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    • 专利摘要:
    A device for transport of ions and/or charged molecules between a source and a target electrolyte, comprising: a first electrode provided at or in said source electrolyte, and a second electrode provided at or in said target electrolyte; and wherein said first and second electrodes provides an electrical control of an ion flow, and further comprising means for limiting an electronic current between said source and said target electrodes, such that at least after a voltage is applied a potential difference between said source and target electrodes is maintained, which effects ion transport from said source to said target electrode; wherein the device further comprises an ionand/or permselective polyelectrolyte for transport ions and/or charged molecules via electrophoresis and functions as an ion-selective membrane; and wherein said polyelectrolyte comprises a cross-linked hyperbranched polymer.
    公开号:SE1651192A1
    申请号:SE1651192
    申请日:2016-09-05
    公开日:2018-03-06
    发明作者:Gabrielsson Roger；Sandberg Mats；Berggren Magnus
    申请人:Oboe Ipr Ab；
    IPC主号:
    专利说明:

    ION PUMP WITH HYPERBRANCHED POLYMERS Technical field of the lnvention The present invention relates to a device for transport of ions and/orcharged molecules between a source and a target e|ectro|yte comprising apolyelectrolyte. The present invention further relates to a method forpreparing a polyelectrolyte.
    Backqround of the lnvention ln recent years, a range of organic electronic tools has beendeveloped1'4 which enable precise dynamic delivery of small ionic molecules. lon-selective electrophoretic delivery so called “ion-pumping”, i.e.migration of ions through a charged membrane/gel by an electric field, is nowa proven method for delivery of small molecular ions with electronic precision, as well as a good spatial and temporal control of delivery.
    The organic electronic ionic pump (OEIP) is one of these technologiesand was developed primarily for application to mammalian systems to enablediffusive synapse-like delivery of neurosignaling compounds (alkali ions,Recently, OEIP devices have been demonstrated for a variety of in vitro5f6 as well as in vivo neurotransmitters) with high spatiotemporal resolution.applications7, including therapy in awake animals8. OElPs are electrophoreticdelivery devices that leverage the unique ionic and electronic properties ofconducting polymers and polyelectrolytes to convert electronic signals intoionic fluxes. The OElP's polymer delivery channel (i.e., electrophoresischannel) is composed of a polycationic (or polyanionic) material with a highdensity of fixed charge groups that allows for the selective transport of anions(or cations). The electrophoretic transport utilized by OEIP devices is flow-free - only the intended molecules are delivered to the target region, notadditional liquid or oppositely charged counter-ions that may be present in thesource solution. The selective electrophoretic transport of the desired 2 molecular species through an OEIP device results in high concentrationgradients Iocalized at the OEIP outlet6, on the scale of ~100 um - 1 mm.Additionally, electronic addressing to the OEIP enables the molecular deliveryto be rapidly switched on and off, and importantly, the electrical drivingcurrent can be directly correlated with the ionic delivery rate. These devicecharacteristics allow for the precise control of chemical concentrationgradients with high spatial and temporal resolution.
    EP 1 862 799 B1 discloses a device for electrically controlled transportof ions from a source to a target electrolyte. The device comprises a sourceelectrode and a target electrode, each capable of conducting said ions andelectrons. The source electrode is arranged to receive said ions from thesource electrolyte and the target electrode is arranged to release the ions tothe target electrolyte. The device further comprises an ion-conductive channelarranged to receive the ions from the source electrode, to release the ions tothe target electrode and to provide an ionic connection between the sourceand the target electrodes. The electrodes and the ion-conductive channel areformed of solid or semi-solid materials which are directly or indirectly attachedto a support. Further, the device comprises means for limiting an electroniccurrent between the source and the target electrodes, such that at least aftera voltage is applied across the channel a potential difference between thesource and target electrodes is maintained, which effects ion transport fromthe source to the target electrode. The device comprises means for retainingone of the source and target electrolytes on the device, comprising walls forretaining the electrolyte, and being arranged such that the electrolyte is incontact with the desired electrode.
    Another route to cross-linked networks, with ionic groups, is tocopolymerize ionic monomers with di-functional monomers. One drawbackwith that route is that unreacted monomers left in the network must beremoved, otherwise, ion-selectivity is lost. Post-functionalization ofpolyelectrolytes is a possibility, but limited by the poor solubility in solventssuitable for functionalization; polyelectrolytes are typically only soluble inwater. The number of available polyelectrolyte materials suitable for OEIP 3 device technologies is limited. lt is therefore a wish for improving the currentstate of the art.
    Summary of the lnvention lt is an object of the present invention to improve the current state ofthe art and to mitigate at least some of the above mentioned problems. Theseand other objects are achieved by a device for transport of ions and/orcharged molecules.
    According to a first aspect of the present invention there is provided adevice for transport of ions and/or charged molecules between a source anda target electrolyte, comprising: a first electrode provided at or in said sourceelectrolyte, and a second electrode provided at or in said target electrolyte;and wherein said first and second electrodes provides an electrical control ofan ion flow, and further comprising means for limiting an electronic currentbetween said source and said target electrodes, such that at least after avoltage is applied a potential difference between said source and targetelectrodes is maintained, which effects ion transport from said source to saidtarget electrode; wherein the device further comprises an ion- and/orpermselective polyelectrolyte for transport ions and/or charged molecules viaelectrophoresis and functions as an ion-selective membrane; and whereinsaid polyelectrolyte comprises a cross-linked hyperbranched polymer.
    The present invention is based on the realization of transporting largerions and/or charged molecules. This is realized by the use of cross-linkedhyperbranched polymers. Fundamental limitations of previous devices fortransporting ions and/or charged molecules can be addressed and overcomeby the means of the present invention, such as swelling and rigidity of thepolymer network which can be controlled by cross-linking; and transport of“larger” or reactive aromatic substances can be facilitated by tuning the voidfraction distribution and effective porosity of the bulk. Example of such adevice is an organic electronic ion pump (OEIP). ln this application oranicelectronic ion pump as well as the abbrivation OEIP will be usedinterchangebly with device for transporting ions and/or charged molecules. 4 The linear polymers which are traditionally used for this kind of devicesresults in a tighter network as compared with the now discoveredhyperbranched polymer. The tighter network results in small porous pathwaysand thus trough the ion-selective membrane. Hence, this type of polymersresults in an ion-selective membrane that works only for smaller molecules.Moreover, the more traditional linear polymers are harder to functionalize andmost often post-functionalization has to be used which results in the chargesjust being distributed over the surface of the network and not evenlydistributed throughout the bulk.
