WO2015021145A1 - Billes de silice colorées à impression moléculaire - Google Patents

Billes de silice colorées à impression moléculaire Download PDF

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Publication number
WO2015021145A1
WO2015021145A1 PCT/US2014/049929 US2014049929W WO2015021145A1 WO 2015021145 A1 WO2015021145 A1 WO 2015021145A1 US 2014049929 W US2014049929 W US 2014049929W WO 2015021145 A1 WO2015021145 A1 WO 2015021145A1
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Prior art keywords
imprinted
silica
bead
template
polymerized
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PCT/US2014/049929
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English (en)
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Thomas Boland
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Board Of Regents, The University Of Texas System
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Publication of WO2015021145A1 publication Critical patent/WO2015021145A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/551—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being inorganic
    • G01N33/552—Glass or silica
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/551—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being inorganic
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2600/00—Assays involving molecular imprinted polymers/polymers created around a molecular template

Definitions

  • the disclosed embodiments relate to imprinting polymers.
  • the disclosed embodiments relate to molecular imprinting of high molecular weight compounds.
  • the disclosed embodiments also relate to colored silica beads with imprinted antibody binding sites.
  • Protein imprinting creates artificial receptors by the formation of a polymer network around a template molecule.
  • Protein imprinting relates to obtaining an imprint of a protein in a polymer network. After imprinting, imprinted proteins are washed away, degraded, or digested, thus leaving behind a cavity which preferentially binds that protein.
  • Protein imprinting can be effective for molecules with low molecular weight ( ⁇ 1500 Da). Imprinting high molecular weight proteins or hormones, and compounds such as DNA, viruses, and bacteria within polymer matrices has been extremely challenging. For large template molecules, polymer crosslink densities seriously hinder mass transfer of the template, leading to slow template removal and rebinding kinetics or, in the worst case, permanent entrapment of the template in the polymer network due to physical immobilization. In previous proposed solutions, template rebinding is unreliably quantified, results are not evaluated critically, and often lack statistical analysis. Physicocbemical properties such as charge or hydrophobicity can strongly vary in different regions of the protein template, whereas similar regions may be present in other templates.
  • the synthesis environment is usually too aggressive for the template, where the template solvent often denatures the template before an imprint is formed. [0004] Therefore, a need exists for quantifiable imprinted molecules having a high molecular weight.
  • the disclosed beads are utilized as diagnostics in low resource settings as no temperature control is required.
  • the disclosed embodiments relate to imprinting polymers.
  • the disclosed embodiments relate to molecular imprinting of high molecular weight compounds.
  • the disclosed embodiments further relate to colored silica beads with imprinted antibody binding sites.
  • a composition of a macromolecular imprinted silica particles (“MIP”) in the presence of polymer grafted carbon black is disclosed.
  • the disclosed molecular imprinted beads can detect disease in body fluids.
  • TEGS tetraethyl orthosilicate
  • APS 3aminopropy/triethoxysilane
  • Carbon black was added to the sol-gel process, yielding black silica particles.
  • sodium dodecyl sulfate (“SDS”) was used as a structure-directing agent to increase network diffusion of the template.
  • MIP's were synthetized in parallel with variables that evaluate the role of key reactants in the synthesis procedure. Agglomeration tests were performed with all 18 MIP's in the presence of their template, alongside their respective controls using only phosphate buffered saline ("PBS"). Each of the M!Ps was evaluated using a novel device capable of simultaneously measuring up to four samples for near infrared transmission.
  • PBS phosphate buffered saline
  • FIG. 1 illustrates an exemplary pictorial illustration of creating artificial receptors by the formation of a polymer network around a template molecule, according to a preferred embodiment
  • FIG. 2 illustrates an exemplary pictorial illustration of hCG incubated beads binding to the hCG antibody in a nitrocellulose membrane, in accordance with the disclosed embodiments
  • FIG. 3 illustrates an exemplary graphical illustration of the near IR transmission through a cuvette in the presence of dispersed beads for each pair as function of time, in accordance with the disclosed embodiments
  • FIG. 4A illustrates an exemplary pictorial illustration of SEM images demonstrating surface morphology, specifically black anti-WN particles at 1200X, showing macroparticle shape, in accordance with the disclosed embodiments;
  • FIG. 4B illustrates an exemplary pictorial illustration of SEM images demonstrating surface morphology, specifically black anti-WN particles at 22,000X illustrating aggregate morphology of macroparticles, in accordance with the disclosed embodiments;
  • FIG. 5 illustrates an exemplary pictorial illustration of agglomeration test of UV red, carbon black, and non-colored silica particles, in accordance with the disclosed embodiments; and [0018]
  • FIG. 6 illustrates an exemplary pictorial illustration of conical tubes containin imprinted silica particles that were re-suspended after overnight precipitation, i accordance with the disclosed embodiments.
