Title of Invention

IMPROVED DETECTION SIGNAL AND CAPTURE IN DIPSTICK ASSAYS

Abstract

Improved dipstick assays for testing for the presence of a target nucleic acid in a sample solution are described. A dipstick is provided which comprises a contact end for contacting the sample solution and a capture zone remote from the contact end for capturing target nucleic acid. Sample solution is contacted with the contact end to cause sample solution to move by capillary action to the capture zone. Target nucleic acid in the sample solution is captured at the capture zone and is detected by a plurality of different labelled detection probes each capable of hybridising to a different region of the target nucleic acid. The detection signal is thereby enhanced. In other methods a plurality of different capture probes are added to the sample solution which can then be bound by a capture moiety at the capture zone to indirectly capture target nucleic acid. Capture of target nucleic acid is thereby improved. Kits and dipsticks for carrying out such methods are also described.

Full Text

Inr^rcved Detection Sicr.al and Caot'j.re In Diostick Assavs The Dreser-t ir.vsntion relates to improved sensitivity cf nucleic acid detection by dipsticks. Dipsticks of the invention are iised to detect, the presence cf a target nucleic acid in a samole solution, for example to identify whether a patient is infected with a disease causing microorganism such as Chlamydia trachomatis. Some conventional tests for detecting the presence of a target nucleic acid in a sample solution rely on amplification cf the target nucleic acid using the polymerase chain reaction (?CR). Whilst this reaction allows detection cf small quantities of target nucleic acid, it can take several hours before a result is obtained. This can be a significant disadvantage because it is often desired to obtain the result as soon as possible, for example, to keep patient waiting times to a minimum. Further disadvantages of such methods are the requirement for expensive specialise equipment to perform the reaction and the relatively high' cost of the reagents. In contrast, dipsticks can detect unamplified target nucleic acid without the requirement for any specialist equipment and the results can be obtained much more rapidly than ?C?.-based methods and, therefore, in a single visit from a , patient. The patient can then be treated in the same visit. This is particula.rly advantageous V7here the patient is unlikely to, or., cannot, return form treatment at a later date. The cost of performing a dipstick test can also be A' significantly lower than the cost of a PCR-based test. In a t'v-pical cor.ve-rional dipstick assay, described in US 5,310,65 0, a single stranded DNA capture probe is immobilised en a nitrccelluloss filter at a capture zone remote from one end of the filter (the contact end) . Part of the sequence cf the capture probe is complementary to the sequence cf a first region cf the target nucleic acid to be detected. A labelled single stranded DNA detection probe is immobilised on the nitrocellulose filter at a probe zone located between the capture zone and the contact end of the filter. The detection probe has sequence complementary to the sequence cf a second region (distinct from the first region) of the target nucleic acid. To detect single stranded target DNA in a sample solution thought to contain target DNA, the contact end of the nitrocellulose filter is contacted with the sainple solution. The sample solution wicks up the filter by capillary action and passes the probe zone and the capture zone. As the sample solution passes the probe zone, it mobilises the detection probe and causes it to rise with the sample solution towards the capture zone. Mobilised detection probe can then hybridise to the second region of any target DNA present in the sarrrole solution. When the hybridised detection probe and target DNA arrive at the capture zone, the first region of the target DNA can hybridise to the immobilised capture probe. A ternary coirrolex is thereby formed between the target nucleic acid, the capture probe and the labelled detection probe. Presence of label at the captizre zone, therefore, indicates that target DNA is present in the sample solution. lE^belled 1^1"--. dezecticn probe is not irrirriobilised on one —r 2, w !roo s" I-Oi - £ 5 z'i.lt.so. Zn5ti.55.'!i tne ci3;i£;otii.on oro-be i-S S-onsc. to the sa~ple solution under conditions allovrinc hybridisation of the detection probe to any target n-ccieic acid in the 'saniple' scluticn. The nitrocellulose filter is then contacted with the sample solution and any target nucleic acid v/nich is hybridised to the detection probe is captured at the capt^are zone by the capture probe. It has been fcjnd, however, that the sensitivity'of nucleic acid detection by conventional dipsticks can be low, particularly if the target nucleic acid is double stranded. Consequently, the presence of target nucleic acid in a sample scluticn can sometimes be xindetected. Circular double stranded target nucleic acid is thought to be virtually -.undetectable _ using conventional dipstick tests. It is desired, therefore, to improve the sensitivity of target nucleic acid detection by diosticks. According to a first aspect of the invention there is provided 'cse of a pl^-urality of different detection probes in a dipstick assay for testing for the presence of a target nucleic acid on a samble solution, each detection orobe being capable of hybridising to a different region of the target nucleic acid, thereby allowing detection of the target nucleic acid utilising the detection probe. The term ""dipstick assay" as used herein means any assay using a dipstick in which sairole solution is contacted with the dipstick to cause sarrole solution to move by capillary action to a capture zone of the dipstick thereby allowing and detected =t the capture zone. According to the first aspect of the invention there is also provided a kit for testing for the presence cf target nucleic acid in a sainple solution which comprises: i) a dipstick comprising: a chromatographic strip having a contact end for contacting the sample solution; and a capture moiety immobilised at a capture zone remote from the contact end, the capture moiety being capable of binding directly or indirectly to the target nucleic acid; and ii) a plurality cf detection probes, each detection probe being capable of hybridising to a different region of the target nucleic acid and thereby allowing detection of the target nucleic acid utilising the detection probes. According to the first aspect of the invention there is also provided a dipstick for testing for the presence cf target nucleic acid in a sample solution which comprises: _ a chromatographic strip having a contact end for contacting the sample solution; a capture moiety immobilised at a capture zone remote from the contact end, the capture moiety being capable of binding directly or indirectly to the target nucleic acid; and a plurality of detection probes releasably immobilised at a probe zone of the chromatographic strip located between the contact end and the capture zone, each detection probe being capable of hybridising to a different region of the target nucleic acid thereby., allowing detection of the target nucleic acid utilising the detection probes. -crcoes, each detecticr. prrbe may comprise a label allowing direc" dstec^icr, cf "lie target nucleic acid utilising the detection probe, or each detection probe may comprise a ' detection ligand allov;ing indirect detection of the target nucleic acid utilising the detection probe. Each detection probe miay comprise a plurality of labels or a plurality of detection ligands. If the detection probe comprises a detection ligand, indirect detection of target nucleic acid utilising the detection probe can be achieved by use of a labelled detection ligand binding moiety. In some embodiments, the detection ligand binding moiety may be multiply labelled, for example a multiply labelled antibody capable of binding the detection ligand. The term 'chron-iatographic strip' is used herein to mean any porous strip of material capable of transporting a solution by capillarity. Dipsticks and kits of the first aspect of the invention may be used in methods for detecting target nucleic acid which are similar to those described above for the conventional dipstick assays. In those methods a capture p:jobe capable cf hybridising to the target nucleic acid is immobilised at the capture of the dipstick. However, there are a number of other arrangements by which the target nucleic acid can be captured to the capturre zone and which are within the scope cf the invention. A capture moiety immobilised at the capture zone may be capable of binding directly or indirectly to the target . riucleic acid by