WO2014117225A1 - Metal organic frameworks - Google Patents

Abstract

The present invention relates to a substrate having particles of Metal Organic Framework (MOF) fixed thereto, said particles being partially embedded into a surface of the substrate.

Description

METAL ORGANIC FRAMEWORKS

FIELD OF THE INVENTION

The present invention relates in general to Metal Organic Frameworks (MOFs). In particular, the invention relates to MOFs that are fixed to a substrate and to a method for fixing MOFs to a substrate.

BACKGROUND OF THE INVENTION

MOFs are hybrid coordination structures formed by metal ions or clusters comprising metal ions, e.g. metal oxides, coordinated by multi-functional organic linkers. This results in the formation of highly ordered one-, two- or three-dimensional structures that can be highly porous. As synthesized, MOFs are generally available as crystals with an average size ranging from tenths of micron to several millimeters.

Depending on the particular choice of metal ions and organic linkers, a variety of open micro- and mesoporous MOF structures are available. These structures are characterized by a surface area in the order of thousands of square meters per gram. In addition, the particularly ordered arrangement of metal ions/clusters and organic linkers further results in a very narrow distribution of pore size. Advantageously, the chemical properties of the pore surface can be also tailored using traditional organic chemistry applied to the organic counterpart of a MOF structure.

These porosity characteristics make MOFs extremely attractive materials for applications in gas storage/separation devices, catalysis, drug delivery, optoelectronics, and sensing. However, the possibility to take advantage of MOFs ideal porosity features in a usable device can depend upon their availability on a substrate. Accordingly, considerable research effort is currently being spent to develop and optimize protocols to securely anchor MOFs on a surface of a substrate. To date, most research effort has been directed towards promoting formation of MOF structures directly on suitably functionalized surfaces by way of "bottom-up" approaches.

These approaches rely on the initial functionalisation of a substrate surface with chemical groups that are capable of coordinating metal ions. When these substrates are immersed into a solution containing conventional MOF precursors, they promote homogeneous nucleation of MOF structures.

Other more sophisticated bottom-up approaches involve using a micro-tip of either an Atomic Force Microscope (AFM) or a Scanning Probe Microscope (SPM) to deposit micro-droplets of a MOF precursor solution on specific sites on a substrate, thus promoting highly localized MOF formation by crystal precipitation from within the deposited micro- droplets.

However, most bottom-up approaches are inherently unsuitable for mass production of MOF-based devices because they are either too expensive or involve rather sophisticated procedures. In addition, the resulting MOF structures adhere quite poorly to the substrate. Furthermore, not all substrate materials are readily functionalised with the specific surface moieties required for MOF formation. Indeed, this limits the choice of available substrate materials.

An opportunity therefore remains to develop MOF/substrate systems that can be readily mass produced in an efficient and cost effective manner. It is also desirable that such MOF/substrate systems can be prepared without excessive limitations on the type of substrate or MOF employed.

SUMMARY OF THE INVENTION

The present invention therefore provides a substrate having particles of Metal Organic Framework (MOF) fixed thereto, said particles being partially embedded into a surface of the substrate. It has now been found that MOFs can be securely fixed to a diverse array of substrates by partially embedding them into a surface of the substrate. By only partially embedding the MOFs, a portion of the MOF structure is located within the substrate and the remaining portion remains exposed to the external environment, thereby retaining its activity relative to that environment. Surprisingly, the MOFs can be partially embedded in the substrate without substantially altering their chemical and morphologic structure. By this approach, the unique properties of MOFs can be effectively exploited in MOF-based devices.

Provided that the MOF particles can be partially embedded in its surface, there is no particular limitation concerning the material from which the substrate is made.

In some embodiments, the substrate material into which the MOF particles are partially embedded is polymer. The polymer may be a homo-polymer, a co-polymer, a hybrid polymer, or a blend of at least two of such polymers. In one embodiment, the substrate material into which the MOF particles are partially embedded is a thermoplastic polymer.

In another embodiment, the substrate material into which the MOF particles are partially embedded is a metal. In a further embodiment, the substrate material is an alloy of two or more metals.

There is no particular limitation concerning the shape or configuration of the substrate to be used in accordance with the invention. In some embodiments, the substrate is in the form of a monolith, i.e. a self-supporting solid-phase material.

In other embodiments, the substrate is provided on a support, for example the substrate may be in the form of a continuous film or layer deposited on a support. Provided it can carry the substrate, there is no particular limitation concerning the composition, shape or configuration of the support. A support may be employed where the substrate used does not have the required physical/mechanical properties. In that case, the support may provide the required physical/mechanical properties to the overall so formed structure. In yet further embodiments, the substrate into which the MOF particles are partially embedded is in the form of a plurality of micro-features and/or nano-features. In that case, such micro-features and/or nano-features may be fixed on a support. The micro-features and/or nano-features can be formed by way of a lithographic technique.

MOFs suitable for use according to the invention are typically porous metal-organic frameworks that comprise at least two metal clusters and at least one charged multi-dentate bridging ligand connecting adjacent clusters. The MOFs will generally be crystalline and can be provided in a particulate form.

As used herein, the expression "MOF particle" is intended to mean a small unit of MOF material of any shape, which largest dimension ranges from tens of nanometers to units of millimeters.

According to the present invention, MOF particles are fixed to a surface of a substrate. The MOF particles are therefore securely attached or anchored to the substrate such that they are not readily displaced. This can be advantageous, for example, when a substrate according to the present invention is used in a sensing device that is exposed to a gas or a liquid stream during its operation. In the context of the present invention, MOF particles are fixed to a substrate by way of being partially embedded into a surface of the substrate.

The present invention also provides a method of fixing particles of MOF to a substrate, said method comprising locating the particles between two surfaces, at least one of which is a surface of the substrate to which the particles of MOF are to be fixed, and compressing the particles with the two surfaces such that particles in contact with a surface of the substrate become partially embedded therein and consequently fixed to the substrate.

The method of the present invention advantageously provides for substrates having MOF particles securely anchored on their surface. This is achieved by compressing MOF particles such that they penetrate into the substrate and become fixed thereto. Notably, only sufficient penetration into the substrate occurs so that at least part of the MOF particles is exposed to the environment external of the substrate.

To date, fabrication techniques using/applying MOFs have been designed to accommodate gentle processing condition due to the intrinsic mechanical fragility of MOF materials. However, it has now been surprisingly found that MOF particles can sustain, under certain conditions, the mechanical stress associated with compressive forces without incurring substantial alteration of their chemical structure, morphologic structure, or porosity properties. For example, compressing crystalline MOFs according to the method of the present invention has been shown to have little if no adverse impact on their crystalline structure. Indeed, the X-ray diffraction patterns generated from crystalline MOFs before and after the compression step of the present invention have been found to be substantially the same.

In some embodiments, heat is applied to the substrate. As a result, the hardness of the substrate can be reduced, i.e. the substrate softens, thus facilitating the penetration of the MOF particles into the surface of the substrate.

In an alternative embodiment, the substrate is exposed to a solvent. For example, the substrate may be exposed to solvent liquid or vapors. As a result, the hardness of the substrate can be reduced, i.e. the substrate softens, thus facilitating the penetration of the MOF particles into the surface of the substrate.

Further aspects and/or embodiments of the invention are discussed in more detail below. BRIEF DESCRIPTION OF THE DRAWINGS

The invention will herein be described with reference to the following non-limiting drawings in which:

Figure 1 shows a graphic representation of a 4-step embodiment of the method of the present invention.

Figure 2 shows a Scanning Electron Microscope (SEM) ima e of MOF particles fixed on the surface of lithographed squared micro-features attached t a support, according to a embodiment of the Invention.

Figure 3 shows an SEM Image of MOF particles fixed on the surface of lithographed curvilinear miem-feaiures attached to & support, according to an embodiment of the invention.

Figure 4 shows X-ray diffraction (XRD) patterns of a) M!L-53 (At) on silicon and b) particles of amlno~M!L<-S3(Al) MOF partially embedded on a surface of SI micro-features that have been lithographed on a silicon wafer. The Figure relates io the characterisation of the sample obtained according to Example I.