    According to at least one example embodiment of the inventionhyperbranched polymers are highly branched three-dimensional (3D)macromolecules. Their spherical architectures give them unique propertiessuch as intramolecular cavities, low viscosity and/or high solubility. Moreover,they can be equipped with plenty of functionalized groups. The cross-linkedhyperbranched polymer provides large porous pathways in and through thepolyelectrolyte due to their intermolecular cavities and thus through the ion-selective membrane. Crosslinking large “spherical” hyperbranched bearingcrosslinkable and ionic groups, resulting in membranes and/or gels that havecontrollable selectivity and large porous pathways. This means that it ispossible to transport larger molecules, for instance larger drug moleculessuch as phospholipids. The polyelectrolyte has a homogenously distributedcharge. The high solubility of the hyperbranched molecules is due to theiramphiphilic character.
    The charges are more homogeneously spread throughout thepolyelectrolyte and thereby it is possible to reduce the current needed fortransporting ions trough the material as compared with the conventionalOEIP. Hence, the device also provides for way of transporting smallermolecules in a more lenient manner. By avoiding large currents being used,side-reactions usually connected with these, such as water-splitting, can beavoided. Moreover, the reduced amount of current needed reduces the riskheating water. Too warm condition may cause unwished crystallization withinthe membrane. 5 The hyperbranched polymer may comprise chemical formulas 1, 2, 3, CH ä; WWWW D = Chemical forrnuia 1L 2 Chemical forrnuia 2T = Chemical formula 3 wherein in the chemical formulas 2 and 3, R1 is sulphonate,phosphonates or carboxylates, R2 is ammonium or phosphonium, R3 is(meth)acry|oxy groups, (meth)acry|amido groups, and vinyl groups, R1, R2,R3 terminates alkyl group with C1~C20, a aryl group with C6~C20, aheteroaryl group with C2~C20, a cyc|oa|ky| group with C6~C20, and aheterocyclic group with C2~C20. This means that the formula shown on theleft side represents the hyperbranched polymer core and the final derivatie isshown on the right side with crosslinkable and ionic groups.
    The hyperbranched polymer may be functionalized with ketone-,aldehyde-, alcohol- and/or iminegroups.
    The wide variety of groups which may be used for functionalization ofthe hyperbranched polymer enables for a variety of properties of the materialit self.
    The hyperbranched polymer may have a degree of branching of 0,05-1or a degree of branching of 0,2-0,9, or a degree of branching of 0,3-0,8, or adegree of branching of 0,4-0,8.
    The degree of branching of a linear polymer would be 0. A degree ofbranching of 1 corresponds to a dendrimer. The properties of ahyperbranched polymerwith a high degree of branching are similar to theproperties of a dendrimer.
    The hyperbranched polymer may be a hyperbranched polyglycerol. 6 Polyglycerol is a very cheap hyperbranched molecule which thereforemakes it the most frequently used alternative. The monomer used for thesynthesis, glycerol, is an easily achieved triol used in a variety of applications.
    The molecules being pumped or transported in the device may be anyone of monovalent and divalent atomic ions, multivalent biomolecules,charged aromatic molecules, and nonaromatic molecules.
    As an example of mono- and di-valent atomic ions is Na+, Cl". As anexample of nonaromatic molecules is acetylcholine, and aromatic moleculesmay be for instance benzoic acid molecules. The substances or moleculesbeing transported in the device may comprise both endogenous and syntheticsubstances, such as drugs. Some examples of endogenous molecules thatmay be transported include neurotransmitters such as gamma-aminobutyricacid (GABA) and dopamine. The molecules that may be pumped ortransported through the membrane are thus molecules that are larger thanwhat has previously been possible in the known OPElPs.
    According to at least one the device may be used for transporting auxinand/or phospholipids.
    According to a second aspect there is provided a method for preparinga polyelectrolyte for a device, for transport of ions and/or charged moleculesbetween a source and a target electrolyte comprising the steps of i) providing a solution comprising a hyperbranched polymer havinghaving polymerizable groups and groups that are ionic or ionizable, ii) depositing said solution on a support; and iii) crosslinking said hyperbranched polymer.
    Effects and features of this second aspect of the present invention arelargely analogous to those described above in connection with the first aspectof the inventive concept. Embodiments mentioned in relation to the firstaspect of the present invention are largely compatible with the second aspectof the invention.
    According to the second aspect there is further provided a method forpreparing a polyelectrolyte for a device for transport of ions and/or chargedmolecules between a source and a target electrolyte comprising the steps of 7 i) providing a solution with a hyperbranched polymer havingpolymerizable groups and groups that are ionic or ionizable and a solvent, ii) mixing a photoinitiator and crossiinker with said solution; iii) depositing a support with said mixture; iv) photo-induced curing of the deposited mixture for crosslinking of thehyperbranched polymer.
    The preparation of a polyelectrolyte may thus be done as a so called“one-pot 3 component synthesis”. This means that the hyperbranchedpolymer, the cross-linker and the photo-initiator are mixed in one solvent. Thisis being made possible by the so|ubi|ity properties of the hyperbranchedpolymer. The one-pot synthesis facilitates the preparation of thepolyelectrolyte and the productio of the device, since the po|yee|ctro|yte maybe placed directly onto a support and then crosslinked without the necessityfor further treatment steps. After the crosslink step any by products may beremoved on the surface of the membrane and support. The ion conductivemembrane thus filled or formed from the crosslinked hyperbranched polymerpolyeelectrolyte can be used in a variety of applications such as for fuel cells,electrophoresis, in microfluidics and in bio-printing.
    According to at least one example embodiment of the invention themethod for preparing the polyelectrolyte is divided into three steps: The first step (i) of the polyelectrolyte is a so called one-pot synthesis.This is enabled due the amphiphilic character of the hyperbranched polymerwhich makes it easy to dissolve in a variety of solvents. The threecomponents, the hyperbranched polymer, the cross-linker and the photo-initiator is mixed together before deposition of the mixture. This enables ahomogeneous distribution of bulk charges. ln a following step (ii) the mixture from step i) is deposited. The one-potsynthesis as well as the amphiphilic character of the hyperbranched polymeroffers a high degree of compatibility with a variety of deposition andpatterning processes. The deposition method used for the preparation of thepolyelectrolyte may for example be spin-coating, printing and/or any othersolution based method. 8 After deposition the mixture will be photo-induced cured (iii). Thiscuring may for example UV-curing.
    The hyperbranched polymer may have a degree of branching in therange of 0,05-1 or in the range of 0,1 to 1, or in the range of 0,5 to 1, or in therange of 0,7 to 1.
    The method according to any one of claims 7 to 9, wherein thehyperbranched polymer comprises chemical formulas 1, 2, 3, HO O / »»»» g /.- o on mo o < ø m* 0,3 ~ orcwRf 2un» i, ï 3Û »»»» »b p »Mox /Moßl O(C,,)R oícnlRl 2o(cn)R3 D = Ghemiaal formula *lL 1 chfšmiCâl füfmlålê 2T I Chernical formula 3 wherein in the chemical formulas 2 and 3, R1 is sulphonate,phosphonates or carboxylates, R2 is ammonium or phosphonium, R3 is(meth)acryloxy groups, (meth)acrylamido groups, and vinyl groups, R1, R2,R3 terminates alkyl group with C1~C20, a aryl group with C6~C20, aheteroaryl group with C2~C20, a cycloalkyl group with C6~C20, and aheterocyclic group with C2~C20.
