WO1997022410A1

WO1997022410A1 - Imprinted materials

Info

Publication number: WO1997022410A1
Application number: PCT/GB1996/003136
Authority: WO
Inventors: Mark Philip Byfield
Original assignee: Gec-Marconi Limited
Priority date: 1995-12-20
Filing date: 1996-12-18
Publication date: 1997-06-26
Also published as: EP0956156A1; GB2308369B; GB9602009D0; GB2308369A

Abstract

The present invention relates to an imprinted material, to a method suitable for use in the preparation of an imprinted material, to a sensor, to a test-kit and to methods of using an imprinted material. The invention provides, inter alia, an imprinted material, which imprinted material is suitable for permitting selective association of relatively small species with the said imprinted material. The invention also provides, inter alia, a method suitable for use in the preparation of an imprinted material, which imprinted material is suitable for permitting selective association of relatively small species with the said imprinted material, which method includes the use of a selected species and a companion species for the selected species. The invention also provides, inter alia, a sensor, which sensor includes an imprinted material, which imprinted material is an imprinted material in accordance with the present invention.

Description

Imprinted Materials

The present Invention relates to an imprinted material, to a method suitable for use in the preparation of an imprinted material, to a εenεor, to a teεt-Jcit and to methods of using an imprinted material.

According to one aspect of the present invention there is provided an imprinted material, which imprinted material is suitable for permitting selective association of relatively small species with the said imprinted material.

According to another aspect of the present invention there is provided a method suitable for use in the preparation of an imprinted material, which imprinted material is suitable for permitting selective association of relatively small species with the said imprinted material, which method includes the use of a selected species and a companion species for the selected species.

An imprinted material in accordance with the present invention may be, for example, a material which is capable of selective recognition of a given species or is capable of selective recognition of a given species associated with a companion species.

The term "molecular imprinting" may be applied to the preparation of materials which have a three-dimensional structure (which may be polymeric in nature) , which materials have cavities of highly optimised size and chemical functionality towards a "template" molecule (which may be considered to be an "imprint" molecule) .

Methods used in preparing olecularly imprinted materials often include forming a three-dimensional structure (which may be a matrix structure) in the presence of a "template" molecule, so as to form a material which incorporates the template molecule, and subsequently removing the template molecule to give a molecularly imprinted material. By way or example, in some known methods of preparing a molecularly imprinted material the following steps may be used: (a) a template molecule is added to a mixture of monomers/polymer precursors, (b) polymerisation is initiated so as to cause a three—dimensional matrix to form around the template molecule, and (c) the template molecule is removed from the matrix to leave a molecularly imprinted material (MI ) -

With εo e Known techniques for preparation of molecularly imprinted materials it may be difficult, or even impossible, to prepare imprinted materials having acceptable properties (e.g. acceptable specificity for a "target" species) where a template molecule is a relatively small species. Thus, for example, molecular imprinting may be difficult or impossible with template molecules which have molecule weights of, say, 150 or less (e.g. <150) . it may be postulated, but is by no means certain, that difficulties encountered when seeking to prepare imprinted materials for relatively small species may be due, for example, to the fact that with relatively small species energetically unfavourable and restrictive stereochemical and geometrical requirements may be imposed on the materials used in seeking to form an imprinted material; for example, it may be postulated, although by no means certain, that a looser and less optimised cavity is formed with relatively small species as compared with the cavities Which may be obtained when preparing imprinted materials with larger molecules.

It may be further postulated, but is by no means certain, that relatively small species may lack sufficient chemical functionality to allow preparation of imprinted materials having an acceptable level of specificity for a given "target" species.

The present invention may be used, by way of example, substantially to avoid, or substantially to overcome, difficulties which may be encountered when seeking to prepare a material which is "imprinted" with respect to relatively small molecules. Thus, by way of example, in one aspect the present invention may facilitate the preparation of imprinted materials suitable for use in selective recognition of relatively small species.

By way of example only, it may be observed that, species with a molecular weight of, say, 150 or less (e.g. <150) may present problems when seeking to prepare an imprinted material; however, the term "relatively small species" is not necessarily restricted to species of molecular weight of ISO or less (e.g. <150) and the term "relatively small species" as used in this Specification embraces, for example, any species the size of which leads to unacceptable difficulties in the preparation of an imprinted material and/or the size of which leads to a material of unacceptably low selectivity for the species.

By way of example, it is to be understood that, with respect to a given imprinted material, a "target" species may be a species that it is desired to be selectively associated with the given imprinted material.

Thus, for example, a "target" species may be a species which it is desired to separate or detect (e.g. quantitatively or qualitatively) .

An imprinted material in accordance with the present invention may be, for example, a material which has the capability of selectivity recognising either a selected relatively small species as-such, or the capability of selectively recognising a combination of a selected relatively small species in combination with a companion species for the relatively small species.

By way of example, it will be appreciated that an imprinted material may be considered to be capable of selectively recognising a given species, or given combination of species, if the imprinted material is capable of permitting selective association with the imprinted material of, respectively, said given species or said given combination of species.

For example, imprinted material of the present invention may be, for example, such that a relatively small species per se may become selectively associated with the imprinted material; alternatively, by way of example, imprinted material of the present invention may be such that a combination of relatively small species associated with a companion species, may become selectively associated with the imprinted material such that the relatively small species becomes selectively associated with the imprinted material by being part of the combination.

Thus, for example, the imprinted material may be such that a relatively small species such as a gas molecule may become selectively associated with the imprinted material; alternatively, for example, the imprinted material may be such that a combination comprising a complex of a relatively small species, such as a gas molecule, and a companion species, comprising a complexing agent, may be selectively associated with the imprinted material.

A combination of a relatively small species and a companion species may be considered, for example, to be a "combined species".