Figure S shows (g, b) SEM images* (c-f) Energy Dispersive X-ra analysis, (g) an opt cal microscope image and (h, i) a Fourier Transform Infrared (FT1R) spectroscopy mapping of Aminc- !L^«53(A!> MOP particles partially embedded into a surface of SU-S lithographed micro-features.

Figure 6 shows (a) F^'TIM spectra of NH MlL-53>(Ai) MOF measured after several washing cycles, and ( ) the corresponds rsg values of the integrated area .of the spectra in the 3600-3300 em^*1 region,

Figure ? shows Energy Dispersive X-ray analysis performed o NHrMlL-53(AI) MOF as a powder (a) and H.r IL-53(AI) MOF partially embedded into SO -8 (b)_t both infiltrated with Palladium. The inset in Figure ?(¾} shows the small angle X-ray severin (SAXS) signal measured on the corresponding sample.

Figure 8 shows 1 ,2-Berranlhraeene uptake fluorescence kinetics, expressed as a percentage of benzanihracene remaining in solution, of: MIL-53(A1) MOP partially embedded into SU-S (green), 1L~S3(A1) MOF powder (orange), and SU-8 substrate (gray). Figure 9 shows a schematic of the β-GJueosidase· enzymes grafting procedure and s bsequent reaction with D-{-)-Ssl.cm.

Figure 10 shows a) Schematic of the reaction on the- SU4 having partially embedded therein MOF particles decorated with β-Gkcosidass- enzyme. The enzyme hydrolyses

D^v(-)-Sailcin into Glucose and Salicylic Alcohol; b) D-(-)-Saiioin hydrolysis efficiency calculated for an ammo-ftaictionafeed silicon substrate and the H₂-MiL 3(Al) MOF particles partially embedded into an SU-8 substrate.

Figure II illustrates SEM images of C (bic) MOF particfe(s) partially embedded into a polymer resist at different magnifications.

Figure 12 illustrates (a) a SEM micrograph of a cross-sectional Interface showing Cu(btc) MOFs partially embedded into a polystyrene substrate, ED^'X analysis showing (b) the presence of carbon in both the substrate and the MOF--PS interface, (c) the alumini m background of the sample mounting block, and (d) copper from the Cu(bte) MOF,

Some Figures contain colour representations or entities. Coloured versions of the Figures are available upon request.

DETAILED INSCRIPTION OF THE INVENTION

The present invention provides for substrates having MOF particles partially embedded into a surface thereof.

By the MOF particles being "partially embedded" into a surface of the substrate is meant tha a portion (i.e. not ail) of the particle is implanted into the surface of the substrate and In contact with the substrate material, while the remaining portion of the particle is not contact with the substrate. In other words, a portion of the MOF particles must bo exposed to the environment that is external to the s«bstrate^« OF assembly or the MOF is not fully encapsulated by the substrate. As a consequence, molecules can access the MOF structure directly from the external environment (i.e. without having to diffuse through the substrate first).

Impregnation tests can be performed to show accessibility of the pores of partially embedded MOF particles from the external environment. Examples of such tests are described in Examples 3 and 4.

Provided that at least some of the MOF particle is not embedded into a surface of the substrate, there is no particular limitation concerning the portion of the particle that is embedded into a surface of the substrate. For example, at least 0.1 %, at least 1 %, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95%, and in any case less than 100%, of the total external surface area of the particle, may be embedded into a surface of the substrate.

All of the MOF particles may not be partially embedded into a surface to the same degree or depth of penetration. In other words, the % of the total external surface area of each MOF particle that penetrates into a surface of the substrate may be the same or different.

It will be understood that the expression "total external surface area" of a MOF particle identifies the outermost surface of the particle, i.e. the surface which spatially defines the exterior shape of the particle.

As a result of the MOF particles being partially embedded into a surface of the substrate, the MOF particles become fixed to the substrate.

By the MOF particles being "fixed" to the substrate is meant that the particles are securely anchored to the substrate such that they are not readily displaced. This can be advantageous, for example, when a substrate according to the present invention is used in a sensing device that is exposed to a gas or a liquid stream during its operation. Without being limited by any particular theory, it is believed the MOF particles are anchored to the substrate through being mechanically locked into the substrate and/or other fixing forces such as chemical bonds and Van der Waals interactions.

By not being "readily displaced" it is meant that the partially embedded MOF particles are not washed off the substrate after a certain number of washing cycles according to a set protocol. A "washing cycle" is here intended as immersing a substrate of the invention into ethanol and withdrawing it vertically at a withdrawal rate of about lOcm/second. The assessment of whether MOF particles have been washed off after a cycle is made by comparing the integration area of the FTIR absorbance spectra (measured on the substrate) in the 3600-3300 cm^"1 wavelength region calculated before and after one or more washing cycles. For the purpose of the invention, MOF particles are considered to be not readily displaced if the decrease of the integration value of the FTIR absorbance spectra in the 3600-3300 cm^"1 wavelength region calculated before and after 50 washing cycles is less than 20%, and the drop of the integral area between the 10^th and the 50^th washing cycle is less than 5%.

In some embodiments, the substrate material into which the MOF particles are partially embedded is a polymer such as a thermoplastic polymer.

The polymer may be a homo-polymer or a co-polymer. Such polymers include, but are not limited to, acrylonitrile butadiene styrene (ABS), acrylics, polyacrylates (such as polymethylmetacrylate, PMMA), celluloid, cellulose acetate, cyclo-olefin co-polymer (COC), ethylene-vinyl acetate (EVA), ethylene vinyl alcohol (EVOH), fluoroplastics (such as PTFE, alongside with FEP, PFA, CTFE, ECTFE, ETFE), ionomers, Kydex (a trademarked acrylic/PVC alloy), liquid crystal polymers (LCPs), polyacetal (POM or Acetal), polyacrylonitrile (PAN or acrylonitrile), polyamide (PA or Nylon), polyamide- imide (PAI), polyaryletherketone (PAEK or Ketone), polybutadiene (PBD), polybutylene (PB), polybutylene terephthalate (PBT), polycaprolactone (PCL), polychlorotrifluoroethylene (PCTFE), polyethylene terephthalate (PET), polycyclohexylene dimethylene terephthalate (PCT), polycarbonate (PC), polyhydroxyalkanoates (PHAs), polyketone (PK), polyester polyethylene (PE), polyetheretherketone (PEEK), polyetherketoneketone (PEKK), polyetherimide (PEI), polyethersulfone (PES), polysulfone polyethylenechlorinates (PEC), polyimide (PI), polylactic acid (PLA), polymethylpentene (PMP), polyphenylene oxide (PPO), polyphenylene sulfide (PPS), polyphthalamide (PPA), polypropylene (PP), polystyrene (PS), polysulfone (PSU), polytrimethylene terephthalate (PTT), polyurethane (PU), polyvinyl acetate (PVA), polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), styrene-acrylonitrile (SAN), and copolymers or blends thereof.

In other embodiments, the substrate is derived from a photo-resist composition. Photoresist compositions are typically photo-polymerizable compositions comprising monomers and one or more photoinitiators. Example of polymer substrate materials that can be derived from photo-resist compositions include poly(methyl methacrylate) (PMMA), poly(methyl glutarimide) (PMGI), phenol formaldehyde resins (DNQ/Novolac), epoxy- resins such as SU-8, and combinations thereof.

In one embodiment, the substrate material into which the MOF particles are partially embedded is a photo-resist composition comprising an epoxy resin.

The substrate into which the MOF particles are partially embedded may also comprise or be a hybrid polymer. As used herein, the expression "hybrid polymer" is intended to mean a continuous network of inorganic and organic moieties that form a homogeneous single- phase material. Hybrid polymers suitable for use according to the present invention may comprise metal oxides derived from metal alkoxides.

The expression "metal oxide" denotes any oxide, hydrated oxide, hydroxide or mixed oxide/hydroxide of any trivalent or higher-valence "metal elements" from period 3 and higher periods and groups 3 and higher groups of the IUPAC Periodic Table of the Elements, comprising Al, Si, Sc, Ti, V, Ge, Sn, Hf, Ce, or combinations thereof. The expression "metal alkoxide" refers to "metal elements" as noted above when covalent coupled to an alkoxide. An "alkoxide" is a chemical moiety that can be represented by the formula R-0-, in which R is an organic moiety. For example, R may be an optionally substituted hydrocarbyl.

