines in foods Food Chem. 2007 103 1475 1486 10.1016/j.foodchem.2006.08.028 Proestos C. Loukatos P. Komaitis M. Determination of biogenic amines in wines by HPLC with precolumn dansylation and fluorimetric detection Food Chem. 2008 106 1218 1224 10.1016/j.foodchem.2007.06.048 Bjornsdottir-Butler K. Bencsath F.A. Benner J.R.A. Modification and single-laboratory validation of aoac official method 977.13 for histamine in seafood to improve sample throughput J. AOAC Int. 2015 98 622 627 26086251 Patange S.B. Mukundan M.K. Ashok Kumar K. A simple and rapid method for colorimetric determination of histamine in fish flesh Food Control 2005 16 465 472 10.1016/j.foodcont.2004.05.008 Pessatti T.L. Fontana J.D. Pessatti M.L. Spectrophotometric determination of histamine in fisheries using an enzyme immunoassay method Meth. Mol. Biol. 2004 268 311 316 Cinquina A.L. Longo F. Calı̀ A. De Santis L. Baccelliere R. Cozzani R. Validation and comparison of analytical methods for the determination of histamine in tuna fish samples J. Chromatogr. A 2004 1032 79 85 10.1016/j.chroma.2003.11.033 15065780 Ben-Gigirey B. Craven C. An H. Histamine formation in albacore muscle analyzed by aoac and enzymatic methods J. Food Sci. 1998 63 210 214 10.1111/j.1365-2621.1998.tb15711.x Stojanović Z.S. Mehmeti E. Kalcher K. Guzsvány V. Stanković D.M. Swcnt-modified carbon paste electrode as an electrochemical sensor for histamine determination in alcoholic beverages Food Anal. Methods 2016 9 2701 2710 10.1007/s12161-016-0452-3 Degefu H. Amare M. Tessema M. Admassie S. Lignin modified glassy carbon electrode for the electrochemical determination of histamine in human urine and wine samples Electrochim. Acta 2014 121 307 314 10.1016/j.electacta.2013.12.133 Geto A. Tessema M. Admassie S. Determination of histamine in fish muscle at multi-walled carbon nanotubes coated conducting polymer modified glassy carbon electrode Synth. Met. 2014 191 135 140 10.1016/j.synthmet.2014.03.005 Bao L. Sun D. Tachikawa H. Davidson V.L. Improved sensitivity of a histamine sensor using an engineered methylamine dehydrogenase Anal. Chem. 2002 74 1144 1148 10.1021/ac0106086 11924976 Keow C.M. Abu Bakar F. Salleh A.B. Heng L.Y. Wagiran R. Bean L.S. An amperometric biosensor for the rapid assessment of histamine level in tiger prawn (penaeus monodon) spoilage Food Chem. 2007 105 1636 1641 10.1016/j.foodchem.2007.04.027 Niculescu M. Frébort I. Peč P. Galuszka P. Mattiasson B. Csöregi E. Amine oxidase based amperometric biosensors forhistamine detection Electroanalysis 2000 12 369 375 10.1002/(SICI)1521-4109(20000301)12:5<369::AID-ELAN369>3.0.CO;2-J Yamamoto K. Takagi K. Kano K. Ikeda T. Bioelectrocatalytic detection of histamine using quinohemoprotein amine dehydrogenase and the native electron acceptor cytochrome c-550 Electroanalysis 2001 13 375 379 10.1002/1521-4109(200104)13:5<375::AID-ELAN375>3.0.CO;2-R Zeng K. Tachikawa H. Zhu Z. Davidson V.L. Amperometric detection of histamine with a methylamine dehydrogenase polypyrrole-based sensor Anal. Chem. 2000 72 2211 2215 10.1021/ac9911138 10845365 Sarada B.V. Rao T.N. Tryk D.A. Fujishima A. Electrochemical oxidation of histamine and serotonin at highly boron-doped diamond electrodes Anal. Chem. 2000 72 1632 1638 10.1021/ac9908748 10763262 Barbara G. Stanghellini V. De Giorgio R. Cremon C. Cottrell G.S. Santini D. Pasquinelli G. Morselli-Labate A.M. Grady E.F. Bunnett N.W. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome Gastroenterology 2004 126 693 702 10.1053/j.gastro.2003.11.055 14988823 Wood J.D. Histamine, mast cells, and the enteric nervous system in the irritable bowel syndrome, enteritis, and food allergies Gut 2006 55 445 447 10.1136/gut.2005.079046 16531524 Lin R.Y. Schwartz L.B. Curry A. Pesola G.R. Knight R.J. Lee H.-S. Bakalchuk L. Tenenbaum C. Westfal R.E. Histamine and tryptase levels in patients with acute allergic reactions: An emergency department–based study J. Allergy Clin. Immunol. 