sensors Review Molecular Imprinting Applications in Forensic Science Erkut Yılmaz 1, Bora Garipcan 2, Hirak K. Patra 3 and Lokman Uzun 4,* 1 Department of Biotechnology and Molecular Biology, Aksaray University, 68100 Aksaray, Turkey; [email protected] 2 Institute of Biomedical Engineering, Bogazici University, 34684 Istanbul, Turkey; [email protected] 3 Department of Clinical and Experimental Medicine, Linkoping University, 58225 Linköping, Sweden; [email protected] 4 Department of Chemistry, Hacettepe University, 06381 Ankara, Turkey * Correspondence: [email protected] or [email protected]; Tel.: +90-312-780-7337; Fax: +90-312-299-2163 Academic Editors: Bo Mattiasson and Gizem Ertürk Received: 16 February 2017; Accepted: 23 March 2017; Published: 28 March 2017 Abstract: Producing molecular imprinting-based materials has received increasing attention due to recognition selectivity, stability, cast effectiveness, and ease of production in various forms for a wide range of applications. The molecular imprinting technique has a variety of applications in the areas of the food industry, environmental monitoring, and medicine for diverse purposes like sample pretreatment, sensing, and separation/purification. A versatile usage, stability and recognition capabilities also make them perfect candidates for use in forensic sciences. Forensic science is a demanding area and there is a growing interest in molecularly imprinted polymers (MIPs) in this field. In this review, recent molecular imprinting applications in the related areas of forensic sciences are discussed while considering the literature of last two decades. Not only direct forensic applications but also studies of possible forensic value were taken into account like illicit drugs, banned sport drugs, effective toxins and chemical warfare agents in a review of over 100 articles. The literature was classified according to targets, material shapes, production strategies, detection method, and instrumentation. We aimed to summarize the current applications of MIPs in forensic science and put forth a projection of their potential uses as promising alternatives for benchmark competitors. Keywords: molecular imprinting; forensic science; toxicology; analytical methods; pre-concentration 1. Introduction The area of forensic science emerged due to the need for scientific techniques for investigating and proving crimes. Forensic science is quite a multidisciplinary area of study with ten and more subdivisions like chemistry, biology, toxicology, geology, archeology, anthropology, astronomy, engineering, etc. All these subdivisions have different methods for problem solving and use a series of specialized tools. In general, “problem solving” in the area of forensic analysis have two meanings: First, identifying the physical evidence or a questioned sample, and the second one is comparing the results with a known material to find the origin of the questioned sample. Molecular imprinting techniques present solutions for both of these requirements as well. Due to their versatility, molecular imprinted polymers (MIPs) have gained many applications in a variety of areas [1]. Versatile usage, stability and recognition capabilities make them a perfect candidate for the use in forensic sciences [2]. MIPs can be prepared in different physical shape and sizes while conferring them with some multi-functional smart material capabilities, like magnetic, stimuli-responsive, fluorescence labelling, etc. These functions support many possible application areas in the field of forensic sciences. Sensors 2017, 17, 691; doi:10.3390/s17040691 www.mdpi.com/journal/sensors Sensors 2017, 17, 691 2 of 25 Sensors 2017, 17, 691 2 of 25 Sensors 2017, 17, 691 2 of 24 multi-functionalmulti-functional smart smart material material capabilities,capabilities, like magnetic, stimuli-responsive, fluorescence fluorescence labelling, labelling, etc.etc. These These functions functions support support manymany possiblepossible application areas inin thethe fieldfield ofof forensicforensic sciences. sciences. 