Examples of suitable metal alkoxides include tributoxyaluminium, tetraethoxysilane (TEOS), methyltriethoxysilane (MTES), tetra-isopropoxysilane, tetrabutoxytitanium, tripropoxytitanium acetoacetonate, tributoxytitanium acetate, tetrabutoxyzirconium, tripropoxyzirconium, tetraethoxytin, and combinations thereof.

Suitable hybrid polymer may be derived from organo-metal alkoxides where at least one organic group is covalently coupled through a carbon atom to the metal atom. The at least one organic group may comprise a polymerisable group. In some embodiments, the polymerisable group is an epoxy, a vinyl, or a methacryloxy moiety.

The hybrid polymer may be conveniently obtained from compositions that are commonly used in lithographic processes. These include, albeit are not limited to, ORMOSILs, ceramers, ORMOCERs, and nanomers. In some embodiments, hybrid polymers are derived from compositions comprising vinyltrimethoxysilane (VTMS), vinyltriethoxysilane (VTES), (3-glycidoxypropyl)trimethoxysilane (GPTMS), and (3-methacryloxypropyl)trimethoxysilane (MPTMS), phenyltriethoxysilane, phenyltrimethoxysilane.

Where the substrate into which the MOF particles are partially embedded is a polymer, the polymer may be cross-linked.

In some embodiments, the substrate material into which the MOF particles are partially embedded is a metal. In other embodiments, the substrate material into which the MOF particles are partially embedded is an alloy of two or more metals. Provided that the MOF particles can be partially embedded in its surface, there is no particular limitation concerning the type of metal or metal alloy from which the substrate is made. Particularly suited are malleable metals and metal alloys, i.e. metals and metal alloys that deform under compression at temperatures that are not adverse to the properties of the MOF particles.

Suitable metals for use as the substrate material include, but are not limited to, copper, lead, tin, aluminium, bismuth, chromium, cobalt, gallium, gold, indium, iron, magnesium, mercury, nickel, potassium, plutonium, rhodium, scandium, silver, sodium, titanium, uranium, zinc, and zirconium. Suitable metal alloys for use as the substrate material include, but are not limited to, alloys made of at least two of the previously listed metals, as well as AA-8000, Al-Li, alnico, duralumin, hiduminium, kryron, magnalium, nambe, cerrosafe, rose metal, wood's metal, chromium hydride, megallium, stellite, talonite, ultimet, vitallium, arsenical copper, beryllium copper, billon, brass, calamine brass, Chinese silver, Dutch metal, gilding metal, muntz metal, pinchbeck, prince's metal, and tombac.

MOFs suitable for use according to the present invention include those having at least two metal clusters coordinated by at least one organic ligand. As used herein, the expression "metal cluster" is intended to mean a chemical moiety that contains at least one atom or ion of at least one metal or metalloid. This definition embraces single atoms or ions and groups of atoms or ions that optionally include ligands or covalently bonded groups. Accordingly, the expression "metal ion" includes metal ions and metalloid ions.

Typically, suitable metal ions that form part of a MOF structure can be selected from Group 1 through 16 metals of the IUPAC Periodic Table of the Elements including actinides, and lanthanides, and combinations thereof. The metal ion may be selected from Li⁺, Na⁺, K⁺, Rb⁺, Be²⁺, Mg²⁺, Ca²⁺, Sr²⁺, Ba²⁺, Sc³⁺, Y³⁺, Ti⁴⁺, Zr⁴⁺, U V⁴⁺, V³⁺, V²⁺, Nb³⁺, Ta³⁺, Cr³⁺, Mo³⁺, W³⁺, Mn³⁺, Mn²⁺, Re³⁺, Re²⁺, Fe³⁺, Fe²⁺, Ru³⁺, Ru ⁺, Os³⁺, Os²⁺, Co³⁺, Co²⁺, Rh²⁺, Rh⁺, Ir²⁺, Ir⁺, Ni²⁺, Ni⁺, Pd²⁺, Pd⁺, Pt²⁺, Pt⁺, Cu²⁺, Cu⁺, Ag⁺, Au⁺, Zn²⁺, Cd²⁺, Hg²⁺, B³⁺, B⁵⁺, Al³⁺, Ga³⁺, In³⁺, TI³⁺, Si⁴⁺, Si²⁺, Ge⁴⁺, Ge²⁺, Sn⁴⁺, Sn²⁺, Pb⁴⁺, Pb²⁺, As⁵⁺, As³⁺, As⁺, Sb⁵⁺, Sb³⁺, Sb⁺, Bi⁵⁺, Bi³⁺, Bi⁺, and combinations thereof. In some embodiments, the organic ligands that coordinate the metal ion clusters in a MOF structure are molecules that have at least two chemical moieties capable of coordinating a metal ion. In some embodiments, these groups comprise carboxylates, phosphonates, sulphonates, N-heterocyclic groups, and combinations thereof. Organic ligands suitable for the purpose of the invention comprise ligands that are listed in WO 2010/075610 and Filipe A. Almeida Paz, Jacek Klinowski, Sergio M. F. Vilela, Joao P. C. Tome, Jose A. S. Cavaleiro, Joao Rocha, Ligand design for functional metal-organic frameworks, Chemical Society Reviews, 2012, Volume 41, pages 1088-1 1 10, the contents of which are included herein in their entirety.

Suitable metal ion coordinating ligands can be derived from oxalic acid, malonic acid, succinic acid, glutaric acid, phtalic acid, isophtalic acid, terephthalic acid, citric acid, trimesic acid, 1 ,2,3-triazole, pyrrodiazole, or squaric acid. In some embodiments, ligands are selected from 4,4',4"-[benzene-l,3,5-triyl-tris(ethyne-2,l -diyl)]tribenzoate, biphenyl- 4,4 '-dicarboxylate, 4,4',4 "-[benzene- 1 ,3 ,5 -triyl-tris(benzene-4, 1 -diyl)]tribenzoate, 1,3,5- benzenetribenzoate, 1 ,4-benzenedicarboxylate, benzene- 1,3, 5 -tris(lH-tetrazole), 1,3,5- benzenetricarboxylic acid, terephthalic acid, or mixtures thereof. It will be understood that ligands can also be functionalised ligands, for example any one of the ligands listed above may be additionally characterized by the presence of amino-, such as 2-aminoterephthalic acid, urethane-, acetamide-, or amide-. The ligand can be functionalised before being used as precursor for MOF formation, or alternatively the MOF itself can be chemically treated to functionalise its bridging ligands.

A skilled person in the art will be aware of suitable chemical protocols for functionalizing MOFs with functional groups, either by pre-functionalizing ligands used to synthesize MOFs or by post-functionalizing pre-formed MOFs.

Accordingly, suitable functional groups that may be provided on the MOFs include -NHR, -N(R)₂, -NH₂, -N0₂, -NH(aryl), halides, aryl, aralkyl, alkenyl, alkynyl, pyridyl, bipyridyl, terpyridyl, anilino, -O(alkyl), cycloalkyl, cycloalkenyl, cycloalkynyl, sulfonamido, hydroxyl, cyano, -(CO)R, -(S0₂)R, -(C0₂)R, -SH, -S(alkyl), -S0₃H, -S0^3"M⁺, -COOH, COO^"M⁺, -P0₃H₂, -P0₃H^~M⁺, -P03^2"M²⁺, -C0₂H, silyl derivatives, borane derivatives, ferrocenes and other metallocenes, where M is a metal atom, such as an alkali, transition or rare earth metal atom, and R is Ci-i₀ alkyl.

Generally, MOFs that can be used in the present invention are crystalline. A crystalline MOF is made of an ordered spatial disposition of clusters coordinated by organic linkers. Such a disposition comprises a geometrically regular network made of repeating units of cluster/ligand arrangements. A crystalline MOF generates diffraction patterns when characterized by commonly known crystallographic characterization techniques. These include, for example, X-ray powder diffraction (XPD), grazing incidence X-ray diffraction, small angle X-ray scattering (SAXS), electron diffraction, neutron diffraction and other techniques that would be known to the skilled person in the field of crystallography of materials.

