Porous solid structure with active control

Abstract

In a first aspect, the present invention relates to a system comprising: i) porous solid structure, comprising: a network formed of a plurality of interconnected electrically conductive wires, and a layer comprising a dielectric conformally coating the network; and ii) a controller for powering the network of interconnected electrically conductive wires; wherein the system is such that a retention of a target molecule by the porous solid structure can be altered by powering the network of interconnected electrically conductive wires.

Description

[0001] DESCRIPTION

[0002] POROUS SOLID STRUCTURE WITH ACTIVE CONTROL

[0003] Technical field of the invention

[0004]

[0001] The present invention relates to the field of materials science, more specifically to porous solid structures which can be actively powered.

[0005] Background of the invention

[0006]

[0002] In the realm of life sciences, the manipulation and analysis of biological samples are critical for advancements in diagnostics, therapeutics, and research. A common challenge in these processes is the handling and processing of complex biological fluids, which often require precise control over molecular interactions and separations.

[0007]

[0003] In this context, it is known to use a permeable — e.g. porous — material to enact some degree of retention on a target molecule. Examples thereof were for instance disclosed by Lafleur et al. (LAFLEUR, Josiane P., et al. Rapid and simple preparation of thiol-ene emulsion-templated monoliths and their application as enzymatic microreactors. Lab on a Chip, 2015, 15.10: 2162-2172.) and Costantini etal. (COSTANTINI, Marco, etal. 3D-Printing of Functionally Graded Porous Materials Using On-Demand Reconfigurable Microfluidics. Angewandte Chemie International Edition, 2019, 58.23: 7620-7625.).

[0008]

[0004] However, there is still a need in the art for better systems comprising a permeable (e.g. porous) material.

[0009] Summary of the invention

[0010]

[0005] The ways permeable materials as described in the background section have been used up to now, while effective in certain applications, often fall short in providing the necessary control and specificity required to unlock more advanced and / or delicate procedures. For example, certain promising applications are currently hindered by buffer limitations — e.g. imposed by sample stability and / or GMP (good manufacturing practices) — , with no effective way to circumvent these limitations. Additionally, the retention properties of permeable materials as used in systems up to now are relatively fixed after fabrication of the system, with no tangible way to control these during and / or between procedures (at least, while keeping the system intact and without making substantial modifications to the system).

[0011]

[0006] It is therefore an object of the present invention to provide a permeable (e.g. porous) material with active control over the retention of a target molecule through said material (e.g. through active control of surface properties, material temperature, chemical reactions, forces, etc.). It is a further object of the present invention to provide good methods and uses associated therewith. This objective is accomplished by systems methods and uses according to the present invention.

[0012]

[0007] It is an advantage of embodiments of the present invention that the retention of a target molecule can be actively controlled. It is a further advantage of the present invention that this can be realized in numerous ways (e.g. using various physicochemical principles and / or various device architectures).

[0008] It is an advantage of embodiments of the present invention that the physicochemical properties (e.g. electrical potential bias, temperature, pH, etc.) in the pore can be actively controlled.

[0013]

[0009] It is an advantage of embodiments of the present invention that they can be effectively used to perform one or a combination of a measurement, separation, purification, synthesis and / or flow control.

[0014]

[0010] In a first aspect, the present invention relates to a system comprising: i) porous solid structure, comprising: a network formed of a plurality of interconnected electrically conductive wires, and a layer comprising a dielectric conformally coating the network; and ii) a controller for powering the network of interconnected electrically conductive wires; wherein the system is such that a retention of a target molecule by the porous solid structure can be altered by powering the network of interconnected electrically conductive wires.

[0015]

[0011] In a second aspect, the present invention relates to a method for performing a procedure using the porous solid structure as defined in any embodiment of the first aspect, comprising a) flowing the target molecule through the porous solid structure; and b) powering the network of interconnected electrically conductive wires, thereby altering a retention of the target molecule by the porous solid structure.

[0016]

[0012] In a third aspect, the present invention relates to a use of a porous solid structure as defined in any embodiments of the first aspect, for biochemical applications.

[0017]

[0013] Particular and preferred aspects of the invention are set out in the accompanying independent and dependent claims. Features from the dependent claims may be combined with features of the independent claims and with features of other dependent claims as appropriate and not merely as explicitly set out in the claims.

[0018]

[0014] Although there has been constant improvement, change and evolution of devices in this field, the present concepts are believed to represent substantial new and novel improvements, including departures from prior practices, resulting in the provision of more efficient, stable and reliable devices of this nature.

[0019]

[0015] The above and other characteristics, features and advantages of the present invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, which illustrate, byway of example, the principles of the invention. This description is given for the sake of example only, without limiting the scope of the invention. The reference figures quoted below refer to the attached drawings.

[0020] Brief description of the drawings

[0021]

[0016] FIG 1 is a schematic representation of a cross-section of a porous solid structure that may be used in a system in accordance with embodiments of the present invention.

[0022]

[0017] FIG 2 is a schematic representation of a cross-section of an illustrative system in accordance with embodiments of the present invention.

[0023]

[0018] FIG 3 is a schematic representation of a perspective view of a first illustrative system in accordance with embodiments of the present invention.

[0019] FIG 4 is a schematic representation giving a closer perspective view of the left side of the illustrative system of FIG 3.

[0024]

[0020] FIG 5 is a schematic representation of a cross-section of an illustrative system in accordance with embodiments of the present invention, wherein the network is capacitively coupled to one of a pair of electrodes, and resistively to another one of the pair of electrodes.

[0025]

[0021] FIG 6 is a close-up of part of the system of FIG 5.

[0026]

[0022] FIG 7 is a schematic representation of a cross-section of an illustrative system in accordance with embodiments of the present invention, wherein the network is resistively coupled to two electrodes.

