CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to International Application No. PCT/EP2017/072169, filed Sep. 5, 2017 and titled “ION PUMP WITH HYPERBRANCHED POLYMERS,” which in turn claims priority from a Swedish Application having serial number 1651192-5, filed Sep. 5, 2016, and titled “ION PUMP WITH HYPERBRANCHED POLYMERS,” both of which are incorporated herein by reference in their entireties.

TECHNICAL FIELD OF THE INVENTION

The present invention relates to a device for transport of ions and/or charged molecules between a source and a target electrolyte comprising a polyelectrolyte. The present invention further relates to a method for preparing a polyelectrolyte.

BACKGROUND OF THE INVENTION

In recent years, a range of organic electronic tools has been developed1-4which enable precise dynamic delivery of small ionic molecules.

Ion-selective electrophoretic delivery so called “ion-pumping”, i.e. migration of ions through a charged membrane/gel by an electric field, is now a 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 technologies and was developed primarily for application to mammalian systems to enable diffusive synapse-like delivery of neurosignaling compounds (alkali ions, neurotransmitters) with high spatiotemporal resolution. Recently, OEIP devices have been demonstrated for a variety of in vitro5,6as well as in vivo applications7, including therapy in awake animals8. OEIPs are electrophoretic delivery devices that leverage the unique ionic and electronic properties of conducting polymers and polyelectrolytes to convert electronic signals into ionic fluxes. The OEIP's polymer delivery channel (i.e., electrophoresis channel) is composed of a polycationic (or polyanionic) material with a high density 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, not additional liquid or oppositely charged counter-ions that may be present in the source solution. The selective electrophoretic transport of the desired molecular species through an OEIP device results in high concentration gradients localized at the OEIP outlet6, on the scale of ˜100 μm-1 mm. Additionally, electronic addressing to the OEIP enables the molecular delivery to be rapidly switched on and off, and importantly, the electrical driving current can be directly correlated with the ionic delivery rate. These device characteristics allow for the precise control of chemical concentration gradients with high spatial and temporal resolution.

EP 1 862 799 B1 discloses a device for electrically controlled transport of ions from a source to a target electrolyte. The device comprises a source electrode and a target electrode, each capable of conducting said ions and electrons. The source electrode is arranged to receive said ions from the source electrolyte and the target electrode is arranged to release the ions to the target electrolyte. The device further comprises an ion-conductive channel arranged to receive the ions from the source electrode, to release the ions to the target electrode and to provide an ionic connection between the source and the target electrodes. The electrodes and the ion-conductive channel are formed of solid or semi-solid materials which are directly or indirectly attached to a support. Further, the device comprises means for limiting an electronic current between the source and the target electrodes, such that at least after a voltage is applied across the channel a potential difference between the source and target electrodes is maintained, which effects ion transport from the source to the target electrode. The device comprises means for retaining one of the source and target electrolytes on the device, comprising walls for retaining the electrolyte, and being arranged such that the electrolyte is in contact with the desired electrode.

Another route to cross-linked networks, with ionic groups, is to copolymerize ionic monomers with di-functional monomers. One drawback with that route is that unreacted monomers left in the network must be removed, otherwise, ion-selectivity is lost. Post-functionalization of polyelectrolytes is a possibility, but limited by the poor solubility in solvents suitable for functionalization; polyelectrolytes are typically only soluble in water. The number of available polyelectrolyte materials suitable for OEIP device technologies is limited. It is therefore a wish for improving the current state of the art.

SUMMARY OF THE INVENTION

It is an object of the present invention to improve the current state of the art and to mitigate at least some of the above mentioned problems. These and other objects are achieved by a device for transport of ions and/or charged molecules.

According to a first aspect of the present invention there is provided 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 ion- and/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.