MOFs may be of any known composition. In some embodiments, MOFs are selected from carboxylate-based MOFs, heterocyclic azolate-based MOFs, and metal-cyanide MOFs. Specific examples of MOFs that may be suitable for use in the present invention include those commonly known in the art as CD-MOF-1, CD-MOF-2, CD-MOF-3, CPM-13, FJI- 1, FMOF-1 , HKUST-1, IRMOF-1, IRMOF-2, IRMOF-3, IRMOF-6, IRMOF-8, IRMOF-9, IRMOF-13, IRMOF-20, JUC-48, JUC-62, MIL-101, MIL-100, MIL101, MIL-125, MIL- 53, MOF-5, MOF-74, MOF-177, MOF-210, MOF-200, MOF-205, MOF-505, MOROF-2, MOROF-1, NOTT-100, NOTT-101, NOTT-102, NOTT-103, NOTT-105, NOTT-106, NOTT-107, NOTT-109, NOTT-110, NOTT-1 1 1 , NOTT-1 12, NOTT-1 13, NOTT-1 14, NOTT-140, NU-100, rho-ZMOF, PCN-6, PCN-6', PCN9, PCN10, PCN12, PCN12', PCN14, PCN16, PCN-17, PCN-21, PCN46, PCN66, PCN68, PMOF-2(Cu), PMOF-3, SNU-5, SNU-15', SNU-21S, SNU-21H, SNU-50, SNU-77H, soc-MOF, sod-ZMOF, TUDMOF-1, UMCM-2, UMCM-150, UTSA-20, ZIF-8, ZIF-9, ZIF-20, ZIF-67, ZIF-90.

In some embodiments, MOFs are selected from mixed component MOFs, known as MC- MOFs. MC-MOFs have a structure that is characterised by more than one kind of ligand and/or metal. MC-MOFs can be obtained by using different ligands and/or metals directly in the MOF precursor solution, or by post-synthesis substitution of ligands and/or metals species of existing MOFs. Specific examples of MC-MOFs and corresponding synthesis methods can be found in A.D. Burrows, CrystEngComm 201 1, Volume 13, pages 3623- 3642, which content is included herein in its entirety.

MOF particles for the purpose of the present invention are not limited to any particular shape or dimension. In some embodiments, MOF particles can be particles having a largest dimension of between about 10 nm and about 10 mm, between about 50 nm and about 1 mm, between about 100 nm and about 500 μιη, between about 500 nm and about 500 μπι, between about 750 nm and about 250 μπι, between about 1 μηι and 250 μη , between about 5 μιη and 200 μηι, between about 10 μηι and 200 μηι, between about 10 μηι and 150 μπι, or between about 10 μπι and 100 μηι.

A substrate according to the present invention can be used as a component in a device that performs tasks based on physical and/or chemical interactions between that component and a target compound. Such devices include, although they are not limited to, sensors (such as chemical sensors including biosensors), biological assays, and devices used in the conversion of a first compound into a second compound, for example a catalytic converter.

Accordingly, the present invention also provides a sensor, for example a chemical sensor, that comprises a substrate as described herein. That is, the invention provides a sensor comprising a substrate having particles of MOF fixed thereto, said particles being partially embedded into a surface of the substrate.

A particular class of device in which a substrate of the invention can be also used is that of miniaturized devices in the field of, for example, biomedics and biology (e.g. micro- bioreactors, micro total analysis systems, micro-biological assays etc.). Such devices require the spatial control of materials with active chemical and/or biological functionalities at a small scale. Since MOFs with different functional properties can be confined to precise locations according to this invention this attribute is thus well suited to their application as components for miniaturized sensing, catalytic, and biomedical devices.

The porosity characteristics and the possibility to customize their chemical structure make MOFs ideal candidates for use in chemical sensors. The possibility to efficiently concentrate target molecules at higher levels than are present in the external atmosphere makes MOFs suitable materials for detection of chemical compounds, and particularly for trace compounds in liquid or gaseous mixtures (i.e. being present in concentration ranging from units of ppb to units of ppm). Also, the narrow size distribution of their pores, as well as the possibility to tailor the chemical nature of the pore walls make MOFs inherently adapt to enhance the selectivity of the sensor (by acting as a molecular sieve) as well as its sensitivity (by increasing the number of active sites for interaction with the target compound). Further, high molecular diffusivity of both gaseous and liquid species through the porosity network of MOFs would contribute to fast detection rate of the sensor.

As used herein a "sensor" is a device that converts a physical or a chemical quantity, or a change thereof, into a signal which can be read by a user, typically through an instrument in the form of an analytical signal.

Accordingly, a "chemical sensor" is intended as a device having a component that undergo a change of one or more of its physical/chemical properties upon a chemical interaction with the target compound. Examples of such interaction are a chemical reaction or the chemi-sorption of the target compound onto a surface of the component. The a change of the physical/chemical property of the component can be observed and measured by a user, typically through an instrument as an analytical signal. Advantageously, a substrate of the present invention can be used as such component in a chemical sensor.

The physical/chemical property of the substrate of the invention which changes upon contact with the target compound may be, but is not limited to, optical emission, optical absorbance, refractive index, electric conductivity, electric resistance, temperature, or mass. The change of the physical/chemical property of the substrate may generate from the mere physical adsorption of the target compound on a surface of the MOF particles, as well as from a chemical reaction involving the target compound and that is promoted by the MOF particles.

Such chemical reaction may also result in the formation of product compounds that are more readily identifiable by a user than the target compound.

Target compounds that are detectable with a sensor of the invention comprise compounds in liquid and gaseous form. Typically such compounds are contained in a liquid solution or a gaseous mixture. The sensor would have means to accommodate either a liquid or a gaseous stream so that the mixture contacts the MOF particles located on the substrate within the sensor. A skilled person will be aware of effective sensor configurations for the effective detection of the target compound either in liquid or gaseous form.

Specific sensing mechanisms of MOF-based sensors are described in Lauren E. Kreno et al. Meta Organic Framework Materials as Chemical Sensors, Chemical Reviews, 2012, 1 12, 1 105-1125, which content is incorporated herein in its entirety.

All types of MOFs described herein may be suitable for use in a sensor according to the invention. These include those commonly known in the art as CD-MOF-1 , CD-MOF-2, CD-MOF-3, CPM-13, FJI-1 , FMOF-1, HKUST-1, IRMOF-1, IRMOF-2, IRMOF-3, IRMOF-6, IRMOF-8, IRMOF-9, IRMOF-13, IRMOF-20, JUC-48, JUC-62, MIL-101, MIL- 100, MIL 101, MIL-125, MIL-53, MOF-5, MOF-74, MOF-177, MOF-210, MOF-200, MOF-205, MOF-505, MOROF-2, MOROF-1, NOTT-100, NOTT-101, NOTT-102, NOTT-103, NOTT-105, NOTT-106, NOTT-107, NOTT-109, NOTT-1 10, NOTT-1 1 1, NOTT-1 12, NOTT-1 13, NOTT-1 14, NOTT-140, NU-100, rho-ZMOF, PCN-6, PCN-6', PCN9, PCN10, PCN12, PCN12', PCN14, PCN16, PCN-17, PCN-21, PCN46, PCN66, PCN68, PMOF-2(Cu), PMOF-3, SNU-5, SNU-15', SNU-21 S, SNU-21H, SNU-50, SNU- 77H, soc-MOF, sod-ZMOF, TUDMOF-1, UMCM-2, UMCM-150, UTSA-20, ZIF-8, ZIF- 9, ZIF-20, ZIF-67, ZIF-90, or mixed component MOFs (MC-MOFs).

Also suitable for use in a sensor according to the invention are MOFs functionalized with -NHR, -N(R)₂, -NH₂, -N0₂, -NH(aryl), halides, aryl, aralkyl, alkenyl, alkynyl, pyridyl, bipyridyl, terpyridyl, anilino, -O(alkyl), cycloalkyl, cycloalkenyl, cycloalkynyl, sulfonamido, hydroxyl, cyano, -(CO)R, -(S0₂)R, -(C0₂)R, -SH, -S(alkyl), -S0₃H, -S0^3~M⁺, -COOH, COO^~M⁺, -P0₃H₂, -P0₃H^"M⁺, -P03^2"M²⁺, -C0₂H, silyl derivatives, borane derivatives, ferrocenes and other metallocenes. In the chemical formulas listed above, M is a metal atom, such as an alkali, transition or rare earth metal atom, and R is Ci-io alkyl.