[0027]

[0023] FIG 8 is a schematic representation of a perspective view of a further illustrative system in accordance with embodiments of the present invention.

[0028]

[0024] In the different figures, the same reference signs refer to the same or analogous elements.

[0029] Description of illustrative embodiments

[0030]

[0025] The present invention will be described with respect to particular embodiments and with reference to certain drawings but the invention is not limited thereto but only by the claims. The drawings described are only schematic and are non-limiting. In the drawings, the size of some of the elements may be exaggerated and not drawn on scale for illustrative purposes. The dimensions and the relative dimensions do not correspond to actual reductions to practice of the invention.

[0031]

[0026] Furthermore, the terms first, second, third and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequence, either temporally, spatially, in ranking or in any other manner. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other sequences than described or illustrated herein.

[0032]

[0027] Moreover, the terms top, bottom, over, under and the like in the description and the claims are used for descriptive purposes and not necessarily for describing relative positions. It is to be understood that the terms so used are interchangeable with their antonyms under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other orientations than described or illustrated herein.

[0033]

[0028] It is to be noticed that the term ‘comprising’, used in the claims, should not be interpreted as being restricted to the means listed thereafter; it does not exclude other elements or steps. It is thus to be interpreted as specifying the presence of the stated features, integers, steps or components as referred to, but does not preclude the presence or addition of one or more other features, integers, steps or components, or groups thereof. The term ‘comprising’ therefore covers the situation where only the stated features are present and the situation where these features and one or more other features are present. Thus, the scope of the expression ‘a device comprising means A and B’ should not be interpreted as being limited to devices consisting only of components A and B. It means that with respect to the present invention, the only relevant components of the device are A and B.

[0034]

[0029] Similarly, it is to be noticed that the term ‘coupled’, also used in the claims, should not be interpreted as being restricted to direct connections only. The terms ‘coupled’ and ‘connected’, along with their derivatives, may be used. It should be understood that these terms are not intended as synonyms for each other. Thus, the scope of the expression ‘a device A coupled to a device B’ shouldnot be limited to devices or systems wherein an output of device A is directly connected to an input of device B. It means that there exists a path between an output of A and an input of B which may be a path including other devices or means. ‘Coupled’ may mean that two or more elements are either in direct physical or electrical contact, or that two or more elements are not in direct contact with each other but yet still co-operate or interact with each other.

[0035]

[0030] Reference throughout this specification to ‘one embodiment’ or ‘an embodiment’ means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases ‘in one embodiment’ or ‘in an embodiment’ in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to one of ordinary skill in the art from this disclosure, in one or more embodiments.

[0036]

[0031] Similarly, it should be appreciated that in the description of exemplary embodiments of the invention, various features of the invention are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects. This method of disclosure, however, is not to be interpreted as reflecting an intention that the claimed invention requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects lie in less than all features of a single foregoing disclosed embodiment. Thus, the claims following the detailed description are hereby expressly incorporated into this detailed description, with each claim standing on its own as a separate embodiment of this invention.

[0037]

[0032] Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form different embodiments, as would be understood by those in the art. For example, in the following claims, any of the claimed embodiments can be used in any combination.

[0038]

[0033] In the description provided herein, numerous specific details are set forth. However, it is understood that embodiments of the invention may be practised without these specific details. In other instances, well-known methods, structures and techniques have not been shown in detail in order not to obscure an understanding of this description.

[0039]

[0034] The following terms are provided solely to aid in the understanding of the invention.

[0040]

[0035] As used herein, and unless otherwise specified, the term ‘porous solid structure’ refers to a (continuous) structure that is solid and contains pores (which may also be referred to as ‘voids’, ‘spaces’ or ‘empty volume’) within its volume. The porous solid structures used in the present invention are moreover permeable, allowing a fluid (e.g. comprising the target molecule) to pass therethrough. The porosity (or ‘void fraction’) is a measure of the amount of empty volume within over the total (i.e. envelope) volume of the structure; typically expressed as a fraction (between 0 and 1) or percentage (between 0% and 100%). The porosity is experimentally accessible through various forms of porosimetry, porometry or pycnometry. Depending on the type used, these techniques can characterize voids in the order of nm to >10 pm.

[0036] As used herein, and unless otherwise specified, the term ‘network’ refers to a physical structure of interconnected components, such as electrically conductive wires. Examples of networks include, but are not limited to, meshes, grids, lattices, and three-dimensional wireframe structures.

[0041]

[0037] As used herein, and unless otherwise specified, the term ‘electrically conductive wires’ refers to elongated structures capable of conducting electricity. Examples of electrically conductive wires include, but are not limited to, metal wires, metal alloy wires, or semiconductor wires. The electrically conductive wires preferably have a conductivity of at least 1 S / cm, preferably at least 10 S / cm, more preferably at least 102S / cm, yet more preferably at least 103S / cm, still yet more preferably at least 104S / cm, most preferably at least 105S / cm. In bulk, metals such as copper or nickel typically have remarkably high electrical conductivity values above 105S / cm, while carbon materials such as graphite have electrical conductivity values in the order of 102S / cm. The electrical conductivity of a conductive material is also related to its porosity. For example, metallic foams of high porosity (e.g.

[0042] 90% to 99% porosity) have 100 times to 1000 times reduced electrical conductivity as compared to the bulk metal, e.g. 102— 103S / cm. By comparison, porous carbon materials such as compressed carbon blacks (e.g. 75% to 90% porosity), compressed carbon nanotubes (e.g. 80% to 90% porosity) or compressed graphene (e.g. 80% to 90% porosity) show conductivities in the range between 102S / cm and 1 S / cm.

