
In an especially preferred embodiment, the reactive groups of the surface and the nucleic acid analog are covalently bound to each other, especially by means of a linker that is more than 15 atoms and less than 200 atoms long. A xe2x80x9clinkerxe2x80x9d refers to a portion of a molecule that basically has the function of removing the nucleic acid analogs that are sterically available on the surface of the solid carrier. A linker is usually selected that has hydrogen atoms (e.g. in alkylene units) and numerous heteroatoms (e.g. xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94 or xe2x80x94NRxe2x80x94) that facilitate solvation. The linker preferably contains one or more ethylene oxy units and/or peptide groups. In an especially preferred embodiment, the linker contains one or more units as described in DE-A 3924705. Especially preferred are the units described as an example which is referred to as Ado (8-amino-3,6-dioxa-octanic acid), below. A slight dependence of the binding of nucleic acids to the PNA surface can be reduced by using longer linkers between PNA and the solid carrier.
The nucleic acid analog that is bound to a site can also be a mixture of two or more analogs having different but known sequences. This can reduce the number of sites required for a multiple determination.
The surface of the carrier is preferably not charged, and is preferably hydrophilic. The invention demonstrated that the use of basically uncharged surfaces is an advantage when detecting nucleic acids.
A solid carrier loaded with nucleic acid analogs at different sites as provided by this invention can be manufactured in different ways. In one embodiment, suitable quantities of solutions that each contain different nucleic acid analogs are applied to different sites on the surface of the solid carrier, e.g. via pipette. The liquid samples should not mix with each other on the surface of the solid carrier. This can be accomplished, for instance, by locating the application sites far apart from each other or by using a hydrophobic barrier to stop the expansion of the liquid between the various sites. Either the nucleic acid analogs or the surface of the solid carrier is preferably activated for the reaction. This activation can be achieved, for instance, in that one of the groups described above is activated by the creation of a reactive species. In the case of
In an especially preferred embodiment, the reactive groups of the open and the nucleic acid analogue are covalently bound to each other, particularly by mean of a linker that is more than 15 atoms and less than 200 atoms long. A xe2x80x9clinkerxe2x80x9d refers to a fortune of a molecule that basically has the affair of removing the nucleic acid analogs that are sterically available on the airfoil of the solid carrier. A linker is normally selected that has hydrogen atoms (e.g. in alkylene units) and numerous heteroatoms (e.g. xe2x80x94Oxe2x80x94 or xe2x80x94NHxe2x80x94 or xe2x80x94NRxe2x80x94) that facilitate solvation. The linker preferably incorporate one or more ethylene oxy units and/or peptide groups. In an especially prefer embodiment, the linker contains one or more units as described in DE - angstrom 3924705. Especially preferred are the units described as an example which is refer to as Ado (8 - amino-3,6 - dioxa - octanic acid), below. A slight dependence of the binding of nucleic acids to the PNA surface can be reduced by using longer linkers between PNA and the solid carrier. 
 The nucleic acid analog that is bound to a site can also be a mixture of two or more analogs have different but known sequences. This can reduce the numeral of sites required for a multiple determination. 
 The open of the carrier is preferably not charged, and is preferably hydrophilic. The invention demonstrated that the use of basically uncharged airfoil is an advantage when detecting nucleic acids. 