base pairing or ncn base pairing interaction. For exairole, tbe capture moiety may comprise a capt^jre probe capahle cf hybridising directly to the target nucleic acid or to a hook captiire probe bound to the taxget nucleic acid. The hook capture probe comprises a first region capable of hybridising to the target nucleic .acid ajid a second region capable of hybridising to the capture probe. The hook capture probe can be added to the sample solution so that it can. bind to target nucleic acid in the sample solution and be captured by the capture probe as sample solution wicks up the dipstick" by capillary action. The capture moiety may alternatively be a capture liaand binding moiety capable of binding to a capture licand coupled to a capture probe bound to the target nucleic acid, thereby allowing indirect binding of the capture moiety to the target nucleic acid. For exarrrole the capture moiety may be an. antibody or an antibody fragment. In this axrangement, the capture probe may be added to the sample solution and hybridised to target nucleic acid in the sample solution before travelling up the dipstick by capillary action. The capture probe, the hook capture probe and the detection probe may each comprise at least one nucleic acid or nucleic acid analogue. Where a probe comprises more than one nucleic acid or nucleic acid analogue, they are preferably hybridised together. I- According to a second aspect of the invention there is provided use of a detection probe in a-dipstick assay for ; • testingtfor ■ the presence of 'a target • nucleic ;acid -in a j: detecticn prcbe co-rises a pliirality cf labels allo'v^'ing direct detection cf the target nucleic acid when the detection probe has hybridised to the target nucleic acid, or wherein one detection probe comprises a plurality of detection ligands which can be bound by a detection ligand binding moiety thereby allowing indirect detection of the target nucleic acid when the detection probe has hybridised to the target nucleic acid. According to the second aspect of the invention there is also provided a kit for testing for the presence cf target nucleic acid in a sample solution which comprises: i) a dipstick comprising: a chromatographic strip having a contact end for contacting the sarnple solution; a capture moiety immobilised at a capt"'ure zone remote from the contact end, the capture moiety being capable of binding directly or indirectly to the target nucleic acid; and ii) a detection probe capable of hybridising to the target nucleic acid, wherein the detection probe comprises a plurality of labels allowing direct detection of the target nucleic acid utilising the detection probe, or w'herein the detection probe comprises a plurality of detection ligands allowing indirect detection of the target nucleic acid utilising the detection probe. According to a second aspect cf the invention there is also provided a dipstick ^or testing for the presence of target nucleic acid, in a sample solution which cotrrorises: a chromatographic strip having a contact end for contacting the sample solution; a capt'ore TTiciery i^robilised at a capture zone remote from the contact end, the capt'ore moiety being capable of binding directly cr indirecrly to the target nucleic acid; and a detection probe releasably imm.obilised at a probe zone of the chromatographic strip located between the contact end —ai:ad--trhe-Gap-t-u^i^e--ssne7—trh^—detrec-fe-^^ capable- of hybridising to the target nucleic acid, wherein the detection probe comprises a plurality of laiels allowing direct detection of the target nucleic acid utilising the detection probe or wherein the detection probe comprises a plurality of detection ligands allowing indirect detection of the target nucleic acid utilising the detection probe. The capture moiety of the second aspect of the invention may comprise a capture probe capable of hybridising directly to the target nucleic acid cr to a hook capture probe bound to the target nucleic acid, or the capture moiety may comprise a capture ligand binding moiety capable of binding to a capture ligand of a captture probe bound to the target nucleic acid. If the capture moiety comprises a capture ligand binding moiety capable of binding to a capture ligand, kits or dipsticks of the invention may further comprise a capture probe corrrorising a capture ligand. According to a third aspect of the invention there is provided use of a plxnrality of different captuxe probes in a dipstick assay for testing for the presence of a target nucleic acid in a- sample solution, each capture probe being capable of hybridising to a different region of the target nucleic acid, thereby allowing capture of the target nucleic acid to the dipstick by a capture . tnoiety; which, is Accordi:25 to the third aspect of the inver-tior, there is also provided a kit for testing fox the presence of target nucleic acid in a sairple solution v'hich comprises: i) a dipstick comprising: a chromatocraohic strin having a contact end for contacting the sample solution; and a capture moiety immobilised at a capture zone remote from the contact end; ii) a plurality of capture probes, each capture probe being capable of hybridising to a different region of the target nucleic acid and each capture probe capable of being bound by the capture moiety when the capture probe has hybridised to the target nucleic acid; and ootionallv iii) a detection probe capable of hybridising to the target nucleic acid and thereby allowing detection of the target nucleic acid utilising the detection probe, the detection probe being releasably immobilised to a probe zone of the chromatographic strip located between the contact end and the capture zone of the chromatographJ.c strip, or the detection probe being separate from the dipstick. According to the third aspect of the invention there is also provided a dipstick for testing for the presence of target nucleic acid in a sample solution whiich comprises: a chromatographic strip having a contact end for contacting the sample solution; a capture moiety, immobilised at a capture zone remote from the contact end; and a plurality of capttire probes releasably immobilised at a probe zone of the chromatographic strip Ip.cated between the conti5.cc snc c^c ^Ci'S Cc^c""j.'**2 Zen's 6:~'"'"' '"—n^'^^'s ■c^*""'^-^ ii)""^nc capahle cf hyirridising "o a different region of the target nucleic acid and each capture probe capable of being bound by the capture moiety when the capture probe has hybridised to the target nucleic acid. Each capture probe cf the third aspect of the invention roay comprise a capture ligand which can be bound by the capture moiety. Each capt'ure probe of the third aspect of the invention iray comprise a plurality of capture ligands each of which can be bound by the capture moiety. According to a fourth aspect of the invention there is provided use cf a capture probe in a dipstick assay for testing for the presence cf a target nucleic acid in a sample solution, the capture probe being capable cf hybridising to the target nucleic acid, wherein the capture probe comprises a plurality of capture ligands w^hich can be bound by a capture ligand binding moiety of the dipstick, thereby allowing capture cf the target nucleic acid to the dipstick. According to a fourth aspect of the invention there is provided a kit for, testing for the presence of target nucleic acid in a sample solution which corrrorises: i) a dipstick comprising: a chromatographic strip having a contact end for contacting the sample solution; and a capture moiety immobilised at a capture zone, remote from * the contact end; nucleic acid, wherein che capture prcbe is ccuplad to a the capt'jire rr.ciety vhen the capture probe has hybridised tc the target nucleic acid; and optionally iii) a deteccicn crcbe capable of hybridising to the target nucleic acid and chereby allowing detection of the target nucleic acid utilising the detection probe, the detection probe being releasably iir.nobilised to a probe zone of the chroTiatographic strip located between the contact end. and the capture cone of the chromatographic strip, or the detection probe being separate from the dipstick. According to the fourth aspect of the invention there, is also provided a dipstick for testing for the presence of target nucleic acid in a sample solution which comprises: a chromatographic strip having a contact end for contacting the sameIs solution; a capture moiety immobilised at a d&pture zone remote from the contact end; and a capture probe releasably immobilised to a probe zone cf the chxcmatographic strip located between the contact end and the capture cone, the caoture probe being capable of hybridising to the target nucleic acid, v/herein the capture probe comp'rises a plurality of capture licands each- of which can be bound by the capt^ure moiety