[0043]

[0038] As used herein, and unless otherwise specified, the term ‘dielectric’ refers to material which — which at least in bulk — is an electrically insulating material and that can be polarised by an applied electric field. Examples of dielectrics include, but are not limited to, oxides (e.g. e.g. SiCh, TiC>2, AI2O3, MnOx, ZrC>2 or ZnOx), phosphates (e.g. I 3PO4 or Ca3(PC>4)2), nitrides (e.g. SisN4 or TiN), metalorganic frameworks (MOFs) or (non-conductive) polymers (e.g. polyethylene (PE), polytetrafluoroethylene (PTFE) or polyimide (PI)).

[0044]

[0039] As used herein, and unless otherwise specified, the term ‘electrical insulating material’ refers to a material that as such has a high electrical resistance and can prevent or limit the flow of electric current.

[0045]

[0040] As used herein, and unless otherwise specified, the term ‘conformally coating’ refers to a coating that follows the contours or shape of the surface it is applied to. Examples of conformal coating techniques include, but are not limited to, electrochemical deposition, atomic layer deposition (ALD) and chemical vapor deposition (CVD). In embodiments, such a coating may also maintain a relatively uniform thickness. For example, the coating thickness may have a relative standard deviation (i.e. the ratio of the thickness’ standard deviation to its arithmetic mean) of 10% or less, preferably 5% or less, more preferably 2% or less, most preferably 1% or less; and / or may have a standard deviation of 3 nm or less. In some instances, a coating may be considered uniform if it meets at least one of the two aforementioned criteria.

[0046]

[0041] As used herein, and unless otherwise specified, the term ‘target molecule’ refers to a molecule of interest that is intended to be retained, captured and / or separated by the porous solid structure. Examples of target molecules include, but are not limited to, biomolecules (cf. infra), small molecules and ionic species.

[0047]

[0042] As used herein, and unless otherwise specified, the term ‘retention’ (as e.g. also used in chromatography) refers to the degree to which the (target) molecule is retained compared to themobile phase (e.g. fluid) in which the molecule is comprised. ‘Retention by the porous solid structure’ refers to the retention of the target molecule as it passes through the porous solid structure. The retention may be quantified in terms of a retardation factor (7?) — i.e. the fraction of the target molecule (compared to the total amount of target molecule) which is present in the mobile phase at equilibrium — or a retention factor ( / <) — i.e. the ratio of time the target molecule is retained in the stationary phase (e.g. captured by the porous solid structure) to the time it is retained in the mobile phase. The retardation factor (7?) and retention factor ( / <) may typically be related as: 7? = l / (fc + 1). Within the present invention, the retention factor ( / <) is actively controlled / modified, and the degree of change (e.g. the ratio of the maximum retention factor to the minimum retention factor) may therein play a more decisive role than the absolute value as such. Notwithstanding, the retention factor may in embodiments be adjustable upto a maximum of at least 10, preferably at least 102, more preferably at least 103, yet more preferably at least 104, most preferably at least 105, such as at least 106. In some embodiments, the target molecule may be retainable by the porous solid structure substantially indefinitely (i.e. having a maximum retention factor tending to infinity).

[0048]

[0043] As used herein, and unless otherwise specified, the term ‘biomolecules’ refers to molecules that are derived from or are involved in biological processes. Examples of biomolecules include, but are not limited to, proteins, enzymes, antibodies, nucleic acids (such as DNA or RNA), lipids and carbohydrates.

[0049]

[0044] As used herein, and unless otherwise specified, the term ‘macromolecule’ — as defined by IUPAC — refers to a molecule of high relative molecular mass, the structure of which essentially comprises the multiple repetition of units derived, actually or conceptually, from molecules of low relative molecular mass. Such a molecule may for example comprise in excess of 1000 atoms. Many of the biomolecules mentioned above are also macromolecules.

[0050]

[0045] As used herein, and unless otherwise specified, the term ‘nanoporous’ refers to a material or structure that has pores with dimensions in the nanometre range. A nanoporous material may for example have an average pore size of about 1 to 10 nm.

[0051]

[0046] As used herein, and unless otherwise specified, the term ‘near’ in relation to the porous solid structure refers to a distance of 30 nm or less from the surface of the porous solid structure (e.g. from the layer comprising the dielectric); preferably 20 nm or less, more preferably 15 nm or less, yet more preferably 10 nm or less, most preferably 5 nm or less. In some embodiments, near the porous solid structure may correspond to ‘within a pore of the porous solid structure’.

[0052]

[0047] As used herein, and unless otherwise specified, the term ‘effective pore size’ refers to the size of the pore effectively accessible to the target molecule. In some cases, the pore can comprise an entity (e.g. an electric double layer or a macromolecule) that takes up a part of the pore, making said part essentially inaccessible to the target molecule. Moreover, in some embodiments (cf. infra), the size of this entity may vary depending on the physicochemical properties (e.g. electrical potential bias, temperature, pH, etc.) in the pore, thereby changing the effective pore size.

[0053]

[0048] In a first aspect, the present invention relates to a system comprising: i) porous solid structure, comprising: a network formed of a plurality of interconnected electrically conductive wires, and a layer comprising a dielectric conformally coating the network; and ii) a controller for powering the networkof interconnected electrically conductive wires; wherein the system is such that a retention of a target molecule by the porous solid structure can be altered by powering the network of interconnected electrically conductive wires.