    The solvent may be any one of deionozed water, methanol, ethano,propanol, NMP, DMSO and DMF.
    According to the second aspectthe the proprotion of of saidphotoinitiator and said crosslinker in step (ii) may be in the range of 0.1 to 10parts by weight with respect to 100 parts by weight of said mixed solution.
    According to a third aspect there is provided a device for transport ofions and/or charged molecules between a source and a target electrolyte,wherein said device comprises a polyelectrolyte and wherein saidpolyelectrolyte is synthesized according to the second aspect, and wherein 9 said polyelectrolyte is able to transport ions and/or charged molecules viaelectrophoresis.
    Effects and features of this third aspect of the present invention arelargely analogous to those described above in connection with the first andsecond aspects of the inventive concept. Embodiments mentioned in relationto the first and second aspects of the present invention are largely compatiblewith the third aspect of the invention.
    According to a fourth aspect there is provided the use of a device according to the first aspect or the third aspect for drug delivery.
    Brief description of the drawinqs The above objects, as well as additional objects, features andadvantages of the present invention, will be more fully appreciated byreference to the following illustrative and non-limiting detailed description ofpreferred embodiments of the present invention, when taken in conjunctionwith the accompanying drawings, wherein: Fig. 1 shows schematic diagrams representing different features of theinvention in accordance with at least one embodiment of the invention; Fig. 2 shows a diagram of the total OEIP-delivered auxin as a functionof time in accordance with at least one embodiment of the invention; Fig. 3 shows an in vivo set-up at seedling roots and mounting onvertical macroscope stage in accordance with at least one embodiment of theinvention; Fig. 4 shows OElP-mediated root growth in accordance with at leastone embodiment of the invention; Fig. 5 shows imaging of OElP-induced auxin responses in accordancewith at least one embodiment of the invention.
    Fig. 6 shows a schematic scheme for the synthesis of thehyperbranched polymer in accordance with at least one embodiment of theinvenfion.
    Detailed description of the drawinqsln the present detailed description, embodiments of the present invention will be discussed with the accompanying figures. lt should be notedthat this by no means limits the scope of the invention, which is alsoapplicable in other circumstances for instance with other types or variants ofdevices for transporting ions and/or charged molecules than the embodimentsshown in the appended drawings. Further, that specific features arementioned in connection to an embodiment of the invention does not meanthat those components cannot be used to an advantage together with otherembodiments of the invention. The embodiments described below are merelyexamples of possible device architectures and the present invention shouldnot be limited thereto. The scope of the invention is as defined ny theappended claims. The term "ion" as used herein encompasses not onlypositively or negatively charged monovalent or multivalent ionic species ofatomic elements, but also other molecular species carrying a net positive ornegative charge. Hence, in an embodiment of the invention it is intended totransport charged biologically active molecules or macromolecules such ascharged amino acids, DNA, DNA sequences/fragments or plasmids, proteins,vitamins, peptides or hormones. ln one embodiment of the invention, the ionsthat may be transported are cations, for example metal ions, such aspotassium or calcium ions. ln another embodiment of the invention the ionsthat may be transported are anions. The transported "ions" may act as stimulifor the cells. These stimuli may turn on a cellular process or turn off a cellularprocess, or act as an inhibitor. A non-limiting example is potassium whichmay act as stimuli for neuronal cells by opening the voltage-operated Ca2+channels in the cell membrane. A non-limiting example of an inhibitor may becadmium which may block the voltage-operated Ca2+ channels in the cellmembrane. The term ion also encompasses species that may be charged bysetting a certain pH of the electrolyte solution or channel. The pH needed tocharge these species may be calculated from the pKa of these molecules.The term ion also encompasses molecules which may be chemically modified to obtain a net charge, e.g. by attaching an ion to them. ion-conductive 11 channel used in the invention is made of a solid or semi-solid material whichis able to conduct ions. According to one embodiment of the invention the ion-conductive channel may be essentially electronically nonconductive, i.e. the capability of conducting electrons is substantially limited.
    The general configuration of an organic electronic ion pump (OEIP) has beendescribed in the art. ln for instance EP2232260B1 a general description of theproduction and the configuration of an OEIP is provided. The substrate ontowhich the OEIP may be placed, or printed i.e. be fabricated preferably iselectrically and ionically insulating and may comprise rigid materials such asSi wafers with an insulating oxide (SiOx) or nitride layer (Si3N4), glass waferssuch as pyrex wafers, glass substrates, such as microscope slides, plasticsubstrates such as PET, polystyrene, used in petridishes, and ceramics. Thesubstrates may also be flexible such as plastic films, Orgacon films (bothplastic and paper), or paper based materials. The ion transport deviceaccording to the invention is also particularly advantageous in that it can beeasily realized on a support, such as polymer film or paper. Thus, the differentcomponents can be deposited on the support by means of conventionalprinting techniques such as screen printing, offset printing, gravure printing,ink-jet printing and flexographic printing, or coating techniques such as knifecoating, doctor blade coating, extrusion coating and curtain coating. The ion-conductive channel or membrane (ion channel), may thus be depositedthrough in situ polymerization and crosslinking. An aspect of the inventionprovides such processes for the manufacture of an ion transport device fromthe materials specified herein. The device, comprising electrodes and the ionconductive membrane may be directly or indirectly attached to a solid supportsuch as glass or to a flexible support such as polymer film or paper. The ion transport device according to the invention may preferably beencapsulated, in part or entirely, for protection of the device. The deviceaccording to the invention may also present further features, which facilitateuse of the device. Such features include for example terminals for connectinga voltage source to the electrodes of the device, means for encapsulating thedevice in order to make it more robust to handling, and to prevent evaporation 12 or contamination of liquid electrolytes. The general configuration of an OEIPas described in for instance EP2232260 may be used also for the productionand configuration of a device according to the present invention. Below isdescribed a number of embodiments comprising the hyperbranched polymerhaving has polymerizable groups and groups that are ionic or ionizable,wherein the hyperbranched polymer is crosslinked, and forming apolyelectrolyte for the delivery of different molecules such as drugs.
    Fig. 1 illustrates a design of an organic electronic ion pump (OEIP)delivering auxin in vitro. Fig. 1a is a schematic diagrams of a OEIP devicematerials and geometries. Fig. 1b is a schematic diagram of aconceptualization of the cationic dendric polyglycerol polyelectrolytemembrane. Anionic species such as auxin indole-3-acetic acid (lAA) areselectively transported and migrate through the ion conducting channel inproportion to the applied potential gradient. Fig. 1c is a photograph of the fullyfabricated OEIP device. Fig. 1d illustrates dendric polyglycerol -basedpolyelectrolyte system showing crosslinking (green), terminal groups(orange), and positive charge functionalization (blue).