A further advantage correlated to the use of a substrate according to the invention in a sensing device is the possibility to miniaturize the actual device, particularly if the substrate is in the form of a lithographed nano- or micro-feature of the kind described herein.

Chemical sensors within the meaning given herein include biosensors, which are a particular class of chemical sensors in which the source of the analytical signal that can be observed and measured by a user is a biochemical process. Typically such process involves a biologically derived material (hereinafter a 'biomaterial') capable of selectively interacting with the target compound. The target compound itself may be a bio-material.

Examples of bio-materials useful for the purpose of the invention include, but are not limited to, living organisms, tissues, cells, organelles, membranes, as well as bio-molecules such as proteins (including enzymes and antibodies), polysaccharides, lipids, nucleic acids including DNA (deoxyribonucleic acid) and RNA (ribonucleic acid), primary metabolites, and secondary metabolites.

Accordingly, the present invention also provides a biosensor comprising a substrate as described herein. That is, the invention provides a biosensor comprising a substrate having particles of MOF fixed thereto, said particles being partially embedded into a surface of the substrate.

In some embodiments, the particles comprise a bio-material.

In other embodiments, the bio-material is located inside the pores of the MOF particles.

In some embodiments, the bio-material is grafted on a surface of the partially embedded MOF particles, for example on an external surface of the particles. In this configuration it has been observed that the specific interaction between the bio-material and the target compound is advantageously enhanced compared to what is observed using systems in which the same bio-molecules are grafted on a flat surface of a support, e.g. a silicon wafer or a glass slide, according to traditional bio-functionalisation protocols. Experimental data in this sense is reported in Example 5, with reference also to Figures 9 and 10.

In some embodiments, where the substrate of the invention is used in a biosensor, the substrate material into which the MOF particles are partially embedded can be in the form of a lithographed nano- and/or micro- feature of the kind described herein.

When the substrate material into which the MOF particles are partially embedded is in the form of a plurality of lithographed nano- and/or micro- features of the kind described herein and a bio-material is grafted on a surface of the partially embedded MOF particles, the substrate according to the invention can form part of a biological assay kit or be used to perform biological assays.

Advantageously, when the bio-material is grafted on an external surface of the MOF particles the interaction between the bio-material and the target compound is enhanced compared to traditional bio-essays obtained by grafting the bio-material on the surface of a flat support like a silicon wafer or a glass slide (see Example 5 and Figures 9 and 10). Devices that catalyze the conversion of a first compound into a second compound can also be produced using a substrate according to the invention. Such devices would have means to accommodate a fluid mixture comprising a first compound. The fluid mixture would contact the substrate provided in the device such that the first compound would adsorb on a surface of the MOF particles, thereby being converted into a second compound.

In some embodiments, the MOF particles used for this purpose are functionalised with at least one functional group of the ones listed above. Such functional groups will be of a type that promote catalytic conversion of the first compound into the second compound. In some embodiments, the MOF particles are functionalised with metals including palladium, platinum, gold, ruthenium, rhodium, osmium, nickel or iridium, iron cobalt, copper and silver, and/or metal oxides including transition metal oxides, alkali metal oxides and rare earth metal oxides.

The method of the present invention comprises providing MOF particles between two surfaces, at least one of which is a surface of the substrate. For convenience, the surface other than the surface of the substrate may herein be referred to as the "complementary surface". Such a complementary surface is not limited to a particular configuration or material. In some instances, the complementary surface may be the surface of a material made of metal, an alloy, a semiconductor, for example silicon, or polymer. In some embodiments, the complementary surface is a surface of a material that is made of the same material as the substrate. In that case, the method of the invention may result in MOF particles being fixed onto both the surface of the substrate and the complementary surface by being partially embedded into those surfaces.

The MOF particles may be provided between a surface of the substrate and a complementary surface by first depositing MOF particles on the surface of the substrate, followed by positioning the complementary surface on the deposited particles. Alternatively, MOF particles may be first positioned on the complementary surface, followed by positioning a surface of the substrate on the deposited particles. Once MOF particles are provided between the two surfaces, the particles are compressed with the surfaces. This compression can be achieved by allowing the two surfaces to press against each other along a direction that is generally perpendicular to the two opposing surfaces. In the context of the invention, the term "compression" (and grammatical variations thereof) is therefore used to describe the practical effect of any force being applied to MOF particles in contact with a surface of a substrate that causes partial embedding the particles into the surface of the substrate.

The force that is applied to promote the compression may solely be a gravitational force, or it can include an "applied" mechanical or pressure force.

The two surfaces can be pressed against each other by any suitable means. For example, the two surfaces may be pressed against each other along a direction that is generally perpendicular to the two surfaces, such that the distance between the opposing surfaces tends to reduce.

In some embodiments, the two surfaces lie on a horizontal plane, with the complementary surface lying on top of the MOF particles. In these cases, MOF compression may be achieved either by virtue of the force of gravity acting on the material providing for that complementary surface, or by virtue of a vertical non-gravitational force that is applied to that body in a downward direction. Such vertical non-gravitational force may be applied by any means that would be known to a skilled person.

Alternatively, the two surfaces may still lie on a horizontal plane, but with a surface of the substrate lying on top of the MOF particles. In that case, MOF compression may be achieved by virtue of the force of gravity acting on the substrate, or by virtue of a vertical non-gravitational force that is applied to the substrate in a downward direction. Such vertical non-gravitational force may be applied by any means that would be known to a skilled person. It will be understood that the force applied to promote compression of the MOF may be applied directly to the substrate, for example when the substrate is in the form of a monolith, or applied to a support on which the substrate is attached, for example when the substrate is in the form of a film/layer deposited on a support.

In some other embodiments, a first force is applied to the substrate and a second force is contemporaneously applied to the complementary surface. In such embodiments, the two forces are co-axial and opposite to one another, and may be of the same or different intensity.

The force applied to one or both of the two surfaces that promotes the compression and results in the MOF particles being partially embedded into a surface of the substrate will typically provide for a pressure between the two surfaces of at least about 0.01 g/cm , at

2 2 2

least about 0.02 g/cm , at least about 0.05 g/cm , at least about 0.1 g/cm , at least about 0.2 g/cm², at least about 0.5 g/cm², at least about 1 g/cm², at least about 5 g/cm², at least about 10 g/cm², at least about 15 g/cm², at least about 20 g/cm², at least about 30 g/cm², at least about 40 g/cm², at least about 50 g/cm², at least about 60 g/cm², at least about 70 g/cm², at

9 9

least about 80 g/cm , at least about 90 g/cm , at least about 100 g/cm , at least about 150 g/cm², at least about 300 g/cm², at least about 500 g cm², or at least about 1000 g/cm², but in any event not exceeding about 1000 g/cm².

The intensity of any force used to promote the compression will typically depend on the chemical and physical nature of the material forming the surface of the substrate into which MOF particles are to be partially embedded and/or or the nature of the MOF that is to be partially embedded . In general, the substrate will locally deform to accommodate MOF particles within its volume during the compression step, such that the particles will become partially embedded into the surface of the substrate once the compression ceases.

In one embodiment, local deformation of the substrate to accommodate the MOF is facilitated by providing heat to the substrate. The heat may be applied before and/or during compression so that the substrate material softens and can be penetrated by the MOF particles. This can be achieved by heating the substrate by any suitable means. The appropriate softening temperature will generally depend on the chemical and physical nature of the substrate material.

Where the substrate material is a thermoplastic polymer, a convenient reference point for the temperature at which the polymer will soften is the glass transition temperature (Tg) of the polymer. A skilled person will be able to identify the appropriate temperature range around the Tg of the polymer that will promote softening of the polymer.

As used herein, the term "Tg" is a reference to the glass transition temperature of a polymer that is measured using Differential Scanning Calorimetry (DSC) according to the procedure set out in the ASTM D7426-2008 "Standard Test Method for Assignment of the DSC Procedure for Determining Tg of a Polymer or an Elastomeric Compound".

