Science method

Molecular Imprinting - Science method

Molecular Imprinting is a methodology for chemically synthesizing polymer molds of specific molecules or recognition sites of specific molecules. Applications for molecularly imprinted polymers (MIPs) include separations, assays and biosensors, and catalysis.
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In many researches, the mixture of MeOH and acetic acid (= 9 : 1 , for example) is commonly used, in order to remove the template molecular in molecular imprinted polymer (MIPs).
I wonder why this mixture solution is widely used, and what the meaning of this operation is.
I can imagine that the aim is to change the pH of slurry solution of MIP so that the structure of template molecular changes, and affinity and interaction between template molecular and monomer decreases.
But, I have a concern about my hypothesis.
In my research, I use 17β-estradiol (contains -OH) as a template molecular, MAA (pKa: about 4.6) as monomer. The interaction is related by hydrogen bond between "-OH of 17β-estradiol" and "-COOH of MAA".
If I take the pH condition of my reaction solution into consideration, I hypothesize that the lower pH leads to the more ratio of molecular form of MAA, so that the hydrogen bond get stronger.
However, the mixture of MeOH and acetic acid (the lower pH than the solvent of reaction solution, toluene) is used for removing molecular, according to the research which I refer to.
Are my hypotheses correct or incorrect?
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17β-estradiol (contains -OH) as a template molecular, MAA (pKa: about 4.6) as monomer. The interaction is related by hydrogen bond between "-OH of 17β-estradiol" and "-COOH of MAA". the lower pH in aqueous solution leads to enhance of hydrogen bonds.
Regarding the MeOH and acetic acid (= 9 : 1 , for example) template removal solution the HAc has significantly different pKa value compare to water and the also MeOH weaken hydrophobic interactions.
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the addition of the template in the preparation of the MIP led to a low cross-linking degree and low phase transition temperature
could someone elaborate on this?
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Pourya Zarshenas Thank you for sharing the articles.
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I'm looking for a commercially accessible template that's suitable for OTA imprinting polymer and is also affordable.
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Dear Foad Mashayekhi Suzaei, you can use OTA itself as a template. Please have a look at the following document. My Regards
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molecular imprinted polymerization what will be the ratio of mixing the cross linker monomer and template to make good MIP
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Dear Junaid ul Aalam, in most cases PVAl is used in conjunction with other polymers. For what purpose it is to be designed and what is the template. My Regards
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Hello, I'm biologist and currently working on MIP. I wanted to know is there any literature that mention the influence of monomer structure (for example size of molecule) on MIP selectivity and performance? I've seeh a lot of literature about influence of functional group of monomer but not about influence of its overall structure.
I'll gladly receive any recommendations on this question.
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Dear Anton Honcharenko, in addition to the monomer structure, spécial importance should be given to the template/porogenic solvent. Please check the attached files. My Regards
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in other word what is the best cross linker used to activate the nano-particles for their further reaction with Molecular imprinted polymer
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@Nasim sanadgol thank you very much
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I'm working on magnetic molecular imprinting of proteins with chitosan and sodium alginate. At the first step, I coat the fe3o4 nanoparticles with sodium alginate and then coat the result with chitosan and protein. Then, I remove the protein to make MIPs. The problem is that the MIPs absorb both specific imprinted protein (albumin) and nonspecific protein (lysozyme). Does anyone know the reason or a certain method for this kind of imprinting?
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Hi,
Dear Postforosh
Call me at 6 to 8 in the evening, please
Good luck
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AlBN - azobisisobutyronitrile
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Dear all, you have to choose the initiator that has close half-life time to that of AIBN at the same temperature. I think benzoyl peroxide may be the best condidates. My Regards
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I am looking to buy Cortisol MIPs to use them in my research, I have seen a website can provide it but the price was too high ( 70k £). If you know any companies can provide this MIPs service please let me know.
Thank you
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In the molecular imprinted method, if anybody works with unconductive polymer for electropolymerization and determination of electroactive analyze in the presence of K3Fe(CN)6/K4Fe(CN)6 should the increased current be followed or decreased current? please help me!
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If your polymer as well as the analyte are non-conductive but your functional monomer is capable of undergoing electropolymerization (eg: scopoletin, orthophenylene diamine, etc) you will observe a decrease in the current signal with an increasing concentration of your analyte following template removal. Ideally, when you perform cumulative rebinding experiments, you can observe a signal suppression relative to the template removal peak (but obviously a higher signal than in case of templates polymer).