when the capture probe has hybridised to the target nucleic acid. The detection, probe cf kits of the fo-urth aspect of the invention may comprise a label allowing direct detection of the target nucleic acid utilising the detection probe, or a - detection ligand allowing indirect detection of the target nucleic acid utilising the detection probe. Kits ajn.d dipsticks cz the invention which include a detection probe ccrriprising one or more detection iigands iriay further comprise a l3±)elled detection ligand binding moiety for detecting detection probe bound to target nucleic acid at the capture zone of the dipstick. Preferably the or each label is non radioactive. Examples of suitable labels include textile dyes, a metal sol such as colloidal gold, and coloured particles such as coloured latex particles. Examples of suitable ligands include biotin (detected for example by a labelled anti-biotin antibody, or by a labelled streptavidin or avidin comprising moiety) , fluorescein (detected fcr example by a labelled an.ti-flourescein antibody) and DNV (detected for example by a labelled anti-DN? antibody) . It will be appreciated that kits of the invention m^ay f^urther comprise any reagent required for the detection of target nucleic acid in a sample solution. Where appropriate, dipsticks and kits of the invention may be used in the following types of dipstick assay to test for the presence cf a target nucleic acid in a sample solution: 1) A dipstick is provided which comprises a chxomiatogxaphic strip having a contact end and a captiire probe immobilised at a capture zone remote from the contact end, the capture probe being capable of hybridising to the target nucleic acid. A detection probe (or a plurality of different detection probes) is,-contacted with the sample solution under conditions for hybridisation of the detection probe (or probes) to the target nucleic acid. The sample solution is contacted with the contact end of tlie dipstick to cause ^" zor^e/ thereby ailDv:inr target nucleic acid aad the detecticr. probe (cr prcbes) ro move with the saniple solution to the capture ZOTI'Z:, and target nucleic acid to be capoured at the capture zone. Detection probe (or -Drobes) can then be detected for at the capture cone. The presence of detection probe (or probes) at the capture zone indicates that target nucleic acid was present in the sample solution. In a variation of this assay, the detection probe (or probes) rriay be releasably irrjnobilised to the dipstick between the contact end and the capture zone instead of being separate from the dipstick. When the contact end of the dipstick is contacted with the sample solution causing the sample solution to move by capillary action to the capture zone, the detection probe (or probes) is released into the sample solution so that released detection probe (or probes) can hybridise to target nucleic acid in the sample solution as it moves to the capture zone. In f-'urther variations of this assay, the detection probe (or probes) may be separate from the sample solution and contacted with the capt'ure cone of the dipstick. This vrill usually be done after the contact end of the dipstick has been contacted with the sample solution. The detection probe (or probes) may be contacted directly with the capture zone, or the detection probe (or probes) may be in a separate probe solution which is contacted with the contact end of the dipstick to cause the probe solution to move hy capillary action to the capture zone. 2) A dipstick is provided which comprises a chromotographic strip having a contact end and a capture moiety immobilised ■ at a captiire zcne ren^.ore from the contact end, the capture moiety being capable cf binding a capture probe hybridised to the targec nucleic acid. The capt'.ire probe (or a plurality cf different capture probes) is contacted with the : sample solution under conditions for hybridisation of the capture probe (or probes) to the target nucleic acid. The sample solution is contacted with the contact end of the dipstick to cause sample solution to move by capillary • action to the capture zone, thereby allowing target nucleic ' acid and the capture probe (or probes) to oiove with the sample solution to the capture zone, and target nucleic acid to be captured at the capture zone by binding of the capt-ure moiety to the capture probe. Target nucleic acid can then be detected' for at the capture zone. Target nucleic acid may be detected using a detection probe (or probes) as described for assay (1). The detection probe (or probes) may be added to the sample solution with the capture probe or separately from the capture probe (in any order). Alternatively the detection probe (or probes) may be releasably immobilised to the dipstick between the contact end and the capture zone, or may be contacted separately with the capture zone as described for assay (1) . In a variation of assay (2), the capture probe (or probes) instead cf being mdxed with the sample solution, may be releasably immobilised to the dipstick between the contact end -and the capture zone. When the contact end of the dipstick is contacted with the sanrole solution causing the sample solution to move by capillary action to the capture zone, the capture probe (or probes) is released into the sample solution so that released capture probe (or probes) is released into the sample solutioii so -that released captxixe probe (or probes) can hybridise to target nucleic "/ probe (cr prcbes) v.-hicr. may be contacted. v.-ith the sancle solution; releasably immobilised to the dipstick between the contact end and the capture zone, cr contacted separately with the capture zone. In a further variation of assay (2), the capture probe (or probes) may be contacted with the capture zone before, (or exceptionally, at the same tim.e as) the sample solution reaches the capfore zone by capillary action. . This will allow the capture probe (or probes) to be bound by the capture moiety at the capture zone so that target nucleic acid may be captured. The capt^ure probe (or probes) may be in a separate capture probe solution which is contacted separately with the capture zone by directly applying it to the capture zone, or by contacting the capture probe •solution with the contact end of the dipstick to cause the capture probe (or probes) to move by capillary action to the capture zone.- Subsequent contact of the contact end of the dipstick with the sample solution will allow target nucleic acid reaching the capture zone by capillary action to be captured there. Again, target nucleic acid may be detected for using a detection probe (or probes) which may be contacted with the sample solution, releasably immobilised to the dipstick between the contact end and the capture zone, or contacted separately with the capture zone. As an alternative to use of a detection probe (or probes) in assay (2) , the target nucleic acid may be labelled directly in the sample solution, for, example by covalent attachment of a label to the 'target nucleic acid. This may be achieved by contact of a precursor label with the satrple solution and , incubation of the sample solution and precursor label vmder concii-t i.cr^3 z.c^ cov5.I.~n- E.titi2.ciimsn^ O'z tins 1 HJD-^" Z.O -3.x"~5" nucleic acid. The capture roiety cf assay (2) may be a universal capture probe capable cf hybridising to the capture probe, or the capture moiety rriay be capable of binding by non base pairing interaction to the capture probe. For example, when the capture probe comprises one or more capture ligands, the capture moiety is a capture ligand binding moiety. Where the dipstick assay uses more than one probe capable cf hybridising to the target nucleic acid it is preferred that all the probes are added to the sample solution and that hybridisation is carried out in a single step. This simplifies the assay, making it easier and quicker to perform. It has been found that the sensitivity cf detection of tairget nucleic acid using a one step hybridisation assay is about eq'j.al to the sensitivity cf detection when hybridisation is carried out in multiple steps. Multiple step hybridisation may be carried out by sequential hybridisation of the different probes to the target nucleic acid in the sample solution, or by contacting the dipstick with different solutions each containing a different probe.