When the substrate material is metal or metal alloy, a skilled person will be aware of the amount of heat required and the mode of administering heat to the substrate in order to perform the method of the invention.

In an embodiment, heat is provided to the substrate before and/or while compressing the MOF particles.

In a further embodiment, local deformation of the substrate to embed the MOF is facilitated by exposing the substrate to solvent. The solvent can be any substance that is capable of penetrating into the substrate and cause a reduction in hardness (i.e. to soften) of the substrate (or exposed part thereof). For this embodiment, the substrate material will typically be a polymer. For the purposes of the invention, the substrate can be softened by exposing it to the solvent, which includes exposing the substrate to liquid solvent or solvent vapors. The degree of softening required will be sufficient to allow for the MOF particles to penetrate into a surface of the substrate when compressed. A skilled person will be able to identify effective procedures and suitable values of the relevant parameters involved in softening the substrate material by exposure to solvent. This includes, for example, determining the type and amount of solvent that should be employed, and the contact time between the solvent and the substrate that would be appropriate, to soften the substrate for the purpose of the invention.

Suitable solvents for the purpose of softening a substrate used in the present invention include acetone, acetonitrile, amyl acetate, aniline, benzene, biphenyl ether, butyl acetate, butyl alcohol, butyl butyrate, carbon disulfide, carbon tetrachloride, chlorobenzene, chloroform, chlorophenol, cresol, cyclohexanol, diamyl ether, diamyl phthalate, dibenzyl ether, dibutyl phthalate, dibutyl sebacate, 1 ,2-dichlorobenzene, dichloromethane, diethyl carbonate, di(ethylene glycol), di(ethylene glycol) monobutyl ether, di(ethylene glycol) monoethyl ether, diethyl ether, diethyl ketone, diethyl phthalate, di-n-hexyl phthalate, diisodecyl phthalate, diisopropyl ether, Ν,Ν-dimethylacetamide, dimethyl ether, Ν,Ν-dimethylformamide, dimethyl phthalate, dimethylsiloxanes, dimethyl sulfoxide, dioctyl adipate, dioctyl phthalate, dioctyl sebacate, 1,4-dioxane, di(propylene glycol), di(propylene glycol) monomethyl ether, dipropyl phthalate, ethanol, ethyl acetate, ethyl amyl ketone, ethyl metyl ketone, ethyl n-butyrate, ethylene carbonate, ethylene dichloride, ethylene glycol, ethylene glycol diacetate, ethylene glycol diethyl ether, ethylene glycol dimethyl ether, ethylene glycol monobutyl ether, ethylene glycol monoethyl ether, furfuryl alcohol, glycerol, heptane, hexane, isooctane, isopropyl alcohol, n-propanol, n-butanol, isopropyl amine, methanol, methyl amyl ketone, methylene chloride, methyl ethyl ketone, methyl isobutyl ketone, pentane, phenyl ether, propyl acetate, 1,2-propylenecarbonate, propylene glycol, propylene glycol methyl ether, pyridine, richloroacetaldeide, tetrachloro benzene, 1 ,1,2,2-tetrachloroethane, tetrachloroethylene (perchloroethylene), tetrahydrofuran, toluene, xylene, o-xylene, water or any combinations thereof.

In another embodiment, the substrate is exposed to solvent before and/or while compressing the MOF particles. The solvent may be liquid solvent or solvent vapors.

In an additional embodiment, the substrate is in the form of a coating that is provided on a support as described herein. The coating may be an adhesive, which comprises a polymer or a pre-polymer. For example, the coating may comprise a polymer or a pre-polymer dispersed in a solvent.

The surfaces can be pressed against each other for any length of time that a skilled person may consider appropriate, provided that when a surface of the substrate and the complementary surface are eventually separated the so compressed MOF particles are partially embedded into a surface of a substrate. In some embodiments, the compression can be applied for at least about 1 second, for at least about 30 seconds, for at least about 1 minute, for at least about 5 minutes, for at least about 10 minutes, for at least about 15 minutes, for at least about 30 minutes, for at least about 1 hour, or for at least about 2 hours. In any event, the compression is not applied for more than 5 hours.

In some embodiments, the substrate into which the MOF particles are partially embedded is in the form of a micro- and/or nano- feature that is attached to a support. The micro- and/or nano-feature is not limited to any particular shape or dimension, provided that at least one of its dimension is at least 10 nm and less than about 50 run, less than about 75 nm, less than about 100 nm, less than about 150 nm, less than about 250 nm, less than about 500 nm, less than about 750 nm, less than about 1 μπι, less than about 5 μιη, less than about 10 μηι, less than about 25 μηι, less than about 50 μηι, less than about 75 μπι, less than about 100 μπι, less than about 150 μηι, less than about 200 μηι, less than about 500 μηι, or less than about 1 mm.

Where the substrate material into which the MOF particles are partially embedded has micro- and/or nano- features, such features may be obtained by conventionally known photo-lithographic techniques. In a photo-lithographic process a support, for example a silicon wafer, is coated with a layer of a photo-resist composition. The coated support is then exposed to a radiation beam through a mask, which is positioned between the radiation source and the coated support. The coating would be facing the radiation source. The radiation source can be an electron source, a photon source, or an ion source. The mask comprises areas that are transparent to the radiation beam, and other areas that are not transparent to the radiation beam. The shape of the transparent areas can be any shape, provided that at least one dimension of said shapes is in the μηι or sub-μπι size range. As a result, regions of the resist coating having the same shape of the transparent areas of the mask would be directly exposed to the radiation beam. Photo-chemical reactions change the chemical and physical properties of the exposed regions of the photo-resist. These changes of chemical properties result in a differential solubility of the exposed/unexposed regions to certain solvents. The more soluble regions of the photo-resist can eventually be removed using an appropriate solvent, thus leaving only the less soluble regions attached to the support. These regions are in the form of micro- and/or nano- features attached to the support.

Suitable photo-lithographic techniques for the purpose of producing a substrate material that can be used according to the invention comprise, albeit are not limited to, deep-UV lithography, UV lithography, soft X-ray lithography, hard X-ray lithography, deep X-ray lithography, electron-beam lithography, ion-beam lithography, laser-lithography, interference lithography, and laser lithography.

The micro- and/or nano- features can also be obtained by soft-lithography. This kind of lithography includes techniques that do not involve the use of a radiation source, and comprise, for example, mechanical patterning using a mold (also called template) that shapes the photo-resist layer into micro- and/or nano- features. In soft-lithography, an elastomeric stamp with patterned relief structures on its surface is used to generate patterns and structures with feature sizes ranging from 20 nm to 100 μπ . The elastomeric stamp can be a silicone-based or a silicone derivative stamp such as a poly(dimethylsiloxance) (PDMS) stamp. Soft-lithography techniques comprise microcontact printing (CP), replica molding (REM), micro-transfer molding (TM), micro-molding in capillaries (MIMIC), and solvent-assisted micromolding (SAMIM).

To assist with describing certain features of the invention, reference is made to Figure 1 which shows a schematic representation of an embodiment of the method of the present invention. In a), MOF particles (1) are provided on a complementary surface (2). A surface of a substrate material (3) is then positioned above the layer of MOF particles. In this embodiment, the substrate material (3) is a polymer having a plurality of micro- and/or nano-features that is anchored to a support (4). These features can be obtained by lithography. In b), a surface of the substrate material (3) is then placed in contact with the MOF particles that are layered on the complementary surface (2), and a force (5) perpendicular to the surface of the support (4) is applied on the support (4), so as to compress the particles that are located between the opposing surfaces. Upon compression, MOF particles penetrate into the surface of the substrate material (3) and become partially embedded into it. MOF particles that are not in contact with the substrate material (3) remain merely deposited on the complementary surface (2). After a suitable time, with reference to c), the substrate material (3) is lifted from the complementary surface (2) resulting in removal of the force (5). As a result of the compression, a layer of MOF particles become fixed to a surface of the substrate material (3) by being partially embedded into it. The end product of this embodiment is depicted in d), which shows MOF particles fixed on a surface of the substrate material (3). Excess MOF particles, i.e. particles that did not penetrate into the surface of the substrate, can be removed by a washing procedure, as described in Example 2 below. The Example also shows that the washing procedure does not remove MOF particles that are partially embedded into, and fixed to, the substrate.