An imprinted material, in accordance with the present invention, may find application in chemical separation, biochemical separation, in assays (e.g. quantitative assays and qualitative assays) and in sensing (e.g. chemical sensing). By way of example imprinted material, in accordance with the present invention, may take part in an affinity separation whereby a selected relatively small species (e.g. a molecule) may be selectively separated and become selectively associated with the imprinted material.

Thus, for example, an imprinted material, in accordance with the present invention, may be such that, under given conditions, it may selectively extract a given selected species (e.g. a "target" species) from a given medium (e.g. a fluid medium such as gaseous medium or a liquid medium) .

In accordance with the present invention, a combination of a selected species and a companion species for the selected species may be used to produce an imprinted material. Thus, for example, a selected relatively small species (which itself may be too small to permit satisfactory preparation of an imprinted material) may be associated with α companion species such that the combination of selected relatively small species and companion species produces a "combined species" which is of sufficient size to permit satisfactory preparation of an imprinted material.

In some cases, for example, the "combined species" may be a "bound complex" of a selected relatively small species and a companion species.

For example, the "combined species" may be a non- covalently bound complex in which a selected relatively small species is coordinated to or entrapped by a companion species (which companion species may be considered to be a binder species) .

The companion species may be, for example, chosen such that when associated with a selected relatively small species a combined species is formed which combined species has a molecular weight of >150.

Any suitable companion species may be used. By way of example, the companion species chosen may be a relatively large species (e.g. with a molecular weight of 200 or more (e.g. >200) . However, as will be understood from the immediately preceding paragraph, the companion species need not necessarily be a relatively large species providing, for example, that a companion species is such that a combined species of companion species and selected relatively small species is of sufficient size to permit satisfactory preparation of an imprinted material.

The companion species may be, for example, optionally chosen so as to process a high level of chemical functionality.

By way of example, it is to be understood that, in a "combined species", relatively small species may, if appropriate, be substantially similar (e.g. substantially identical) in type to a chosen "target" species such that an imprinted material may be produced which imprinted material iε suitable for permitting selective association of "target" species with the imprinted material-

Any suitable preparation procedure may be adopted to prepare an imprinted material in accordance with the present invention.

The following are given by way of example:

(A) By way of example, the following steps may optionally be employed:

(a) prepare a combined species (comprising a selected relatively small species and a companion species) ,

(b) mix the combined species with monomeric precursor materials,

(c) initiate polymerisation to form a material incorporating the combined species,

(d) remove the combined species.

After carrying out these steps, an imprinted material is obtained, which material may selectively "recognise" the combined species and, for example, may be used to permit selective association of the combined species with the imprinted material. Thus, a βelected relatively small species may be selectively associated with the imprinted material by means of including the selected relatively small species in a combined species comprising selected relatively small species and companion species and arranging for the combined species to become selectively associated with the imprinted material. The imprinted material prepared as immediately hereinbefore disclosed requires that companion species is present so that the combined species may be selectively associated with the imprinted material.

Thus, where for example the combined species is a complex, the imprinted material may be such that it permits selective association of the complex (but not selective association of the selected relatively small species alone) .

(B) By way of further example, as an alternative, instead of removing the combined species in the step (A) (d) hereinbefore disclosed, the selected relatively small species may be removed (leaving the companion species as part of the imprinted material) to give an imprinted material which may selectively "recognise" the selected relatively small species alone and thus, for example, may be used to permit selective association of the selected relatively small species with the imprinted material.

For example, where the combined species is a complex of selected relatively small species and complexing agent, the selected relatively small species may be removed to leave the complexing agent as part of the imprinted material. (C) By way of further example, optionally, the following steps may be employed in the preparation of an imprinted material:

(a) a companion species may be linked (e.g. covalently) to one or more monomer precursors to produce companion species-monomer entities,

(b) a selected relatively small species may be added to a poly erisable mixture (which includes companion species-monomer precursor entities) ,

(c) polymerisation is effected, and

(d) selected relatively small species is removed.

The steps immediately hereinbefore disclosed may be used to prepare an imprinted material which is suitable for permitting selective association of the selected relatively small species itself, since the companion species is covalently bound in the material and thus forms part thereof.

For example, where a combined species is formed comprising a complex of a selected relatively small species and a complexing agent (comprising, in this example, a companion species-monomer entity) , the selected relatively small species may be removed to leave the complexing agent as part of the imprinted material. (D) By way of further example, optionally, the following steps may be employed to prepare an imprinted material:

(a) mix a selected relatively small species with a companion species and a monomer mixture (i.e. without first forming a "combined species") ,

(b) polymerise,

(c) either (i) remove a combined species (comprising selected relatively small species and companion species, or (ii) remove selected relatively small species only.

It will be appreciated that the procedure of (c) (i) may produce an imprinted material which may permit selective association of combined species whereas the procedure of (c) (ii) may produce an imprinted material which may provide selective association of a selected relatively small species itself. Thus, for example, where the companion species is a complexing agent, procedure (c) (i) may give an imprinted material which may permit selective association of a complex of selected relatively small species and complexing agent whereas procedure (c) (ii) may give an imprinted material which may permit selective association of a selected relatively small species itself. It will be appreciated that any other suitable procedures may be used to prepare an imprinted material in accordance with the present invention.

Thus, for example, the following variations of the procedures hereinbefore described may be employed:

(E) (i) add a selected relatively small species to a monomer mixture, (ii) initiate polymerisation,

(iii)add companion species during polymerisation stage, (iv) remove (e.g. after polymerisation) either combined species or selected relatively small species as hereinbefore disclosed as desired.