  • molecular imprinting is a technique used to create artificial receptors for molecules or proteins by the formation of a polymer network around a template molecule. As shown in (A) of FIG.
  • the template, functional monomers, and crosslinker (-*-) form a pre-polymerization complex.
  • polymerization of monomers and crosslinker fixes the complex.
  • removal of the template leaves rebinding cavities.
  • MIPs macromolecular imprinted polymers
  • the synthesis of macromolecular imprinted polymers ⁇ "MIPs" must occur at an environment where the template can maintain proper folding and 3D structures for sufficient time frames to allow the formation of the imprints.
  • the process must allow recapturing the template for its reutilization. If new template must be used for each synthesis, the key advantages of M IPs such as scalability and cost effectiveness are eliminated; the process would be more expensive than using traditional antibodies. There are cases, however, where the availability of MIPs available as sensors or markers trump the use of antibodies, for example, in remote and low resourced settings or for defense applications.
  • the next step is the selection of an appropriate polymer matrix, in which high affinity binding sites can be created, ideally without introducing aspecific interactions.
  • an appropriate polymer matrix in which high affinity binding sites can be created, ideally without introducing aspecific interactions.
  • several possible interactions such as hydrophobic interactions, hydrogen bonds, Van der Waals forces, and electrostatic interactions determine the spatial arrangement of monomers around the protein template. This spatial arrangement is then fixed by polymerization of monomers and crosslinker.
  • Biological macromolecuies are very complex and possess many potential recognition sites at their surface, such as charged amino acids and hydrophobic/hydrophilic regions.
  • imprints of proteins in silica microbeads are obtained from a mixture of 1 .32 ml TEOS, 0.235 ml DI water, 0.33 ml of 0.1 M, and 0.4 ml of absolute ethanol. 0.33 ml of 3-aminopropyltrietboxysilane (APS) mixed with 1 .5 mg of Human chorionic gonadotropin (hCG), 0.5 ml of 0.1 M SDS and 0.5 ml HP black ink. The two mixtures are combined in 10 ml of water, which causes the polymerization to proceed immediately. The resulting polymers are washed, dried, ground, and separated by centrifugation.
  • APS 3-aminopropyltrietboxysilane
  • the resulting beads (1 -5 microns in diameter) are washed in acetic acid/methanol (50/50) 10-20 times or until absorbance at 280nm is below 0.04.
  • the imprinted beads are able to rebind hCG in an antibody-based pregnancy test, such as, for example, First ResponseTM or EPTTM.
  • FIG. 2 illustrates an exemplary pictorial illustration 200 of hCG incubated beads binding to the hCG antibody in a nitrocellulose membrane, in accordance with the disclosed embodiments.
  • This is a sandwich assay, where 1/2 of the sandwich is the traditional antibody assay.
  • Antibodies are more expensive than the silica beads and expire at high or low temperatures, whereas silica beads are very stable.
  • silica process in the presence of polymer grafted carbon black is disclosed.
  • the presence of polymer-bound carbon black in a silica gel matrix improves solvent uptake. Hydrogen bonds are formed between carbonyl groups in grafted polymer and residual silanol groups in the silica gel network. Thus carbon black macromolecular imprinted silica particles are synthetized.
  • TEOS tetraethyl orthosilicate
  • APS 3-Aminopropyi triethoxysilane
  • SDS sodium dodecyl sulfate
  • Surfactants have been used for the synthesis of mesostructured silica materials with large porosity made of uniform mesopores. The importance of mesopores in MIPs particles was seen as a way of increasing template absorption in the particle, while at the same time enhancing the template removal process and limiting permanent template encapsulation by enhancing network diffusion. To test the role of surfactants in the synthesis, all chemical reactions were carried in the presence of SDS and again repeated in the absence of such.
  • a total of 16 MIPs were synthetized, four variables were used: water concentration, ionic content, ethanol presence, SDS presence. Each variable had two test conditions, yielding 24 reactions.