The present invention is based on the realization of transporting larger ions and/or charged molecules. This is realized by the use of cross-linked hyperbranched polymers. Fundamental limitations of previous devices for transporting ions and/or charged molecules can be addressed and overcome by the means of the present invention, such as swelling and rigidity of the polymer network which can be controlled by cross-linking; and transport of “larger” or reactive aromatic substances can be facilitated by tuning the void fraction distribution and effective porosity of the bulk. Example of such a device is an organic electronic ion pump (OEIP). In this application organic electronic ion pump as well as the abbreviation OEIP will be used interchangebly with device for transporting ions and/or charged molecules.

The linear polymers which are traditionally used for this kind of devices results in a tighter network as compared with the now discovered hyperbranched polymer. The tighter network results in small porous pathways and thus trough the ion-selective membrane. Hence, this type of polymers results in an ion-selective membrane that works only for smaller molecules. Moreover, the more traditional linear polymers are harder to functionalize and most often post-functionalization has to be used which results in the charges just being distributed over the surface of the network and not evenly distributed throughout the bulk.

According to at least one example embodiment of the invention hyperbranched polymers are highly branched three-dimensional (3D) macromolecules. Their spherical architectures give them unique properties such as intramolecular cavities, low viscosity and/or high solubility. Moreover, they can be equipped with plenty of functionalized groups. The cross-linked hyperbranched polymer provides large porous pathways in and through the polyelectrolyte due to their intermolecular cavities and thus through the ion-selective membrane. Crosslinking large “spherical” hyperbranched bearing crosslinkable and ionic groups, resulting in membranes and/or gels that have controllable selectivity and large porous pathways. This means that it is possible to transport larger molecules, for instance larger drug molecules such as phospholipids. The polyelectrolyte has a homogenously distributed charge. The high solubility of the hyperbranched molecules is due to their amphiphilic character.

The charges are more homogeneously spread throughout the polyelectrolyte and thereby it is possible to reduce the current needed for transporting ions trough the material as compared with the conventional OEIP. Hence, the device also provides for way of transporting smaller molecules in a more lenient manner. By avoiding large currents being used, side-reactions usually connected with these, such as water-splitting, can be avoided. Moreover, the reduced amount of current needed reduces the risk heating water. Too warm condition may cause unwished crystallization within the membrane.

The hyperbranched polymer may comprise chemical formulas 1, 2, 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 heteroaryl group with C2˜C20, a cycloalkyl group with C6˜C20, and a heterocyclic group with C2˜C20. This means that the formula shown on the left side represents the hyperbranched polymer core and the final derivative is shown on the right side with crosslinkable and ionic groups.

The hyperbranched polymer may be functionalized with ketone-, aldehyde-, alcohol- and/or imine groups.

The wide variety of groups which may be used for functionalization of the hyperbranched polymer enables for a variety of properties of the material itself.

The hyperbranched polymer may have a degree of branching of 0.05-1 or a degree of branching of 0.2-0.9, or a degree of branching of 0.3-0.8, or a degree of branching of 0.4-0.8.

The degree of branching of a linear polymer would be 0. A degree of branching of 1 corresponds to a dendrimer. The properties of a hyperbranched polymer with a high degree of branching are similar to the properties of a dendrimer.

The hyperbranched polymer may be a hyperbranched polyglycerol.

Polyglycerol is a very cheap hyperbranched molecule which therefore makes it the most frequently used alternative. The monomer used for the synthesis, glycerol, is an easily achieved triol used in a variety of applications.

The molecules being pumped or transported in the device may be any one 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 an example of nonaromatic molecules is acetylcholine, and aromatic molecules may be for instance benzoic acid molecules. The substances or molecules being transported in the device may comprise both endogenous and synthetic substances, such as drugs. Some examples of endogenous molecules that may be transported include neurotransmitters such as gamma-aminobutyric acid (GABA) and dopamine. The molecules that may be pumped or transported through the membrane are thus molecules that are larger than what has previously been possible in the known OPEIPs.

According to at least one the device may be used for transporting auxin and/or phospholipids.