    Fig. 2 illustrates the lAA delivered via OEIP. Total (summed) OEIP-delivered auxin vs time, e.g., 30 min time-point is sum of 15 minmeasurement plus 30 min measurement (as marked by dot-lines). Error bars indicate standard deviation.
    Fig. 3 illustrates an in vivo set-up at seedling roots and mounting onvertical macroscope stage. Fig. 3a shows an OEIP mounted to a motorizedmicro-manipulator and A. thaliana plant seedlings positioned vertically ongrowth-agar plates. Fig. 3b shows an OEIP positioned in proximity to theseedling root apical meristem (AM) and elongation zone (EZ). Fig. 3c, OEIPdelivery tip and root cross section shown submerged in the growth agar gel.Delivery of lAA is pictured as a diffusive concentration gradient from the OEIPdelivery tip through the agar gel and exogenous to the root tissue.
    Fig. 4 shows an OEIP-mediated root growth inhibition by auxin. Brightfield images at different time intervals during continuous OEIP delivery of lAA. 13 The position of the 25 um wide polyelectrolyte channel is highlighted in green.Fig. 4a shows the growth rate of Dll-Venus root tips are plotted as a functionof OEIP delivery time (Averages i SEM from n = 5 independent treatmentsare displayed from a time interval of 15 min) of IAA, benzoic acid, and fornon-targeted control. Fig. 4b shows the reduction in growth rate can beobserved during delivery of IAA compared to benzoic acid negative controlover the same time interval. Start and end root tip positions are indicated withblue dashed lines, image area matching 5b highlighted. Fig. 4c, DR5seedlings with image area matching Fig 5c highlighted. Scale bar 250 um.
    Fig. 5 illustrates the imaging of OElP-induced auxin responses. Fig 5ashows the fluorescence intensity of Dll-Venus reporter seedlings plotted forOEIP delivery of IAA, benzoic acid, and non-targeteted. Averages i SEMfrom n = 5 independent treatments are displayed. Fig. 5b shows the confocalfluorescent image sequence of the root tip of Dll-Venus reporter seedling atintervals 0, 30, 60 min. Fig. 5c shows the confocal fluorescent imagesequence of the elongation zone of DR5rev::GFP reporter seedlings atintervals 0, 1, 2, and 3 h. lmage intensities were summed from 16 z-stacklayers with 3 um spacing. Lateral fluorescent intensity across the rootelongation zone is summed vertically, normalized and superimposed. Scalebars, 50 um. Images are representative of five roots treated.
    Fig. 6 illustrates the synthetic method for achieving one example of ahyperbranched polymer. Here, the hyperbranched polymer is a dendritichyperbranched polyglycerols (dPG). ln the figure the dPG is marked HBPG(hyperbranched polyglycerol). The synthetic route to dPGs having negative(anionic), sulfonic acid, and allyl groups for cross-linking is outlined in Fig. 6.The density of stationary ionic and cross-linking points in dPG's are controlledby the degree of substitution for the appropriate groups. The process forformation of the crosslinked dPGs is also crucial. We have opted for photo-initiated radical coupling in inert atmosphere to generate stable covalentgroups forming the membrane/gels. A high conversion of the cross-linking and binding to the substrate is necessary to provide the cohesive and 14 adhesive strength of the channel to withstand the stress of exposure tolithographic process media, as well as the operation environment.
    Fig. 6a illustrates the schematics over the core material used in thesynthesis, dendritic hyperbranched polyglycerol of molecular weight 10 kDa.Fig. 6b illustrates the schematics over the synthesis of the functionalizeddPGs with allyl- and sulfonate groups.
    The ski|ed person realizes that a number of modifications of theembodiments described herein are possible without departing from the scope of the invention, which is defined in the appended claims.
    Examples To address the need for OEIP technologies capable of transporting largerionic compounds, hyperbranched polymers” were investigated as thefoundation for a new class of polyelectrolyte materials. Hyperbranchedpolymers are generally spherical and possess a high number of terminalfunctional groups that define their customizable physio-chemical properties24.Hyperbranched polymers based on homogenous, flexible polyether alcohols(e.g., dendritic hyperbranched polyglycerols, dPGs), make it possible to tunethe density of ionic and cross-linking groups by synthesis25. ln this way,fundamental limitations of previous OElPs can be addressed: swelling andrigidity of the polymer network can be controlled by cross-linking; andtransport of “larger” or reactive aromatic substances can be facilitated bytuning the void fraction distribution and effective porosity of the bulk.lmportantly, dPG-based polyelectrolytes enable processing from a “one-pot”3-component mixture of synthesized dPG, crosslinker, and photoinitiatordissolved in methanol. One-pot mixing enables a homogeneous distribution ofbulk charge and crosslinking in the membrane, and further offers a highdegree of compatibility with a variety of patterning processes such as printing or lithographic techniques. ln this work, the cross-over of molecular delivery technology to plantapplications and the capability of transporting aromatic compounds enabledby the newly-developed dPG-based polyelectrolyte is also discovered, Fig1b,d. OEIP devices were prepared by photolithographic patterning of thecationically-functionalized dPG film (2 um thick) on a flexible PET plasticsubstrate. The shape and dimensions of the resulting OEIP device structureare illustrated and pictured in Fig 1a,c.
    Mass spectrometry was used to quantify the capability of dPG-based OElPsto transport lAA. ln this regard, lAA played the dual role biologically-relevantplant hormone and model aromatic substance. The OEIP was operatedcontinuously at 1 uA and samples were collected in 15 min intervals for 135min. Fig 2 shows the summed amounts of measured lAA vs. time. Underthese conditions, OEIP operation was observed to achieve an averaged lAAdelivery rate of 0.45*_f0.16 pmol min'1, corresponding to nanomolarconcentrations in close proximity to the delivery tip. For example, 10 pmol oflAA delivered to a 50 ul volume corresponds to a concentration of 200 nM in15 min. These results indicate that the cationic dPG polymer material systemis capable of transporting lAA in biologically active quantities26. Traceamounts of 2-oxindole-3-acetic acid (oxlAA), a known lAA catabolite27, werealso detected during mass spectrometry measurements, typically inconcentrations 100 - 1000xlower than the measured lAA. However, oxlAA has been reported to be inactive in previous bioassays27.
    The dPG-based OElPs were used for in vivo experiments on a highlyaccessible model plant system suitable for live-cell imaging in the intactorganism. Specifically, the apical root meristem and early elongation zone offour-day-old Arabidoposis thaliana seedlings positioned on agar gel weretargeted for delivery of lAA via the OEIP. Root tips were monitored using ahorizontally oriented Nikon AZ100 spectral macro-confocal laser-scanningmicroscope system schematically illustrated in Fig. 3a. ln this arrangement, seedlings were positioned and imaged vertical/y. 16 The root apical meristem of A. thaliana seedlings with IAA (Fig. 2b,c), weretargeted ising the OEIP devices. Root growth was used as a rapidlyaccessible parameter to demonstrate the physiological activity of OEIPdelivered IAA. lt is well established that increased levels of IAA inhibit rootgrowth2628. As a negative control, benzoic acid29 was delivered by the OEIPdevice, operated in the same configuration.