- Usually, the latter m.ethod of multiple step hybridisation will involve washing the dipstick between each contact with a different probe solution. Whilst there may be circumstances in which multiple step hybridisation is preferred, it will be appreciated that the simpler and quicker format of one step hybridisation will usually be preferred. It is most, preferred that the sample solution is of suitable composition to allow the hybridisation reactions to take : base pairing interacticr.s to take place (for £xa~ple betveen. a detection ligar.d and a detection ligand binding rr.oiety and betv;een a capt'jjre ligand and a capture ligand binding moiety) and transport a complex comprising target nucleic acid and one cr mere hybridised probes and (optionally) ligand binding moieties by capillary action up the dipstick. Using such a sample solution, it will be appreciated that the hybridisation reactions can then be carried out in a. single step, and any ligand-ligand binding mciety interactions can take place, before the sample solution is contacted directly with the contact end of the dipstick (without the need to first dilute or alter the sample solution) . Ligand-ligand binding moiety interactions can additionally cr alternatively take place on the dipstick if desired as the sample solution travels to the captxire zone. Simple and rapid dipstick detection cf target nucleic acid is thereby facilitated. V?e have found that such results are achieved with sample solutions comprising a standard hybridisation buffer (such as SS?E buffer or Tris buffer) with salt, detergent and a blocking protein such as ESA or powdered rrdlk. Th^ sensitivity of detection of target nucleic acid using such assays has been found to be about equal to or better than that of other dipstick assays. Preferably the regions of the. target nucleic acid to which the capture probe (s) and detection probe (s) bind are at least 10 nucleotides anart- There is also provided according to the invention use of a dipstick or a kit of the invention for testing for the Preferably ::he career nucleic acid is Chlairydia tracho:riB.tis nucleic acid. There is also provided according to the invention a probe for detectin3 or capturing target nucleic acid which comprises a nucleic acid cr nucleic acid analogue capable of hybridising to the target nucleic acid^ wherein the nucleic acid or nucleic acid analogue is coupled to a plurality of labels allowing direct detection of the target nucleic acid when the probe has hybridised to the target nucleic acid, or wherein the nucleic acid "is coilpled to a plurality of ligands which can be bound by a ligand binding moiety to detect or capture the target nucleic acid ^h'^n the probe has hybridised to the target nucleic acid. In order to link the ligand or the label to the nucleic acid or nucleic acid analogue it will sometimes be necessary to use a modifier comprisina a first reactive crouo ca-oable of reacting with the nucleic acid or nucleic acid analogue and a second reactive group capable of reacting with the ligand or label. For example, the first reactive group iriay comprise phosphoramidite which is capable of reacting with a hydroiyl group of the nucleic acid or nucleic acid analogue. If the ligand or label comprises a carboxyl group, the second reactive group may comprise a primary amino group. An example of a suitable modifier for linking a ligand cr label to a 5^-OH cr 3'i-OH of the nucleic acid or analogue is 6-(trifluoroacetylamino) hexyl- (2-cyanoethyl)- {N,N-diisopropyl) -phosphoramidite , (C6-TFA) . The chemical structTores of some other modifiers suitable to link a ligand ar.alow-ie are sh.ov.T- in Fig'^re 5. These modifiers further coTT.prise a third reacoive group (a protected OH group) to react with a phosphate group thereby en.abling nucleotides to be joined together by reaction with the phoshporarr.idite and prooecteo OH croups. Fi^g^ure 5 shows the chemical structures after reaction with biotin. Once the modifier has reacted with the nucleic acid or nucleic acid analogue and the ligand or label to link the nucleic acid or nucleic acid analogue to- the ligand or label, the reacted modifier is termed herein a 'linker'. For each label or ligand of the plurality of labels or ligands a linker may covalently couple the label or ligand to the nucleic acid or nucleic acid analogue. A comb-like structure is thereby formed (see Figure 4). The plurality cf labels or ligands may be covalently coupled to the nucleic acid or nucleic acid analogue by a branched linlier. A fork-like str^actvure is thereby formed (see Fig'ure 4) . The cr each linker preferably comprises a non-nucleotide, preferably polyethylene glycol. Preferably the ligand or label is coupled to the nucleic acid or nucleic acid analogue by a spacer- In order -to link the ligand or the label to the sapcer it will sometimes be necessary to use a modifier comprising a first reactive group capable of reacting with the spacer and a second reactive group capable of reacting with the ligand or label. An example of a s\iitable modifier is C6-TFA. Once the modifier h=3 reacted v.'ith the spacer ar-d the lig=r-d cr label to lirJ-: the spacer to the ligar-d or label, the reacted modifier is terr^ed herein a 'linker'. Preferably the spaoer comprises a nucleotide cr hexaethyleneclyool phosphate, Preferably the label is a nonradioactive label. Embodiments of the invention are now described by way of exarrole with reference to the accompanying drawings in which: Figure 1 illustrates a method for testing for the presence of target nucleic acid in a sample solutions-Figure 2 illustrates schematically the ei-iperimental setup for example 1; Figure 3 illustrates schematically the experimental setup for example 2; Figure 4 shows schematically two different arrangements of detection probe coupled to multiple detection ligands; and Figure 5 shows the chemical structures of examples of linkers linked to biotin detection ligands for reaction with a detection probe; Figure 6 shows the effect of probe labelling on assay s ens i t ivi ty; and Figure 7 shows the results of a one-step hybridisation assay The following examples relate to detection of a DNA fragment of the cryptic plasrrdd of Chlamydia trachomatis (CT) . CT is one of the most common causes of sexually transmitted disease. CT infections can cause infertility and,- d^^ring pregnancy, can result .in spontaneous abortion, still birth or postpartum endometritis. In neonates, CT infection can cause blindness and chronic respiratory disease, ^^proximately 10% of infected, men and upto .70% of infected accurate diarr.csis cf CT infeccion is imocrtar.c so that early treacrie-c cf che disease can be initiated. In examples 1 and 3 to 5 below, a dipstick 10 is used to try to detect dcjible stranded CT target nucleic acid 12 in a sample solution 14. The dipstick 10 comprises a strip of nitrocellulose 16 having a contact end 18 for contacting the sample solution 14 and a capture probe 2 0 immobilised at a capture zone 22 of the nitrocellulose strip IG reirote from the contact end IS, An anti-biotin antibody-dye conjugate 24 is releasably immobilised at a conjugate zone 25 of the nitrocellulose strip located between the contact end 18 and the capture zone 22. The capture probe 20 is capable cf hybridising to a first sequence of one strand (the first strand) cf the target nucleic acid 12. A detecticn probe 23 (or detection probes) and a helper probe 30 (or helper probes) each capable of hy-bridising to distinct regions of the first strand cf the double stranded target nucleic acid 12 are then added-to the sample solution 14. The detection probe 23 comiprises a nucleic acid coupled to biotin (using methods well known to those of skill in the art) . The sample solution 14 containing the detection probe 2S and the helper probe 3 0 is then heated to a temperature sufficient to separate the complementary strands of the double stranded target nucleic acid 12 from each other- s-t least in the region of the first strand to which the detection probe 28 axid helper probe 3 0 bind/ and is then cooled to allow, hybriciisation of the detection probe 28 and the helper probe 3 0 to the first strand of the double stranded target nucleic acid. Hybridisation of the detection probe and helper probe to the first strand prevents the secozid str=r-i frcT. ra-H.rj::ealinc to the first strand; a- least in "h= recion cf the first strand to v.hich the detection prche and the helper probe are bound. The contact er.d 13 of the dipstick 10 is then contacted with the sample soliition 14. The sample solution 14 and any target nucleic acid 12 hybridised to the detection probe 23 and the helper probe 3 0 moves up the dipstick 10 by capillary action. As the sample solution 14 passes the conjugate zone 2S, it mobilises the anti-biotin antibody-dye conjugate 24. H.eleased anti-biotin antibody-dye conjugate 24 can then bind to the biotin of the detection probe 23 hybridised to the target nucleic acid 12. Complex formed between the anti-biotin antibody-dye conjugate 24, the detection probe 28, the helper probe 30 and the target nucleic acid 12 then wicks up the dipstick 10 to the capture cone 22 where the target nucleic acid of the complex can hybridise to the immobilised capture probe 20. The helper probe 3 0 is thought to facilitate hybridisation of the target