Prof Sergey A Piletsky

Professor in Bioanalytical Chemistry

Postgraduate Admissions Tutor

Sergey Piletsky

Tel: +44 (0)116 294 4666
Email: sp523@le.ac.uk

Personal details

Research of my group is focussed largely on polymer chemistry and its use in biotechnology, medicine and analytical chemistry.

Awards received

  • JSPS Fellowship (1995)
  • Award of President of Ukraine (1996-1997)
  • DFG Fellowship (1997)
  • Leverhulme Trust Fellowship (1998-1999)
  • Business/University Collaboration Award for East of England (2005)
  • Royal Society Wolfson Research Merit Award (2002-2007)

Publications

  1. Piletsky S. A., Matuschewski H., Schedler U., Wilpert A., Piletska E. V., Thiele T. A., Ulbricht M. (2000). Surface functionalization of porous polypropylene membranes with molecularly imprinted polymers by photo-graft copolymerization in water. Macromolecules, 33, 3092-3098. DOI: 10.1021/ma991087f
  2. Piletsky S. A., Piletska E. V., Chen B., Karim K., Weston D., Barrett G., Lowe P., Turner A. P. F. (2000). Chemical grafting of molecularly imprinted homopolymers to the surface of microplates. Application of artificial adrenergic receptor in enzyme-linked assay for β-agonists determination. Analytical Chemistry, 72, 4381-4385. DOI: 10.1021/ac0002184
  3. Bossi A., Piletsky S. A., Piletska E. V., Righetti P. G., Turner A. P. F. (2001). Surface-grafted molecularly imprinted polymers for proteins recognition. Analytical Chemistry, 73, 5281-5286. DOI: 10.1021/ac0006526
  4. Chianella I., Lotierzo M., Piletsky S. A., Tothill I. E., Chen B., Karim K., Turner A. P. F. (2002). Rational design of a polymer specific for microcystin-LR using a computational approach. Analytical Chemistry, 74, 1288-1293. DOI: 10.1021/ac010840b
  5. Piletsky S. A., Piletska E. V., Karim K., Freebairn K. W., Legge C. H., Turner A. P. F. (2002). Polymer cookery: influence of polymerization conditions on the performance of molecularly imprinted polymers. Macromolecules, 35, 7499-7504. DOI: 10.1021/ma0205562
  6. Guerreiro A. R., Chianella I., Piletska E., Whitcombe M. J., Piletsky S. A. (2009). Selection of imprinted nanoparticles by affinity chromatography. Biosensors & Bioelectronics, 24, 2740-2743. DOI: 10.1016/j.bios.2009.01.013
  7. Lakshmi D., Bossi A., Whitcombe M. J., Chianella I., Fowler S. A., Subrahmanyam S., Piletska E. V., Piletsky S. A. (2009). Electrochemical sensor for catechol and dopamine based on a catalytic molecularly imprinted polymer-conducting polymer hybrid recognition element. Analytical Chemistry, 81, 3576-3584. DOI: 10.1021/ac802536p
  8. Piletska E., Guerreiro A., Whitcombe M., Piletsky S. (2009). Influence of the polymerization conditions on the performance of molecularly imprinted polymers. Macromolecules, 42, 4921-4928. DOI: 10.1021/ma900432z
  9. Poma A., Turner A. P. F., Piletsky S. A. (2010). Advances in the manufacture of MIP nanoparticles. Trends in Biotechnology, 28, 629-637. DOI: 10.1016/j.tibtech.2010.08.006
  10. Piletska E. V., Stavroulakis L. D., Whitcombe M. J., Sharma A., Primrose S., Robinson G. K., Piletsky S. A. (2011). Passive control of quorum sensing: prevention of pseudomonas aeruginosa biofilm formation by imprinted polymers. Biomacromolecules, 12, 1066-1071. DOI: 10.1021/bm101410q
  11. Whitcombe M. J., Chianella I., Larcombe L. Piletsky S. A, Noble J., Porter R., Horgan A. (2011). The rational development of molecularly imprinted polymer-based sensors for protein detection. Chemical Society Reviews, 40, 1547-1571. DOI: 10.1039/C0CS00049C
  12. Ivanova-Mitseva P. K., Guerreiro A., Piletska E. V., Whitcombe M. J., Zhou Z., Mitsev P. A., Davis F., Piletsky S. A. (2012). Cubic MIP nanoparticles with fluorescent core. Angewandte Chemie International Edition, 124, 5286-5289. DOI: 10.1002/anie.201107644
  13. Poma A., Guerreiro A., Whitcombe M. J., Piletska E., Turner A. P. F., Piletsky S. (2013). Solid-phase synthesis of molecularly imprinted polymer nanoparticles with a reusable template (“plastic antibodies"). Advanced Functional Materials, 23, 2821-2827. DOI: 10.1002/adfm.201202397
  14. Moczko E., Poma A., Guerreiro A., de Vargas Sansalvador I. P., Caygill S., Canfarotta F., Whitcombe M. J., Piletsky S. (2013). Surface-modified multifunctional MIP nanoparticles. Nanoscale, 5, 3733-3741. DOI: 10.1039/C3NR00354J
  15. Moczko E., Guerreiro A., Piletska E., Piletsky S. (2013). PEG-stabilized core-shell surface-imprinted nanoparticles. Langmuir, 29, 9891-9896. DOI: 10.1021/la401891f
  16. Chianella I., Guerreiro A., Moczko E., Caygill J. S., Piletska E. V., Perez De Vargas Sansalvador I. M., Whitcombe M. J., Piletsky S. A. (2013). Direct replacement of antibodies with molecularly imprinted polymer (MIP) nanoparticles in ELISA – development of a novel assay for vancomycin. Analytical Chemistry, 85, 8462-8468. DOI: 10.1021/ac402102j