[0054]

[0049] This system advantageously allows active control over the retention of the target molecule, through controlling the degree of powering (e.g. the electrical potential bias applied to and / or the amount of electrical current running through; i.e. energizing) the network of interconnected electrically conductive wires. Accordingly, it enables to modify the retention within a procedure or between procedures (without making substantial modifications to the system and while keeping the system intact). In embodiments, controlling the degree of powering may allow to alter (i.e. increase and / or decrease) the retention factor between a minimum and a maximum, the maximum being at least 2 times higher than the minimum; preferably at least 5 times higher, more preferably at least 10 higher, still more preferably at least 20 times higher, yet still more preferably at least 50 times higher, most preferably at least 100 times higher, such as 200, 500 or 1000 times higher. This in turn allows not only to easily vary (and thus e.g. experiment with, for example to find an optimal value therefor) the retention, but also to enact control over the flow of the target molecule independent of that of the rest of the fluid. Indeed, by turning the retention up and down, the target molecule can first be retained and subsequently released by the porous solid structure. This can be done in a binary way (i.e. turning the retention ‘on’ and ‘off’), but can also be controlled more gradually or even modulated continuously. Accordingly, by controlling the retention of the target molecule, flow control over target molecule can be realized, but the same can also be used to concentrate the target molecule — e.g. in anticipation of a measurement or synthesis to be performed (which may be performed inside or outside the porous solid structure) — or simply to purify or separate the target molecule. In both cases, when the target molecule is the analyte of interest, the target molecule can be retained and the contaminants flush / washed out, thereby concentrating the target molecule and removing the contaminants, after which the (concentrated and purified / separated) target molecule can be used or collected. For the latter case, when the target molecule is a contaminant, by retaining the target molecule the fluid can be purified / separated simply by flowing it through the porous solid structure (with the option of regenerating the porous solid structure by releasing the contaminants and evacuating them when — or before — the porous solid structure becomes saturated).

[0055]

[0050] The above active control over the retention of the target molecule can be realized in numerous ways, including — but not necessarily limited to — the following (or a combination thereof). First, the retention of the target molecule by the porous solid structure may be altered through changing an affinity of the porous solid structure for the target molecule (e.g. through changing the electrostatic interactions between the porous solid structure and the target molecule). This may also include altering an affinity of an auxiliary molecule in the porous solid structure for the target molecule (e.g. through the conformation or oxidation state of the auxiliary molecule). Second, it may be done by altering an effective pore size of the porous solid structure (e.g. through changing the size of an entity — e.g. an electric double layer or a macromolecule — in the pore; cf. supra). Third, it may be done by altering a force acting on the target molecule (e.g. by generating a non-uniform electric field to realize a dielectrophoretic force on the target molecule). Herein, the alteration may be in the porous solid structure / auxiliary molecule / effective pore size / force and / or in the target molecule as such. Theabove can all be achieved by powering the network, which — as the case may be — either realizes the desired effect more or less directly (e.g. in the form of generating a field and corresponding force, or by inducing a change electrochemically); or does so via a change in physicochemical properties in the pore — for example in the form of electrical potential bias, temperature (e.g. through Joule heating), pH (e.g. through an electrochemical reaction involving the generation or reduction of H+), etc. — which in turn affect one or more species (e.g. the target molecule or an auxiliary molecule) in the pore.

[0056]

[0051] In embodiments, the porous solid structure may have a porosity of at least 60%; preferably at least 70%, more preferably at least 80%, most preferably at least 90%. A high porosity advantageously enables efficient flow-through of the fluid comprising the target material. Moreover, it increases the (accessible) surface area of the porous solid structure, thereby increasing the area where auxiliary molecules can be functionalized or where they can react (e.g. electrochemically) with the porous solid structure. In embodiments, the network may have a volumetric surface area of from 10-3m2 / cm3to 100 m2 / cm3. In embodiments, the porous solid structure may have a typical pore size in the order of nanometre to tens of nanometre; e.g. 5 to 500 nm, preferably 10 to 300 nm. In embodiments, the porous solid structure may have a width in the order of micrometre to centimetres; e.g. from 1 pm to 10 cm, preferably from 10 pm to 5 cm, more preferably from to 50 pm to 2 cm. In embodiments, the porous solid structure may have a length in the order of micrometres to decimetres; e.g. from 10 pm to 10 dm, preferably from 100 pm to 5 dm, more preferably from to 1 mm to 2 dm. In embodiments, the porous solid structure may have a height in the order of tens of nanometres to tens of micrometres; e.g. from 100 nm to 500 pm, preferably from 1 pm to 200 pm, more preferably from to 10 pm to 100 pm.

[0057]

[0052] In embodiments, the electrically conductive wires may comprise a metal (e.g. Ni, Cu, Ag, Au or Pt), metal alloy (e.g. an alloy comprising at least one of the aforementioned metals) or semiconductor (e.g. Si, Ge, SixGey). These materials advantageously have high electrical conductivity and can be provided in the form of the desired network of electrically conductive wires. In embodiments, the electrically conductive wires may comprise a core (e.g. made of a metal, metal alloy or semiconductor as mentioned above) coated by (e.g. a few nm of) an outer layer (e.g. made of another metal, metal alloy or semiconductor as mentioned above). For instance, a Pt surface may be preferred for certain applications, but e.g. Ni wires may be more easily fabricated, stronger and cheaper. In this case, a Ni network coated with a thin layer of Pt can be used. In embodiments, the network of electrically conductive wires may be formed as was disclosed in W02019016033A1 or EP2980014A1 ; which are incorporated herein by reference. These — and especially the one from W02019016033A1 — are relatively facile and scalable processes for fabricating a highly tailorable array of vertical and horizontal interconnected nanowires with regular interwire spacing. The various dimensions (e.g. total dimensions, wire thickness, wire spacing; and thereby thus also porosity and volumetric area, cf. supra) can be tuned through the fabrication process. In embodiments, the electrically conductive wires may have a diameter in the order of nanometres to tens of nanometres; e.g. from 5 to 100 nm, preferably from 10 to 75 nm, more preferably from 20 to 60 nm, such as 40 nm.