nucleic acid to the capture probe 20 on the dipstick. The capture probe 20 is immobilised at. the capture zone 22 in such a way that it canjiot be mobilised by the sample solution 14 as it moves past the capture 2one 22. Consequently, the complex bound to the capture probe remains in the capture zone and can be detected by the presence of the dye' cf the anti-biotin antibody-dye conjugate at the capture zone. • If there is no CT target nucleic acid in the sample solution, the detection probe 28 cannot" be ^capt\ired at the • zone. If there is CT target nucleic acid in the sample solution, bui insufficient amo^Lints of the target: nucleic acid can be captured at the capture zone the presence of the target nucleic acid in the sample solution will not be detected. The capture of target nucleic acid described above is referred to as direct probe capture, la example 2 an. antibody capture technique is used. In this technique, an antibody is irnmobilised at the capture zone cf _the dipstick instead of the capture probe. The capture probe is coupled to a capture ligand (such as biotin) which can be bound by the antibody and is added to the sample solution with the helper and detection probes. The capture probe hybridises to the target nucleic acid at 'the same time as the helper and detection probes. The d'etection probe is coupled to dye particles, The contact end of the dipstick is contacted with the sample solution after the caoture, helper and detection probes have hybridised to the target nucleic acid. Complex containing the target nucleic acid, capture probe, helper probe and detection probe is then captiired at the capture zone by the antibody immobilised at the caoture zone. Presence of tarcet nucleic acid in the sample solution is detected by the presence cf the dye particle at the capture zone. Thus, hybridisation of the capture probe to" the tarcet occurs in the sample solution rather than on the dipstick. It has heen found that the sensitivity of detection of target nucleic acid can be reduced if the distance between-, the region cf the target nucleic acid to-which the capture r-vmc-ses is .ess *ir,c^zi 2€ "uclaotides. Thus, it 13 least 2 5 . nuc lee tiles and preferably at least 2 30 nucleotides. The probes used in the examples are selected frr;m' the nc 11 owrncj trcbe S'^c~'^n^^s ■ SEQ ID No 1: 5' GAT J-J^A l^.TC CCT TTA CCC ATG PJJi SEQ ID No 2 : 5 ' CTT OCT GCA AAG ATA AAA TCC CTT SEQ ID No 3 : 5 ' TAA A\T GTC CTG ATT AGT GAA ATA AT SEQ ID No 4 : 5 ' TCG GTA TTT TTT TAT ATA A^C ATG AA^ A SEQ ID No 5 : 5 ' TGC A^G ATA TCG AGT ATG CGT TGT TA SEQ ID NO 6: 5' AAA GGG AAA. ACT CTT GCA GA SEQ ID No 7:5' TCT TTT CTA AAG AC^. AA^. A^iG ATC CTC GAT SEQ ID No B : 5 ' 7GC A^^C TCT TGG TGG TAG ACT TTG C SEQ ID No S: 5' GCG CAC AGA CGA TCT ATT TTT TGC A SEQ ID No 10: 5' CGG GCG ATT TGC CTT AAC CCC ACC A SEQ ID No 11: 5' CC\ AGC TTA AGA CTT GAG AGG AGC G SEQ ID No 12: 5' CAT GCG TTT CCA ATA GGA TTC TTG G S2Q ID No 13 : 5 ' CAC AGT CAG AAA TTG GAG TGC TGG C SEQ ID No 14: 5' CTT GCT GCT CGA ACT TGT TTA GTA C SEQ ID No 15: 5' AGA AGT CTT GGC AGA GGA AAC TTT T SEQ ID No 1£: 5' CTA GA^. TTA GAT TAT GAT TTA AA^^ GGG SEQ ID No 17: 5' TTC ATA TCC AAG GAC AAT AGA CCA A SEQ ID No 15: 5' TGA TCT ACA AGT ATG TTT GTT GAG T SEQ ID No IS: 5' TGC ATA ATA ACT TCG AAT A^iG GAG A^.G SEQ ID No 20: 5' TCC CTC GTG A.TA TAA CCT ATG CG^ SEQ ID No 21: 5' CAG GTT GTT AAC AGG A.TA GCA. CGC SEQ ID No 22: 5' CTC GTT CCG AAA TAG A-AA ATC GCA. SEQ ID No 23: 5* GGT AAA. GCT CTG A.TA TTT ClAA "GAC SEQ ID No 24: 5' CTG AGG CAG CTT GCT A.AT TAT GAG T v-.-y-—.V^ ""— ■ -,^-^^.y- — ^ ^^,--';^^^",, -,^,,^~^ ■^""'0 V-— —-— •! . ^*— ^ ^ -^ w*J _. «... > ."— ' -^ ^^^^.— 1:--. V L-w"—^_^_ ; *_ - w. -- L_w —-^ biotin lirJ-:ed to a lirJcer ccnprising a reacrive group (phosphcrar.idite) was reacted with a nucleotide cf the detection cr capture probe or with a spacer lirJ:ed to a nucleotide cf the deteccion or capture probe. The reactive group cf the iirier was reacted with the nucleotide or spacer using a PerSeptive Biosystems E>:pedite 8 903 synthesiser. The lirJ-zer may be of linear or branched structure and cf nucleotide or, preferably, non-nucleotide tv-pe (Fig 5A and B) . More preferably the lirJ Example 1 £>nDerimental set un: The e>:perimencal setup is sho\\'n schematically in Figure 2. Capture: direct probe capture using probe Seq ID No 22 imiTiobilised to the dipstick by BSA; Detection fcrmat: one cr more detection probes comprising a probe of Sec ID No 20, 21, 23 and 24 at 10" copies, each probe is coupled to biotin and is detected by an anti-biotin antibody-dye conjugate;. Helper probes: SEQ ID No 4 and S'^^Q. ID ^o 5, at 10-- copies; Target: 572 bp double stranded DNA at 10"° copies. Results 1 Detection Sec Z'D S^z^ ID S^q^ ID -Stri ID Prcbe ■ No 2 0 No 21 No 23 No 2 4 Probes ::3 23 ::r 2j No 23 No 21 No 21 No 22 a: ^1 (i 2^ tc 24 £: 2-3 5: 24 5: *. 4 Signal 3.0 2.C 3.0 3.0 2.5 3.5 3 Detect icr. 5eq 12) No Probes 23Sc21&23 Signal 4.0 4 Detection Seq ID No 20 Probes -5c2lS:23 «24 Signal 4.5 These results show that increasing the number of detection probes increases the senstivity of detection cf target nucleic acid. Example 2 2>rosritri'en.tal setuo Capture fcrr^at: antibody capture - anti-biotin ar.tibody irrraobilised to the diostick. Canture probe Seq ID Nos 20, 21, 22, 23 and 24 coupled to biotin at 10- copies. Detection format: detection probe comprising a probe of Seq ID No 17 coupled to a dye particle by 3SA; Helper probes: SEQ ID No- 6 and SEQ ID No 7, These helper probes hybridise to regions cf the target nucleic acid adjacent the region recognised by SSQ. ID No 17; Target: 872 bp as DNA at 10'- to 10' copies. r.es'-ilt: Capture £er II Seq IZ £er ID Ser ID Ser ID All probe (s) x:^ 2: M- 21 Nc 22 No 23 Kz 24 5 Signal* 10 1115 (w3.rc:6t ID"" copies) These results show that the sensitivitv of tarcet nucleic acid detectic- is improved by the use of multiple detection probes. Example 3 E^roerindental setuo Capture fcrmat: direct probe capture (cp) using Seq ID No 21 cr Seq ID No 2 2 iTTjnobilised to the dipstick; Detection prcbe: biotin detection ligand linked to a lin]-:er coTTiprising a reactive (phcsphoraoiidite) group was reacted with a spacer coupled to the detection probe (dp) Seq ID No 2 0 cr with each cf two spacers coupled at different positions to the detection probe (dp) Seq ID No 2 0. Different lengths and t\'pes cf spacers were used. The detection prcbe was present at 10-* conies. Detection fcrrrat: anti-biotin antibody-dye conjugate; Helper probes: SEQ ID No 3 and S5Q ID No 4 (these helper probes hybridise to regions of the target nucleic acid adjacent the region recognised by SEQ ID No 21), or SEQ ID No 4 and -SEQ ID No 5 (these helper probes hybridise to ■regions of the target nucleic acid adjacent the region recognised-by SEQ ID No 22) at 10*^ copies; Results Capture probe Seq ID No 21 Seq ID No 22 Copies target DNA 10'° 10' 10" 10^ dp-Ng-5'" 4.0 0.0 3.0 0.0 dp-Ng-B-N^-B^' 4.0 1.5 4.0 1.5 dp-Ng-B-Ng-B^' 4.5 2.0 4.5 2.0 dp-N5-3-SN.5N3-5^' 4.5 2.0 4.0 2.0 BNg-dp-N^B^* 4.0 1.0 3.Q 0.5 B = biotin coupled to a' lirJier N = nucleotide spaoer (the nuinber designates the nurriber cf Fxucleotide mononners) 3 = Hexasthyleneglycol phosohate spacer Conclusions These results show that there are slight differences in the strength of the detection signal when spacers of different . length and type are used, but these differences are not sufficient to significantly alter the sensitivity of detection. Other experiments showed that the sensitivity of detection was not fo'-ind to be significantly different if a plurality of biotin detection ligands were linked to a single position of the detection probe using one or more branched linkers, compared to use of a separate lirJcer to link each of a plurality of biotin detection ligands to a different position cf the detection probe (these different types are 5ti.'*~'J.c"^'U.'^"s *■ ~ " ^33 c"^"^~*^zr'*"~d 0*3c3.MSs ^ji— v'i.el.d cd 'CiroO'S i.i_ri]"iec. tZD c'"^" c!L'_izr5."" "" C' c— G-s^scti-on Z*~^n.-d.3 "Ls u.3'—5.12.