Mol. Impr. 2016; 4: 1–12 Review Open Access Wei Chen, Zihui Meng*, Min Xue, Kenneth J Shea Molecular imprinted photonic crystal for sensing of biomolecules DOI 10.1515/molim-2016-0001 environmental monitoring and food quality control. Thus, Received December 8, 2015; accepted January 29, 2016 different biochemical sensors have been developed to detect biologically active molecules and determine the Abstract: Molecularly imprinted polymers (MIPs) concentration of these molecules. Due to the structure are highly cross-linked polymers with high binding complexity and large size of the biomolecules, it is a big capacity and selectivity to the target molecules. MIPs challenge to develop a good biosensor. An ideal biosensor become increasingly important because of the potential should possess the advantages of high specificity, applications in drug delivery, purification and separation. sensitivity, quick response rate as well as low cost. Thus, In spite of the tremendous progress that has been made in developing new technology for biomolecules detection the molecular imprinting field, many challenges remain has attracted much attention. [2-5] to be addressed, especially in transforming the binding The common detection methods include high event into a detectable optical signal. The combination performance liquid chromatography (HPLC) [6-7], mass of photonic crystal and molecular imprinting technique spectrometry (MS) [8-9], fluorescence [10-11], surface- is becoming a popular research idea. Compared to the enhanced Raman scattering (SERS) [12-14], enzyme- conventional MIPs, the molecularly imprinted photonic linked immunosorbent assay [15-16] and immunoassays crystal sensors (MIPCB) have the advantage of directly [17-18]. Each of these methods suffers from one or more convert the molecule recognition process into optical disadvantages, such as require complicated screening and signal. This review comprehensively summarizes various concentration processes prior to sensing, high cost and MIPCB, including the principle of molecular imprinted time consuming. Among those methods, immunoassays photonic crystal sensors, recent development, some using labeled antibodies are the most popular methods challenges and effective strategies for MIPCB. for the detection of biomolecules with high sensitivity and selectivity [19]. However, labeling protocols are time- Keywords: Molecularly imprinted polymer, photonic consuming and expensive, and may lead to denature of the crystal, biomolecules, sensors antibodies. Therefore, label-free detectors for biomolecules have drawn increasing interest for researches in the field of proteomics, clinical diagnostics and environmental 1 Introduction monitoring. In label-free sensors, target molecules are detected in their natural forms without any label process. Biomolecules are present in living organisms, including These types of sensors have the advantages of eliminating large macromolecules such as proteins, polysaccharides, the time-consuming and expensive labeling steps, as lipids, and nucleic acids, as well as small molecules such well as allowing for kinetic measurement of molecular as glycolipids, sterols, glycerolipids and vitamins. [1] interactions. Recently, molecularly imprinted photonic Detection and quantification of biomolecules has attracted crystal biosensors as a new kind of bioassay techniques considerable attention in the fields of clinical diagnostics, have attracted substantial interest due to their great potential for label-free detection of biomolecular [20-22]. In this review, we provide an overview of different *Corresponding author Zihui Meng, School of Chemical Engineering molecularly imprinted photonic crystal biosensors & Environment, Beijing Institute of Technology, Beijing, 100081, P.R. China, E-mail: [email protected] (MIPCB) developed until now (Table 1). After introducing Wei Chen, Min Xue, School of Chemical Engineering & Environment, the concept of molecularly imprinting and photonic Beijing Institute of Technology, Beijing, 100081, P.R. China crystal sensors, we focus on the applications of molecular Kenneth J Shea, Department of Chemistry, University of California, imprinted photonic crystal biosensors. Finally, we Irvine, California, 92697, United States © 2016 Wei Chen et al., published by De Gruyter Open. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License. Unauthenticated Download Date | 4/28/16 10:14 AM 2 W. Chen, et al. Table 1 Overview of different MIPCB Template Monomer and cross-linker Structure Reference Protein BSA MAA,EGDMA Inverse opal [20] Hb IDA, PTMS, APTMS Opal [23] IDA, PTMS, APTMS Hollow spheres array [24] Hb, HRP, BSA AAm, BIS Inverse opal [21] Chiral biomolecules L-Dopa MAA,EGDMA Inverse opal [25] L-Phenylalanine AAm, MAA,BIS Inverse opal [26] MAH-β-CD, AAc, BIS Inverse opal [27] (-)-Norephedrine G0-3TCOOH Opal [28] Other biomolecules Cholic acid MAA, EGDMA Inverse opal [29] Atropine MAA, EGDMA Inverse opal [30] Diethylstilbestrol MMA, AAm, Opal [31] Imidacloprid MAA, EGDMA Inverse opal [5] Theophylline, ephed- MAA, EGDMA Inverse opal [32] rine Tetracyclines AAm, AAc, BIS Inverse opal [22] Cholesterol MAA, EGDMA Inverse opal [33] Bisphenol A MMA,EGDMA Opal [34] MMA,EGDMA Inverse opal [35] 17β-estradiol MMA, AAm, BIS Opal [36] Vanillin MAA,EGDMA Inverse opal [37] Atrazine MAA,EGDMA Inverse opal [30] considered the challenges presently encountered and MIPs were created by the polymerization of a mixture of some feasible resolutions. cross-linkers and functional monomers in the presence of a template dissolved in proper solvent, followed by the removal of template from polymer, specific recognition 2 Molecular imprinting polymers and binding sites exhibit high selectivity to the target MIPs molecule was formed in the highly cross-linked polymer network, the detailed process was demonstrated in Molecularly imprinted polymers (MIPs) have been called Figure 1. Compared to the antibody in nature, molecularly ‘‘antibody mimics’’ or “plastic antibodies” because these imprinting polymers have higher physical strength, systems attempt to mimic the specific recognition between flexibility, robustness and resistance to elevated pressure antibodies and antigen in the immune system [38-40]. which make them attractive in usage for bioreceptor Figure 1 representation of the molecular imprinting process. Reprinted with permission from Reference 43. Copyright 2013, Royal Society of Chemistry. Unauthenticated Download Date | 4/28/16 10:14 AM Molecular imprinted photonic crystal for sensing of biomolecules 3 and cost-effective detect materials. In general terms, the stable emulsion of a cross-linking monomer. The binding approaches to molecular imprinting can be distinguished experiments showed that bacterial recognition on the BIP by the interaction between the template molecules and beads is dependent on the nature of the pre-polymers and the functional monomers. They are covalent molecular the target bacteria. The functional materials for microbial imprinting, non-covalent molecular imprinting and recognition showed great potential for constructing metal-coordinating molecular imprinting [41-42]. cell-cell communication networks, biosensors, and new Since the idea of molecular imprinting was first put platforms for testing antibiotic drugs. forward by Pauling in 1940s [43], over the past decades, Despite the advantages of MIPs with high selectivity it is well known that molecular imprinting is a very and strong affinity, there remains some drawback of promising and rapidly evolving technology, with many the difficulty in transforming the binding event into a possible applications such as preparative analytical detectable optical signal which is a hurdle for the wider separations [44-45], enzyme-like catalysis [46-47], solid- applications. phase extractions [48-49], chemical sensors [50-51] and drug delivery [52-53], etc. Molecular imprinting has proven to be particularly successful for small molecules. Recent 3 Photonic crystals years, much attention has been paid to the imprinting Photonic crystals (PhCs) are composed of a periodic of biomolecules such as proteins [54-55], DNA [56], and arrangement of regularly shaped materials with different even whole cells [57] and viruses [58-59] for its potential dielectric constants, owing to the periodicity in dielectric, applications in biomaterials separation, purification, these materials exhibit a photonic band gap (PBG), biosensor, and mimicking enzyme and antibody [60]. certain wavelength of light located in the band gap can’t Rossetti et al. synthesized molecularly imprinted polymers (MIPs) targeting the proteotypic peptide of ProGRP by surface-initiated reversible addition-fragmentation chain transfer polymerization. [40] As shown in Figure 2, the polymerization was performed on the surface of RAFT- modified wide-pore silica beads using hydrophobic cross- linker divinylbenzene (DVB) and functional monomers N-(2-aminoethyl) methacrylamide hydrochloride (EAMA). The MIPs have high affinity and selectivity for a proteotypic peptide in aqueous buffered media. Also the MIPs were used as sorbents for the cleanup and enrichment of a ProGRP signature peptide from typically treated serum samples. This fundamental property makes the MIPs promising in biological sample cleanup and cost-effective biomarker analysis. In another study, a bacteria-imprinted polymer (BIP) was prepared by Ye et al. using Pickering emulsion polymerization [61]. The imprinting process was described in