  • Human Chorionic Gonadotropin (hCG) was used as the template for all syntheses. After template removal and particle washing, agglomeration tests were performed with all 16 MI P's in the presence of their template, alongside their respective controls using only PBS.
  • Each MIPs were evaluated using an in-house built device capable of simultaneously measuring up to four samples for near infrared transmission.
  • Tetraethyl orthosilicate (TEOS) and 3-aminopropyl triethoxysilane (APS) were obtained from SigmaTM.
  • Human chorionic gonadotropin (hCG) was obtained lyophilized from SigmaTM; a solution of 20 mg/ml was prepared in PBS buffer.
  • Sodium dodecyl sulfate was in powder from sigma and a 10% w/v solution was prepared using ultrapure water.
  • Hydrochloric acid (37%), ethanol, anhydrous acetic acid and methanol were acquired from Fisher ScientificTM.
  • Ammonium hydroxide was obtained from sigma at 30% concentration.
  • Polymer grafted carbon black was obtained by collecting ink from HPTM 33 cartridges.
  • Average sizes of this carbon black is found to be 15 nm and grafted with 2-PyrroIidone as per MSDS.
  • Ultrapure water was obtained from a Mi!li-Q Mil!ipore unit with a water quality of at least 18.2 ⁇ .
  • 0.2M MES buffer was obtained from Fisher ScientificTM in 500 ml pouches.
  • IX PBS 200 ml tablets were obtained from SigmaTM.
  • Imprinted silica particles were prepared by the sol-gel method. Due to the complex reaction kinetics of the silica sol-gel process, a muitivariabie test was performed in order to better understand the role of key reagents in the mixture. Variables for the batch process were: water content: high or low, ionic content distilled or 0.2 MES, ethanol presence: yes or no, SDS presence: yes or no. A total of 18 parallel reactions were performed.
  • solution 1 a was composed of 8 ml of ink, 8 ml of SDS, and 6.08 ml of ammonium hydroxide.
  • solution 1 b was composed of 8 ml of ink and 6.08 ml of ammonium hydroxide.
  • Solution two was devised to promote monomer nucleation, which occurs in a solution at or just below a pH of 4.7. Afterwards, functional monomer was added, which neutralizes the solution pH. Since a neutral pH does not favor nucleation, TEOS is allowed to hydrolyze prior to functional monomer addition, as the basicity and quantity of the monomer neutralizes the reaction's pH; TEOS hydrolysis is determined by the solution's return to room temperature. Once the solution achieves a neutral pH, the solution matches physiological conditions of the template. For our particular batch, pH was left as is on all solutions and HCG template was added.
  • Solutions 2A-2D have two common variables, despite of this, each solution was prepared individually. Briefly, these solutions were prepared using 1 .5 ml of deionized water each. For solutions 2A and 2B, 820 ⁇ of ethanol was added, respectively. Then 6 ⁇ of HCl was added to all solutions. All solutions were gently agitated by hand; reactions were then allowed to return to room temperature before any further reagent addition . Afterwards, 35 ⁇ of APS was added, followed by 25 ⁇ of HCl. it Is at this stage where pH should be neutral as determined by prior experimentation.
  • Solutions 2I-2L prepared using 2.4 m! of deionized water each.
  • solutions 21 and 2J 820 ⁇ of ethanol was added followed by 8 ⁇ of HCL All solutions were gently agitated by hand; reactions were then allowed to return to room temperature before any further reagent addition.
  • 58 ⁇ of APS was added, followed by 25 ⁇ of HCL
  • 100 ⁇ of hCG template was added. A short amount of time is allowed for template adsorption at nucleating sites of the silica sol; solutions are gently agitated by hand during this process.
  • 1 15 ⁇ of APS was added followed by the appropriate solution one; for solutions 2! and 2K solution 1 a and solutions 2J and 2L solution 1 b was used.
  • Solutions 2M-2P were prepared as 2I-2L with the exception of using 0.2 M MES buffer instead of deionized water.
  • absorbance values were larger than 0.040, solutions were washed again in 40 ml of elutson solution and rinsed in triplicate. Finally, particles were centrifuged at 4000 RPM for 10 minutes and suspended in a 1 x PBS solution and stored at room temperature until needed. Particle concentrations were found to be at 58 ⁇ 18 mg/ml.