*/ lower than v.'ith coui-like srr-uctures. Example 4 Experimental setu'o Capture f crmat: direct probe capture icp) Seq ID No 17 immobilised to the dipstick; Detection probe: detection probe (dp) comprising a probe of Seq ID No 2 0 coupled to one or multipl^e biotin detection ligands. Each biotin detection licand was coupled to its probe by a six nucleotide spacer. Detection probe was used at 10-* copies. Detection format: anti-biotin antibody-dye conjugate; Helper probes: SEQ ID No G and SEQ ID No 7 (these helper probes hybridise to regions of the target nucleic acid adjacent the region recognised by SEQ ID No 17);-SEQ ID No 1 and SEQ ID No 3 (these helper probes hybridise to regions of the target nucleic acid adjacent the region recognised by SEQ ID No 20) at 10- copies; Target DNA: 372 bp ds DNA fragment cr 101B6 bp plasmld DNA. cargel DNA 1x3 C.J 0.0 2x3 1.5 CO 3x3 2.0 C .5 4x3 3.0 1,0 5x3 3.5 1.5 Sx3 4.5 2.5 7x3 4.5 2.5 8x3 4.0* 2.5 * B = biotir* coupled to a lirJ-;er Conclusior.s These results show that increasing the nun?h)er of biotin detection ligands per detection probe increases .the sensitivity of target nucleic acid detection, Th::ree or more biotin detection ligands per detection probe causes a greater than 4-fold amplification of the detection signal compared to a single biotin detection ligand per detection probe. Under the conditions used in this example, rriajciTTium signal amplifioation was obtained .with S and 7 biotin detection ligands per detection probe. Exainple 5 : Sffect of probe labelling on assay sensitivity Experimental 5et-un - Capture format: oligonucleotide probe capture Seg: CGT CTG TTG TGT GAG TCT GG (SEQ ID NO 2S) immobilised on dipstick merrbrane; Detectic" f-rr.at: ar.ti-bioriri ar.tibody - collcidal gcli coniucate; Target r.uclei" arid: ?Xn amplicon, 12 0 nt, sjj^T.thesised by NASBA amplification reaction of HIV positive sa~le. One arrplification reaction gives about 10** copies of RMA target modecule. Results: Ficure 6 Conclusion: Multiple biotin labelled detector probe gives more that two orders cf rr^agnitude iniprovement of the assay* sensitivity. Example 6: Cne-step Nucleic Acid Dipstick Assay Detection of Chi amydl a tra choma t i s E:>merirriental Set-uo: Reagents: Capture f crrriat: oligonucleotide probe capture immobilised on dipstick merirane via BSA carrier; Detection f crmat: muItiole biotin 1abelled detector probe; anti-biotin antibody - colloidal gold conjugate; Sample "oreriaration: Chlamydia trachomatis (Ct) elementary bodies (EB) celles were prepared in ceoncentrations from 10^ copies/^il to 10- copies/^il in PBS buffer and heated at lOO'C ' for 2 0 minutes; Hvbr i di s a t i en / dio s _ i c >: running buffer : Standard hybridisation buffer comprising salt, detergent and a blocking protein sucn as 3SA or powdered milk. Method: The detection probe, helper probe and 5x10^ - 5x10^ copies of EB diluted in hybridisation buffer made up to 8 0 ^1 and heated at lOO^C for 7 minutes. The mlxure was then centrifuged briefly to collect all the liquid and mixed with 20 1^1 anti-biotin Ab colloidal gold. The whole 100;il mixture were wicked up on dipstick and let to develop a signal. Results and Discussion The results presented In the Table and Figure 7 showed that about 10* copies of Ct E3 could be detected with one step nucleic acid dipstick assay in less than an hour including the sarrrole preparation step. Although the so presented dipstick detection assay has a sensitivity of detection about equal to other samdwdch hybridisation assays it has the major advantages of soeed and simolicitv. A. sandwich hybridisation assay for detection of Ct disclosed in PCT WO 93/1322 for example, is a complex multi-component microtitre plate format assay, which coul dnot be accoirolished for less than 5 hours. This" assay is a multi-step assay, which requires a gradual addition of its conponents in a defined order with incubations and washing The nucleic acid dipstick assay subject of this inventior. could be dene in one step with no need of different steps f or addition of components and washings . This sandwich hybridisation assay does not require more than one solution conditions in order to render them advantageous for hybridisation and other affinity pair formations. The same solution conditions could serve a free migration of the components through the dipstick membrane as well. Figure legends Figure 2 210 - capture probe 24 0 - helper probes 250 - dipstick membrane 2c0 - Anti"3iotin Ab/Dye conjugate Figure 3 310 - capture probe coupled to biotin 3 20 - detection probe - dye conjugate 33 0 - 872 bp dsDNA Target 3 40 - helper probe 3 50 - Antibiotin antibody immobilised to the dipstick membrane Figure 4 A) Comb-like type B) Fork-like type Filled circles = detection ligand Br = branch generating monomer Figure 6 ' ' Effect of probe labeling on sensitivity Figure 7 One-step nucleic acid dipstick assay detection of Chlamydia. trachomatis, The numbers indicate the number of elementary bodies of Chlamydia trachomatis *NC: Negative control Figure 8 . One-step nucleic acid dipstick assay detection of ^Chlamydia trachoma tir Claims 1- A kit for testing for the presence of target nucleio acid in a sample solution which comprises: i) a dipstick comprising: a chromatographic strip having a contact end for contacting the sample solution; a capture moiety, immobilised at a capture zone remote from the contact end; ii) a plurality of capture probes, each capture probe being capable of hybridising to a different region of the ^ target nucleic acid and each capture probe capable of being bound by the capture moiety when the capture probe has hybridised to the target nucleic acid; and optionally iii) a detection probe capable of hybridising to the target nucleic acid and thereby allowing detection of the target nucleic acid utilising the detection probe, the detection probe being releasably immobilised to a probe sone of the chromatographic strip located between the contact end and the capture zone of the chjromatographic strip, or the detection probe being separate from the dipstick. 2. A dipstick for testing for the presence of target nucleic acid in a sample solution which comprises: a chromatographic strip having a contact end for contacting the sample solution; a capture moiety, immobilised at a capture zone remote from the contact end; and a plurality of captirre probes releasably immpbilised at a probe zone of the chromatogxaphic strip located between the contact end and the capture zone, each capture probe being capable of hybridising to a different region of the target nucleic acid and each-captiore probe capable of being bound by the caprure moiety v/nen the capture probe has hybridisef to th"^ tar~et nucleicr acid.. 3. A kit according to claim 1 or a dipstick according to claim 2 in which each capture probe comprises a capture ligand which can be bo^and by the capture moiety to bind the capture probe to the capture moiety. 4. A kit or dipstick according to claim 3 in which each capture probe comprises a plurality of capture ligands each of which can be bound by the capture moiety. 5. A kit or dipstick according to any of claims 1 to 4 in which the detection probe comprises a label allowing direct detection of the target nucleic acid utilising the detection probe, or in which the detection probe comprises a detection ligand allowing indirect detection of the target nucleic acid utilising the detection probe, 6. A kit or dipstick according to claim 5 in which the detection probe comprises a plurality of labels or a plurality of detection ligands. 7. A kit or dipstick according to' any of claims 1 to 4 in which the detection probe is a plurality of detection probes, each detection probe being capable of hybridising to a different region of the target nucleic acid and thereby allowing detection of the target nucleic acid utilising the detection probe. * 8. A kit according to claim 7 in which -each detection . probe .couprises a plurality of l^els or : a plurality detection ligands. 9. A kit fcr testing for the presence cf target nucleic acid in a sample solution which comprises: i) a dipstick conprising: a chromatographic strip having a contact end for contacting the sample solution; and a capture moiery immobilised at a capture zone remote from the contact end; ii) a capture probe capable of hybridising to the target nucleic acid, wherein the capture probe comprises a plurality of capture ligands each of which can be bcJind by the capture moiety when the capture probe has hybridised to the target nucleic acid; and optionally iii) a detection probe capable of hybridising to the target nucleic acid and thereby allowing detection of the target nucleic acid utilising the detection probe, the detection probe being releasably immobilised to a probe zone of the chromatographic strip located between the contact end and the capture zone of the chromatographic strip, or the ■ detection, probe being separate from the dipstick. 10,. A dipstick for testing for the presence of target nucleic acid in a sample solution which comprises: a chromatographic strip having a contact end for contacting the sairrole solution; a capture moiety immobilised at a capture zone remote from the contact end; and a capture probe releasably immobilised to a probe zone of the ciiromatographic strip located between the contact end and the capture zone, the capture probe being capable cf hybridising to the target nucleic acid, wherein the capture 11. A kit according to clairr. 