Embodiment of the invention will be described by way of the following non-limiting Example.

EXAMPLES

EXAMPLE 1

MOF Preparation: NH₂-MIL-53(A1) MOF was prepared according to a procedure described in S. Couck et al, Journal of the American Chemical Society, 2009, Volume 131, pages 6326-6327. A solution of 2.10 mmol aluminium nitrate nonahydrate in 15 mL dimethylformamide (DMF) and a solution of 3.12 mmol 2-aminoterephthalic acid in 15 mL DMF were mixed together in a Teflon lined autoclave and heated to 130 °C for 3 days. The resulting yellow gel was filtered and washed with acetone, dried under vacuum and rewashed with a methanol reflux overnight. The final product was dried under vacuum at 1 10 °C for 8 h, to obtain a MOF particulate.

UV Lithography: SU-8 was used as the photo-resist. SU-8 micro-features were prepared on a silicon wafer support by UV lithography according to a method described in P. Falcaro et al. Journal of Materials Chemistry C, 2013, DOI: 10.1039/c2tc00241h. MicroChem SU-8 2050 solution was spin-coated onto the pre-cleaned silicon wafer at 3000 rpm for 30 seconds prior to soft-baking at 65 °C for 3 minutes and 95 °C for 9 minutes. The substrate was then exposed to UV light at 200mJ/cm using a mask, followed by post-heating at 65 °C for 2 minutes and 95 °C for 7 minutes. The photo-resist was immersed in SU-8 developer for 6 minutes, rinsed with isopropyl alcohol and Milli-Q water then dried under a N₂ flow. The SU-8 pattern was made to a thickness of 25 μιη.

MOF Patterning/Imprinting: the MOF particles were fixed on a surface of the SU-8 structures by pressing the lithographed substrate onto layers of MOF crystals. The MOF particles were first suspended in methanol, and the suspension was drop-casted onto cleaned silicon wafers. The methanol was then evaporated at room conditions to allow for the MOF particles to deposit in form of a layer. The SU-8 patterned substrate was initially heated to 95 °C (above the SU-8 glass transition) to soften the photoresist and was then placed on top of the MOF particle layer. A 2kg weight was applied (-0.5 kg/cm ) for approximately 5 minutes to induce embossing and partial inclusion of the crystals into the softened SU-8. The resulting films were then cooled and ready for characterisation.

Characterisation: XRD was performed on the patterned MOF films to ensure that the MOFs retained their crystallinity after the imprinting process. The XRD patterns illustrated in Figure 4 show that the MOF particles maintained their crystallinity through the compression step.

Scanning electron microscope images (SEM) were taken on a Philips XL30 Field Emission Scanning Electron Microscope (FESEM) equipped with an Energy Dispersive X-ray detector (EDS, Oxford Instruments). The samples were coated with gold prior to measurement. Imaging was performed at 5 keV, and images of the samples that have been obtained are shown in Figures 2 and 3.

EDS measurements were taken at 10 keV over 2 hours, on the portion of sample that is depicted in the SEM and back-scattering SEM of, respectively, Figure 5(a) and 5(b). EDS atomic mappings are reported in Figure 5 (c-f), which shows spatially localised emissions of (c) oxygen, (d) carbon, (e) aluminium and (f) silicon species. Emissions shown in (c-e) identify the MOF particles, while (f) is generated by the silicon species of the support wafer.

Fourier transform infrared (FTIR) spectroscopy mapping was performed in reflection mode on the Perkin Elmer Spectrum Two Infrared Microscope. Figure 5(g) shows an optical microscope image of the sampled area. Figure 5(h) shows the integrated IR absorption signal recorded at wavenumber 3670 cm^"1, which is representative of the v(OH) vibration band of hydroxyl groups belonging to the trans-corner sharing octrahedra A10₄(OH)₂ in the MOF structure. Figure 5(i) shows the integrated IR absorption signal recorded at wavenumber 3490 cm^"1, representative of the asymmetric stretching vibration of N-H bonds of the primary amines located in the bridging ligands of the MOF structure.

EXAMPLE 2

Any excess of MOF particles that do not penetrate into the substrate following the compression procedure can be easily removed via washing cycles. To demonstrate the stability of the partially embedded MOFs, in this example, partially embedded particles of NH₂-MIL-53(A1) MOF obtained according to the procedure described in Example 1 was characterized after several washing cycles using FITR. The results show that after 10 cycles only a weak loss of MOF particles is detected (Figure 6), while almost no degradation of signal (and hence stability) is observed after thorough washing for 50 cycles, hence emphasizing the durability of the pattered MOF films. EXAMPLE 3

NH₂-MIL-53(A1) MOF was impregnated with Palladium (Pd) according to the below techniques.

Palladium absorption and reduction using loose MOF particles.

A 75 mM solution of H₂PdCl₄ was prepared by mixing PdCl₂ (200 mg, 1.13 mmol) in 12.4 mM aqueous HC1 (15 mL). NH₂-MIL-53(A1) (50 mg) were dispersed in water (4 mL) at pH 4 and H₂PdCl₄ solution were added (1.5mL, H₂PdCl₄ final concentration: 20 mM). After 8 hrs of mixing, the powder was washed with water and methanol by centrifugation and dispersed in water (1 mL). For the reduction, a solution of NaBH₄ (50 mM, 1 mL) was added. The powder became dark after few seconds and was mixed for a further 3 hours, then washed as above and dried at room temperature

Palladium absorption and reduction using MOF particles partially embedded into an SU-8 substrate.

A substrate made of SU-8 and having MOF particles partially embedded therein obtained according to a procedure described in Example 1 was immersed in H₂PdCl₄ solution (5.5 mL) and kept for three hours at room temperature. The substrate was removed and washed by immersion in water and methanol (25 times each), then dried at room temperature.

Subsequently, the substrate was immersed in water (4 mL) and an aqueous NaBH₄ solution (50 mM, 1 mL) was added in small portions (10 aliquots, 100 microliters each; final concentration: 10 mM). The film became dark after the first 30 seconds, and the reduction was continued for 10 minutes. Then the film was again washed in water and methanol as above and dried at room temperature.

The amount of metal ions collected by the partially embedded MOFs corresponds to the amount collected by the same quantity of MOF in the powder state. Figure 7 shows the X-ray analysis performed on NH₂-MIL-53(A1) MOF as a powder (orange spectra) and NH₂-MIL-53(A1) MOF partially embedded in SU-8 (green spectra) and indicates that in both cases Palladium infiltrates the MOF to the same extent. The ratio between the intensity of the signal associated with the MOF particles and the intensity of the signal associated to the infiltrated Pd is 7.33 for the loose MOF particles and 7.26 for the MOF particles partially embedded into SU-8. The values confirm that the partially embedded MOFs have open access for further impregnation/functionalization processes. The inset in Figure 7 represents the SAXS diffraction pattern which confirms that the MOF network is still crystalline after the Pd functionalization.

EXAMPLE 4

Kinetic measurements of the uptake of 1 ,2-Benzanthracene by MOF particles partially embedded into SU-8

A second method confirming the accessibility of the pores of MOF particles partially embedded into SU-8 was illustrated by monitoring the fluorescence kinetics due to the uptake of an polycyclic aromatic hydrocarbon (1,2-benzanthracene).

The experiment was performed by taking a 0.7 mm2 silicon wafer with SU-8, having MIL- 53(A1) MOF (0.5 mg) partially embedded within and placing it on the bottom of a quartz cuvette. A tetrahydrofuran (THF) solution containing 1 ,2-benzanthracene (0.05 mM, 2000 μΐ,) was carefully poured on top. The benzanthracene absorption kinetics were followed using a Varian Cary Eclipse spectrofluorimeter, with an excitation wavelength at 347 nm, collecting the emission signal at 387 nm. The same experiment was performed using an analogous amount of MOF dispersed in the solution, and on a similar SU-8 wafer without any MOF.