    Figure 4b shows bright field images taken of the OEIP device and seedlingroot tips at the beginning, and after 60 min, of delivery of IAA or benzoic acid.Root tip position was measured at 15-min intervals and averaged over 5trials, and the growth rate of roots targeted with IAA was compared to benzoicacid negative control and non-targeted A. thaliana seedlings. For seedlingstargeted with IAA, a rapid decrease in growth rate was observed starting at 15min of delivery, from 4.711 .O um min'1 to 2.410] um min'1 after 60 min, whileboth benzoic acid and non-targeted control seedlings maintained their growthrates (Fig. 4a). The reduction in growth rate of plant seedlings by delivery ofIAA via the OEIP is consistent with previous findings on exogenousapplication of IAAZG.
    To detect, visualize and monitor IAA delivery in near real-time, two widelyused engineered transgenic A. thaliana lines were utilized expressing thesemi-quantitative Dll-Venusso or DR5rev::GFP31 fluorescent auxin-responsereporters, both of which are dynamically sensitive to the presence of IAA. TheDll-Venus reporter is characterized by absence or reduction in fluorescentsignal intensity in the presence of auxin or increasing auxin levels,respectively. Conversely, in DR5, the presence or gain of fluorescent signalintensity indicates presence or increase of auxin concentrations, respectively.The relative auxin abundance is visualized faster by Dll-Venus than by DR529,because the Dll-Venus signal relies on a protein degradation mechanismrather than the slower transcriptional and translational productionmechanisms of DR5. 17 Using Dll-Venus seedlings, the fluorescent signal intensity was monitored andonset of strong fluorescence reduction was observed between 30 to 60 min(Fig. 5 a,b). Similar roots targeted with the control molecule benzoic acidpreserved their fluorescence. Quantitative analyses comparing normalizedfluorescent intensities of Dll-Venus seedlings targeted with IAA or benzoicacid, as well as non-targeted controls, revealed a strong and significantdecrease in fluorescence only after IAA delivery via the OEIP (Fig. 3b). ln the second experiment, the dPG-based OEIP was used to target theelongation zone of DR5rev::GFP reporter seedlings with IAA. Confocalimages of the root elongation zone cells revealed the onset of fluorescence inplant tissues after 1 hour and the signal continued to increase between 2 and3 hours (Fig 5c). From the image sequence and lateral intensity profile,significant variation in the lateral fluorescent intensity can be observed - withcells on the left side (OEIP side) of the root being brighter than those on theright. Roots targeted with the control molecule benzoic acid, did not displayalterations in fluorescent intensity of the DR5 reporter. ln this study fabricated organic electronic devices were fabricated from anewly developed hyperbranched dendritic core-shell polyelectrolyte systemthat addresses many of the previous limitations of OElPs and other ”“iontronic””technologies. The hyperbranched dendritic polyglycerols (dPG)polyelectrolyte system overcomes the limited control of material parameterssuch as porosity, swelling, and process-ability. The resulting dPG-basedOEIP devices were used to demonstrate delivery of the aromatic plantsignaling hormone IAA auxin to elicit rapid physiological changes indeveloping Arabidopsis thaliana roots. Further, the induction of dynamicauxin-response alterations measured by two different fluorescent auxinreporters in transgenic A. thaliana seedlings was demonstrated. ln addition tothe natural auxin hormone IAA, the aromatic delivery capability of the dPG-based OEIP devices was also verified with the synthetic auxin analog 1-NAA. 18 Given that the majority of plant hormones such as abscisic acid,brassinosteroids, gibberellins, and cytokinins all include cyc|ic or aromaticmolecular Structures, this work provides the foundation for organic electronicdevices that interact with plants' fundamental chemical signaling systems with5 unprecedented spatial and temporal resolution. This technology will be usedto test a range of previously known bioactive molecules and observe theireffect on plant growth and behavior at previously unattainable length and timescales. This new technology is anticipated to be the starting point for moresophisticated tools to precisely regulate the chemical signaling networks in -10 and between -living plants and other living systems. 19 Methods summary The invention provides a method for manufacturing an ion-conductingmembrane filled with crossiinked hyperbranched polymer eiectroiytes, whichmay comprise the steps of: i) providing a solution comprising a hyperbranched polymer havingpolymerizable groups and groups that are ionic or ionizable ii) depositing said solution on a support iii) crosslinking said hyperbranched polymer.
    One method for forming the crossiinked hyperbranched polymer is through aphoto-initiated radical coupling, preferably in inert atmosphere to generatestable covalent groups forming the membrane/gels. The general method maythen comprise the steps of: (A) providing a solution of a hyperbranched polymer having polymerizablegroups and groups that are ionic or ionizable and a solvent, (B) mixing said solution with a photoinitiator and crosslinker; (C) deposit a support with the mixture of stap (B); (D) crosslinking an electrolyte-membrane support and irradiating theelectrolyte-membrane with ultraviolet rays; and (E), removing byproduct on the surface of the membrane, support after thecrosslinking step.
    More particularly, the invention provides a method for manufacturing an ion-conducting membrane filled with crossiinked hyperbranched polymereiectroiytes, comprising the steps of: (A) mixing the hyperbranched polymercomprised with chemical formula 1, 2, 3, a solvent, which may be deionizedwater, methanol, ethanol, propanol, NMP, DMSO, DMF; (B) mixing 0.1 to 10parts by weight of a photoinitiator and crosslinker with respect to 100 parts byweight of the mixed solution; (C) deposit a support with support with the solution; (D) crosslinking an electrolyte-membrane support by coating the electrolyte-membrane on a polyethylelenterephthalate (PET) film andirradiating the electrolyte-membrane with ultraviolet rays at an intensity of 30to 150 mJ/cm2 ; and (E), removing any byproducts present on the surface of the membrane, support after the crosslinking step.
    The hyperbranched polymer may for instance be a so called dendritichyperbranched polyglycerol (dPG). The photoinitiator may for instance beThiocure 1300 and the crosslinker may for instance be lrgacure 2959.
    This means that thorugh the inventive method, and a so called “one-pot 3-component mixture” an OEIP canbe very easily manufactured. The need forsubsequent treatments before use, is very limited if at all required.
    The primary advantages of the proposed concept/s over existing materialsare simplicity, potential for low-cost devices and tuneable sensitivity ofmaterial properties. The main application for the functionalized dPGmembranes are drug-delivery, where bio-active molecules are delivered byOEIP (electrophoretic) selective transport.
    The second advantage is the one-pot 3-component mixture itself. Themixture, dPGs:lrgacure:Thiocure, in water or methanol, is easily to depositedon many types of surfaces, more importantly, with a homogenic bulk ofcharge and crosslinks after UV-Curing.