2000 106 65 71 10.1067/mai.2000.107600 10887307 Chhabra J. Li Y.Z. Alkhouri H. Blake A.E. Ge Q. Armour C.L. Hughes J.M. Histamine and tryptase modulate asthmatic airway smooth muscle gm-csf and rantes release Eur. Respir. J. 2007 29 861 10.1183/09031936.00106306 17470620 Adlesic M. Verdrengh M. Bokarewa M. Dahlberg L. Foster S.J. Tarkowski A. Histamine in rheumatoid arthritis Scand. J. Immunol. 2007 65 530 537 10.1111/j.1365-3083.2007.01938.x 17523945 Peeters M. Troost F.J. Mingels R.H.G. Welsch T. van Grinsven B. Vranken T. Ingebrandt S. Thoelen R. Cleij T.J. Wagner P. Impedimetric detection of histamine in bowel fluids using synthetic receptors with ph-optimized binding characteristics Anal. Chem. 2013 85 1475 1483 10.1021/ac3026288 23249279 Trikka F.A. Yoshimatsu K. Ye L. Kyriakidis D.A. Molecularly imprinted polymers for histamine recognition in aqueous environment Amino Acids 2012 43 2113 2124 10.1007/s00726-012-1297-8 22526245 Allender C.J. Richardson C. Woodhouse B. Heard C.M. Brain K.R. Pharmaceutical applications for molecularly imprinted polymers Int. J. Pharm. 2000 195 39 43 10.1016/S0378-5173(99)00355-5 Tong A. Dong H. Li L. Molecular imprinting-based fluorescent chemosensor for histamine using zinc(ii)–protoporphyrin as a functional monomer Anal. Chim. Acta 2002 466 31 37 10.1016/S0003-2670(02)00471-3 Gao F. Grant E. Lu X. Determination of histamine in canned tuna by molecularly imprinted polymers-surface enhanced raman spectroscopy Anal. Chim. Acta 2015 901 68 75 10.1016/j.aca.2015.10.025 26614059 Peeters M. Kobben S. Jiménez-Monroy K.L. Modesto L. Kraus M. Vandenryt T. Gaulke A. van Grinsven B. Ingebrandt S. Junkers T. Thermal detection of histamine with a graphene oxide based molecularly imprinted polymer platform prepared by reversible addition–fragmentation chain transfer polymerization Sens. Actuators B Chem. 2014 203 527 535 10.1016/j.snb.2014.07.013 Horemans F. Alenus J. Bongaers E. Weustenraed A. Thoelen R. Duchateau J. Lutsen L. Vanderzande D. Wagner P. Cleij T.J. MIP-based sensor platforms for the detection of histamine in the nano- and micromolar range in aqueous media Sens. Actuators B Chem. 2010 148 392 398 10.1016/j.snb.2010.05.003 Pietrzyk A. Suriyanarayanan S. Kutner W. Chitta R. D’Souza F. Selective histamine piezoelectric chemosensor using a recognition film of the molecularly imprinted polymer of bis(bithiophene) derivatives Anal. Chem. 2009 81 2633 2643 10.1021/ac8025652 19278237 Bongaers E. Alenus J. Horemans F. Weustenraed A. Lutsen L. Vanderzande D. Cleij T.J. Troost F.J. Brummer R.J. Wagner P. A MIP-based biomimetic sensor for the impedimetric detection of histamine in different ph environments Phys. Status Solidi (A) 2010 207 837 843 10.1002/pssa.200983307 Sellergren B. Molecular imprinting by noncovalent interactions. Enantioselectivity and binding capacity of polymers prepared under conditions favoring the formation of template complexes Die Makromol. Chem. 1989 190 2703 2711 10.1002/macp.1989.021901104 Yan M. Molecularly Imprinted Materials: Science and Technology CRC Press Boca Raton, FL, USA 2004 Henao-Escobar W. del Torno-de Román L. Domínguez-Renedo O. Alonso-Lomillo M.A. Arcos-Martínez M.J. Dual enzymatic biosensor for simultaneous amperometric determination of histamine and putrescine Food Chem. 2016 190 818 823 10.1016/j.foodchem.2015.06.035 26213043 Veseli A. Vasjari M. Arbneshi T. Hajrizi A. Švorc Ľ. Samphao A. Kalcher K. Electrochemical determination of histamine in fish sauce using heterogeneous carbon electrodes modified with rhenium(IV) oxide Sens. Actuators B Chem. 2016 228 774 781 10.1016/j.snb.2016.01.085 Stojanović Z.S. Švarc-Gajić J.V. A simple and rapid method for histamine determination in fermented sausages by mediated chronopotentiometry Food Control 2011 22 2013 2019 10.1016/j.foodcont.2011.05.022 Švarc-Gajić J. Stojanović Z. Determination of histamine in cheese by chronopotentiometry on a thin film mercury electrode Food Chem. 2011 124 1172 1176 10.1016/j.foodchem.2010.07.030 Akbari-adergani B. Norouzi P. Ganjali M.R. Dinarvand R. Ultrasensitive flow-injection electrochemical method for determination of histamine in tuna fish samples Food Res. Int. 2010 43 1116 1122 10.1016/j.foodres.2010.02.007 Figures and Tables