  • Tetraethyl orthosilicate (TEOS) and 3-Aminopropyl triethoxysilane (APS) were obtained from Sigma and used as is. Hydrochloric acid (37%), ethanol, and methanol were acquired from Fisher Scientific ® . Anhydrous acetic acid was also from Fisher Scientific. Polymer grafted carbon black was obtained by collecting ink from HP 33 cartridges. According to literature, carbon black are 15 nm carbon particles [7] grafted with 2- Pyrrolidone as per HP MSDS. Ultrapure water was obtained from a Milii-Q Millipore unit with a water quality of at least 18.2 ⁇ . 0.1 M MES buffer was obtained as powder pouches from Fisher Scientific ® .
  • Imprinted silica particles were prepared by the sol-gel method, !n order to maximize particle retention, a two-step synthesis protocol was devised. The main protocol focuses on molecular imprinting which produces a broad range of molecular imprinted particles in the nanometer scale. In order to contain these, a silica gel is produced where the particles are suspended and trapped in a silica gel matrix resulting in fewer particle losses during washing and regeneration protocols. The order of reagents is of utmost importance and if not properly followed, nucleation and gelation might occur prior to the addition of the template, thus reducing or inhibiting molecular imprinting. It is noted that all disclosed reactions are scalable.
  • MIP particle encapsulation 487 ⁇ of TEOS is added to a 5 ml glass tube, MIP particles are resuspended in solution and the entire contents are added to the glass tube, 97.3 ⁇ of APS and 24.3 ⁇ of cAPS are then added and mixed by pipetting vigorously, followed by 208 ⁇ of ink, and finally 684 ⁇ of ethanol are added. After an hour, the solution becomes a gel which is then transferred to a HPLC column or a centrifuge column depending on test.
  • Particles were loaded to an HPLC column for non -specificity and protein retention testing. This was accomplished by transferring gel during curing time before the gelation point or after gelation by resuspending gel in 1 ml of 2X PBS and pipetting the gel to the column. A total of 3 M!P columns and 3 non-imprinted (NIP) columns were created. Column packing was achieved by monitoring column backpressure to no more than 150 psi. Depending on batch, flow rates varied from 0.6 ml/min to 1 ml/min. If backpressure was exceeded for extended periods, column clogged and repacking was necessary.
  • particles were loaded to centrifuge columns by transferring MIP gel after suspending in 1 ml 2X PBS, A total of X MIP columns and Y NIP columns were fabricated. Each column was loaded with 800 ⁇ of gel and 4 ml of elution buffer. Columns were then centrifuged at 180 g's for 5 minutes. Compacted gel was resuspended with remaining solution with a vortex. Columns were centrifuged and steps were repeated until columns were free of solution. A total of 12 ml of elution buffer was used; no protein was detected in final elution with micro BCA kit. Columns were then stabilized with 6 ml of 2X PBS in the same manner as before.
  • a device was built with 4 sensors capable of reading infrared transmission changes per time in a standard disposable cuvette.
  • the device is capable of collecting changes from full dispersion up to almost full precipitation with a resolution of 1024 bits.
  • the device was programed to collect values of all sensors simultaneously every 2 seconds and values where recorded and transferred to a spread sheet for processing and evaluation.
  • FIG. 3 illustrates an exemplary graphical illustration 300 of the near IR transmission through a cuvette in the presence of dispersed beads for each pair as function of time, in accordance with the disclosed embodiments.
  • all solutions block nearly all transmission initially, but become more transparent as the particles settle due to gravity and agglomeration.
  • the rate of precipitation is determined by the slope of the curves.
  • the ratio of the rates when hCG was added to the rates in solvent alone were calculated.
  • a successful imprint was determined if a ratio equal or greater than 2 was observed, meaning that the rate of precipitation for the template containing solution must be at least twice as fast as the rate of precipitation of its own control.
  • Hi A Estimated values from prior observations. Particles were not available for testing with device.
  • group 1 there was no successful imprinting in any of the particles A to D. in group 2, only particles 2E were successful in rebinding their template, but had the smallest slope ratio of all other successful imprints.
  • group 3 particles 21 , 21 and 2L would rebind their target, whereas 3L had the least slope ratio from the group and second smallest from the batch.
  • group 4 particles 2M and 2P rebound to their template and particles 2M showed the greatest measured slope ratio from all other particles in the batch. Even though particles 2P were not measured by the device as the particles were exhausted prior to the device being ready for use, prior observational experiments would point to a very high ratio of precipitation slopes.
  • FIG. 4A Illustrates an exemplary pictorial illustration 400 of SEM images demonstrating surface morphology, specifically black anti-WN particles at 1200X, showing macroparticle shape, in accordance with the disclosed embodiments.