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I used a liquid pesticide to make molecular imprinted polymer but did not form polymers, even using different solvents did not help.
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HI Since I was working on 3 pesticides at the same time, I had to remove the liquid sample because it was expensive.
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I am looking at performing electropolymerization of molecular imprinted polymers using a template and a pyrrole. I need to add the template along with the dopant to my buffer solution before running glavanommetry. Must the template be soluble in the buffer, or could the template be just dispersed into it ?
Thank you,
Abbas
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My recommendation is to ensure the complete solubility of the template and monomer. This is important to allow adequate pre-polymerization interaction between the molecules that will subsequently leads to the creation of memory for target recognition in the imprinted material.
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IN Molecular Imprinted polymer How can I determine the optimum ratio between the tempelate and the monomer also the amounts added. Is it just trial and error or do they have base which I can determine upon ? also the base upon which I choose the optimum solvent.
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Actually there is not any concrete rule!
But you can rationally design the MIP by Molecular Dynamic simulation.
However, as a rule of thumb, if the template is a small molecule you can start the trail-error! with 1:4:20 molar ratio for template/monomer/crosslinker.
If the template is a macromolecule or a protein, the polymer matrix has to be soft and therefore the crosslinker should be as low as possible.
Concerning the porogenic solvent, it is recommended to use an aprotic solvent such as acetonitrile. However, it is preferred to possess low dielectric constant as well.
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I made a molecular imprinted polymer ( MIP) and had characterized it using BET. the isoterm graph for adsorption-desorption are closed each other. The data of surface area from multi point BET plot is 261.611m2/g (slope 13,211, intercept 1,007e-01, r 0.999780, C 132.255). The average pore size 8.14759e+01A. Total pore volume 1.066e+00 cc/g for pores smaller than 1530.7 A (radius) at P/Po = 0.99371.
From BJH method adsorption the surface area =157.200m2/g, pore volume 1.008 cc/g, pore radius 15.278 A and from BJH method desorption the surface area 182.695 m2/g, pore volume 1.002 cc/g, pore radius 19.121 A.
which data should I use and why?
I don't know whether should use the BET or BJH and why. I read that BET to know the surface area and BJH to know the pore size and volume but still don't understand the reason.
Please help me.. thank you
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Use DFT method instead of BJH to calculate pore size distributions, especially if you have µ-porous materials
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MIP sensors usually suffer from lack of reproducibility, how we can improve it?
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Hello Fatemeh,
What do you mean in terms of reproducibility? Reproducibility of the detection limits? The batch-to-batch response? Or the ability to reproduce the biorecognition layer for re-use?
Accuracy is generally improved when imprinting with entire proteins, but this can lead to issues of cross-reactivity and reduced selectivity in the presence of small polypeptides (e.g., complex media). Surface imprinting tends to provide better performance than bulk imprininting due to the improved access of the binding sites and favourable binding kinetics: http://www.mdpi.com/1424-8220/17/2/288
In terms of batch-to-batch reproducibility, performing the MIP on larger areas tends to minimise the variance between devices.
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Hey, I want to ask what is the practical challenges for molecular imprinted polymer (MIP) sensors? Does it have good selectivity? How about consistency? Does it have major challenges during the manufacturing process? Any insights is welcome. Thanks.
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Dear Kelvin,
The template leakage happens after preparation of MIP when the template extraction is not complete. Usually, it is difficult or impossible to extract all the template, so during the use of the MIP, the entrapped templates gradually release from the MIP and interact with target sensing, affect the limit and of detection, and influence the accuracy of detection in trace analysis.
Yes, there couple of commercialized MIP-based products.
e.g.
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Molecular biology, biochemistry, physical chemistry, molecular imprinting, Polymerization, molecular imprinting polymers 
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" it was proposed that,  there will be a formation of molecular imprints" Plz, reference from a peer review journal. 
"Suppose."   In science we do not suppose, we do experiments. Try to make a solution of  "Sodium Chloride in 1:100 proportion with ethyl alcohol." The solubility of NaCl in ethanol is 0.65 g per 1 kg of solvent. 
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Hello, As far I know that in molecular imprinting Theory People Usually Take a target molecule which will be imprint and then in the last step by using significant procedure they remove the target molecules. So whenever the imprinted thing will have the target molecule it will grab it. My question is is it possible to use solvents like IPA and Acetone to use as target molecule to imprint.