Research

  • Biomimetic molecularly imprinted polymers (MIPs)
  • Computational design and molecular modelling
  • Bioanalytical chemistry - design of sensors and assays for clinical and environmental diagnostics
  • Nanoparticles for diagnostics and therapeutic applications

Biomimetic polymers (MIPs)

The concept of molecular imprinting describes the creation of artificial molecular recognition sites in a functional synthetic polymer by the process of forming said polymers in the presence of a template (Figure 1).

SP 2
Figure 1. Schematic representation of the imprinting (template) polymerisation process
Complementary interactions between polymer-forming components and the template species are preserved in their spatial arrangement by the polymerisation process and are stabilised by cross-linking. MIPs are capable of selective recognition of their target species in the template-derived sites. Importantly, molecular imprinting of polymers represents the most generic, versatile, scalable and cost-effective approach to the creation of synthetic molecular receptors to date. Three particular features have made MIPs the target of intense investigation: (i) their high affinity and selectivity, which are similar to those of natural receptors; (ii) their unique stability which is superior to that demonstrated by natural biomolecules; and (iii) the simplicity of their preparation and the ease of adaptation to different practical applications. Our principle activities in this area include:

  • Fundamental work analysing the impact of various physico-chemical factors on the recognition properties of imprinted polymers (Piletska et al., 2009, Macromolecules, 42, 4921)
  • Investigation of the “gate effect” – the ability of a MIP to change its conformation upon interaction with its template - and the application of this phenomenon in membranes and sensors (Piletsky et al., 1998, Macromolecules, 31, 2137)
  • Study of the transport and recognition properties of MIP-based membranes (Piletsky et al., 1999, Journal of Membrane Science, 157, 263; Sergeyeva et al., 2003, Macromolecules, 36, 7352)
  • Development of computational approaches in the design of synthetic receptors and the transformation of these methods into reliable tools for the routine preparation of high-performance imprinted polymers (Chianella et al., 2002, Analytical Chemistry, 74, 1288)

Computational design and molecular modelling

The broad range of functional monomers currently available makes it possible to design MIPs specific to practically any type of stable chemical compound. As a consequence, selection of the best monomers for polymer preparation is one of the most crucial decisions in the molecular imprinting process. Our solution to this problem involves the application of molecular modelling software, originally developed for dug design, namely SYBYL™ (Tripos, UK). We model the interactions that take place between monomers, cross-linker, template and solvent, the energetic state of which can be quantified by applying the equation proposed by Williams (Williams et al., 1991, Journal of the American Chemical Society, 113, 7020).

SP 3
Where the individual contribution of the Gibbs free energy of complex formation, ∆Gbind are: ∆Gt+r, loss of translational and rotational degrees of freedom; ∆Gr, restriction of rotors upon complexation; ∆Gh, hydrophobic interactions; ∆Gvib residual soft vibrational modes; ∑∆Gp, the sum of interacting polar group contributions; ∆Gconf, adverse conformational changes; and ∆GvdW, unfavourable van der Waals interactions.

In our approach we created a virtual library of functional monomers that can be screened against target compounds using the algorithm Leapfrog™, part of the SYBYL software suite of programs (Figure 2). The initial selection of monomers is based upon the strengths of their interactions with the template (Piletsky et al., 2001, Analyst, 126, 1826; Chianella et al., 2002, Analytical Chemistry, 74, 1288).

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Figure 2. Modelling of monomer-template interactions.
An analysis of the strength of monomer-monomer interactions, the impact of the choice of solvent and cross-linker on complex formation, and a prediction of the influence of temperature on the strength of complexation, is performed during simulated annealing experiments with energy calculations made after each iteration (Subrahmanyam et al., Advanced Materials, 12, 722). The computational design of MIPs is a quick and efficient process that can be performed in just a couple of hours, significantly reducing the time and effort required for determining the optimum polymer composition. This approach became a popular tool to aid MIP preparation and is used regularly in our laboratory and many others worldwide (Breton et al., Biosensors & Bioelectronics, 22, 1948; Piletska et al., 2005, Journal of Controlled Release, 108, 132; Muhammad et al., 2012, Analyst, 137, 2623; Bakas et al., 2013, Journal of Chromatography A, 1274, 13; Lakshmi et al., 2013, Industrial & Engineering Chemistry Research, 52, 13910). Our current research interests involve using computational design to aid the production of high performance MIPs for application in separations and diagnostics.