  • FIG. 4B illustrates an exemplary pictorial illustration 450 of SEM images demonstrating surface morphology, specifically black anti-WN particles at 22,000X illustrating aggregate morphology of macroparticles, in accordance with the disclosed embodiments.
  • FIG. 5 illustrates an exemplary pictorial illustration 500 of agglomeration test of UV red, carbon black, and non-colored silica particles, in accordance with the disclosed embodiments.
  • A, D, G samples are UV red, carbon black, and non-colored silica particles in the presence of anti-WN template respectively.
  • B, E, H samples are UV red, carbon black, and non-colored silica particles in the presence of HCG as a false positive control.
  • C, F, I samples are UV red, carbon black, and non-colored silica particles in PBS as standard control.
  • FIG. 8 illustrates an exemplary pictorial illustration 800 of conical tubes containing imprinted silica particles that were re-suspended after overnight precipitation, in accordance with the disclosed embodiments.
  • FIG. 6 (A) indicates anti-West Nile imprinted silica particles in presence of mouse anti-WN antibody containing serum; (B) indicates anti-WN beads in PBS; (C) indicates WNP in presence of mouse anti-Dengue antibody containing serum; (D) indicates hCG imprinted silica particles in presence of mouse anti-WN antibody containing serum; and (E) indicates hCG imprinted silica particles in PBS.
  • a method of imprinting silica beads can be implemented.
  • the method can include adding polymerized silica, a precursor, and carbon black in a presence of a molecular template; polymerizing the polymerized silica, the precursor, and the carbon black around the molecular template and forming a polymerized matrix bead; and washing the molecular template out of the polymerized matrix bead, wherein an imprint of the precursor remains in the polymerized matrix bead as an imprinted matrix space.
  • the silica comprises macromo!ecular imprinted silica particles
  • the precursor comprises at least one of an antibody, a virus, a protein, a hormone, an antigen, an enzyme, a molecule, a molecule with a molecular weight less than or equal to 1500 Da, and a molecule with a molecular weight greater than 1500 Da.
  • the molecular template leaves a chemically and sterically complementary void or imprint in the polymerized matrix bead, wherein the void rebinds the molecular template.
  • a step can be implemented for utilizing a silica gel matrix and tetraethy!
  • silica particles are prepared utilizing sol-gel affinity columns, further comprising utilizing sodium dodecyl sulfate (SDS) as a structure-directing agent by forming mesopores that increase template absorption, enhance molecular template removal, and limit permanent template encapsulation by enhancing network diffusion.
  • SDS sodium dodecyl sulfate
  • a step can be implemented for imprinting the precursor in the polymerized matrix bead and forming a colored polymer bead of a preferred diameter range measuring from 1 micron to 8 microns.
  • a step can be implemented for synthesizing imprinted materials in a presence of polymer-grafted carbon black, wherein the imprinted materials rebind high molecular weight templates.
  • a step can be implemented for injecting the imprinted polymerized matrix bead into a living specimen and the living specimen selectively producing antibodies that fill the imprinted matrix space, thus creating a vaccine.
  • an imprinted silica bead is disclosed.
  • the imprinted silica bead can include polymerized silica, a precursor, and carbon black in a presence of a molecular template, wherein an imprint of the precursor remains in the polymerized matrix bead as an imprinted matrix space.
  • the silica comprises macromolecular imprinted silica particles.
  • the precursor comprises at least one of an antibody, a virus, a protein, a hormone, an antigen, an enzyme, a molecule, a molecule with a molecular weight less than or equal to 1500 Da, and a molecule with a molecular weight greater than 1500 Da.
  • the molecular template comprises a chemically and sterically complementary void or imprint in the polymerized matrix bead, wherein the void is capable of rebinding the molecular template.
  • the precursor is imprinted in the polymerized matrix bead.
  • the colored polymer bead has a preferred diameter range measuring from 1 micron to 8 microns.
  • an imprinted silica microbead in another embodiment, is disclosed.
  • the imprinted silica microbead can include polymerized silica; a molecule with a high molecular weight imprinted in a location of the polymerized silica; and an artificial receptor at the location of the imprinted molecule, wherein the artificial receptor selectively binds molecules, in an embodiment, the silica comprises macromolecu!ar imprinted silica particles.
  • the precursor comprises at least one of an antibody, a virus, a protein, a hormone, an antigen, an enzyme, a molecule, a molecule with a molecular weight less than or equal to 1500 Da, and a molecule with a molecular weight greater than 1500 Da.