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A good porogenic solvent can be an aprotic solvent with relatively low dielectric constant such as acetonitrile and chloroform. However, if there is a problem with the solubility or stability of the template or the polymer ingredients in such solvents, one has to go for other solvents such as water, ethanol, IPA, etc. 
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If I would like to introduce a specific molecular imprinted polymers with a transducer to develop a biosensor, then which type of transducers can I apply. What are the different physico-chemical changes produces after binding of a MIPs with its target analyte?
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Difficult question. It depends on the format you produce(d) your MIPs: nanoparticles, powder, layers etc. The most general transducers are mass-dependent ones, such as QMB (quartz microbalances) and similar ones. The transduction step is one of the most critical issues of MIP sensors. In recent papers [see link], the use of fluorescence was shown. However, the development of such systems is not easy.
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material i have-methaacrylic acid + methaacrylamide (1:3) ( monomers)
DMSO/methanol (solvent)
AMA ( initiator)
EDGA (cross-linker)
i have been following thermal method but polymerization is not happening. please guide. thank you 
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AMA is the abbreviation for allyl methacrylate. This is not an initiator but a branching and cross linking monomer. You should add a real initiator like AIBN, benzoyl peroxide or another peroxide. Peroxides can be further activated by adding a tertiary amine, e.g. ethyl-4-dimethylamino benzoate, dimethylamino toluidine or N,N-bishydroxyethyl aniline. Without activation the polymerization runs at 60-90°C, with activation at 20-60°C.
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I would like to make and take a rational decision while designing my first MIP (inshaa' Allah). I've learned during my MBA study that market research reports help a researcher to gain birds eye view for the market of interest. However, it's very costly for an early stage researcher like me to buy a market research report from a firm like bccmarket research. Accordingly, is there an open source panel that can provide me with a free of charge market research report?
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Dear Dr. Prosper,
In the main, I'd like to thank you for your kind contribution.
Second, I've accessed  Forrester, yet they don't have a specific industry report to the MIP market. Accordingly, if you can share with me a pertinent report in the realm of MIP-based biosensors, I'll be thankful.
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I have synthesized an HPMIP with the help of MCM-48. But on mounting the cartridge (properly fitted with the fritts) on the SPE manifold, I still get a leakage with the eluate i.e, On conditioning the cartridge, I still get some of the white fluid with the eluate. Kindly suggest.
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Jiangnan University China. All experiment in food science technology machine including NMR
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what is the exact concentration of materials/reactants needed to be added for the same.
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I conducted a research of MIP synthesis using various ratio of monomer-template. The amount of crosslinker (EGDMA) was about 6 times of the amount of the monomer (MAA). However the amount of template leached from the polimer was quite a little so the efficiency of adsorption also low. Why? I got confused as I had to repeat my research but if I don't know why the extraction percentage ( template leached) was very low, how can I improve it?
Would you like to give me explanation?
Thank you
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Dear Researchers,
I hope this question finds you doing well.
I have coded an MIP model on Cplex, but when I run it, it gives a relaxed solution. However, the model has a global solution on another solver. I guess that I have to modify the run setup in Cplex to force Cplex to search for the global solution.
Best Regards,
Mahmoud
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Dear Mahmoud
Make sure that you coded the model correctly, relaxed solution means that solution is infeasible.  you can check conflict  and relaxation windows in cplex to see the reasons for relaxation.
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I am trying to figure out what typical ratios are for monomer/cross-linker/template solution in MIPs to have a starting point for my experiments. Also, if it appears there needs to be some modifications to the polymer, which of the three factors should be adjusted?
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monomer : template most important and should be estimated from the functionality of template (number of functional groups to form non-covalent bonds with monomer) and functionality of monomer and then take monomer in an excess. E.g. template has 4 hydroxyls and monomer one carbonyl group, thus estimated ratio 1:4 but to shift the equilibrium to pre-polymerization complex formation one should prefer 1:5 or even 1:5  
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I wanted to use silica as support material for molecular imprinting. I wanted to skip the method of silynation and activation of silica. I prefered the readily available functionalized one.  I search for different functionalized silica.  I found the 3-(ethylenediamino) propyl functionalized silica gel.  I am not sure if it is possible to do molecular imprinting on its surface.  I hope I can have answers. I also hope to have more suggestions of what to use instead of doing the lengthy functionalization. Thanks a lot.
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Does this mean if I will not used vinyl functionalized silica, there will be a tendency that MAA will free polymerized not on the surface of silica as expected? 
Sir: If you wouldn't mind, do you know in particular of a commercially available Vinyl functionalized silica, more approproriate to be used? 