    The ion conducting membrane filled with crosslinked hyperbranched polymerelectrolytes according to the present invention can be used widely in theindustrial field of fuel cells, electrophoresis, microfluidics, bio-printing.
    Synthesis of polyelectrolytes having polymerizable groups is generallycomplicated. Direct polymerization to form a polymer having polymerizablegroups requires monomers having two different types of polymerizablegroups, one forming the polymer, and the other type not taking part in thepolymerization reaction, but remaining unreacted for later cross-linking. Thisrequires a high selectivity of polymerizability between the groups, or the use 21 of different types of polymerizing groups. Molecules having both acrylicgroups and epoxide groups is a common example of monomers that can forma polymer having polymerizable groups. However, epoxide poiymerization isnot suited in the presence of ionic groups, such as in a polyelectrolyte.
    The alternative, synthesis of a polyelectrolyte having functional groups,followed by a substitution reaction whereby the functional groups are replacedby polymerizable groups is complicated by the fact that most polyelectrolytesare soluble only in water or alcohols, media in which such substitutionreactions are difficult to carry out.
    Dendrimers consisting of ether bonds, and having hydroxyl terminal groupsare on the other hand soluble in solvents suitable for a wide range ofsubstitution reactions, in contrast to unbranched poymers having hydroxylgroups. The latter type of polymers are difficult to dissolve in other media thanwater or strong acids, media in which substitution reactions leading topolymerizable groups are difficult to carry out, while hydroxyl-terminateddendrimers can be dissolved in a variety of solvents. ln ion-pumps, the ion transport medium can be exposed to extreme pHvalues. This calls for the use of polymers and cross-links of made up of bondthat are stable to hydrolysis. We have used dendrimers built up of etherbonds and cross-linking reactions leading to carbon-carbon bonds to ensurethat the ion-transport medium is not hydrolyzed under conditions of ion-pumping.
    Molecules that have been succesfully pumped using the above describedpolyelctolyte as an ion conductive channel or membrane in an ion pumpdevice are monavalent or divalent atomic ions such as H+, Na+, K+ and Cl-.Aromatic molecules molecules such as indole-3-acetic-acid (lAA, auxin), planthormone, 1-naphthaleneacetic acid (1-NAA), plant hormone analog,naphthalene-2-acetic acid (2-NAA), plant hormone analog, benzoic acid,aromatic control substance, cytokinin, and plant hormone.
    Examples 22 Hyperbranched dendritic polyglycerol (dPG) synthesis, dPG Membraneand OEIP device preparation Circular polyethylene terephthalate (PET) substrates (Policrom Screens)with diameter 101.6 mm (4 inch) were washed with acetone and water andsubsequently dried at 110 °C for 10 min before they were treated with 02plasma (150 W, 60 s). The activated substrates were spin-coated with a2 mL solution of 5% (3-glycidyloxypropyl)trimethoxysilane (GOPS, AlfaAesar) in water at 500 rpm for 30 s and allowed to rest in open air for 15min. The surfaces were washed with ethanol (EtOH) and dried at 110 °Cfor 10 min. Treated surfaces were spin-coated with 2 ml MeOH stocksolution containing 264 mg of dPG (compound 4 in SupplementaryInformation), 18 mg Thiocure 1300 (Bruno Bock Chemische Fabrik GmbH& Co) and 18 mg lrgacure 2959 (Sigma-Aldrich). UV crosslinking wascarried out under nitrogen atmosphere inside a glove box and the films wereexposed to UV light (254 nm) for 10 min. lon channels were patterned utilizing photolithography of Microposit S1818photoresist, and developed for 60 s in MF319 (both supplied by Shipley).Unpatterened, crosslinked dPG polymer was removed utilizing a CF4 + 02reactive ion etch (150 W, 90 s) and remaining photoresist was removed withacetone. To facilitate ion exchange, patterned wafers were soaked in 1 MNaCl(aq) for 5 min. OElPs were encapsulated with 2x 10 um bar-coatedDuPont 5018 UV curing ink. Individual OEIP devices were cut out andpackaged in ADW-400 heat shrink tubing containing sealant glue (KacabTeknik AB). The OEIP delivery tips were shaped by hand using a scalpel.
    To hydrate the dPG polyelectrolyte channel, OEIP devices were soaked andstored in deionized water prior to use. Additionally, to reduce the amount ofunreacted polymers and chemical compounds remaining in the polyelectrolyteafter the above processing steps, OEIP devices were preconditioned byoperating the device with 0.1 M KCl(aq) in both the target and source 23 reservoirs. Following the KCI flushing, OEIP devices underwent a loadingphase to exchange the Cl' ions in the polyelectrolyte with lAA', OElPs wereoperated continuously at 250 nA until steady voltage characteristics wereobserved (approximately 12 h).
    Plant material and growth conditions Arabidopsis thaliana seedlings expressing the auxin-responsive fluorescentmarkers 35S::Dll-Venus3° or DR5rev::GFP31 were used to monitor theresponse of lAA delivered via OEIP. To this end, seeds of both genotypesand wild-type Col-0 were surface sterilized with 70% ethanol for 1 min,incubated in pool cleaner (Biltema, Sweden; one tablet per 2000 ml H20) for12 min, and washed four times with sterile, distilled water (dHgO). After 3 daysat 4 °C in the dark, seeds were plated and grown on ß Murashige and Skoog(MS) (Duchefa Biochemie, Haarlem, The Netherlands), 0.5 g/L 2-(N-morpholino)ethanesulfonic acid (MES, Sigma-Aldrich), 1% sucrose, 0.7%plant agar (Duchefa) growth medium plates (120x120 mm square petri-dishes; Gosselin) at pH 5.6 in vertical orientation at 23 °C with 16 h of lightper day. 12 h prior to the start of the experiments, 4 days post-germination(dpg) seedlings were positioned onto fresh plates of identical MS mediacomposition additionally supplemented with 0.01 M KCI.
    Fluorescent Imaging Protocol A custom reoriented macro confocal laser-scanning microscope with avertical stage was used to acquire images (Bergman-Labora, Sweden). Themacro confocal consisted of a horizontally placed AZ100 macroscope (Nikon,Japan) adapted with a specially built XYZ motorized stage (Prior Scientificfitted by Bergman-Labora) and supplied with diascopic white light andepiscopic fluorescence light (Nikon). A climate enclosure with passivehumidification was designed to surround the stage area to keep plants in ahumid, dark environment. The AZ100 macroscope was connected to a C2+ confocal laser scanning system (Nikon) equipped with lasers for 405 nm, 24 457/488/514 nm and 561 nm excitation and a transmitted light detector. Acoarse manipulator, MM-89 (Narishige, Japan), was attached to the stage forplacing and keeping the OEIP at a specific position. A growth agar plate fromwhich the |id was removed was placed vertically on the macroconfocal stageand an OEIP loaded with IAA was placed with the delivery outlet in the growthagar in close proximity of the seedlings. For imaging, a 2x AZ Plan Fluorobjective (NA 0.2, WD 45 mm, Nikon) or a 5x AZ Plan Fluor objective (NA0.5, WD 16 mm, Nikon) were used. Excitation was at 488 nm and emissiondetected with a 525/50 filter. Dll Venus fluorescence intensities from a singlelayer were normalized to initial intensity, averaged and compared (Standarddeviation of the mean). DR5rev::GFP image intensities were summed from16 z-stack layers with 3 um spacing. The lateral fluorescent intensity, plottedat the bottom of each image (Fig. 5c), were summed along the y-axis andnormalized to the maximum intensity of the image sequence. We tested theOElP's ability to deliver the synthetic auxin 1-naphthalene acetic acid (NAA),and observed similar dynamic fluorescence quenching in Dll-Venus reporter seedlings.