Bioanalytical chemistry - design of sensors and assays for clinical and environmental diagnostics

Three particular properties make the application of MIP in sensors and assays a commercially attractive proposition: (i) polymers are highly stable and can be autoclaved; (ii) they are fully compatible with microfabrication technology, and (iii) the low cost of raw materials and ease of polymer preparation in comparison with natural and other artificial receptor systems. Our work in this area is concentrated on resolving the main problems associated with the development of MIP sensors, namely: (i) the difficulty in integrating polymers with a transducer; and (ii) difficulty in transforming the binding event into a processable signal (Piletsky and Turner, 2006, in: Molecular imprinting of polymers, S. Piletsky and A.P.F. Turner (eds.), Landes Bioscience, Georgetown, USA). We integrate MIPs with a variety of sensor platforms, including electrochemical, microgravimetric (piezoelectric) and optical devices. We are collaborating with Government organisations and private

SP 5
Figure 3. MIP-based assay.
companies in order to develop MIP sensors for:

  • Control of industrial processes with extremes of pHs, pressure, temperature, use of organic solvents;
  • Control of biotechnological processes where the sensor needs to be autoclaved;
    Implantable devices;
  • Continuous on-line monitoring;
  • Sensors for defense applications;
  • Robust sensors and assays which do not require a cold chain

The most promising areas for the application of MIP nanoparticles in sensors and assays are medical diagnostics and environmental analyses (Figure 3). An important niche application for MIP sensors is in the detection of chemical and biological warfare agents under battlefield conditions and during civil emergencies. Turning exciting science into practical products is a long and hard path, but it is clear that MIPs have now come of age and serious attempts are being made to realise their huge potential benefits in the form of tangible products that will lead to wealth generation and improvements in the quality of life (Piletsky, Alcock, and Turner, 2001, Trends in Biotechnology, 19, 9).

Nanoparticles for diagnostics and therapeutic applications

Recently we have made a major breakthrough by developing a novel approach to the synthesis of soluble molecularly imprinted nanoparticles (nanoMIPs) that have exquisite specificity and selectivity for their templates. The success came from combining controlled radical polymerisation (Subrahmanyam et al., 2013, European Polymer Journal, 49, 100) with an affinity separation step performed on surface-immobilised template (Guerreiro et al., Biosensors & Bioelectronics 2009, 24, 2740). The particles are small enough to possess 1-2 binding sites per particles and have affinities similar to antibodies (Figure 4). This work resulted in the construction of a prototype automated nanoMIP synthesiser, the first of its kind (Poma et al., 2013, Advanced Functional Materials, 23, 2821). The process of MIP synthesis using the automated reactor is as follows.

SP 6
Figure 4. SEM image of MIP nanoparticles.
The monomer mixture is injected into a reactor containing a solid support with the immobilised template, and irradiated with UV light to initiate controlled free radical polymerisation; after the polymerisation phase, monomer mixture and low affinity polymer is eluted with a wash step; the temperature of the column is raised and the higher affinity particles eluted at 60 °C. To validate this approach we have generated high affinity plastic antibodies selective for a range of templates, including melamine, vancomycin, peptides and proteins. All synthesised MIP nanoparticles have affinity and specificity similar to natural monoclonal antibodies (KD = 0.01 - 1 nM). A further feature of the system is the possibility to post-functionalise the particles before elution from the column, either using a second polymerisation mixture and/or chemically coupling reagents (Moczko et al., 2013, Nanoscale, 5, 3733). This allows high affinity particles with electroactive or fluorescent properties to be produced. Newly developed methods for computer-controlled synthesis allow, for the first time, precise control to be exercised over their production, yielding inter- and intra-batch consistency of particles which can be tailored for a range of specific diagnostic and potentially biological functions (Piletsky et al., 2006, Biopolymer and Cell, 22, 63; Poma, Whitcombe and Piletsky, 2013, in: Piletsky S. A., Whitcombe M. (Eds.) Designing receptors for the next generation of biosensors. Springer Series on Chemical Sensors and Biosensors, 12, 260 p).

Our research priorities include:

  • Development of robust sensors and assays where MIP nanoparticles are used as replacements for natural antibodies (Chianella et al., 2013, Analytical Chemistry, 85, 8462)
  • Application of MIP nanoparticles in bioimaging (Canfarotta et al., 2013, Biotechnology Advances, 31, 1585)
  • Therapeutic application of MIP nanoparticles (supramolecular drugs)

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Contact Details

Department of Chemistry
University of Leicester
Leicester, LE1 7RH, UK

Email: chemistry@le.ac.uk

Tel: [+44] (0)116 252 2100

Fax: [+44] (0)116 252 3789

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