(F) (i) add companion species to a monomer mixture, (ii) initiate polymerisation,

(iii)add selected relatively small species during polymerisation stage,

(iv) remove (e.g. after polymerisation) either combined species or selected relatively small species as hereinbefore disclosed as desired. (G) Use preformed short polymer chains (e.g. oligoraer chains), having covalently attached companion species, as one of the monomers in a monomer mixture for subsequent polymerisation.

Such short chains may be used in any convenient procedure to prepare an imprinted material.

As will be apparent from the foregoing disclosure, the present invention may be utilised to prepare imprinted materials, which material may permit selective association of selected relatively small species with said materials.

Where the selected relatively small species is one which is, for example, to be separated and/or detected, the species may be considered to be a "target" material.

An imprinted material which is capable of permitting selective association of a selected relatively small species may be said, for example, to be capable of "recognising" the selected relatively small species. imprinted materials, in accordance with the present invention, may be such as to be capable for permitting selective association, with the imprinted material, of any suitable relatively small species (e.g. an imprinted material may be such as to be capable of "recognising" any suitable relatively small species) and examples of such relatively small species are oxygen, carbon dioxide, carbon monoxide, hydrogen, sulphur dioxide, hydrogen sulphide, nitric oxide, nitrogen dioxide, ammonia, amines, benzene, acetylene, phosphines, ethers, esters, nitriles and ketones.

By way of example, there are hereinafter given examples of (i) relatively small species and (ii) combined species (e.g. complexes), comprising relatively small species in combination with a companion species, which combined species may be used to prepare imprinted materials which are capable of permitting selective association of the said relatively s all species (e.g. capable of recognising the said relatively small species) .

(I) Where an imprinted material is to be prepared which is suitable for permitting selective association of oxygen molecules (0₂) (e.g. where an imprinted material which may selectively recognise oxygen molecules (θ₂) is to be prepared) the combined species for use in imprinting may be, for example: (a) a cobalt-Schiff'ε base complex, or (b) a metalloporphyrin.

An example of (a) is N,N'disalicyclidene- ethylenedia ine-cobalt (II) (L)0₂, where L is a nitrogenous base (e.g. pyridine) .

An example of (b) is meso- , ' , a ' ' , cr'"- tetrakis(ortho-pivalamidophenyl)porphinato cobalt (II) (l-methylimidazole)-o₂.

(II) Where an imprinted material is to be prepared which is suitable for permitting selective association of carbon dioxide molecules (C0₂) (e.g. where an imprinted material which may selectively recognise carbon dioxide molecules (C0₂) is to be prepared) the combined species for use in imprinting may be, for example, a rhodium complex (e.g. a rhodium (I) complex such as Rh(I)Cl(Cθ₂) (PR₃)₂ where R = aryl

(HI) where an imprinted material is to be prepared which is suitable for permitting selective association of carbon monoxide molecules (CO) (e.g. where an imprinted material which may selectively recognise carbon monoxide molecules (CO) is to be prepared) the combined species for use in imprinting may be, for example, an iron complex (e.g. Fe(II) (TIM) (PhCN)co where TIM = tetramethyl tetraazacylo tetradecane tetraene and Ph = phenyl) .

(IV) Where an imprinted material is to be prepared which is suitable for permitting selective association of hydrogen molecules (H₇) (e.g. where an imprinted material which may selectively recognise hydrogen - 11- molecules (H₂) is to be prepared) the combined species for use in imprinting may be, for example, a rhodium complex (e.g. a rhodium (I) complex such as Rh(I)Cl(H₂) (PR₃)₂ where R = aryl (e.g. CJHJ) ) .

(V) Where an imprinted material is to be prepared which is suitable for permitting selective association of sulphur dioxide molecules (Sθ₂) (e.g. where an imprinted material which may selectively recognise sulphur dioxide molecules (SO-) is to be prepared) the combined species for use in imprinting may be, for example, a nickel(O) complex (e.g. Ni(np3)S0₂ where np3 = N(CH₂CH₂PPh₂)₃ in which Ph = phenyl).

(VI) Where an imprinted material is to be prepared which is suitable for permitting selective association of hydrogen sulphide molecules (H₂S) (e.g. where an imprinted material which may selectively recognise hydrogen sulphide molecules (H₇S) is to be prepared) the combined species for use in imprinting may be, for example:

(a) a tungsten carbonyl complex (e.g. W(co)_jH_jS), or

(b) an osmium carbonyl complex (e.g. Os₃(CO),H₂S) , or

(c) a ruthenium carbonyl complex (e.g. RU_jfCOj_jH_jS) .

(vii) where an imprinted material is to be prepared which is suitable for permitting selective association of nitric oxide molecules (NO) (e.g. where an imprinted material which may selectively recognise nitric oxide molecules (NO) is to be prepared) the combined species for use in imprinting may be, for example, an iron carbonyl comple (e.g. Fe(CO)₂(NO)₂).

(VIII) Where an imprinted material is to be prepared which is suitable for permitting selective association of nitrogen dioxide molecules (Nθ₃) (e.g. where an imprinted material which may selectively recognise nitrogen dioxide molecules (NO_j) is to be prepared) the combined species for use in imprinting may be, for example, a metallophthalocyanine (e.g. copper phthalocyanine-Nθ₂.

(IX) where an imprinted material is to be prepared which is suitable for permitting selective association of ammonia molecules (NH₃) (e.g. where an imprinted material which may selectively recognise ammonia molecules (NH₃) is to be prepared) the combined species for use in imprinting may be, for example: a chromium halide complex (e.g. Cr(II) (NH₃)₆Cl₂) .

