Ultrasonic Synthesis of Molecularly Imprinted Polymers (MIPs)
What are Molecularly Imprinted Polymers?
A molecularly imprinted polymer (MIP) is polymeric materials with antibody-like recognition characteristics that has been produced using the molecular imprinting technique. The molecular imprinting technique produces molecularly imprinted polymer in regards to a specific target molecule. The molecularly imprinted polymer has cavities in its polymer matrix with an affinity for the specific “template” molecule. The process usually involves initiating the polymerization of monomers in the presence of a template molecule that is extracted afterwards, leaving behind complementary cavities. These polymers have affinity for the original molecule and have been used in applications such as chemical separations, catalysis, or molecular sensors. Molecular imprinted molecules can be compared to a molecular lock, that matches a molecular key (the so-called template molecule). Molecularly imprinted polymers (MIPs) are characterised by specifically tailored binding sites that match the template molecules in shape, size and functional groups. The “lock – key” feature allows to use molecular imprinted polymers for various applications, where a specific type of molecule is recognised and attached to the molecular lock, i.e. the molecular imprinted polymer.
Molecularly imprinted polymers (MIPs) have a wide field of applications and are used to separate and purify specified biological or chemical molecules including amino acids and proteins, nucleotide derivatives, pollutants, as well as drugs and food. The application areas range from separation and purification to chemical sensors, catalytic reactions, drug delivery, biological antibodies and receptors systems. (cf. Vasapollo et al. 2011)
For example, MIP technology is used as solid-phase micro-extraction technique to operate and purify cannabis-derived molecules such as CBD or THC from the full spectrum extract in order to obtain cannabinoid isolates and distillates.
Ultrasonic Synthesis of Molecularly Imprinted Molecules
Depending on the target (template) type and the final application of the MIP, MIPs can by synthesized in different formats such as nano- and micron-sized spherical particles, nanowires, nano-rods, nano-filaments, or thin films. In order to produce a specific MIP form, different polymerization techniques such as bulk imprinting, precipitation, emulsion polymerization, suspension, dispersion, gelation, and multi-step swelling polymerization can be applied.
The application of low-frequency, high-intensity ultrasonics offers a highly efficient, versatile and simple technique to synthesise polymeric nanostructures.
Sonication brings several advantages in MIP synthesis when compared with traditional polymerization processes, because it promotes higher reaction rates, more homogeneous polymer chain growth, higher yields, and milder conditions (e.g., low reaction temperature). Furthermore, it can alter the binding site population distribution, and thus, the morphology of the final polymer. (Svenson 2011)
By applying sonochemical energy to the polymerisation of MIPs, polymerization reactions are initiated and positively impacted. Simultaneously, sonication promotes effective degassing of the polymer mixture without sacrificing binding capacity or rigidity.
Ultrasonic homogenization, dispersing and emulsification offers superior mixing and agitation to form homogeneous suspensions and to provide initiation energy for polymerization processes. Viveiros et al. (2019) investigated the potential of ultrasonic MIP synthesis and state that “MIPs prepared ultrasonically presented binding properties similar or superior to the conventional methods”.
MIPs in nano-format open promising possibilities for improving the homogeneity of the binding sites. Ultrasonication is well-known for its exceptional results in the preparation of nanodispersions and nanoemulsions.
Ultrasonic Nano-Emulsion Polymerization
MIPs can be synthesised by emulsion polymerization. Emulsion polymerization is commonly achieved by forming an oil-in-water emulsion under addition of a surfactant. To form a stable, nano-sized, a high-performance emulsification technique is required. Ultrasonic emulsification is a well-established technique to prepare nano- and mini-emulsions.
Read more about ultrasonic nano-emulsification!
Ultrasonic Extraction of the Template
After the synthesis of molecularly imprinted polymers, the template must be removed from the binding site in order to obtain an active molecularly imprinted polymer. The intense mixing forces of sonication promote solubility, diffusivity, penetration and transport of solvent and template molecules. Thereby, the templates are rapidly removed from the binding sites.
Ultrasonic extraction can be also combined with Soxhlet extraction to remove the template from the imprinted polymer.
