An Overview of Bio-Inspired Intelligent Imprinted Polymers for Virus Determination

Abstract

The molecular imprinting polymers (MIPs) have shown their potential in various applications including pharmaceuticals, chemical sensing and biosensing, medical diagnosis, and environmental related issues, owing to their artificial selective biomimetic recognition ability. Despite the challenges posed in the imprinting and recognition of biomacromolecules, the use of MIP for the imprinting of large biomolecular oragnism such as viruses is of huge interest because of the necessity of early diagnosis of virus-induced diseases for clinical and point-of-care (POC) purposes. Thus, many fascinating works have been documented in which such synthetic systems undoubtedly explore a variety of potential implementations, from virus elimination, purification, and diagnosis to virus and bacteria-borne disease therapy. This study is focused comprehensively on the fabrication strategies and their usage in many virus-imprinted works that have appeared in the literature. The drawbacks, challenges, and perspectives are also highlighted.

Keywords: biosensors; molecular imprinted polymers; selectivity; strategies; virus.

Figure 1

AFM images of (a) the H1N3 influenza A virus used as a template, (b) the corresponding H1N3 based MIPs at 200 nm resolution. The MIP cavities in the latter have been found to be between 80 and 120 nm in diameter, which is the expected size of influenza A. Also illustrated is the structure of the MIP with (c) and without template bound (d) displayed at 2 mm resolution. The white spots present in the template bound structure (d) are indicative of bound virus (some bound virus is marked by dark arrows) (Reproduced with permission from Reference [53]).

Figure 2

Schematic of H5N1 virus binding to a MIP (top) and inhibition of the process due to a conformational change in the H5N1-probe complex (Reproduced with permission from Reference [54]).

Figure 3

Principle of preparation of the virus-MIPs and detection of virus (Reproduced with permission from Reference [59]).

Figure 4

(a) Preparation of “double imprinted” diffraction grating bioimprinted hydrogels for MIP-GLaDiS materials. (b) Schematic of the laser diffraction apparatus used for the measurement of the laser diffraction pattern projected onto a desk ruler (left). Outline of the bioimprinting process used to create virus responsive super-aptamer hydrogels. NIPAM = N-isopropylacrylamide, AM = acrylamide, MBAA = N,N’-methylene bisacrylamide, APS = ammonium persulfate, TEMED = N,N,N’,N’-tetramethylethylendiamine, PBS = phosphate-buffered saline (right) (Reproduced with permission from Reference [68]).

Figure 5

Contact mode AFM images of polyurethane layers: (a) nonimprinted polymer, (b) human rhinovirus (HRV) self-assembled on a surface, (c) molecular imprinting polymer (MIP) with partially removed template, and (d) MIP after washing (Reproduced with permission from Reference [69]).

Figure 6

Binding of virions of the templated turnip yellow mosaic virus (TYMV) and non-templated tomato bushy stunt virus (TBSV) to virus imprinted polymers (VIPs) and non-imprinted particles (NIPs). Symbols are for TYMV (open squares) and for TBSV (solid squares). Binding time, selectivity, composition and thickness of the recognition layer were compared. (a–d) Four types of particles were assayed: (a) VIPs_OM, (b) NIPs_OM, (c) VIPs_AT, and (d) NIPs_AT; OM and AT particles with 8-mm-thick recognition layers. (e–h) Nanoparticles with recognition layers of increasing thicknesses (mean ± s.e.m.) were assayed: (e) VIPs_OM, (f) NIPs_OM, (g) VIPs_AT, and (h) NIPs_AT. All values are presented normalized in percentage of initial virus concentration (mean ± s.e.m.)(The term VIPs_OM stands for particles imprinted with TYMV virions and having a recognition layer composed of an organosilanes mixture (OM), and the term non-imprinted particles (NIPs)_OM for NIPs produced in the absence of template using the same OM. As controls, we selected two additional formulations, one with tetraethyl orthosilicate (TEOS) alone and one with a mixture of APTES and TEOS (AT). The corresponding VIPs are abbreviated VIPs_AT for TYMV imprinted particles having a recognition layer made of AT and NIPs_AT for those produced under the same conditions in the absence of template) ((Reproduced with permission from Reference [72]).