(X) where an imprinted material is to be prepared which is suitable for permitting selective association of an amine molecule (e.g. an amine of the type RNH₂ where R = alkyl or aryl (e.g. C₆H₅) ) (e.g. where an imprinted material which may selectively recognise an amine molecule (e.g. an amine of the type RNH₂ where R = alkyl or aryl (e.g. C l_s) ) is to be prepared) the combined species for use in imprinting may be, for example, a titanium amine complex (e.g. TiCl₂(RNH)₂ where R = alkyl or aryl (e.g. C-_JH_J)) .

(XI) Where an imprinted material is to be prepared which is suitable for permitting selective association of an aromatic species such as benzene (C₆HJ_J) (e.g. where an imprinted material which may selectively recognise an aromatic species such as benzene (C^) is to be prepared) the combined species for use in imprinting may be, for example, a chromium complex (e.g. Cr(C₆H_j)₃(THF)_J where THF = tetrahydro uran).

(XII) where an imprinted material is to be prepared which is suitable for permitting selective association of an alkyne molecule (e.g. acetylene c₂H₂) (e.g. where an imprinted material which may selectively recognise an alkyne molecule (e.g. acetylene C_JH_J) iε to be prepared) the combined species for use in imprinting may be, for example, a copper (I) halide complex (e.g. cu(I)cl(C₂H₂) ) . 13 -

(XIII) Where an imprinted material is to be prepared which is suitable for permitting selective association of a phoεphine molecule (e.g. where an imprinted material which may selectively recognise a phosphine molecule is to be prepared) the combined species for use in imprinting may be, for example, a complex formed with a covalent metal halide (e.g. a complex formed with CrCl₃) .

(XIV) Where an imprinted material is to be prepared which is suitable for permitting selective association of an ether species (e.g. where an imprinted material which may selectively recognise an ether species iε to be prepared) the combined species for use in imprinting may be, for example, a complex formed with a covalent metal halide (e.g. a complex formed with CrCl,) .

(XV) Where an imprinted material is to be prepared which is suitable for permitting selective association of an ester species (e.g. where an imprinted material which may selectively recognise an ester species is to be prepared) the combined species for use in imprinting may be, for example, a complex formed with a covalent metal halide (e.g. a complex formed with CrCl_j) .

(XVI) Where an imprinted material is to be prepared which is suitable for permitting selective association of a nitrile species (e.g. where an imprinted material which may selectively recognise a nitrile species is to be prepared) the combined species for use in imprinting may be, for example, a complex formed with a covalent metal halide (e.g. a complex formed with CrCl₃) .

(XVII) Where an imprinted material is to be prepared which is suitable for permitting selective association of a ketone species (e.g. where an imprinted material which may selectively recognise a ketone species is to be prepared) the combined species for use in imprinting may be, for example, a complex formed with a covalent metal halide (e.g. a complex formed with CrCl_j) .

According to a further aspect of the present invention there is provided a sensor, which sensor includes an imprinted material which imprinted material is an imprinted material in accordance with the present invention.

Thus, for example, the present invention may provide a sensor, suitable for use in the sensing of relatively small species, which sensor includes an imprinted material which imprinted material is an imprinted material in accordance with the present invention.

It will be appreciated that a sensor m accordance with the present invention may be, for example, such as to facilitate sensing of a relatively small species per εe , or may be, for example, such as to facilitate sensing of a combined species, which combined species includes a relatively small species, such that relatively small species may be sensed by being part of the combined species; thus, for example, a sensor may include an imprinted material in accordance with the present invention which imprinted material is suitable for permitting selective association of relatively small species per se with the imprinted material, or, by way of example, a sensor may include an imprinted material in accordance with the present invention which imprinted material is suitable for permitting selective association of a combined species with the imprinted material, said combined species including a relatively small species.

According to a further aspect of the present invention there is provided a test-kit, which test-kit includes an imprinted material which imprinted material is an imprinted material in accordance the present invention.

Thus, for example, the present invention may provide a test-kit, suitable for use in the detection of relatively small species, which test-kit includes an imprinted material which imprinted material is an imprinted material in accordance the present invention. It will be appreciated that in a test-kit in accordance with the present invention an imprinted material in accordance with the present invention may be, for example, such as to be suitable for permitting selective association of relatively small species per sβ with the imprinted material, or may be such, for example, as to be suitable for permitting selective association of a combined species with the imprinted material which combined species includes a relatively small species.

According to a further aspect of the present invention there is provided a separation method which method includes the use of an imprinted material which imprinted material is an imprinted material in accordance with the present invention.

Thus, for example, the present invention may provide a separation method, which method is suitable for use in the separation of relatively small species, which method includes the use of an imprinted material which imprinted material is an imprinted material in accordance with the present invention.

By way of example, in accordance with the immediately preceding aspect of the present invention, an imprinted material in accordance with the present invention may be contacted with a medium containing a relatively small species such that a relatively small εpecies may become selectively associated with the imprinted material in order to facilitate separation.

By way of further example, in accordance with the immediately preceding aspect of the present invention, an imprinted material in accordance with the present invention may be contacted with a medium containing a combined species which combined species includes a relatively small species, such that combined species, and thus relatively small species, may become selectively associated with the imprinted material in order to facilitate separation.

According to a further aspect of the present invention there iε provided an extraction method, which method includes the use of an imprinted material, which imprinted material is an ⁱmprinted material in accordance with t_he present invention.

Thus, for example, the present invention may provide an extraction method, which method is suitable for use in the extraction of relatively small species which method includes the us^e of an imprinted material, which imprinted material is an imprinted material in accordance with the present invention.

By way of example, in accordance with the immediately preceding aspect of the present invention, an imprinte_d material in accordance with the present invention may _be contacted with a medium containing a relatively small species such that a relatively small species may become selectively associated with the imprinted material in order to facilitate extraction.