2.2. A A Brief Brief TheoryTheory ofof MolecularMolecular ImprintingImprinting 2. A Brief Theory of Molecular Imprinting MolecularMolecular imprintingimprinting is the method of of producin producingg tailor-made tailor-made complement complementaryary cavities cavities against against a Molecular imprinting is the method of producing tailor-made complementary cavities against a atargeted targeted structure structure called called the the template. template. By By means means of of these these smart smart and and complementary complementary cavities, cavities, the the targeted structure called the template. By means of these smart and complementary cavities, the resultingresulting molecules molecules have have bothboth chemicalchemical andand physical recognition capabilities; capabilities; therefore, therefore, they they are are also also resulting molecules have both chemical and physical recognition capabilities; therefore, they are also classifiedclassified asas biomimeticbiomimetic receptorsreceptors oror plasticplastic antibodiesantibodies [[3].3]. Molecular Molecular imprinting imprinting is is a a method method for for classified as biomimetic receptors or plastic antibodies [3]. Molecular imprinting is a method for producingproducing selective selective binding binding sites sites in highlyin highly cross-linked cross-linked synthetic synthetic polymeric polymeric matrices matrices [4]. It is [4]. generally It is producing selective binding sites in highly cross-linked synthetic polymeric matrices [4]. It is achievedgenerally via achieved the self-assembly via the self-assembly of functional of monomers functional around monomers a “template” around anda “template” then polymerization and then generally achieved via the self-assembly of functional monomers around a “template” and then ofpolymerization these pre-polymer of these complexes pre-polymer in the complexes presence ofin extensivethe presence crosslinkers, of extensive which crosslinkers, is onlyone which of theis polymerization of these pre-polymer complexes in the presence of extensive crosslinkers, which is generallyonly one followedof the generally synthetic followed routes and synthetic is called routes non-covalent and is called imprinting. non-covalent These monomers imprinting. and These ratio only one of the generally followed synthetic routes and is called non-covalent imprinting. These inmonomers the pre-polymer and ratio complex in the pre-polymer are chosen accordingcomplex are to chosen their affinity according towards to their the affinity template. towards After the the monomers and ratio in the pre-polymer complex are chosen according to their affinity towards the templatetemplate. removal After the from template the polymeric removal matrix, from the the po imprintedlymeric cavitiesmatrix, the come imprinted out with cavities both chemical come out and physicaltemplate.with both recognition After chemical the templateand capabilities physical removal (Figure recognition from1)[5 ]. thecapabilities polymeric (Figure matrix, 1) [5].the imprinted cavities come out with both chemical and physical recognition capabilities (Figure 1) [5]. Figure 1. The molecular imprinting principle. a: functional monomers; b: cross-linker; c: template Figure 1. The molecular imprinting principle. a: functional monomers; b: cross-linker; c: template Figuremolecule; 1. The 1: assembly molecular of theimprinting prepolymerisation principle. complea: functix; onal2: polymerization; monomers; b: 3: cross-linker;extraction; 4: c:rebinding. template molecule; 1: assembly of the prepolymerisation complex; 2: polymerization; 3: extraction; 4: rebinding. molecule;Reprinted 1: with assembly perm issionof the fromprepolymerisation [5]. complex; 2: polymerization; 3: extraction; 4: rebinding. Reprinted with permission from [5]. Reprinted with permission from [5]. In imprinting history, researchers have integrated several polymerization techniques into the imprintingIn imprintingimprinting process history, which has researchersresearchers resulted in havehave five integrated integratedmain types severalseveral of molecular polymerizationpolymerization imprinting techniquestechniques techniques. into These the imprintingcan be summarized process which as covalent, has resultedresulted non-covalent, inin fivefive mainmain semi-covalent, typestypes ofof molecularmolecular ionic, and imprintingimprinting metal coordination techniques.techniques. methods These can[2]. bebe A summarizedsummarizedschematic representation as as covalent, covalent, non-covalent, ofno thesen-covalent, molecular semi-covalent, semi-covalent, imprinting ionic, ionic,techniques and and metal metal is shown coordination coordination in Figure methods methods2. [2]. A[2]. schematic A schematic representation representation of these of these molecular molecular imprinting imprinting techniques techniques is shown is shown in Figure in Figure2. 2. Figure 2. Schematic representation of five main types of interactions used for molecular imprinting purpose. 1: covalent; 2: semi-covalent; 3: covalent; 4: ionic; 5: metal ion coordination. Figure 2. Schematic representation of five main types of interactions used for molecular imprinting Figure 2. Schematic representation of five main types of interactions used for molecular imprinting purpose. 1: covalent; 2: semi-covalent; 3: covalent; 4: ionic; 5: metal ion coordination. purpose. 1: covalent; 2: semi-covalent; 3: covalent; 4: ionic;