Nano- and Micro-sized Molecularly Imprinted Polymer Particles on Solid Surfaces

Abstract

Molecularly imprinted polymers (MIPs) are artificial receptors made by imprinting template molecules in a polymer matrix followed by their removal through washing to obtain a specific and selective template cavities. This property of the MIPs have made them a very efficient material for diverse applications such as chromatography, purification, drug sensing, etc. Recently, zero-dimensional polymer materials, in the present case molecularly imprinted polymer nanoparticles (MIP nanoparticles), have been used widely for the fabrication of various functional materials. The large surface area of MIP nanoparticles leads to better and efficient template binding. Nanoparticles synthesized with a thin and uniform shell (core-shell MIP nanoparticles) have provided additional functional groups (amine, thiols) that can be advantageous for different analytical applications.

In this thesis, the immobilization of both MIP and MIP core-shell nanoparticles on solid surfaces and the application of Surface-enhanced Raman scattering (SERS) on MIP-modified surfaces for the detection of an analyte (propranolol and nicotine) have been studied. In the first part of the thesis different covalent and electrostatic approaches for the immobilization of imprinted polymer nanoparticles on glass, silicon, and Au wafers are reported. The covalent approaches comprises photoconjugation, epoxide ring opening reactions, and carbodiimide chemistry. In the electrostatic approach a polymer interlayer has been used. The particles’ immobilized surfaces are characterized using different surface analytical techniques. The morphology and surface property of the particles’ surfaces are reported using scanning electron microscopy (SEM), atomic force microscopy (AFM), fluorescence microscopy, and water contact angle measurements. Further, the chemical analysis of the surfaces using x-ray photoelectron spectroscopy (XPS) confirms the functionalization of the solid surfaces before and after MIP immobilization. Finally, the template binding property (selectivity and specificity) of the immobilized particles are reported using autoradiography measurements.

In the second part of the thesis I report the different surface morphologies for of the SERS detection of propranolol and nicotine sensing in imprinted nano- and micro sized polymer spheres. Nicotine-imprinted MIP spheres were immobilized on a Au wafer using surface thiols. After the confirmation of stable and dense particle attachment using SEM, the Au surfaces were made SERS active either using Au colloids or replacing Au with Raman-active Klarite surfaces. The propranolol-imprinted nanoparticles are attached to Klarite using a photoconjugation approach. Using SERS as the detection method I analyzed the binding capacity of the polymer sphere-coated transducer surface. The MIPs exhibit good specificity and selectivity in a complex biological sample.

Abstract (Swedish)

Popular Abstract in English

Nanoscience and nanotechnology have existed in this world before scientists actually coined the terms. Nature around us and human beings themselves are all made of nanomaterials (1-100 nm), such as DNA, proteins, liposomes, and enzymes. These building blocks possess molecular recognition properties, resulting in their self-assembly to form various two- and three-dimensional nanostructured materials useful in the field of science and technology. Scientists from different disciplines, including physics, chemistry, biology, and material science, use these nanostructured materials for advanced applications in medicine, energy, etc.

The detection of drugs in therapeutic applications requires selective molecular interaction with the target material. Thus, researchers have designed biosensors for detecting and sensing molecules in biological materials, e.g., glucose biosensors, which are quite important for sensing the glucose levels in the body. Biosensors can work when the biomolecules or the recognition materials are perfectly integrated with the transducer surface. These transducer surfaces are a very important element of the sensor fabrication as they convert the biological recognition event into a detectable signal.

The basic recognition mechanism, the analyte binding by the immobilized biomolecule, depends on the famous “lock and key method” first reported by the Nobel-Prize laureate Emil Fischer in 1894. The interaction between the lock and key should be reversible and stable to ease the operation and for reuse of the chemical sensor. Due to the poor stability of the biological recognition material in different physical and chemical environments, biosensors may give false readings. Further, the binding event is sometimes irreversible, which makes these biosensors suitable for only one-time use, making them more expensive.

To solve this problem, the biomaterials may be replaced by “artificial receptors” or “plastic antibodies,” referred to as molecularly imprinted polymers (MIPs). These polymer materials are synthesized in the presence of template molecules. After the polymerization, the template molecules are extracted, leaving behind “cavities” or “memory sites” with high selectivity and specificity for the template. The feature of molecular “memory” imprinted into the polymers enables them to selectively rebind the templates multiple times, which is similar to the “lock and key mechanism.” The template molecules can be any biomolecule, such as antibodies, enzymes, nucleic acids, microorganisms (bacteria, viruses) or drugs. This makes the MIPs suitable for the detection of drugs or for food-based sensing application studies with their ease of quality control, easy handling and cost effectiveness.

The most important criteria to develop a chemical sensor based on MIPs is their stable and uniform integration with the transducer surface. Therefore, this research investigates different immobilization approaches of spherical and hydrophobic MIP particles on a solid transducer surface. Different covalent and electrostatic chemistries have been studied for the dense, uniform and stable attachment of polymer spheres to chemically functionalized inorganic supports, such as glass, silica, and gold wafers. A detailed investigation of the MIP-integrated surfaces using different surface analytical techniques demonstrated the presence of polymer spheres on the transducer surface with stability in both physical and chemical environments. The MIP surfaces retain their characteristic template-binding property after immobilization on the transducer surface, thus making them suitable for sensing applications.

Ease of fabrication, low cost, sensitivity, selectivity and stability have made MIP sensors popular in physical, chemical, and biological sensing applications, e.g., the detection of various poisonous materials in the environment, food, and humans. Optical-based sensing systems are well known due to their ease, low cost and sensitivity. In principle, MIP-based optical sensors require fluorescent labels to detect the analyte binding, which makes the sensing process long and complicated. In my research, I have developed an easy, reproducible and label-free optical sensor that can be used for direct real-time measurement of analytes at different concentrations. MIP spheres imprinted against two model compounds, nicotine and propranolol, were used. Nicotine is found in cigarettes, and propranolol is a drug used to control anxiety and depression. MIP-based optical sensors were developed by the covalent immobilization of MIP spheres on an optically active transducer surface. The obtained results clearly demonstrated that the MIP surfaces are selective and specific towards analyte (propranolol and nicotine) sensing, even in the biological samples.

The reported immobilization and sensing approach can be used in biomedicine to perform both in vivo and in vitro investigations of molecules and organisms that cause health hazards. Further, these optical sensors have a wide range of applications, such as the identification of chemical warfare agents and of different dyes useful in the defense and art industries. Different immobilization approaches reported in this thesis can also be used to attach large-sized soft polymer spheres onto solid substrates for numerous material-based applications.

• author: Kamra, Tripta
• supervisor: Joachim Schnadt; Lei Ye; Lars Montelius
• opponent: Dr. Chehimi, Mohamed M., Department of Chemistry, University Paris Diderot, Paris
• organization: Synchrotron Radiation Research; Dept. of Synchrotron Radiation Research-lup-obsolete (research group); Nanometer structure consortium (nmC)-lup-obsolete (research group); Synch Rad Res-lup-obsolete (research group)
• publishing date: 2015
• type: Thesis
• publication status: published
• subject: Polymer Chemistry; Nano Technology; Accelerator Physics and Instrumentation
• pages: 227 pages
• defense location: Lecture Hall F (K404) at the Department of Physics
• defense date: 2015-09-14 10:15:00
• ISBN: 978-91-7623-424-2
• language: English
• LU publication?: yes
• id: ca826dc6-898c-4359-b22d-c6fa8eccac06 (old id 7763926)
• date added to LUP: 2016-04-04 11:03:17
• date last changed: 2018-11-21 21:02:23