By way of further example, in accordance with the immediately preceding aspect of the present invention, an imprinted material in accordance with the present invention may be contacted with a medium containing a combined species, which combined species includes a relatively small species, such that combined species, and thus relatively small species, may become selectively associated with the imprinted material in order to facilitate extraction.

According to a further aspect of the present invention, there is provided a method for detection which method includes the use of an imprinted material which imprinted material is an imprinted material in accordance with the present invention.

Thus, for example, the present invention may provide a method suitable for detection of relatively small species, which method includes the use of an imprinted material which imprinted material is an imprinted material in accordance with the present invention.

_By way o_f example, in accordance with the immediately preceding aspect of the present invention, an imprinted material in accordance with the present invention may be contacted with a medium containing a relatively small species such that relatively small species may become selectively aε^βociated with the imprinted material in order to facilitate detection.

By way of example, in accordance with the immediately preceding aspect of the present invention, an imprinted material in accordance with the present invention may be contacted with a medium containing a combined species, which combined species includes a relatively small species, such that combined species, and thus relatively small species, may become selectively associated with the imprinted material in order to facilitate detection.

Detection of a relatively small species using an imprinted material which imprinted material is an imprinted material in accordance with the present invention may be achieved in any suitable manner. For example, any suitable form of assay may utilise an imprinted material which imprinted material is an imprinted material in accordance with the present invention. For example, assay configurations similar to those which may ind application in immunoassayε (e.g. competitive assays) may be used.

By way of example, imprinted material in accordance with the present invention may be used for the selective retention of a relatively small species, thereby to enable a chromatographic technique to be used to detect a relatively email species.

By way of further example, where imprinted material in accordance with the present invention is used in a sensor, the imprinted material may be associated with a quartz crystal detector (e.g. a bulk acoustic wave quartz crystal oscillator, or a surface acoustic wave resonator or a surface acoustic wave delay-line) , or with an optical detector (e.g. one capable of detecting a colour change, or a fluorescence change, or a luminescence change) , or with a detector capable of detecting an electrical change (e.g. an electrical conductivity change or an electrical resistance change) , or with a detector capable of detecting a calori etric signal.

By way of example, where detection is to be effected by means of an electrical conductivity change or by means of an electrical resistance change, the imprinted material may be, for example, such that it is itself an electrically conducting imprinted material.

For example, such an electrically conducting imprinted material may be formed by polymerisation of any suitable monomers (which may, or may not, themselves be electrically conducting) said polymerisation giving rise to an electrically conducting imprinted material (e.g. imprinted polypyrrole) .

By way of example, a sensor in accordance with the present invention may be used individually or an array of sensors (each sensor being in accordance with the present invention) may be used in conjunction with appropriate signal processing (e.g. as an "electronic nose") .

It is to be understood, by way of example, that an imprinted material in accordance with the present invention may be used as such. However, as an alternative, for example, an imprinted material in accordance with the present invention may be used in conjunction with a support material. Thus the present invention, in another aspect, provides an imprinted material, in accordance with the present invention, in conjunction with a support material. For example, an imprinted material may be provided (e.g. formed) in the pores of a support material or may be provided (e.g. formed) as a layer or film (e.g. a thin layer or film) on a surface of a support material. Any suitable support material may be used. Examples of βupport materials are solid phase materials such as a reaction vessel wall, insoluble polyβaccharldes (which may be in particulate form) , microparticleε (e.g. particulate microcellulose) , insoluble polyεaccharides with entrapped iron oxide (e.g. magnetisable particles such as magnetisable micro-particulate materials) , polystyrene (e.g. in the form of beads, tubes, wells, microtitre plates, discs, or dip-sticks) , gelatinous materials (e.g. cross-linked dextran (e.g. Sephadex)) , insoluble polymer structures, glass surfaces, quartz surfaces, derivatised silica surfaces, nylon, a polya ide, a molecular sieve, and metallic surfaces (e.g. the surface of a gold electrode) . Where, for example, an imprinted material is to be used in conjunction with a support material an imprinted material may be, for example, provided on a support material. Where an imprinted material is to be provided on a support material (e.g. as a thin layer or as a film) this may be effected, for example, in any suitable manner and/or by any suitable means or method.

For example, a monomeric precursor material, or a plurality of monomeric precursor materials, may be attached or bound (e.g. by covalent linkage) to a support material and polymerisation may be used as a step in the preparation of an imprinted material. By way of example, an imprinted material may be prepared in situ on the support material.

By way of example a monomeric precursor material may be attached or bound to the support material and polymerisation thereof may be effected, in the presence of a combined species (comprising a selected relatively small species and a companion species) and subsequently either the combined species or the selected relatively small species may be removed to give, on the support material, an imprinted material which may selectively "recognise", respectively, the combined species or the selected relatively small species alone. (It will be appreciated that after polymerisation, removal of the combined species may provide, on the support material, an imprinted material which may selectively "recognise" the combined species and that removal of the selected relatively small species alone may provide, on the support material, an imprinted material which may selectively "recognise" the selected relatively small species alone.)

It is to be understood that detection in accordance with the present invention may be, for example, quantitative or qualitative; it will be further understood that quantitative detection may be considered to be, for example, determination or measurement.

It will be appreciated that detection in accordance with the present invention may be effected on any suitable sample-

The present invention also provides, in a further aspect, an imprinted material when made by a method in accordance with the present invention, said method being suitable for use in the preparation of an imprinted material.

It will be appreciated that an imprinted material in accordance with the present invention may be, for example, such as to be suitable for permitting selective association of a relatively small species per se with the imprinted material, or may be, for example, such as to be suitable for permitting selective association of a combined species with the imprinted material, said combined species including a relatively small species.