Rebinding isotherm of histamine (a) MIP1, NIP1; (b) MIP2, NIP2 in 50 mM PBS buffer (pH 7.4). MIP1 and MIP2 (corresponding NIPs) were prepared in CHCl3 and MeCN, respectively.

MIP-CP electrode responses to histamine. Cyclic voltammograms in different molar concentrations of histamine: 1 × 10−10 (a); 2 × 10−9 (b); 4 × 10−9 (c); 7 × 10−9 (d); 2 × 10−7 (e); and 4 × 10−7 (f). All of the histamine solutions were made in 0.1 M solution of hexacyanoferrate (III) and KCl as blank.

Comparison of voltammetric responses to histamine for different electrode composites. All of the histamine solutions were made in the 0.1 M solution of hexacyanoferrate (III) and KCl as a blank.

Selectivity investigation by cyclic voltammetry; electrochemical response of MIP-CP electrode for histamine and other similar structure compounds. [Histamine and all analytes] = 0.004 µM, scan rate = 50 mV/s, Estep = 10 mV and equilibration time = 5 s.

Calibration curve obtained for the developed sensor; (insets are showing two linear ranges of histamine, 1 × 10−10–7 × 10−9 M and 7 × 10−9–4 × 10−7 M).

 sensors-17-00645-t001_Table 1

Composition of histamine imprinted polymer by bulk polymerization.

Polymer Template (mmol) MAA (mmol) EGDMA (mmol) Solvent
MIP1 0.24 1.2 6 CHCl3
NIP1 - 1.2 6 CHCl3
MIP2 0.24 1.2 6 MeCN
NIP2 - 1.2 6 MeCN
sensors-17-00645-t002_Table 2

Determination of histamine in human serum.

Sample Spiked (mol·L−1) Found (mol·L−1) Recovery (%) RSD (%)
Human serum 5.0 × 10−10 5.2 × 10−10 104 2.02
4.0 × 10−9 4.2 × 10−9 105 3.58
2.0 × 10−7 1.9 × 10−7 95 3.42
sensors-17-00645-t003_Table 3

Comparison of analytical parameters of the proposed sensor and some other previously-reported histamine electrochemical sensors.

Method Electrode Linear Range (mol·L−1) Detection Limit (mol·L−1) Reference
Impedimetry Polymer-coated Al 1.2 × 10−8–2.0 × 10−9 2.0 × 10−9 [42]
Voltammetry Glassy carbon 2.0 × 10−4–5.0 × 10−6 0.3 × 10−6 [21]
Amperometry Screen-printed 6.0 × 10−5–8.0 × 10−6 8.1 × 10−6 [45]
Amperometry Heterogeneous carbon 8.9 × 10−5–4.5 × 10−6 1.8 × 10−6 [46]
Voltammetry SWCNT-modified carbon paste 7.2 × 10−4–4.5 × 10−6 1.3 × 10−6 [20]
Chronopotentiometry Gold 8.9 × 10−4–1.8 × 10−5 2.4 × 10−6 [28]
Chronopotentiometry Glassy carbon 8.1 × 10−4–1.8 × 10−5 1.2 × 10−5 [47]
Amperometry Boron-doped diamond 8.1 × 10−3–4.5 × 10−5 4.0 × 10−5 [48]
Voltammetry Gold micro electrode 4.9 × 10−8–9.9 × 10−12 3.1 × 10−12 [49]
Voltammetry NC/MIP/CPE 4 × 10−7–7 × 10−9 and 7 × 10−9–10 × 10−10 7.4 × 10−11 This work