  • the molecular template comprises a chemically and sterically complementary void or imprint in the polymerized matrix bead, wherein the void is capable of rebinding the molecular template.
  • the precursor is imprinted in the polymerized matrix bead.
  • the colored polymer bead has a preferred diameter range measuring from 1 micron to 8 microns.

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Abstract

La présente invention concerne des particules de silice à impression macromoléculaire ("MIP") en présence de noir de carbone à greffage de polymère. Les billes à impression moléculaire décrites peuvent détecter une maladie dans les fluides corporels. Pour la matrice de gel de silice, l'orthosilicate de tétraéthyle (TEOS) est utilisé en tant que monomères de squelette et le 3-aminopropy/triéthoxysilane (APS) en tant que monomère fonctionnel. Du noir de carbone est ajouté au processus sol-gel, pour obtenir des particules de silice noires. De plus, le dodécylsulfate de sodium (SDS) est utilisé en tant qu'agent dirigeant la structure pour augmenter la diffusion en réseau du modèle. Un total de 16 MIP ont été synthétisés parallèlement avec des variables qui évaluent le rôle de réactifs clés dans la procédure de synthèse. Des tests d'agglomération ont été conduits sur l'ensemble des 16 MIP en présence de leur modèle, avec leurs témoins respectifs au moyen de soluté tamponné par les phosphates ("PBS") seul. Chacun des MIP est évalué en utilisant un nouveau dispositif capable de mesurer simultanément jusqu'à quatre échantillons pour la transmission infrarouge proche.
PCT/US2014/049929 2013-08-06 2014-08-06 Billes de silice colorées à impression moléculaire WO2015021145A1 (fr)

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CN108079974A (zh) * 2017-12-26 2018-05-29 珠海健帆生物科技股份有限公司 一种蛋白印迹高分子吸附剂的制备方法及吸附装置
CN109738401A (zh) * 2018-12-27 2019-05-10 湘潭大学 一种新型病毒分子印迹荧光传感器的制备及应用
CN112808256A (zh) * 2021-01-29 2021-05-18 合肥海关技术中心 一种磁性核壳介孔表面分子印迹复合纳米材料及其制备方法
CN113058575A (zh) * 2021-04-23 2021-07-02 吉林大学 一种生物印迹复合膜及其制备方法
WO2023177301A1 (fr) * 2022-03-18 2023-09-21 Universiteit Maastricht Dispositif de détection pour détecter des analytes à l'aide d'un matériau de base ayant un matériau polymère sur celui-ci, ainsi que procédé de fabrication d'un tel dispositif de détection

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US20120136180A1 (en) * 2009-03-25 2012-05-31 The Trustees Of The University Of Pennsylvania Imprinted Biomimetic Catalysts for Cellulose Hydrolysis
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CN108079974B (zh) * 2017-12-26 2021-03-12 健帆生物科技集团股份有限公司 一种蛋白印迹高分子吸附剂的制备方法及吸附装置
CN109738401A (zh) * 2018-12-27 2019-05-10 湘潭大学 一种新型病毒分子印迹荧光传感器的制备及应用
CN109738401B (zh) * 2018-12-27 2021-07-02 湘潭大学 一种新型病毒分子印迹荧光传感器的制备及应用
CN112808256A (zh) * 2021-01-29 2021-05-18 合肥海关技术中心 一种磁性核壳介孔表面分子印迹复合纳米材料及其制备方法
CN112808256B (zh) * 2021-01-29 2023-01-24 合肥海关技术中心 一种磁性核壳介孔表面分子印迹复合纳米材料及其制备方法
CN113058575A (zh) * 2021-04-23 2021-07-02 吉林大学 一种生物印迹复合膜及其制备方法
CN113058575B (zh) * 2021-04-23 2022-04-19 吉林大学 一种生物印迹复合膜及其制备方法
WO2023177301A1 (fr) * 2022-03-18 2023-09-21 Universiteit Maastricht Dispositif de détection pour détecter des analytes à l'aide d'un matériau de base ayant un matériau polymère sur celui-ci, ainsi que procédé de fabrication d'un tel dispositif de détection
NL2031326B1 (en) * 2022-03-18 2023-09-29 Univ Maastricht A sensing device for detecting analytes using a base material having a polymer material thereon, as well as a method for manufacturing such sensing device.

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