[0058]

[0053] In embodiments, the layer comprising the dielectric may have a thickness of from 1 to 50 nm; preferably from 2 to 30 nm, more preferably from 3 to 20, most preferably from 5 to 15 nm, such asabout 10 nm. In embodiments, the dielectric may be an oxide; preferably TiC>2 or SiC>2, most preferably SiC>2. TiC>2 and SiC>2 advantageously provide excellent insulating properties and are biocompatible. Moreover, the formation / deposition and properties of SiC>2 are extremely well understood from semiconductor processing and / or sol-gel synthesis (cf. infra), and numerous ways are known to further functionalize it (e.g. using silane chemistry and cross linkers, to name but one). In embodiments, the dielectric may be formed by a sol-gel synthesis (e.g. as was disclosed in EP4020626A1 and / or EP3974562A1 ; which are incorporated herein by reference) or molecular layer deposition (MLD). In embodiments, the dielectric layer may have a density of 2.0 g / cm3or less, preferably 1.8 g / cm3or less, more preferably 1.6 g / cm3or less. Materials formed by sol-gel synthesis typically have a lower density than the same material formed through another method (e.g. thermal growth, oxidation or molecular layer deposition).

[0059]

[0054] In embodiments, the layer comprising the dielectric may be nanoporous. In embodiments, the nanoporous layer may have an average pore size of 1 to 10 nm, preferably 1 to 5 nm, most preferably 2 to 3 nm. A nanoporous layer allows (certain; e.g. based on size-exclusion) compounds (e.g. the target molecule or another species) to penetrate the layer and contact the network of interconnected electrically conductive wires, where they can undergo an electrochemical reaction; which is desirable for some applications. In embodiments, the nanopores may be formed via the inclusion (e.g. in solgel synthesis or molecular layer deposition, cf. supra) and subsequent removal of a porogen (see e.g. Example 1). Note that even a nonporous dielectric may in some instances (e.g. depending on the fabrication method used) comprise miniscule (< 1 nm) holes that allow transport of small chemical species (e.g. H2O, OH-and / or H+) through the nonporous dielectric.

[0060]

[0055] In embodiments, the layer comprising the dielectric may be functionalized with auxiliary molecules, such as biomolecules and / or macromolecules. In embodiments, said auxiliary molecules may be chemically bound in the layer (e.g. to the dielectric) or physically incorporated. Such auxiliary molecules may advantageously be directly or indirectly used to affect the retention of the target molecule depending on how the network is powered (e.g. the effect of the molecules may be depending on the physicochemical properties — such as electrical potential bias, temperature, pH, etc. — in the pore). For example, the molecules may have a variable affinity for the target molecule as such. Alternatively, the molecules may have a variable affinity for another species, the attraction / repulsion of which influences the effective pore size (e.g. through increasing or decreasing the size of an electric double layer). In yet another example, the molecules may have a variable conformation, wherein one is relatively condensed — leaving the pore relatively free — , while another is relatively extended — thereby reducing the effective pore size.

[0061]

[0056] Most typically, the controller may be resistively coupled to the network through at least one electrode (cf. infra). Not withstanding, in some embodiments, the controller may be ‘wirelessly’ (e.g. magnetically) coupled to the network. Accordingly, powering the network may in some embodiments use principles akin to wireless charging.

[0062]

[0057] In a first type of embodiments, the network may be resistively coupled to a first electrode and second electrode. This advantageously allows passing a current through the network, for example to induce Joule heating (thereby providing a localized and uniform heat source).

[0058] In a second type of embodiments, the network may be resistively coupled to a first electrode and capacitively coupled to a second electrode. This configuration advantageously enables applying an electrical potential bias (relative to the second electrode) over the network — but without a (significant) current — , thereby creating a capacitive effect affecting the surface charges of the porous solid structure and thereby the attraction / repulsion of charged species — which may be the target molecule or another species — near the porous solid structure.

[0063]

[0059] In operation, the system generally comprises a fluid comprising the target molecule. In this case, the pores typically comprise the fluid (and thus the target molecule). For example, the porous solid structure may be submerged in the biochemical buffer. In embodiments, the system may further comprise: iii) one or more fluidic channels. In embodiment, the porous solid structure may be integrated in one of the fluidic channels. Integration in a fluidic channel advantageously enables flow-through applications. In embodiments, the one or more fluidic channels may comprise (e.g. at least the fluidic channel comprising the porous solid structure may be) a microfluidic channel. For example, the system may be a microfluidic system. Microfluidic channels and systems advantageously enable very convenient (e.g. comparatively small) form factors and requiring minimal sample volume, while nevertheless allowing to perform relatively complex tasks within the system on this small sample volume. In embodiments, the system may further comprise: iv) a flow generator for flowing the target molecule through the porous solid structure. A flow generator advantageously allows controlling the flow of fluid in the system (e.g. through the porous solid structure). In embodiments, the system may further comprise: v) a reservoir for receiving a fraction of the fluid having passed through the porous solid structure. Said fraction may comprise the target molecule (e.g. where the target molecule is an analyte), or may not comprise the target molecule (e.g. where the target molecule is a contaminant).

[0064]

[0060] In embodiments, the target molecule may be a biomolecule or small molecule, preferably a biomolecule. In some embodiments, the target molecule may be an analyte. In other embodiments, the target molecule may be a contaminant.

[0065]

[0061] In embodiments, any feature of any embodiment of the first aspect may independently be as correspondingly described for any embodiment of any of the other aspects.

[0066]

[0062] In a second aspect, the present invention relates to a method for performing a procedure using the porous solid structure as defined in any embodiment of the first aspect, comprising a) flowing the target molecule through the porous solid structure; and b) powering the network of interconnected electrically conductive wires, thereby altering a retention of the target molecule by the porous solid structure.

[0067]

[0063] In embodiments, step b may comprise powering the network such as to induce electrostatic interactions, heating and / or electrochemical reactions in and / or near the network. These effects can advantageously be used to modulate the retention.