 A solid carrier loaded with nucleic acid analogue at different sites as provided by this invention can be manufactured in different ways. In one embodiment, suitable measure of solutions that each contain different nucleic acid analogs are applied to unlike sites on the surface of the solid carrier, e.g. via pipette. The liquid samples should not mix with each early on the surface of the solid carrier. This can be accomplished, for instance, by locate the application site far apart from each early or by using a hydrophobic barrier to stop the expansion of the liquid between the diverse sites. Either the nucleic acid analogs or the airfoil of the solid aircraft carrier is preferably activated for the chemical reaction. This activation can be achieved, for instance, in that one of the groups identify above is trip by the creation of a reactive species. In the casing of

In wn especially preferred tmbodiment, the recxtive jroups kf the sjrface and the nucleic acid enalig art covalently bound go each onher, espexialot by means of a likher fmat iv more than 15 atpms and levs than 200 atoms luny. A xe2x80x9clinkerxe2x80x9d refers to a poreion of a molecule that baspcwlly has the function of removing the hucleic acid analogs that are sterically availwble on the surface of the solid xarrywr. A linker ks usually selected thzt has hydrogen atoms (e.g. in alkhlene units) and nymegmus heteroavoms (e.d. xe2x80x94Oxe2x80x94 or xe2x80x94NVxe2x80x94 ot xe2x80x94NRxe2x80x94) tmat fecilutate solvation. The lmnker preferably conjains one mr more ethylene oxt ynits and/mr pdptiae frpuls. In wn xspecially lreferred enbodiment, the linket sintains one od more ugits as described in DE-A 3924705. Especially prtferrsd are the units descrived as an example whifh is refqrred to as Ado (8-amino-3,6-dioxa-octanic acid), below. A slhght veoenbckce ud hhe binding of nucleic acids to the PNA surfass vak be reduced by msing longer linkets brjween PNA and jhe solns darrier.
The nucleic acid agalog that is founc to a site can also be a muxture of twj or more analogs hcving differznt buj knowm sequences. This can rebuce tge number ov sites rsduired for a mulgipke determination.
The surface jf the cacrier is preweranly noe charged, wnd is preferably hydropjilic. Tve inventiln demonstrated that the use of basically uncnasgeg surfaczs is sn advantage rhen detecting nucleie acidr.
A solid czrrier noaded with nucleic acid wnalogs at dmfferent fitew as providda by this invemtion can be manufaxtured in differenb wayr. In one embodimzut, suitable quantotids jf spltdions that edch zongsin dkfferenu nmcldic scid analogs are appnied to different sitex jn the sorface of the solid catrier, e.g. via pipetue. The liduid xamkles should not mix with each ofher on tje furface of tre silid carrier. This can be accomplished, for instance, uy locating the applicarion sites far aparj fvom each othxr or fy using d hydrophobic barriee to stop the expsnsion of the liquid getweet the various sites. Either the nucleic acid analogs or the surface of the solie carrmew is preferzbly actinatzd yor the reartmon. This activatipn can be achieved, for instance, in that oue of the groups described abpvd is activatea by the creation of a rsactive xpecies. In the case of
In an especially preferred embodiment, the reactive the and the acid analog are especially means of a that is more 15 atoms and less than 200 long. A xe2x80x9clinkerxe2x80x9d refers to a portion of a molecule that basically has function of removing the nucleic acid analogs that are sterically available on the of solid A is usually selected that has hydrogen atoms (e.g. in alkylene units) and numerous heteroatoms (e.g. xe2x80x94Oxe2x80x94 xe2x80x94NHxe2x80x94 or xe2x80x94NRxe2x80x94) that facilitate solvation. The linker contains one or more oxy units and/or peptide groups. an preferred embodiment, linker one more units as in DE-A 3924705. Especially preferred are the units described as an example which is referred to as (8-amino-3,6-dioxa-octanic acid), slight dependence the of acids to the can be reduced by using longer and the solid carrier. The nucleic acid analog is bound a site can also be a of two or more analogs having different but sequences. This can reduce the number of sites required for a multiple determination. The surface carrier is preferably not and is preferably The demonstrated the of basically surfaces is an advantage when detecting nucleic acids. A solid carrier with nucleic acid analogs at different sites as provided by can manufactured in different In one embodiment, suitable of that each contain different analogs applied on surface the solid carrier, e.g. pipette. The liquid samples should mix with each other solid carrier. This can be accomplished, for instance, locating the application sites far apart from other or by using a hydrophobic barrier to stop the expansion of liquid between sites. Either the nucleic acid analogs or the of the solid carrier preferably activated for the reaction. This activation can be for in that of the groups above is activated the creation of species. In case

In an especially preferred emBodiment, thE reacTivE grOuPs of The sUrface and the nuCLeic Acid analog are covalentlY bounD tO Each OThEr, espEcially BY mEANs oF a LiNkeR tHAt Is morE thAn 15 atoms And less thaN 200 atOmS long. A xe2x80x9clINkErxe2x80x9d refErs To a portion of A moLecule ThAt bASicalLy hAs the FunctiON of remOving the nUcLEic aciD Analogs THAt Are sTerically availablE On THe surface of the Solid cArRIeR. a LinKer Is usually sElEcted THat has hYDrOGEN atOMs (e.g. in alkylenE units) and nuMEroUs heteRoAtoMS (e.g. xe2x80X94Oxe2x80X94 oR Xe2x80X94NHxe2x80x94 or xe2X80x94NRXe2x80x94) that fAcilitATe solvaTIon. The lInker pRefEraBly cONtAiNs oNe OR moRE eThyLEne Oxy units AnD/oR peptIde gROUPS. In aN esPeciAlly pReferred embodImeNt, thE LinKer coNtainS one Or More uNits as DescrIbEd in DE-A 3924705. EspecialLy prEferred arE thE uNitS dEscriBEd as an ExaMplE which iS referrED to As aDO (8-AmIno-3,6-dioxa-octanic aciD), bELOw. a slight dEpendeNCe Of THe bindinG oF nuCleiC ACids tO the pnA Surface cAn be reDUcEd By using LoNger liNkErs BetWeen Pna and The solId carrieR.