9 or a cipstic--: according tc claim 10 ir. which the detection probe comprises a label allowing direct detection of the target nucleic acid utilising the detection probe, or in which the detection probe comprises a detection licand allovring indirect detection of the target nucleic acid utilising the detection probe. 12, A kit cr dipstick according to claim 11 in which the detection probe comprises a plurality of labels or detection ligands. 13 . A kit according to claim 9 or a dipstick according to claim 10 in which the detection probe is a plurality of detection probes, each detection probe being capable of hybridising to a different region of the target nucleic acid and thereby allowing detection of the target nucleic acid utilising the detection probe. 14. A kit cr dipstick according to claim 13 in which each detection probe comprises a plurality of labels or detection ligands. 15. A kit for testing for the presence of target nucleic acid in a sample solution which corrorises; i) a dipstick comprising: a chromatographic strip having a contact end for contacting the sample solution; and a capture moiety immobilised at a capture zone remote from the contact end the capture moiety being capable of binding directly or indirectly to the target nucleic acid; and ii).:..._a plTorality of detection probes-, ,eacli.detection probe a chroT.2.togr=p:iic srrip having a cor.tact end for conts.czi'na the sample sclutioz.; a capture mciety ir.raobilised at a capture zone rexote from the contact end, the capture moiety being capaile of binding directly or indirectly to the target nucleic acid; and ii) a detection probe capable of hybridising to the target nucleic acid, wherein the detection probe comprises a plurality of labels allowing direct detection of the target nucleic acid utilising the detection probe, or wherein the detection probe comprises a plurality of detection ligands allowing indirect detection of the target nucleic acid utilising the detection probe. 20. A dipstick for testing for the presence of target nucleic acid in a sample solution which comprises: a chromatographic strip having a contact end for contacting the sample solution; a capture moiety immobilised at a capt^jr-e zone remote from the contact end, the capture moiety being capable of binding directly or indirectly to the target nucleic acid; and a detection probe releasably immobilised at a probe zone of the chromatographic strip located between the contact end and the capture zone, the detection probe being capable of hybridising to the target nucleic acid, vrherein the detection probe comprises a plurality of labels allowing direct detection of the target nucleic acid utilising the detection probe, or wherein the detection probe comprises a plurality of detection ligands allowing indirect detection of the target nucleic acid utilising the detection probe. 21. A kit or dipstick according to any preceding claim in ■ which the capture moiety comprises a capture probe capable^j^^: of hyrridisinr -o che target aucleic acid cr to a hook capture probe bo'jmd to the target niicleic acid. 22. A kit cr dipstick according to any of claims 15 to 20 in which the captizrs moiety comprises a capture licand binding moiety capable of binding to a capture ligand of a capture probe, the capture probe being capable of hybridising to the target nucleic acid so that the capture moiety can thereby bind indirectly to the target nucleic acid. 23. A kit or dipstick according to claim 22 further comprising the capture probe. 24. A kit cr dipstick according to any of claims 5, 6, 8, 11, 12, 14 or 17 to 20 in which the or each label is non radioactive. 25. A kit or dipstick according to any of claims 3, 4, 9, 10, or 22 in which the capture moiety coiiorises an antibody or antibody fragment capable of binding to the or each capture ligand. 25. Use of a dipstick according to any preceding claim for testing for the presence of target nucleic acid in a sample solution. 27. Use according to claim 26 in which the target nucleic acid is Chlamydia trachomatis nucleic acid. 28. A probe for detecting or capturing'target nucleic acid which. comprises a nucleic acid or nucleic acid analogue : ./-*;%f ■ . "■ }■■■■-- "' '*: ■~ \^' ■ ' ■ ■ ' ' '■'- ■,*'-■ .■" ' ■ ,-■'.. :. .. ■ ^ ■ '■ . ■ capable of hybridising to the target nucleic acid/wberein the nucleic acid cr nucleic acid analog^je is coupled to 'a plurality of labels allov/ing direct detection of the target nucleic acid when the probe has hybridised to the target nucleic acid^ or wherein the nucleic acid is coupled to a plurality cf ligands which can be bound hy a ligand binding moiety to detect cr capture the target nucleic acid when the probe has hybridised to the target nucleic acid. 29. A probe according to claim 28 in which for each label cr ligand of the plurality of labels or ligands a linker [as herein defined] covalently couples the label or ligand to the nucleic acid or nucleic acid analogue. 30. A probe according to claim 28 in which the plurality of labels or ligands are covalently coupled to the nucleic acid or nucleic acid analogue by a branched liniter [as herein defined] . 31. A probe according to claim 29 or 30 in which the cr each linker comprises a non-nucleotide, preferably polyethylene glycol. 32. A probe according to any of claims 29 to 31 in which the or each linker is co\'alently coupled to the nucleic acid or nucleic acid analog'ae by a spacer. 33. A probe according to claim 32 in which the- spacer comprises a nucleotide or hexaethyleneglycol phosphate, 34. A probe according to any of claixus 28 to 33 in which the label is a nonradioactive label. 55. Use cf a probe according to any of claims 25 to 34 in a dipstick assay for testing for the presence cf target nucleic acid in a sample solution. 3D. Use cf a plurality of different capture probes in a dipstick assay for testing for the presence of a target nucleic acid in a sample solution, each capture probe being capable of hybridising to a different region of the target nucleic acid, thereby allowing capture of the target nucleic acid to the dipstick by a capture moiety; immobilised to the dipstick, capable of binding the capture probes. 37. Use of a plurality cf different detection probes in a dipstick assay for testing for the presence of a target nucleic acid in a sample solution, each detection probe being capable of hybridising to a different region of the target nucleic acid, thereby allowing detection of the target nucleic acid utilising the detection probe. - ^ 3 8. A method for testing for the presence of target nucleic acid in a sample solution which comprises: providing a dipstick as specified in claim 15; contacting the sample solution with a plurality of detection probes, each detection Torobe being capable of hybridising to a different region of the target nucleic acid thereby allowing direct or indirect detection of the target nucleic acid utilising the detection probes, the detection probes being incubated with the sample solution under conditions for hybridisation of the detection probes with the target nucleic acid; ' • contacting the contact end of the dipstick with the sample solution to cause sample solution to moveJ^by; capillary action to the caDture zone, ther^yfallowing taxget nucleic acid and de-er~icn prcbes to move with zhe saTipie soluticr. to the capture zcr-e, and target nucleic acid tc be capt^ured at the capture cone; and detecting fcr the detection probes at the capture zone. 39. A nethcd fcr testing for the presence of target nucleic acid in a sample solution which comprises: providing a dipstick as specified in claim 16 or 20; contacting the contact end of the dipstick with the sample solution to cause sample solution to move by capillary action to the capture cone, thereby allowing target nucleic acid in the sample solution to be captured at the capture cone and releasing the or each detection probe into the sample solution so that the or each detection probe can hybridise to target nucleic acid; and detecting fcr the or each detection probe at the capture cone. 40. A method for testing for the presence of target nucleic acid in a sample solution which conrorises: providing a dipstick as specified in claim IS; contacting the sample solution with a detection probe capable of hybridising to the target nucleic acid, wherein the detection probe comprises a plurality of labels allowing direct detection of the target nucleic acid utilising the detection probe, or wherein the detection probe comprises a plurality of detection ligands allowing indirect detection of the target nucleic acid utilising the deteciton probe, the detection probe being incubated with the sample solution under conditions for\hybridisation of the detection probe with the target nucleic acid; contacting the contact end of the diDStick with the satnple ■ ^k^W ^^■ '■:' ■■ ^ ■■ "~ ' • : •■■:'■-■■" :: , " / ■ .,;■-/: ,, -■ '■■■:.