The plots of Figure 8 show that samples with partially embedded MOF particles sequester around 8% of the benzanthracene from the solution, compared to 10% sequestered by loose MOF particles. The plots further highlight that the partially embedded MOF particles retained their porosity through the compression process, and allow excluding any significant contribution by the SU-8. Loose MOF particles have a slightly better uptake capability due to the total accessibility of the nanocrystals to the benzanthracene solution.

EXAMPLE 5

This Example describes the use of NH₂-MIL-53(A1) MOF particles as a substrate for the bio-grafting of an enzyme (β-Glucosidase). Here the inventors show that enzymes can be efficiently grafted onto MOFs that have been partially embedded or imprinted at defined positions on a chip.

The two substrates were bioconjugated using a protocol based on glutaraldehyde and a standard washing procedure was used to remove residual enzymes (non-grafted biomolecules). The procedure was performed as previously reported (C. M. Doherty, Y. Gao, B. Marmiroli, H. Amenitsch, F. Lisi, L. Malfatti, K. Okada, M. Takahashi, A. J. Hill, P. Innocenzi, P. Falcaro, J. Mater. Chem. 2012, 22, 16191) using a reference surface with amino groups on silicon wafers and the test surface of NH₂-MIL-53(A1) MOF crystals imprinted on SU-8. A phosphate buffer (100 mM) containing Triton X-100 (0.1% v/v) was used for the experiment. Substrates were covered for 2 hours with buffer (2 mL) containing glutaraldehyde (1% w/v). After washing with the buffer 10 times (2 mL each), they were covered again with buffer (4 mL) containing β-Glucosidase enzyme (35 μg mL^-1), and left to react for 3 hours. Subsequently, another washing cycle was performed (4 washes) and the surfaces used for the glucose assay.

Enzymatic activity assay. The surfaces were covered with D-(-)-Salicin solution (1% w/v in buffer acetate, 4 mL, pH 5.0, 37 °C, 10 minutes). The glucose released from the hydrolysis was detected using the Harding-Folin-Wu colorimetric method with phosphomolybdic acid, measuring the glucose concentration with a standard calibration curve.

Figure 9 shows a schematic of the β-Glucosidase enzymes grafting procedure and subsequent reaction with D-(-)-Salicin. The scheme applies to both the sample made of amino functionalized MOF particles partially embedded on SU-8 and the sample made of amino functionalized silicon wafers.

The amount of glucose produced by the reaction was measured using the Folin-Wu test. The bio-processing capability of the NH₂-MIL-53(Al) MOF/SU-8 substrate was compared with a standard amino-functionalized surface.

The results are shown in Figure 10. The enzyme efficiency of D-(-)-Salicin hydrolysis to glucose has been calculated as 0.003 μηιοΐ of glucose min for every cm for the amino- modified silicon wafer (reference surface) and 0.157 μπιοΐ cm min for MOF crystals on the SU-8 patterned film. This MOFs film presents a superior bio-processing device with approximately a 50 fold increase in response when compared to the standard amino functionalized flat substrate.

EXAMPLE 6

To demonstrate partially embedded MOF particles within the substrate, a uniform Cu(btc) MOF powder film on a glass substrate as described previously was prepared. A substrate made of polystyrene was initially softened by pouring toluene over the top surface for 5 seconds. After waiting 60 seconds, the swollen polystyrene top surface was pressed onto the prepared Cu(btc) MOF powder film, lifted and left at room temperature for the toluene solvent to completely evaporate and the softened polystyrene surface to re-harden.

Figure 1 1 shows SEM images of a cross section of the partially embedded MOF particles at different magnifications. Figures 1 la-c show a uniform layer of MOF particles on top of the polystyrene layer. Figure l id shows a magnified image of MOF particles partially embedded within the polystyrene layer. As seen in figure 1 1, the MOF particles maintain their regular geometrical shape and are partially embedded in the polymer/resist.

Figure 12 shows the SEM and the Energy Dispersive X-ray (EDX) measurements of the resulting interface. Figure 12a shows the cross-section of the polystyrene and the partially embedded Cu(btc) MOF particles. The EDX analysis (12b-c) show the presence of the polystyrene (carbon), the background (aluminium) and the MOF (copper). The copper map shows a gradient where the copper is densest in the top 2μπι of the coating and quickly diminishes through the thickness of the polystyrene substrate. This confirms that the MOF particles are partially embedded within the substrate using the pressing technique. This also highlights the use of this technique using a polymer substrate to embed MOF particles and employing a solvent for the softening mechanism.

Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.

Claims

1. A substrate having particles of Metal Organic Framework (MOF) fixed thereto, said particles being partially embedded into a surface of the substrate.

2. The substrate according to claim 1, wherein the particles of MOF comprise one or more functional group selected from -NHR, -N(R)₂, -NH₂, -N0₂, -NH(aryl), halides, aryl, aralkyl, alkenyl, alkynyl, pyridyl, bipyridyl, terpyridyl, anilino, -O(alkyl), cycloalkyl, cycloalkenyl, cycloalkynyl, sulfonamido, hydroxyl, cyano, -(CO)R, -(S0₂)R, -(C0₂)R, -SH, -S(alkyl), -S0₃H, -S0^3"M⁺, -COOH, C00^"M⁺, -P0₃H₂, -P0₃H^"M⁺, -P03^2"M²⁺, -C0₂H, silyl derivative, borane derivative, metallocene, wherein M is a metal atom, and R is Ci-io alkyl.

3. The substrate according to any one of the preceding claims, wherein the substrate having the particles of MOF fixed thereto is made of polymer.

4. The substrate according to claim 3, wherein the polymer is derived from a photoresist composition comprising poly(methyl methacrylate), poly(methyl glutarimide), phenol formaldehyde resin, epoxy-resin, or combinations thereof.

5. The substrate according to any one of the preceding claims provided on a support.

6. The substrate according to any one of the preceding claims, wherein the substrate having the particles of MOF fixed thereto is in the form of a plurality of nano- and/or micro-features.

7. A method of fixing particles of Metal Organic Framework (MOF) to a substrate, said method comprising:

locating the particles between two surfaces, at least one of which is a surface of the substrate to which the particles are to be fixed, and compressing the particles with the two surfaces such that particles in contact with the surface of the substrate become partially embedded therein and consequently fixed to the substrate.

8. The method according to claim 7, wherein the particles of MOF comprise one or more functional group selected from -NHR, -N(R)₂, -NH₂, -N0₂, -NH(aryl), halides, aryl, aralkyl, alkenyl, alkynyl, pyridyl, bipyridyl, terpyridyl, anilino, -O(alkyl), cycloalkyl, cycloalkenyl, cycloalkynyl, sulfonamido, hydroxyl, cyano, -(CO)R, -(S0₂)R, -(C0₂)R, -SH, -S(alkyl), -S0₃H, -S0³ M⁺, -COOH, COO M⁺, -P0₃H₂, -P0₃H M⁺, -P03² M²⁺, -C0₂H, silyl derivative, borane derivative, metallocene, wherein M is a metal atom, and R is Ci-io alkyl.

9. The method according to claim 7 or 8 further comprising providing heat to the substrate to which the particles are to be fixed to facilitate the particles of MOF becoming become partially embedded therein.

10. The method according to any one of claims 7 to 9 further comprising exposing the substrate to which the particles are to be fixed to a solvent to facilitate the particles of MOF becoming become partially embedded therein.

11. The method according to any one of claims 7 to 10, wherein the substrate to which the particles are to be fixed is derived from a photo-resist compositions comprising poly(methyl methacrylate), poly(methyl glutarimide), phenol formaldehyde resin, epoxy- resin, or combinations thereof.

12. The method according to any one of claims 7 to 1 1, wherein the substrate to which the particles are to be fixed is in the form of a plurality of nano- and/or micro-features.

13. The method according to claim 12, wherein the nano and/or micro-features are obtained by a photo-lithographic technique.

14. Use of a substrate according to any one of claims 1 to 6 in a sensor.

15. A sensor comprising a substrate according to any one of claims 1 to 6.

16. The sensor according to claim 15 in the form of a chemical sensor.

17. The sensor according to claim 15 in the form of a biosensor.

18. The sensor according to claim 17, wherein an enzyme is grafted to an external surface of one or more of the MOF particles.