[0068]

[0064] In embodiments, step b may comprise applying an electrical potential bias to and / or running an electrical current through the network. Applying a bias or current are convenient ways to power the network.

[0069]

[0065] In embodiment, the target molecule may be present alongside one or more non-target molecules (e.g. contaminants) and / or one or more further target molecules (i.e. other species ofinterest). In these embodiments, step b may comprise altering the retention of the target molecule selectively from (i.e. to different degree than) the one or more non-target molecules and / or further target molecules. In doing so, the target molecule can for instance advantageously be separated from the one or more non-target molecules and / or further target molecules.

[0070]

[0066] In embodiments, the procedure may be one ora combination of a measurement, purification, separation, synthesis and / or flow control (e.g. pump or valve).

[0071]

[0067] In embodiments, any feature of any embodiment of the second aspect may independently be as correspondingly described for any embodiment of any of the other aspects.

[0072]

[0068] In a third aspect, the present invention relates to a use of a porous solid structure as defined in any embodiments of the first aspect, for biochemical applications.

[0073]

[0069] The active porous structure is advantageously particularly well-suited for various biochemical applications (cf. background), where active control over the retention has hereto not been (readily) available and facilitates more precise procedures and / or unlocks new procedures that were not previously possible.

[0074]

[0070] In embodiments, the physicochemical properties in and / or nearthe network may be controlled through powering the network of interconnected electrically conductive wires. Controlling the local physicochemical properties advantageously allows to tune the retention behaviour.

[0075]

[0071] In embodiments, any feature of any embodiment of the third aspect may independently be as correspondingly described for any embodiment of any of the other aspects.

[0076]

[0072] The invention will now be described by a detailed description of several embodiments of the invention. It is clear that other embodiments of the invention can be configured according to the knowledge of the person skilled in the art without departing from the true technical teaching of the invention, the invention being limited only by the terms of the appended claims.

[0077] Example 1

[0078] Porous solid structure

[0079]

[0073] A porous solid structure (50) as shown in FIG 1 comprises a network (51) formed of a plurality of interconnected electrically conductive wires, and a layer (52) comprising a dielectric conformally coating the network (51). The coated network defines pores (53) — e.g. interconnected pores — for receiving a liquid containing one or more target molecules. Said pores (53) typically extend throughout the complete network (51), allowing said target molecules to flow or move throughout the network (51) from one side to another. Coupling the porous solid structure (50) to a controller (cf. infra) allows — through powering the network — active control over the retention of target molecules passing through the porous solid structure (50), or (equivalently) passing through the pores defined by the coated network.

[0080]

[0074] The precise nanostructure, wire spacing, diameter and composition of the network (51) can generally be selected depending on the desired properties. Notwithstanding, the network (51) can for instance be formed as was disclosed in WO2019016033A1 or EP2980014A1. For example, forming the network (51) may involve anodizing (e.g. in oxalic acid) a Cu-doped Al layer to form 3D interconnected nanopores in the anodized aluminium oxide (AAO) template. Next, a metal (e.g. Ni)is plated inside the AAO template followed by dissolving the AAO template (e.g. in 0.5 M KOH) to yield a 3D structured, interconnected metallic nanomesh. In one instance, the resulting network consisted of nanowires with a diameter of approximately 40 nm, a spacing of about 64 nm, and a height of 10 pm. Additionally, the network can be prepared supported on a substrate as well as in a freestanding form. In both cases an anodization process as above can be used to form a 3D-porous template. In the case of the freestanding network, this template may first be filled with a sacrificial strike layer and subsequently with the target metal by electrodeposition. A supporting structure can be created by masking (e.g. via inkjet printing) and a second electrodeposition step to overplate the template and to form a mechanically stable support. After template etching and removal of the sacrificial strike layer, the freestanding network lifts off the substrate and can be further processed.

[0081]

[0075] Similarly, the composition, thickness and porosity of the dielectric can generally be selected depending on the desired properties. Notwithstanding, the dielectric can for instance be formed as was disclosed in EP4020626A1 and / or EP3974562A1 . For example, the dielectric may be prepared through an electrochemically induced sol-gel method. In one instance, a silica sol-gel synthesis was performed using an aqueous / organic solvent mixture containing an alkoxysilane precursor. The mildly acidic precursor solution was kinetically stable, allowing the hydrolysis reaction to proceed until equilibrium while inhibiting condensation. The network was submerged in the precursor solution, and electrochemical reactions were used to alterthe pH in the diffusion layer nearthe electrode, triggering local gelation and resulting in the growth of a conformal silica coating of approximately 10 nm on the nanowires and a density of about 1.5 g / cm3. The layer comprising the dielectric may generally be nonporous (cf. present Example 1) or porous (cf.

[0080] ).

[0082] System

[0083]

[0076] A porous solid structure (50) in accordance with the present invention is typically incorporated in a system (10). One example thereof is schematically depicted in FIG 2, showing the porous solid structure (50) and a controller (60) for powering the network (51) of interconnected electrically conductive wires of the porous solid structure (50). Further depicted — but not essential to the present invention — , is a flow channel (41) above the porous solid structure (50), and a counter electrode (32) on a substrate wall (20) of said flow channel (41). The counter electrode (32) may in some implementation also allow to generate with the porous solid structure (50) an electrophoretic force steering the target molecule from the flow channel (41) into the porous solid structure (50) or vice versa; as previously described in EP23219945 (which is at the time of writing not yet published).