Yes, I will also be using EGDMA.  Thank you very much.
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Template characteristics affects molecularly imprinted polymer characteristics if careful selection of reaction components is not done.
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 How will I wash off a chitosan-methacrylic acid polymer film from the surface of a silicon dioxide crystal qcm Chip ?
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I have prepared two batches of blank MIP nanoparticles using an article as a reference, in the Batch-1, i have added MAA(0.475 mmol, 40 ul), EGDMA(1.11mmol, 209 ul) and AIBN(0.09 mmol i.e.15mg) into the 25 ml of ACN taken in 50 ml of RB flask step by step and then purged with nitrogen for 15 min similarly in Batch-2, keeping all same just by changing solvent i.e., 25 ml of ACN and NMP(N-Methyl-2-pyrrolidone) in 2:1 ratio mixture was kept for the reaction at 60 *c on the preheated oil bath for 24 hrs. After 24 hrs, the polymerization mixture is looking clear as it is in the initial. Now how can I determine whether polymerization has occurred or not?
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EGDMA amount is almost same in both experiments. The solvent is playing its role by maintaining stability of initiator radicals and monomer radicals and allowing the crosslinking and polymerization to go to high molecular weight. At higher molecular weight and also in crosslinked state the solvent is not able to hold it in solution and it precipitates. It is thus combination of factors; earlier solvent was not allowing to achieve high molecular weight and was able to keep lowly crosslinked polymer in solution or swelled state.
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I am making a MIP based on MAA as monomer with theophylline as template/ imprinted molecule. I used chloroform as the solvent, EDMA as the cross-linking agent, and the polymerization was initiated by BPO (benzoyl peroxide) (free radical polymerization). First i mixed all of the precursors and then it was polymerized at 60 C. I waited for over 5hours, but it didn't polymerized. it was suppose to be rigid, since i used a bulk polymerization method, but it wasn't. Most of the liquid was gone, leaving some small solids on the bottom of the vial. But they were so small, i couldn't take them out of the vial.
why the polymerization didn't occur?
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Dear Tati Nurhayati, the problem you have faced will encounter generally in many such bulk polymerization method.
Follow these steps in sequence:
Step 1. Dissolve the template in the porogenic solvent (Was Theophylline template completely soluble in chloroform..? (If not try with dimethyl sulfoxide or some other solvents, as polarity of solvents affect the complete dissolution of templates)
Step 2. Then add MAA Monomer and then EDMA in sequence to the template mixture prepared in step 1. (Try with EGDMA if possible).
Step 3. Fill these mixtures to glass ampoules or vial. Then sonicate for about 5 min and Nitrogen gas must be bubbled for 10 minutes (Sonication and N2 gas flushing inside the mixture removes oxygen and maintains inert condition which is essential for free radical formation)
Step 4.  Then add Benzoyl peroxide to the Glass ampoules and then it will be properly sealed under inert condition.
Step.5. The glass ampoule containing the polymerization mixture will be then placed in a circulating water bath maintained at 65°C for 24 h. (In our case we maintained this temperature, and for your template different temperature may apply)
Before starting the experiment calculate the molar ratio of all these (template, monomer, croslinker, initiator and solvents, and use only exact quantities, you may use excess of initiator, no problem.
  A control (reference) imprint i.e. non-imprinted polymer (NIP) will be prepared similar to imprinted polymer except the addition of template
One of our article is enclosed for your reference, Hope I have clarified your doubts… All the best.
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If I would like to introduce phosphate specific molecular imprinted polymers with a transducer to develop a phosphate biosensor, then which type of transducers can I apply. What are the different physico-chemical changes produces after binding of a MIPs with its target analyte?
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Before looking for the best transducer to detect any specific binding I would firstly characterize the selectivity of the MIP binding by chromatography. Only if you got a sufficient selectivity for the matrix in which the sensor will be used, the search for the best transducer should start. During over 30 years’ experience in chemical sensors I have great doubts on the selectivity of MIPs as selective receptors.  
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I need a computer program to form molecularly imprinted polymers and their design by using template molecules. Do you have any suggestions?
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You can use SYBYL modelling, where you need to build your library of monomers.
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molecular imprinted polymer
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  From the view of polymerization models, it is true that it is just the amount of porogen different between bulk and precipitation polymerization. However, the materials obtained by bulk polymerization generally show better MIP effect than that of precipitation polymerization. While precipitation polymerization generally afford materials with uniform shape (such as microbeads).