-^ solution to ^cause sample solution to move :by -capillary action to the capture ccne, thereby allowing target nucleic acid and detection probe to move with the sample solution to the capture cone, and target nucleic acid to be captured at the capture zone; and detecting fcr the detection probe at the capture zone. 41. A method for testing for the presence of a target nucleic acid in a sanple solution which comprises: a) providing a chromatographic strip having a contact end for contacting the sample solution and a capture moiety immobilised at- a capture cone of the chromatographic strip remote from the contact end, the capture moiety being capeible of binding directly or indirectly to the target nucleic acid; b) contacting the contact end of the cliromatographic strip with'the sample solution to cause sanrole solution to • move by capillary action to the capfure zone so that target nucleic acid in the sample solution can be captured at the capture zone by the capt-ure moiety; (c) either: (i) contacting the capture zone with a plurality of detection probes, each detection probe being capable of hybridising to a different region of the target nucleic acid and thereby allowing detection of the target nucleic acid utilising the detection ■ probes; ■ or (ii) contacting the « capture zone with a detection probe capable of hybridising to the target nucleic acid thereby allowing detection of the target nucleic acid utilising the detection-probe,*wherein the detection probe comprises a plurality of labels allowing direct detection of the target nucleic acid utilising the detection probe,•• or wherein the detection probe coirorises. a plurality of detection ligands allowing indirect detection of the target nucleic acid utilising the detection probe; d) re:ncvir-g urihcjnd detection probe from the capture ::one of the chro:r3.tographic strip; and e) detecting for the presence of the or each detectior probe at the captirre zone. ; 42- A method for testing for the presence of target nucleic acid in a sample solution which comprises: providing a dipstick comprising a chromatographic strip having a contact end for contacting the sample solution and a capture moiety immobilised at a capture zone of the chromatographic strip remote from the contact end; contacting the sample solution with a plurality of capture probes, each capture probe being capable of hybridising to a different region of the target nucleic acid and each capture probe capable of being bound by the capture moiety when the capture probe has hybridised to the target nucleic acid; contacting the sample solution with the contact end of the chromatographic strip to cause sample solution to move by capillary action to the capture zone, thereby allowing a comolex comprising taroet nucleic acid and the canture probes to be captured at the capture zone by binding of the capture moiety to the capture probes; and detecting for target nucleic acid at the capture zone. 43 . A method for testing for the presence of target nucleic acid in a sample solution which comprises: providing a dipstick comprising a chromatographic strip having a contact end for contacting the sample solution and . a capture moiety immobilised at a capture zone of the chromatographic strip remote from the contact end; contacting the saimle solution vd.th a capture probe capable 1 of hybridising to the target imcleic^£acid/i^wherein the^ capture probe coraprises a plurality of capt-jxe licands, each of wr-ic]i car. be bo^-rid by the capture mcdety when the capture probe has hybridised tc the target nucleic acid; contactina the saincle solution with the contact end of the chromatographic strip to cause sample solution to move by capillary action -to the capture zone, thereby allowing a complex comprising target nucleic acid and capture probe to be captured at the capture zone by binding of the capture moiety to the capture probe; and detecting for target nucleic acid at the capture zone. 44- A method for testing for the presence of target nucleic acid in a sample solution which comprises: providing a. dipstick comprising a chromatographic strip having: a contact end for contacting the sample solution; a capture moiety immobilised at a capture zone of the chromatographic strip remote from the contact end; and a plurality of capture probes releasably immobilised to the chromatographic strip between the contact end and the capture zone, each capture probe being capable or hybridising to a different region of the target nucleic acid and each capture probe capable of being bound by the capt\rre moiety when the capture probe has hybridised to the target nucleic acid; contacting the sample solution with the contact end Qf the chromatographic strip to cause sample solution to move by capillary action to the capture zone, thereby releasing the capture probes from the chromatographic strip so that they can hybridise to target nucleic acid in the sample solution as it moves to 'the capture zone and allowing a complex detecting fcr targe- nucleic acid at the capture cone. 45. A method fcr testing for the presence cf target nucleic acid in a sample solution which comprises: providing a dipstick comprising a chromatographic strir) having: a contact end for contacting the sample solution; a capture moiety immobilised at a capture sone of the chromatographic strip remote from the contact end; and a capture probe capable of hybridising to the target nucleic acid, the capture probe being releasably immobilised to the chromatographic strip between the contact end and the capture zone,' wherein the capture probe comprises a plurality of capture ligands, each of which can be boimd by the capture moiety when the capture probe has hybridised to the target nucleic acid; contacting the sample solution with the contact end of the chromiatographic strip to cause sample solution to move by capillary action to the capture zone, thereby releasing the capture probe from the chromatographic strip so that it can hvbridise to taraet nucleic acid in the samole solution as the sample solution moves to the capture zone and allowing a complex comprising target nucleic acid and the ■ capture probe to be captured at the capture zone by binding of the capture moiety to the capture probe; and detecting for target nucleic acid at the capture zone. 46- A method for testing for the presence of target nucleic acid in a sample solution which comprises; providing a dipstick comprising a chromatographic strip having a contact end -for contacting the sample solution and a capture moiety immobilised at a capture zone of the chromatographic strip remote from the contact end; ,. ^i providing a pi'-jrality cf capture probes, each capture probe being capable of binding to the capture irioiety and hybridising to a "different region of the target nucleic acid; binding the plurality of capture probes to the capture moiety; contacting the sample solution with the contact end of the chromatographic strip to cause sample .solution to move by capillary action to the capture zone, thereby allowing target nucleic acid in the sample solution to be captured at the capture zone by binding of the target nucleic acid to the plurality of capture probes; and detecting for target nucleic acid at the capture zone. 47. A method for testing, for the presence of target nucleic acid in a sample solution which comprises: providing a dipstick comprising ■ a chromatographic strip having a contact end for contacting the sample solution and a capture moiety immobilised at a capture zone of the chromatographic strip remote from the contact end; providing a plurality of capture probes, each capture probe being capable of binding to the capture moiety and hybridising to a different region of the target nucleic acid; binding the plurality of cauture probes to the capture moiety; contacting the sample solution with the contact end of the chromatographic strip to cause sarrole solution to move by capillary action to the captxire zone, thereby allowing target nucleic acid in the sample solution to be captured at the capture zone by binding of the target nucleic acid to the plurality „of capture probes; and ; detecting for target nucleic acid at the capture zone. A kit for testing for the presence of target nucleic acid in a sample solution substantially as herein described with reference to the accompanying drawings. A probe substantially as herein described with reference to the accompanying drawings.

Documents:

205-chenp-2003-assignement.pdf

205-chenp-2003-claims duplicate.pdf

205-chenp-2003-claims original.pdf

205-chenp-2003-correspondnece-others.pdf

205-chenp-2003-correspondnece-po.pdf

205-chenp-2003-description(complete) duplicate.pdf

205-chenp-2003-description(complete) original.pdf

205-chenp-2003-drawings.pdf

205-chenp-2003-form 1.pdf

205-chenp-2003-form 26.pdf

205-chenp-2003-form 3.pdf

205-chenp-2003-form 5.pdf

205-chenp-2003-other documents.pdf

205-chenp-2003-pct.pdf