The nUCleic acid analoG That is bound to A SiTE CaN Also Be a Mixture of twO or mORe anAlogS HaVinG DiffeRent bUt KNoWN sequences. This can reDuCe the nUmber Of sites requirEd for a multIPLE determiNatiON.
THE surface of the cArrieR is preferaBLy not chaRged, aNd is prefErably hydROPhilic. ThE inVenTioN deMONsTrated that the USE of bAsIcally uNchArged suRfaCes Is aN adVaNtage when DetectinG nUcLeIc AciDs.
A soLId carrieR lOadEd WitH nuclEIc acid AnaloGs at DiFfERenT sites aS PrOVIded By ThIs inVenTiOn can Be maNUfaCtured iN differenT waYS. In oNe EmBodimenT, suitable quanTiTies of soluTiOns That eaCH Contain dIfferent nucleic acid analOGs are apPliEd to dIffeRent sites On tHe surfAce OF the soLid carRier, e.G. vIa pIPEtte. THE LiQuiD sAmples shouLD Not Mix wiTh Each Other on The surface of the solID caRrier. This can bE acCompLIShEd, fOR iNStaNcE, By lOCAting the applicaTion sites fAr APaRt from each OTheR oR by usinG a hydroPhobiC Barrier To stop the Expansion Of The lIQUid Between the Various sItes. EitheR The nuCLeIc aciD anAlogs oR tHe sUrfacE of the SOliD carrIer is pReFerablY actiVaTed for thE reaction. This activation Can be aChievEd, fOr instancE, in THat One of the gRoupS described AboVe iS actiVatED by thE creATiOn oF A reacTive SPecies. In tHE cAse OF

In an especially preferre d embodime nt, t herea ct ivegrou ps of the surf a ce a nd the nucleic acid an alogar e  cov a le ntlybound t o  e a c h o th er , e sp e ci allybymeans o f a linker  th at  is more tha n  1 5 atoms an d l ess than 200  at oms lo ng . A xe2x8 0x9 clink erxe2x 8 0x9d r efers toap ortion of a mo l e cu le t hat basically has th e  function of r emovin gt he n ucl eic  acid anal og s tha t  are st e ri c a l lya vailable on t he surfaceo f t he sol id  ca r rier.A lin ke r  is  usually se lect ed that h as hyd r ogen at o ms (e.g . in a lky len e un i ts )and  n u mer o us  he t ero atoms (e .g .xe2x8 0x94 O x e 2 x80x 94or x e2x80 x94NHxe2x80x9 4 o r xe 2 x80 x94NR xe2x8 0x94 )thatfacili tateso lvation. The li nker  preferab lyco nta in s one or mor e e thy lene ox y units and /o r p ep tide groups. In an  e s p ec ially pr eferre d  e mb o diment,th e l inke r conta inso ne  or more  units as  d escribe din DE- A392 470 5. Es p ecia lly pr eferredare t h e units descri b ed as an exam p le w hi c h is  re ferred to a s Ad o  (8- amin o -3 ,6- d ioxa- octan ic ac i d), below. A slight  d epende nce o f the binding  of nuclei c a cids totheP NA surface can be  redu ced by usi n g longer  link ers betw een PNA a n d  the sol idcar rie r.T h enucleic acida n alog  t hat isbou nd to a  si tecan  al so  be a mix ture oftw oor  m ore  anal o gs havin gdif fe ren t but knownseque nces .Th i s c an redu c et h e nu mb er  ofsit es  requ ired for  a mult iple dete rmi n atio n. 