As has been hereinbefore disclosed, when preparing an imprinted material in accordance with the present invention, a selected species may be used in combination with a companion species. It will be appreciated that the selected species may be, for example, in some embodiments, substantially similar (e.g. substantially identical) in type to the "target" species to which the imprinted material is directed. However, under some circumstances, for example, the selected species need not necessarily be substantially identical to the "target" species; for example, the selected species may be a selected species as such, or may be a precursor for a selected species, or may be a derivative of a selected species. Accordingly, the term "selected species" as used in this Specification may embrace, for example, a selected species as such, or a precursor therefor, or a derivative of a selected species-

By way of further example, in some embodiments the selected species need not necessarily be substantially identical in type to a "target" species since the selected species may be a similar species to the target species.

For example, a similar species to a target species may be a species which is similar in size and/or chemical functionality to a "target" species such that the similar species may be useful in the preparation of an imprinted material which may permit selective association of a target species with the imprinted material. For example, if it is difficult, or impossible, to obtain a suitable "combined species" in the case of some template species (e.g. for some __{2 1} _ target species) , then it may be possible to use a "similar species" in respect of which it is possible to obtain a suitable "combined species" and to use such "combined species" (which includes the similar species) such that an imprinted material may be prepared which imprinted material has acceptable selective properties (e.g. selective "recognition" properties) with respect to the target species. Thus, for example, it may be possible to utilise a template species which is not identical to a target species when preparing an imprinted material.

By way of example, optionally, if desired, more than one type of imprinted material in accordance with the present invention may be used (e.g. simultaneously or sequentially) so as to facilitate the selective association of more than one relatively small species or combined species or a mixture thereof. Thus, for example, a plurality of different imprinted materials in accordance with the present invention may be used to permit selective association of a plurality of relatively small species, or a plurality of combined species, or a mixture of relatively small species and combined species. For example, a first relatively small species or first combined species may be selectively associated with a first imprinted material, a second relatively small species or a second combined species may be selectively associated with a second imprinted material and so forth.

Thus, for example, a sensor, or an array of sensors, or a test-kit, or a separation method, or an extraction method, or a method of detection in accordance with the present invention may, for example, optionally, use a plurality of different imprinted materials, each of which imprinted materials is an imprinted material in accordance with the present invention.

The present invention will now be further described, by way of example only, with reference to the accompanying Drawings in which:

Figure 1 is a diagrammatic representation (not necessarily to scale) of a sensor in accordance with the present invention, and

Figure 2 is a diagrammatic representation (not necessarily to scale) of the sensor in Figure 1 as viewed in the direction of arrow A in Figure 1. Referring now to Figures l and 2 of the Drawings there is shown a sensor 1 having a support material 2 upon which there is provided a layer of imprinted material 3, said imprinted material 3 being in accordance with the present invention.

By way of example, in operation a medium, for example containing a relatively small species or containing a combined species, which combined species includes a relatively small species, may be arranged to contact the sensor 1 such that a relatively small species, or a combined species, may become selectively associated with the imprinted material 3 such as to enable a signal to be generated to indicate the presence of a relatively small species or a combined species. such a signal may be detected by any suitable means (not shown) , the means being chosen as appropriate to the signal generate .

Claims

1. An imprinted material, which imprinted material is suitable for permitting selective association of relatively small species with the said imprinted material.

2. A method suitable for use in the preparation of an imprinted material, which imprinted material is suitable for permitting selective association of relatively small species with the said imprinted material, which method includes the use of a selected species and a companion species for the selected species.

3. An imprinted material or a method as claimed in Claim 1 or Claim 2 wherein the imprinted material is such that a relatively small species per se may become selectively associated with the imprinted material.

4. An imprinted material or a method as claimed in Claim 1 or Claim 2 wherein the imprinted material is such that a combination of a relatively small species associated with a companion species may become selectively associated with the imprinted material such that the relatively small species becomes selectively associated with the imprinted material by being part of the combination.

5. .An imprinted material or a method as claimed in any one of Claims 1 to 3 wherein the relatively small species is a gas molecule.

6. An imprinted material or a method as claimed in any one of claims 1, 2 or 4 wherein the combination is a combined species comprising a complex of a relatively small species and a companion species for the relatively small species.

7. An imprinted material or a method as claimed in Claim 6 wherein the combined species is a complex of a relatively small species and a companion species comprising a complexing agent.

8. An imprinted material or a method as claimed in claim 6 or Claim 7 wherein the combined species is a non-covalently bound complex.

9. An imprinted material or a method as claimed in any one of the preceding Claims wherein the relatively small species is oxygen, carbon dioxide, carbon monoxide, hydrogen, sulphur dioxide, hydrogen sulphide, nitric oxide, nitrogen dioxide, ammonia, an amine, an aromatic species, an alkyne, a

phosphine, an ether, an ester, a nitrile or a ketone.

10. A method as claimed in any one of Claims 2 to 9 wherein a combined species is used to prepare an imprinted material and said combined species comprises a cobalt-Schiff's base complex, a metalloporphyrin, a rhodium complex, an iron complex, a nickel (O) complex, a tungsten carbonyl complex, an osmium carbonyl complex, a ruthenium carbonyl complex, an iron carbonyl complex, a metallophthalocyanine, a chromium halide complex, a titanium amine complex, a chromium complex, a copper (I) halide complex, or a complex formed with a covalent metal halide.

11. A method as claimed in Claim 10 wherein the combined species is N,N'disalicyclidene-ethylenediamine-cobalt

(II) (L)O₂, where L is a nitrogenous base.

12. A method as claimed in Claim ll wherein the nitrogenous base is pyridine.

13. A method as claimed in Claim 10 wherein the

metalloporphyrin is meso-α, α', α' ' , α'''-tetrakis(orthopivalamidophenyl)porphinato cobalt (II) (i-methylimidazole)-o₂.