    OEIP operation lmmediately prior to the experiments, the OElPs were operated in a targetsolution of 10'5 M KCl(aq), and the OEIP device tip was kept from dryingexcessively during sample loading and OEIP positioning. A Keithley 2612bSourceMeter (Keithley Instruments lnc, Cleveland, OH, USA) and customLabVlEW (National Instruments Corporation, Austin, TX, USA ) software wasuse to source current and record voltage. The OEIP device was turned onimmediately prior to the first imaging sequence and operated at a constantelectrical current of 1 uA. For these experiments, the OEIP delivery tip wassubmerged in the MS media in close proximity (100 - 200 um) to the rootepidermal tissue (Fig. 3 b,c) and was held at a fixed position in the growth MS media for the duration of each trial.
    Mass spectrometry measurement protocol The OEIP reservoir was loaded with 80uL of 10% methanol in dHgOcontaining IAA at 10'5 M concentration. OEIP outlet tip was submerged intarget solution of 50uL of 1/2 MS Media, pH 5.7 (see Plant growth conditions)without agar, and containing 0.01 M KCI. Poly(3,4-ethylenedioxythiophene)polystyrene sulfonate (PEDOT:PSS) electrodes on a polyethyleneterephthalate (PET) substrate (cut from Orgacon F-350 film, AGFA-Gevaert)were used in the source reservoir and the target solution. OEIP pump wasoperated sourcing a constant current of 1 uA using a Keithley 2612bSourceMeter and custom LabVlEW software. The target solution wascollected and replaced with fresh solution every 15 minutes - at time intervalsof 15, 30, 45, 60, 75, 90, 105, 120 and 135 minutes. ln-between the analyses,the pump was washed with methanol/dH2O and stored in dHgO. This wasrepeated five times with the same pump.
    To estimate the amount of IAA (and oxlAA) pumped into the target solution,an IAA analysis was performed. Briefly, 20 uL from each target solution wasmixed with 500 uL of dHgO and purified by solid phase-extraction (SPE) usinghydrophilic-lipophilic balance reversed-phase sorbent columns (Oasis HLB; 1 cc/30 mg; Waters, Milford, MA, USA). Prior to purification, 4 pmol of [1366]-IAA and 4 pmol of [13C6]-oxlAA were added to each sample as internalstandards to validate the quantification. Purified samples were analyzed usingan LC-MRM-MS (liquid chromatography-multiple reaction monitoring-massspectrometry) system. The LC-MS system consisted of 1290 Infinity BinaryLC System coupled to 6490 Triple Quad LC/MS System with Jet Stream andDual lon Funnel technologies (Agilent Technologies, Santa Clara, CA, USA).Chromatograms were analyzed using MASSHUNTER software versionB.05.02 (Agilent Technologies). A Milli-Q deionization unit (Millipore, France)was used for preparation of the purified water for mobile phases andsolutions. [13C6]-oxlAA was obtained from Olchemim Ltd(http://wvvw.olchemim.cz/). All other chromatographic solvents and chemicalswere of analytical grade or higher purity from Sigma-Aldrich Chemie GmbH(Steinheim, Germany). 26 References 1 _ LaVan, D. A., McGuire, T. & Langer, R. Small-scale systems for in vivodrug delivery. Nat. Biotechnol. 21, 1184-1191 (2003).
    Abidian, M. R., Kim, D. H. & Martin, D. C. Conducting-polymer nanotubes for controlled drug release. Adv. Mater. 18, 405-409 (2006).
    Xu, Q. et al. Preparation of monodisperse biodegradable polymermicroparticles using a microfluidic flow-focusing device for controlleddrug delivery. Small 5, 1575-1581 (2009).
    Svirskis, D., Travas-Sejdic, J., Rodgers, A. & Garg, S.Electrochemically controlled drug delivery based on intrinsicallyconducting polymers. J. Control. Release 146, 6-15 (2010).
    Isaksson, J. et al. Electronic control of Ca2+ signalling in neuronal cellsusing an organic electronic ion pump. Nat. Mater. 6, 673-679 (2007).
    Tybrandt, K. et al. Translating electronic currents to preciseacetylcholine-induced neuronal signaling using an organicelectrophoretic delivery device. Adv. Mater. 21, 4442-4446 (2009).
    Simon, D. T. et al. Organic electronics for precise delivery ofneurotransmitters to modulate mammalian sensory function. Nat.Mater. 8, 742-746 (2009).
    Jonsson, A. et al. Therapy using implanted organic bioelectronics. Sci.Adv. 1, e1500039-e1500039 (2015).
    Stavrinidou, E. et al. Direct measurement of ion mobility in aconducting polymer. Adv. Mater. 25, 4488-93 (2013). 24. 25. 26. 27. 28. 29. 30. 31. 27 Astruc, D., Boisselier, E. & Ornelas, C. Dendrimers designed forfunctions: From physical, photophysical, and supramolecular propertiesto applications in sensing, catalysis, molecular electronics, photonics,and nanomedicine. Chem. Rev. 110, 1857-1959 (2010).
    Sunder, A., Hanselmann, R., Frey, H. & Mülhaupt, R. Controlledsynthesis of hyperbranched polyglycerols by ring-openingmultibranching polymerization. Macromolecules 32, 4240-4246 (1999).
    Rahman, A. et al. Auxin, actin and growth of the Arabidopsis thalianaprimary root. Plant J. 50, 514-528 (2007).
    Pencik, A. et al. Regulation of Auxin Homeostasis and Gradients inArabidopsis Roots through the Formation of the lndole-3-Acetic AcidCatabolite 2-Oxindole-3-Acetic Acid. Plant Cell 25, 3858-3870 (2013).
    Grieneisen, V. a., Xu, J., Maree, A. F. M., Hogeweg, P. & Scheres, B.Auxin transport is sufficient to generate a maximum and gradientguiding root growth. Nature 449, 1008-1013 (2007).
    Geisler, M., Wang, B. & Zhu, J. Auxin transport during rootgravitropism: transporters and techniques. Plant Biol. 16, 50-57(2014).
    Brunoud, G. et al. A novel sensor to map auxin response anddistribution at high spatio-temporal resolution. Nature 482, 103-106(2012).