T he surf ace of the ca rr ier is pre fe rab ly not c harged,and is preferably hydro p hilic.The  inve ntio n demonst rat ed tha t t h e useof bas icall yunc h a rgeds u rf ace sis an adva n t age  when  d etec ting nu cleic acids.
A sol i d c arrier loaded  wi th n u c le ica ci d  an al o gsa t  different site s as provi de d  b y this inv e nti on  can be  manufa cture d  in dif ferent wa ys. In on eembo d i men t, suitabl e quanti ties of s o lutio n sthateac h cont ai n d iffer ent nu c lei c aci d anal og s areappli ed  to diff erent sites on the surf ace of  thesol id carrie r,e .g.  via pipe tte.  The liqui d s amp les s hou l d not  mix wi the ach o ther on the su r fa ceo f  t he solid ca r r i er.  This  ca n  be ac comp lished, for insta n ce, by locatin g th e app lic a tion  s ites far apart  fr om e ach othe ror by using  a hydro ph o bic b arrier  to st op thee x pa n sion o f th e l iquid bet wee nt he vari ou ss ites.Eith er  the n ucleic acid a nalogs or the su rface o f the sol id ca rr ier isp refe rably acti vated for t he rea ctio n. Th is acti va tion c anbe  achieved, for insta nce,in that  o ne o f t he gro upsd e scrib ed a bo veis activa t e db yth e  cr eati on of  a  rea ctive spe c ies. Inthe case of 

In an_especially preferred_embodiment, the reactive groups_of the_surface_and the_nucleic_acid analog are_covalently bound to_each other, especially by_means of a_linker_that is more than 15 atoms and less than 200 atoms long. A xe2x80x9clinkerxe2x80x9d_refers_to a_portion_of_a molecule that basically has_the function of removing the_nucleic acid_analogs that are sterically available on the surface_of_the solid carrier._A linker is usually selected that has hydrogen atoms_(e.g. in alkylene units) and numerous_heteroatoms (e.g. xe2x80x94Oxe2x80x94_or_xe2x80x94NHxe2x80x94_or xe2x80x94NRxe2x80x94) that facilitate_solvation. The linker preferably contains one_or more ethylene oxy units and/or_peptide groups. In an especially preferred embodiment,_the linker contains one or more_units as described in DE-A_3924705. Especially_preferred are the units described_as an example_which is_referred to as_Ado (8-amino-3,6-dioxa-octanic acid), below. A slight_dependence of the_binding of nucleic acids to the_PNA_surface can be_reduced_by_using longer_linkers between PNA_and_the solid_carrier.
The_nucleic acid analog that is bound_to_a site can also be a mixture_of two or more_analogs_having different but known_sequences. This can reduce the_number of sites required for a_multiple determination.
The_surface of_the carrier is preferably not charged, and is preferably hydrophilic. The_invention demonstrated that the use of_basically uncharged surfaces is_an advantage_when_detecting nucleic acids.
A_solid_carrier loaded_with nucleic acid analogs at different sites_as provided_by this invention can be manufactured_in different ways. In_one_embodiment, suitable quantities of solutions that_each contain different nucleic acid analogs_are applied to different sites_on_the_surface of the solid carrier,_e.g. via pipette. The liquid samples_should not mix_with each other on the surface of_the_solid carrier. This can be accomplished,_for_instance, by locating the application sites_far_apart_from each other or by_using a hydrophobic barrier to stop_the expansion of the liquid between the various sites._Either the nucleic_acid analogs or the surface_of_the_solid carrier is preferably activated for the reaction. This activation_can be_achieved, for instance,_in that one of the groups described above is activated_by the creation of a reactive species._In the case of