14. A method claimed in Claim 10 wherein the rhodium complex is a rhodium (I) complex.

15. A method as claimed in Claim 14 wherein the rhodium (I) complex is Rh(i)Cl(CO₂) (PR₃)₂ where R = aryl.

16. A method as claimed in Claim 15 wherein R = C₆H₅.

17. A method as claimed in Claim 10 wherein the iron complex is Fe(II) (TIM) (PhCN)CO where TIM = tetramethyl tetraazacylo tetradecane tetraene and Ph = phenyl.

18. A method as claimed in claim 10 wherein the nickel (O) complex is Ni(np3)SO₂ where np3 = N(CH₂CH₂PPh₂)₃ in which Ph = phenyl.

19. A method as claimed in Claim 10 wherein the tungsten carbonyl complex is W(CO)₅H₂S, or the osmium carbonyl complex is Os₃(CO)₉H₂S, or the ruthenium carbonyl complex is

Ru₃(CO)₉H₂S, or the iron carbonyl complex is Fe (CO)₂(NO)₂.

20. A method as claimed in Claim 10 wherein the metallophthalocyαnine is copper phthalocyanine-NO₂.

21. A method as claimed in Claim 10 wherein the chromium halide complex is Cr(II) (NH₃)₆Cl₂.

22. A method as claimed in Claim 10 wherein the titanium amine complex is TiCl₂(RNH)₂ where R = alkyl or aryl.

23. A method as claimed in Claim 22 wherein R = C₆H₅.

24. A method as claimed in Claim lo wherein the chromium complex is Cr(C₆H₅) ₃(THF)₃ where THF = tetrahydrofuran.

25. A method as claimed in Claim 10 wherein the copper (I) halide is Cu(I)Cl(C₂H₂).

26. A method as claimed in Claim 10 wherein the complex formed with a covalent metal halide is a complex formed with CrCl₃.

27. A method as claimed in Claim 2 which includes the steps of preparing a combined species, comprising a selected relatively small species and a companion species, mixing the combined species with monomeric precursor materials,

initiating polymerisation to form a material incorporating the combined species and removing the combined species.

28. A method as claimed in Claim 2 which includes the steps of preparing a combined species, comprising a selected relatively small species and a companion species, mixing the combined species with monomeric precursor materials,

initiating polymerisation to form a material incorporating the combined species and removing the selected relatively small species.

29. A method as claimed in Claim 2 which includes the steps of linking a companion species to one or more monomer precursors to produce companion species-monomer entities, adding a selected relatively small species to a polymerisable mixture, which includes companion species-monomer precursor entities, effecting polymerisation, and removing selected relatively small species.

30. A method as claimed in Claim 2 which includes the steps of mixing a selected relatively small species with a

companion species and a monomer mixture, polymerising and rermoving a combined species, comprising selected relatively small species and companion species.

31. A method as claimed in Claim 2 which includes the steps of mixing a selected relatively small species with a

companion species and a monomer mixture, polymerising and removing selected relatively small species.

32. A method as claimed in Claim 2 which includes the steps of adding a selected relatively small species to a monomer mixture, initiating polymerisation, adding a companion species during polymerisation, and removing combined species to give an imprinted material.

33. A method as claimed in Claim 2 which includes the steps of adding a selected relatively small species to a monomer mixture, initiating polymerisation, adding a companion species during polymerisation, and removing selected

relatively small species to give an imprinted material.

34. A method as claimed in Claim 2 which includes adding a companion species to a monomer mixture, initiating

polymerisation, adding selected relatively small species during polymerisation and removing combined species after polymerisation to give an imprinted material.

35. A method as claimed in Claim 2 which includes adding a companion species to a monomer mixture, initiating

polymerisation, adding selected relatively small species during polymerisation and removing selected relatively small species after polymerisation to give an imprinted material.

36. A method as claimed in Claim 2 which includes the use of preformed short polymer chains, having covalently attached companion species, as one of the monomers in a monomer mixture for subsequent polymerisation.

37. A sensor, which sensor includes an imprinted material which imprinted material is an imprinted material as claimed in any one of Claims 1 or 3 to 9.

38. A sensor, suitable for use in the sensing of relatively small species, which sensor includes an imprinted material which imprinted material is an imprinted material as claimed in any one of Claims 1 or 3 to 9.

39. A sensor as claimed in claim 37 or Claim 38 wherein the imprinted material is an imprinted material as claimed in any one of Claims 1 or 3 to 9 and such imprinted material is suitable for permitting selective association of relatively small species per se with the imprinted material.

40. A sensor as claimed in Claim 37 or Claim 38 wherein the imprinted material is an imprinted material as claimed in any one of Claims 1 or 3 to 9 and such imprinted material is suitable for permitting selective association of a combined species with the imprinted material, said combined species including a relatively small species.

41. A sensor as claimed in any one of Claims 37 to 40 wherein an imprinted material as claimed in any one of Claims 1 or 3 to 9 is associated with a quartz crystal detector, or with an optical detector, or with a detector capable of detecting an electrical change, or with a detector capable of detecting a calorimetric signal.

42. A sensor as claimed in Claim 41 wherein the quartz crystal detector is a bulk acoustic wave quartz crystal oscillator, or a surface acoustic wave resonator, or a surface acoustic wave delay-line.

43. A sensor as claimed in Claim 41 wherein the optical detector is one capable of detecting a colour change, or is one capable of detecting a fluorescence change, or is one capable of detecting a luminescence change.

44. A sensor as claimed in Claim 41 wherein the detector capable of detecting an electrical change is one capable of detecting an electrical conductivity change or is one capable of detecting an electrical resistance change.

4b. A sensor as claimed in any one of claims 37 to 41 or Claim 44 wherein the imprinted material is an electrically conducting imprinted material.