- Controlled Radical Polymerization
- Precipitation Polymerization
- Emulsion Polymerization
- Core-Shell Nanoparticle Grafting
- Ultrasonic Synthesis of Magnetc Particles
- Fragmentation of Aggregated Polymers
- Ultrasonic Extraction of the Template
Case Studies: Ultrasonic Applications for Molecularly Imprinted Polymers
Ultrasonic Synthesis of Molecularly Imprinted Polymers
The encapsulation of magnetic nanoparticles by 17β-estradiol-imprinted polymers using an ultrasonic synthesis route achieves fast removal of 17β-estradiol from aqueous environments. For the ultrasonic synthesis of the nanoMIPs, methacrylic acid (MAA) was used as monomer, ethylene glycol dimethylacrylate (EGDMA) as crosslinker, and azobisisobutyronitrile (AIBN) as initiator. The ultrasonic synthesis procedure was carried out for 2h at 65ºC. The average particle size diameters of magnetic NIPs and magnetic MIPs were 200 and 300 nm, respectively. The use of ultrasound not only enhanced the polymerization rate and morphology of the nanoparticles, but also led to an increase in the number of free radicals, and thus, facilitated MIP growth around the magnetic nanoparticles. The adsorption capacity towards to 17β-estradiol was comparable to traditional approaches. [Xia et al. 2012 / Viveiro et al. 2019]
Ultrasonics for Molecularly Imprinted Sensors
Yu et al. designed a molecularly imprinted electrochemical sensor based on nickel nanoparticle-modified electrodes for phenobarbital determination. Reported electrochemical sensor was developed by thermal polymerization with the use of methacrylic acid (MAA) as the functional monomer, 2,2-azobisisobutyronitrile (AIBN) and ethylene glycol maleic rosinate (EGMRA) acrylate as the crosslinking agent, phenobarbitals (PBs) as the template molecule, and dimethyl sulfoxide (DMSO) as an organic solvent. In the sensor fabrication process, 0.0464g PB and 0.0688g MAA were mixed in 3 mL DMSO and sonicated for 10 min. After 5 h, 1.0244g EGMRA and 0.0074g AIBN were added into the mixture and sonicated for 30 min to obtain PB-imprinted polymer solutions. After that, 10 μL of 2.0 mg mL-1Ni nanoparticle solution dropped on the GCE surface and then the sensor was dried at room temperature. Approximately 5 μL of the prepared PB-imprinted polymer solution was then coated on the Ni nanoparticle-modified GCE and vacuum dried at 75◦C for 6 h. Following the thermal polymerization, the imprinted sensor was washed with (acetic acid) HAc/methanol (volume ratio, 3:7) for 7 min to remove the template molecules. (cf. Uygun et al. 2015)
Ultrasonic Micro-Extraction using MIPs
In order to recover nicotinamide analyses from samples, an ultrasonically assisted dispersive solid phase microextraction followed by UV-vis spectrophotometer (UA-DSPME-UV-vis) is applied. For the extraction and preconcentration of nicotinamide (vitamin B3), HKUST-1 metal organic framework (MOF) based molecularly imprinted polymers have been used. (Asfaram et al. 2017)
High-Performance Ultrasonicators for Polymer Applications
From Lab to Production with Linear Scalability: Specifically engineered molecularly imprinted polymers are firstly developed and tested on small lab and bench-top scale, to investigate the feasibility of the polymer synthesis. If feasibility and optimisation of MIPs have been accomplished, the MIP production is scaled to larger volumes. The ultrasonic synthesis routes can be all linearly scaled from bench-top to fully commercial production. Hielscher Ultrasonics offers sonochemical equipment for the polymer synthesis in small lab and bench-top settings up to fully industrial inline ultrasonic systems for the 24/7 production under full load. Ultrasonic can be linearly scaled from test tube size to large production capacities of truckloads per hour. Hielscher Ultrasonics extensive product portfolio from lab to industrial sonochemical systems has the most suitable ultrasonicator for your envisaged process capacity. Our long-time experienced staff will assist you from feasibility tests and process optimisation to the installation of your ultrasonic system on final production level.
Hielscher Ultrasonics – Sophisticated Sonochemical Equipment
Hielscher Ultrasonics product portfolio covers the full range of high-performance ultrasonic extractors from small to large scale. Additional accessories allow for the easy assembly of the most suitable ultrasonic device configuration for your process. The optimal ultrasonic setup depends on the envisaged capacity, volume, material, batch or inline process and timeline. Hielscher helps you to setup the ideal sonochemical process.
Batch and Inline
Hielscher ultrasonicators can be used for batch and continuous flow-through processing. Small and mid-sized volumes can be conveniently sonicated in a batch process (e.g., vials, test, tubes, beakers, tanks or barrels). For large volume processing, inline sonication might be more effective. Whilst batching is more time- and labour-intensive, a continuous inline mixing process is more efficient, faster and requires significantly less labour. Hielscher Ultrasonics has the most suitable extraction setup for your polymerization reaction and process volume.