[0084]

[0077] One possible device architecture is shown in FIG 3 and FIG 4. Therein, the system (10) comprises a fluidic channel (41) in which the porous solid structure (50) is integrated. An electric actuation (not visualized in FIG 3 or FIG 4) is coupled to the network (51) within the porous solid structure (50), which may for instance involve a first electrode, second (counter) electrode and a controller (cf. supra and infra). Further depicted — illustrating additional elements that may optionally present in such a device — are an inlet (71) and outlet (72) for the fluidic channel (30), pillars (81) for fluidic distribution (e.g. in case of a wider channel flow 41) and one or more detectors (82) (e.g. for analysing the contents flowing out of the porous solid structure 50).Active control over the retention of a target molecule

[0085]

[0078] Depending e.g. on the way the porous solid structure (50) is powered — e.g. the way the controller and / or electrodes are coupled to the network (51) and operated — , a system (10) in accordance with embodiments of the present invention can be used in multiple ways to control / alter the retention of the target molecule flowing through the porous solid structure (50).

[0086]

[0079] With reference to FIG 5, the layer (52) comprising the dielectric is for instance nonporous, and the network (51) may be powered by applying a potential bias to the network (51) relative to a counter electrode (32) in the electrolyte (40) in which the porous solid structure (50) is submerged. To this end, the controller (not shown in FIG 5) may be coupled to the network (51) through a first electrode (31) resistively coupled (e.g. directly connected) to said network (51); while the second electrode (32) — which may e.g. be coupled to the controller as well, or to an alternative device, or to ground — may be resistively coupled (e.g. in direct contact with) the electrolyte (40). Since the layer (52) comprising the nonporous dielectric prevents larger molecules (e.g. > 1 nm in size) from passing through it (even while passage of small chemical species — such as H2O, OH-and / or H+— may nevertheless be possible), no direct electrical contact between the electrolyte (40) and the network (51) is possible. In other words, the network (51) is electrically insulated from the electrolyte (40) (and more generally: all larger molecules) by the dielectric, and the second electrode (32) is capacitively coupled to the network (51). FIG 6 shows a close-up of the area of FIG 5 indicated by the dashed box. Schematically depicted therein are the positively charged ions (black dots) and negatively charged ions (white dots) in the electrolyte (40). Accordingly, when a negative bias is applied to the network (51), this creates a capacitive effect, inducing an increase in the positive charges (e.g. in the form of protons in aqueous buffers) at the interface between the dielectric and the electrolyte (40). These positive charges reduce — directly (e.g. by the presence of the positive charges as such) or indirectly (through a reaction with pending groups at the dielectric surface, thereby decreasing the negative and / or increasing the positive pending groups) — the repulsion of negative charges proximate to the interface. This, in turn, promotes the adsorption of nucleic acids or other negatively charged molecules to the dielectric, and / or influences auxiliary molecules with a charge-dependant conformation near (e.g. functionalized to) the surface of the dielectric. Evidently, the application of a positive bias generates the opposite effect.

[0087]

[0080] Accordingly, the retention of the target molecule by the porous solid structure may be altered through changing an affinity of the porous solid structure for the target molecule (e.g. through changing the electrostatic interactions between the porous solid structure and the target molecule). This may also include altering an affinity of an auxiliary molecule in the porous solid structure for the target molecule (e.g. through the conformation or oxidation state of the auxiliary molecule). Alternatively or complementarily, the retention of the target molecule by the porous solid structure may be changed by altering an effective pore size of the porous solid structure (e.g. through changing the size of an entity — e.g. an electric double layer or a macromolecule — in the pore; cf. supra).

[0088] Example 2

[0089]

[0081] Example 1 is repeated, but the layer (52) comprising the dielectric is porous (e.g. nanoporous). Formation of a (nano)porous layer of dielectric may for example be realized by adding a porogen (e.g. soft-template molecules, such as a surfactant — for example cetyltrimethylammoniumbromide, CTAB) during the coating process, leading to the formation of highly organized nanocomposite structures that can be transformed into nanoporous thin films upon removal of the porogen. Alternatively, the nanoporous dielectric coating could for instance also be formed using molecular layer deposition (MLD) to form an oxide-porogen hybrid thin film, followed by porogen removal (e.g. through dissolution thereof in a solvent, such as an alcohol like ethanol) to form the nanopores. Regardless, the dielectric may further be functionalized with auxiliary molecules. These can for instance be provided with the dielectric during the coating process, or subsequently attached to the dielectric (e.g. using silane chemistry and cross linkers).

[0090]

[0082] The layer (52) being porous allows chemical species — e.g. the target molecule and / or a compound in the buffer, such as water or an electrolyte ion — to penetrate through the layer (52) and contact the electrically conductive network (51), where they can undergo an electrochemical reaction under the effect of an applied potential bias. Accordingly, a degree of selection (e.g. by size) of which molecules can penetrate the layer (52) can be achieved by controlling the size of the pores in the porous layer.

[0091]

[0083] Alternatively, such embodiments could function in the same way as described above for Example 1 , provided the potential bias applied is lower than any redox potential of the chemical species present in the porous solid structure (50).

[0092] Example 3

[0093]

[0084] With reference to FIG 7, Example 1 is repeated but the network (51) is powered by running a current through the network (51). To this end, the controller (not shown in FIG 7) may be coupled to the network (51) through both the first electrode (31) and the second electrode (32) being resistively coupled (e.g. directly connected) to said network (51). Accordingly, when a current is run through the network, the resistance of the network (51) generates Joule heating, which is dissipated through the layer (52) comprising the dielectric. Since such Joule heating — compared to an external heat source, like a Peltiers device, which provides heat to only one side of or to a discrete number of specific locations within the network — provides localized and uniform heating of the porous solid structure (50), there is no need for over- or underheating of certain regions, and exposure — which may be detrimental to their stability — of chemical species (e.g. the target molecule or auxiliary molecules functionalized to the porous solid structure) to said over- or underheating may be averted.

[0094] Example 4

[0095]

[0085] Each of Example 1-Example 3 allow to directly or indirectly affect one or more of: an affinity of the porous solid structure (e.g. of the dielectric or of an auxiliary molecule, if present) for the target molecule, and / or an effective pore size of the porous solid structure.