46. An array of sensors each of which sensors in the array is a sensor as claimed in any one of Claims 37 to 45.

47. A test-kit, which test-kit includes an imprinted material which imprinted material is an imprinted material as claimed in any one of Claims 1 or 3 to 9.

48. A test-kit, suitable for use in the detection of

relatively small species, which test-kit includes an

imprinted material which imprinted material is an imprinted material as claimed in any one of Claims 1 or 3 to 9.

49. A test-kit as claimed in Claim 47 or Claim 48 wherein the imprinted material is an imprinted material as claimed in any one of Claims 1 or 3 to 9 and said imprinted material is suitable for permitting selective association of relatively small species per se with the imprinted material.

50. A test-kit as claimed in Claim 47 or Claim 48 wherein the imprinted material is an imprinted material as claimed in any one of Claims 1 or 3 to 9 and said imprinted material is suitable for permitting selective association of combined species with the imprinted material, said combined species including a relatively small species.

51. A separation method which method includes the use of an imprinted material which imprinted material is an imprinted material as claimed in any one of Claims 1 or 3 to 9.

52. A separation method, which method is suitable for use in the separation of relatively small species, which method includes the use of an imprinted material which imprinted material is an imprinted material as claimed in any one of Claims 1 or 3 to 9.

53. A separation method as claimed in claim 51 or Claim 52 wherein an imprinted material as claimed in any one of claims 1 or 3 to 9 is contacted with a medium containing a

relatively small species such that a relatively small species may become selectively associated with the imprinted material in order to facilitate separation.

54. A separation method as claimed in Claim 51 or Claim 52 wherein an imprinted material as claimed in any one of Claims 1 or 3 to 9 is contacted with a medium containing a combined species which combined species includes a relatively small species such that combined species, and thus relatively small species, may become selectively associated with the imprinted material in order to facilitate separation.

55. An extraction method, which method includes the use of an imprinted material, which imprinted material is an imprinted material as claimed in any one of Claims 1 or 3 to 9.

56. An extraction method, which method is suitable for use in the extraction of relatively small species which method incudes the use of an imprinted material, which imprinted material is an imprinted material as claimed in any one of Claims 1 or 3 to 9.

57. An extraction method as claimed in Claim 55 or Claim 56 wherein an imprinted material as claimed in any one of Claims 1 or 3 to 9 is contacted with a medium containing a

relatively small species such that a relatively small species may become selectively associated with the imprinted material in order to facilitate extraction.

58. .An extraction method as claimed in Claim 55 or Claim 56 wherein an imprinted material as claimed in any one of Claims l or 3 to 9 is contacted with a medium containing a combined species, which combined species includes a relatively small species, such that combined species, and thus relatively small species, may become selectively associated with the imprinted material in order to facilitate extraction.

59. A method for detection which method includes the use of an imprinted material which imprinted material is an

imprinted material as claimed in any one of Claims 1 or 3 to 9.

60. A method suitable for detection of relatively small species, which method includes the use of an imprinted material which imprinted material is an imprinted material as claimed in any one of Claims 1 or 3 to 9.

61. A method as claimed in Claim 59 or Claim 60 wherein an imprinted material as claimed in any one of Claims 1 or 3 to 9 is contacted with a medium containing a relatively small species such that relatively small species may become selectively associated with the imprinted material in order to facilitate detection.

62. A method as claimed in Claim 59 or Claim 60 wherein an imprinted material as claimed in any one of Claims 1 or 3 to 9 is contacted with a medium containing a combined species, which combined species includes a relatively small species, such that combined species, and thus relatively small

species, may become selectively associated with the imprinted material in order to facilitate detection.

63. A method as claimed in any one of Claims 53, 54, 57, 58 61 or 62 wherein the medium is a gaseous medium or a liquid medium.

64. A method as claimed in any one of Claims 59 to 62 wherein detection is effected by means of a chromatographic technique.

65. A method as claimed in any one of Claims 59 to 62 wherein detection is effected by means of a suitable assay configuration.

66. A method as claimed in Claim 65 wherein the assay configuration is a competitive assay configuration.

67. An imprinted material as claimed in any one of Claims 1 or 3 to 9 in conjunction with a support material.

68. An imprinted material as claimed in Claim 67 wherein the imprinted material is provided in the pores of a support material or is provided as a layer or film on a surface of a support material.

69. An imprinted material as claimed in claim 67 or Claim 68 wherein a monomeric precursor material, or a plurality of monomeric precursor materials, is attached to a support material and polymerisation is used as a step in the

preparation of an imprinted material.

70. An imprinted material as claimed in any one of Claims 67 to 69 wherein the support material is a reaction vessel wall, an insoluble polysaccharide, a microparticle, an insoluble polysaccharide with entrapped iron oxide, polystyrene, a gelatinous material, an insoluble polymer structure, a glass surface, a quartz surface, a derivatised silica surface, nylon, a polyamide, a molecular sieve, or a metallic surface.

71. An imprinted material when made by a method as claimed in any one of Claims 2 to 36.

72. A sensor, or an array of sensors, or a test-kit, or a separation method, or an extraction method, or a method of detection, or an imprinted material in conjunction with a support material, as claimed in any one of claims 37 to 70 wherein a plurality of different imprinted materials is used, each of the imprinted materials being an imprinted material as claimed in any one of Claims 1 or 3 to 9.

73. A sensor substantially as hereinbefore described with reference to Figure 1 or Figure 2 of the accompanying

Drawings.

74. An imprinted material, or a method, or a sensor, or an array of sensors, or a test—kit, or a separation method, or an extraction method, or a method of detection, or an

imprinted material in conjunction with a support material, as claimed in any one of Claims 1 to 73 wherein a relatively small species has a molecular weight of 150 or less.