According to a second aspect there is provided a method for preparing a polyelectrolyte for a device, for transport of ions and/or charged molecules between a source and a target electrolyte comprising the steps of

i) providing a solution comprising a hyperbranched polymer having having 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 are largely analogous to those described above in connection with the first aspect of the inventive concept. Embodiments mentioned in relation to the first aspect of the present invention are largely compatible with the second aspect of the invention.

According to the second aspect there is further provided a method for preparing a polyelectrolyte for a device for transport of ions and/or charged molecules between a source and a target electrolyte comprising the steps of

i) providing a solution with a hyperbranched polymer having polymerizable groups and groups that are ionic or ionizable and a solvent,

ii) mixing a photoinitiator and crosslinker with said solution;

iii) depositing a support with said mixture;

iv) photo-induced curing of the deposited mixture for crosslinking of the hyperbranched polymer.

The preparation of a polyelectrolyte may thus be done as a so called “one-pot 3 component synthesis”. This means that the hyperbranched polymer, the cross-linker and the photo-initiator are mixed in one solvent. This is being made possible by the solubility properties of the hyperbranched polymer. The one-pot synthesis facilitates the preparation of the polyelectrolyte and the production of the device, since the polyelectrolyte may be placed directly onto a support and then crosslinked without the necessity for further treatment steps. After the crosslink step any by products may be removed on the surface of the membrane and support. The ion conductive membrane thus filled or formed from the crosslinked hyperbranched polymer polyelectrolyte 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 the method 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 polymer which makes it easy to dissolve in a variety of solvents. The three components, the hyperbranched polymer, the cross-linker and the photo-initiator is mixed together before deposition of the mixture. This enables a homogeneous distribution of bulk charges.

In a following step (ii) the mixture from step i) is deposited. The one-pot synthesis as well as the amphiphilic character of the hyperbranched polymer offers a high degree of compatibility with a variety of deposition and patterning processes. The deposition method used for the preparation of the polyelectrolyte may for example be spin-coating, printing and/or any other solution based method.

After deposition the mixture will be photo-induced cured (iii). This curing may for example UV-curing.

According to an alternative there is provided a method for preparing a polyelectrolyte for a device, for transport of ions and/or charged molecules between a source and a target electrolyte, comprising the steps ofa) providing a hyperbranched polymer having polymerizable groups and groups that are ionic or ionizable;b) adding a cross-linking agent to said hyperbranched polymer;c) adding an initiator to hyperbranched polymer and said cross-linking agent;d) dissolving said hyperbranched polymer, said cross-linking agent and said initiator in a solvent solution thereby forming a reagent solution;e) allowing said hyperbranched polymer, said cross-linking agent and said initiator in said reagent solution to react with each other thereby forming a solution comprising said cross-linked hyperbranched polymer.
In the step e) of allowing said hyperbranched polymer, said cross-linking agent and said initiator in said reagent solution to react with each other, this is performed in a reaction container which is degassed and heated for a specific time.

Through this alternative method a meta-stable gels or aggregates in solution may be provided that solidifies into a solid gel upon specific concentration limits.

The hyperbranched polymer may have a degree of branching in the range of 0.05-1 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 to 1.

The method according to any one of the above methods, wherein the hyperbranched polymer comprises chemical formulas 1, 2, 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 heteroaryl group with C2˜C20, a cycloalkyl group with C6˜C20, and a heterocyclic 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 proportion of said photoinitiator and said crosslinker in step (ii) may be in the range of 0.1 to 10 parts 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 of ions and/or charged molecules between a source and a target electrolyte, wherein said device comprises a polyelectrolyte and wherein said polyelectrolyte is synthesized according to the second aspect, and wherein said polyelectrolyte is able to transport ions and/or charged molecules via electrophoresis.

Effects and features of this third aspect of the present invention are largely analogous to those described above in connection with the first and second aspects of the inventive concept. Embodiments mentioned in relation to the first and second aspects of the present invention are largely compatible with 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.