[0096]

[0086] Alternatively or complementary thereto, in any of the configurations above, application of a suitable potential (e.g. to produce a non-uniform electric field) — optionally in collaboration with one or more further electrodes (e.g. counter electrode 32, cf. supra; or electrodes 91 and / or 92, cf. infra) — can allow to the generate a force (e.g. a dielectrophoretic force) directly onto the target molecule.

[0097]

[0087] Thus, regardless of the precise implementation (e.g. any of Example 1-Example 4), the retention of the target molecule in the porous solid structure (50) can generally be controlled by tuning the potential bias and / or current applied by the controller (60) to the network (51). In turn, this produces the desired effect either more or less directly (e.g. in the form of generating a field andcorresponding force, or by inducing a change electrochemically); or via a change in physicochemical properties in the pore — for example in the form of electrical potential bias, temperature (e.g. through Joule heating), pH (e.g. through an electrochemical reaction involving the generation or reduction of H+), etc. — which in turn affect one or more species (e.g. the target molecule or an auxiliary molecule) in the pore.

[0098] Example 5

[0099]

[0088] FIG 8 shows another example of a system (10) in accordance with the present invention. This system (10) is generally similar to that described in Example 1 -Example 4 — including a porous solid structure in accordance with the present invention — , but the porous solid structure (50) is a freestanding membrane which is assembled between two substrates (20). Accordingly, the porous solid structure (50) is suspended by being sandwiched at its edges between the two substrates (20). Optionally, small pillars may be provided (e.g. one or both of the substrates (20) may be outfitted therewith) under and / or above the porous solid structure (50) to further support / sustain it.

[0100]

[0089] Each of the two substrates (20) are further provided with a cavity and an electrode so that — after assembly — the porous solid structure (50) is located between the pair of electrodes (91 and 92), and two flow channels (41 and 42) are defined — respectively between the respective electrode (91 or 92) and the porous solid structure (50).

[0101]

[0090] The above device architecture may generally be better suited towards larger-scale devices, e.g., for industrial applications. Typical dimensions forthe permeable structure and each flow channel may for example be a height (along the z-direction) of in order of tens of micrometres to about 1 cm, and a width (i.e. along the y-direction) and length (i.e. along the x-direction) of in the order of micrometres to tens of centimetres.

[0102]

[0091] In operation, a fluid flow may be generated in each flow channel (41 and 42), and a suitable electrophoretic field may be generated across the porous solid structure (50) with the electrodes (91 and 92); cf. EP23219945. Like in Example 1 -Example 4 however, using a controller (not shown) to powerthe porous solid structure (50), the retention of target molecules in the fluid flowing through the porous solid structure (50) can be controlled.

[0103]

[0092] It is to be understood that although preferred embodiments, specific constructions, configurations and materials have been discussed herein in order to illustrate the present invention. It will be apparent to those skilled in the art that various changes or modifications in form and detail may be made without departing from the scope of the invention as defined in the appended claims.

Claims

CLAIMS1. A system (10) comprising:i) a porous solid structure (50), comprising- a network (51) formed of a plurality of interconnected electrically conductive wires, and - a layer (52) comprising a dielectric conformally coating the network (51); andii) a controller (60) for powering the network (51) of interconnected electrically conductive wires;wherein the system (10) is such that a retention of a target molecule by the porous solid structure (50) can be altered by powering the network (51) of interconnected electrically conductive wires.

2. The system (10) according to claim 1 , wherein the layer (52) comprising the dielectric is functionalized with auxiliary molecules.

3. The system (10) according to any of the previous claims, wherein the dielectric is an oxide, preferably SiCh.

4. The system (10) according to any of the previous claims, wherein the network (51) is resistively coupled to a first electrode (31) and second electrode (32).

5. The system (10) according to any of claims 1 to 4, wherein the network (51) is resistively coupled to a first electrode (31) and capacitively coupled to a second electrode (32).

6. The system (10) according to claim 5, wherein the layer (52) comprising the dielectric is nanoporous.

7. The system (10) according to any of the previous claims, wherein the porous solid structure (50) has a porosity of at least 60%.

8. The system (10) according to any of the previous claims, wherein the network (51) has a volumetric surface area of from 10-3m2 / cm3to 100 m2 / cm3.

9. The system (10) according to any of the previous claims, wherein the electrically conductive wires comprise a metal, metal alloy or semiconductor.

10. The system (10) according to any of the previous claims, further comprisingiii) one or more fluidic channels, the porous solid structure (50) being integrated in one of the fluidic channels.

11. The system (10) according to any of the previous claims, further comprisingiv) a flow generator for flowing the target molecule through the porous solid structure (50).

12. The system (10) according to any of the previous claims, wherein the retention of the target molecule by the porous solid structure (50) can be altered through changing- an affinity of the porous solid structure (50) for the target molecule,- an effective pore size of the porous solid structure (50), and / or- a force acting on the target molecule.

13. A method for performing a procedure using the porous solid structure (50) as defined in any of claims 1 to 11 , comprising:a) flowing the target molecule through the porous solid structure (50); andb) powering the network (51) of interconnected electrically conductive wires, thereby altering a retention of the target molecule by the porous solid structure (50).

14. The method according to any of claims 13, wherein step b comprises powering the network (51) such as to induce electrostatic interactions, heating and / or electrochemical reactions in and / or near the network (51).

15. The method according to any of claims 13 or 14, wherein step b comprises applying an electrical potential bias to the network (51) and / or running an electrical current through the network (51).

16. Use of a porous solid structure (50) as defined in any of claims 1 to 12, for biochemical applications.

17. The use according to claim 16, wherein the physicochemical properties in and / or near the network (51) are controlled through powering the network (51) of interconnected electrically conductive wires.

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