Ultrasonic Probes for Every Product Capacity
Hielscher Ultrasonics product range covers the full spectrum of ultrasonic processors from compact lab ultrasonicators over bench-top and pilot systems to fully-industrial ultrasonic processors with the capacity to process truckloads per hour. The full product range allows us to offer you the most suitable ultrasonic equipment for your polymers, process capacity and production targets.
Ultrasonic benchtop systems are ideal for feasibility tests and process optimization. Linear scale-up based on established process parameters makes it very easy to increase the processing capacities from smaller lots to fully commercial production. Up-scaling can be done by either installing a more powerful ultrasonic extractor unit or clustering several ultrasonicators in parallel. With the UIP16000, Hielscher offers the most powerful ultrasonic unit worldwide.
Precisely Controllable Amplitudes for Optimum Results
All Hielscher ultrasonicators are precisely controllable and thereby reliable work horses in production. The amplitude is one of the crucial process parameters that influence the efficiency and effectiveness of sonochemical reactions including polymerization reactions and synthesis routes.
All Hielscher Ultrasonics’ processors allow for the precise setting of the amplitude. Sonotrodes and booster horns are accessories that allow to modify the amplitude in an even wider range. Hielscher’s industrial ultrasonic processors can deliver very high amplitudes and deliver the required ultrasonic intensity for demanding applications. Amplitudes of up to 200µm can be easily continuously run in 24/7 operation.
Precise amplitude settings and the permanent monitoring of the ultrasonic process parameters via smart software give you the possibility to synthesise your molecularly imprinted polymers with the most effective ultrasonic conditions. Optimal sonication for best polymerization results!
The robustness of Hielscher’s ultrasonic equipment allows for 24/7 operation at heavy duty and in demanding environments. This makes Hielscher’s ultrasonic equipment a reliable work tool that fulfils your sonochemical process requirements.
Easy, Risk-free Testing
Ultrasonic processes can be completely linear scaled. This means every result that you have achieved using a lab or bench-top ultrasonicator, can be scaled to exactly the same output using the exactly same process parameters. This makes ultrasonication ideal for risk-free feasibility testing, process optimization and subsequent implementation into commercial manufacturing. Contact us to learn how sonication can increase your MIP yield and quality.
Highest Quality – Designed and Manufactured in Germany
As a family-owned and family-run business, Hielscher prioritizes highest quality standards for its ultrasonic processors. All ultrasonicators are designed, manufactured and thoroughly tested in our headquarter in Teltow near Berlin, Germany. Robustness and reliability of Hielscher’s ultrasonic equipment make it a work horse in your production. 24/7 operation under full load and in demanding environments is a natural characteristic of Hielscher’s high-performance mixers.
The table below gives you an indication of the approximate processing capacity of our ultrasonicators:
|Batch Volume||Flow Rate||Recommended Devices|
|1 to 500mL||10 to 200mL/min||UP100H|
|10 to 2000mL||20 to 400mL/min||UP200Ht, UP400St|
|0.1 to 20L||0.2 to 4L/min||UIP2000hdT|
|10 to 100L||2 to 10L/min||UIP4000hdT|
|n.a.||10 to 100L/min||UIP16000|
|n.a.||larger||cluster of UIP16000|
You can buy Hielscher ultrasonic processor in any different size and exactly configured to your process requirements. From treating reactants in a small lab tube to the continuous flow-through mixing of polymer slurries on industrial level, Hielscher Ultrasonics offers a suitable ultrasonicator for you! Please contact us – we are glad to recommend you the ideal ultrasonic setup!
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Literature / References
- Raquel Viveiros, Sílvia Rebocho, Teresa Casimiro (2018): Green Strategies for Molecularly Imprinted Polymer Development. Polymers 2018, 10, 306.
- Takayuki Hishiya; Hiroyuki Asanuma; Makoto Komiyama (2003): Molecularly Imprinted Cyclodextrin Polymers as Stationary Phases of High Performance Liquid Chromatography. Polymer Journal, Vol. 35, No. 5, 2003. 440 – 445.
- Doaa Refaat; Mohamed G. Aggour; Ahmed A. Farghali; Rashmi Mahajan; Jesper G. Wiklander; Ian A. Nicholls (2019): Strategies for Molecular Imprinting and the Evolution of MIP Nanoparticles as Plastic Antibodies – Synthesis and Applications. Int. J. Mol. Sci. 2019, 20, 6304.