    Friml, J. et al. Efflux-dependent auxin gradients establish the apical-basal axis of Arabidopsis. Nature 426, 147-153 (2003).
    权利要求:
    Claims (14)
    [1] 1. A device for transport of ions and/or charged molecules between asource and a target electrolyte, comprising: a first electrode provided at or insaid source electrolyte, and a second electrode provided at or in said targetelectrolyte; and wherein said first and second electrodes provides anelectrical control of an ion flow, and further comprising means for limiting anelectronic current between said source and said target electrodes, such thatat least after a voltage is applied a potential difference between said sourceand target electrodes is maintained, which effects ion transport from saidsource to said target electrode; characterized in that the device further comprises an ion- and/or permselectivepolyelectrolyte for transport ions and/or charged molecules viaelectrophoresis and functions as an ion-selective membrane; and wherein said polyelectrolyte comprises a cross-linked hyperbranched polymer.
    [2] 2. The device as claimed in claim 1, wherein said hyperbranched polymerhas polymerizable groups and groups that are ionic or ionizable, andcomprises chemical formulas 1, 2, 3, .«}_“. f)Ho o-~«,_ _, ---- Hft-"Q ff" Û C HHO O f.,i)Ü DšlH9 w É» fi L f_¿* ma. )R1 2C)__ E L, .rio/k *” "i /Ékg/“xïi "g-”j- n'AW 3o « .... Q, fo f, .... .q /WOH Qænfiq'f-Û ' íi .JO ï--of (Koll *brai, ft «»-.,f^-@* s,-~,_» o lm L! o L QOH k “ 1 0ñÉ-xt: OH Ho O-t« 1 ,,,,,, K/ x, »»»»»»» rv. _ :_ Ho OHHG 'O 1 2i' g . D = Chemical formula “i CÅCFJRH31 T br: l. = Chemical forrnula 2 T = Chemical formula 3 29 wherein in the chemical formulas 2 and 3, R1 is sulphonate, phosphonates or carboxylates, R2 is ammonium or phosphonium, R3 is(meth)acry|oxy groups, (meth)acry|amido groups, and vinyl groups, R1, R2,R3 terminates alkyl group with C1~C20, a aryl group with C6~C20, aheteroaryl group with C2~C20, a cycloalkyl group with C6~C20, and aheterocyclic group with C2~C20.
    [3] 3. The device according to any one of claims 1 or 2, wherein saidhyperbranched polymer is functionalized with ketone-, aldehyde-, alcohol- and/or iminegroups.
    [4] 4. The device according to any of the preceding claims wherein thehyperbranched polymer has a degree of branching in the range of 0,05 to 1,or in the range of 0,1 to 1, or in the range of 0,5 to 1, or in the range of 0,7 to1.
    [5] 5. The device according to any of the preceding claims wherein saidhyperbranched polymer is a hyperbranched polyglycerol.
    [6] 6. The device according to any of the preceding claims wherein themolecules being pumped are any one of monovalent and divalent atomicions, multivalent biomolecules, charged aromatic molecules, and nonaromatic molecules.
    [7] 7. A method for preparing a polyelectrolyte for a device, for transport ofions and/or charged molecules between a source and a target electrolytecomprising the steps of i) providing a solution comprising a hyperbranched polymer havinghaving polymerizable groups and groups that are ionic or ionizable, ii) depositing said solution on a support; and iii) crosslinking said hyperbranched polymer.
    [8] 8. A method according to claim 7, for preparing a polyelectrolyte for adevice for transport of ions and/or charged molecules between a source anda target electrolyte comprising the steps of i) providing a solution with a hyperbranched polymer havingpolymerizable groups and groups that are ionic or ionizable and a solvent, ii) mixing a photoinitiator and crossiinker with said solution; iii) depositing a support with said mixture; iv) photo-induced curing of the deposited mixture for crosslinking of thehyperbranched polymer.
    [9] 9. The method according to any one of claim 7 or 8, wherein thehyperbranched polymer has a degree of branching in the range of 0,05-1 or inthe range of 0,1 to 1, or in the range of 0,5 to 1, or in the range of 0,7 to 1.
    [10] 10. The method according to any one of claims 7 to 9, wherein the hyperbranched polymer comprises chemical formulas 1, 2, 3, OH ä), WWWW D = Chemical formula 1L 2 Chemical formula 2T = Chemical formula 3 wherein in the chemical formulas 2 and 3, R1 is sulphonate,phosphonates or carboxylates, R2 is ammonium or phosphonium, R3 is(meth)acryloxy groups, (meth)acrylamido groups, and vinyl groups, R1, R2,R3 terminates alkyl group with C1~C20, a aryl group with C6~C20, a 31 heteroaryl group with C2~C20, a cycloalkyl group with C6~C20, and aheterocyclic group with C2~C20.
    [11] 11.deionozed water, methanol, ethano, propanol, NMP, DMSO and DMF. The method as claimed in claim 8, wherein the solvent is any one of
    [12] 12.of said photoinitiator and said crosslinker is in the range of 0.1 to 10 parts by The method as claimed in claim 8, wherein in step (ii) the proprotion of weight with respect to 100 parts by weight of said mixed solution.
    [13] 13.source and a target electrolyte, wherein said device comprises a A device for transport of ions and/or charged mo|ecu|es between a po|ye|ectro|yte and wherein said po|ye|ectro|yte is synthesized according toclaim 7-12, and wherein said po|ye|ectro|yte is able to transport ions and/or charged mo|ecu|es via electrophoresis.
    [14] 14. for drug delivery. The use of a device according to any one of claims 1 to 6, and claim 13
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    同族专利:
    公开号 | 公开日
    SE540776C2|2018-11-06|
    US20190224472A1|2019-07-25|
    WO2018042046A1|2018-03-08|
    EP3507326A1|2019-07-10|
    CA3035861A1|2018-03-08|
    引用文献:
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    EP2202261B1|2008-12-16|2012-02-01|Samsung Electronics Co., Ltd.|Hyper-branched polymer, electrode for fuel cell including the hyper-branched polymer, electrolyte membrane for fuel cell including the hyper-branched polymer, and fuel cell including at least one of the electrode and the electrolyte membrane|
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    申请号 | 申请日 | 专利标题
    SE1651192A|SE540776C2|2016-09-05|2016-09-05|Ion pump with hyperbranched polymers|SE1651192A| SE540776C2|2016-09-05|2016-09-05|Ion pump with hyperbranched polymers|
    PCT/EP2017/072169| WO2018042046A1|2016-09-05|2017-09-05|Ion pump with hyperbranched polymers|
    EP17768710.0A| EP3507326A1|2016-09-05|2017-09-05|Ion pump with hyperbranched polymers|
    US16/330,183| US20190224472A1|2016-09-05|2017-09-05|Ion pump with hyperbranched polymers|
    CA3035861A| CA3035861A1|2016-09-05|2017-09-05|Ion pump with hyperbranched polymers|
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