Selective fluorescent probes for measuring multidrug transporter activity FIELD OF THE INVENTION The present invention relates to a fluorescent dye accumulation assay for parallel measurements of ABC multidrug transporters, as efflux pump, capable of extruding cyanine dyes. In particular, the invention relates to measurements of the ABCB1 multidrug transporter functions via detecting accumulation of the fluorescent dye in a cell. The invention also includes a diagnostic application of the functional assays in normal and malignant human (blood) cells. TECHNICAL BACKGROUND Members of the ATP-binding cassette (ABC) transporter superfamily play important roles in the active transport of endo- and xenobiotics across the cell membranes and tissue barriers. The ABCB1 transporter (also called P-glycoprotein, Pgp, or MDR1), has a major effect on the absorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) of a large number of pharmacological agents, and causes cancer multidrug resistance by preventing the access of intracellular targets by various antineoplastic agents [1]. The other two major multidrug membrane transporter ABC proteins are the ABCC1 (multidrug resistance protein 1, MRP1) and the ABCG2 (breast cancer resistance protein, BCRP), and the selective functional diagnostic recognition of these transporters is important both in drug development and clinical diagnostics [2–7]. ABCB1-Pgp was the first recognized human ABC multidrug plasma membrane transporter [8,9], and this 170 kDa polypeptide is predominantly expressed in the intestine, blood-brain barrier, liver, pancreas and kidney [4,6,8,10]. Pgp exports neutral or positively charged hydrophobic compounds from cells, thereby protecting them from drugs and xenobiotics [11]. Variable cellular expression of Pgp significantly affects the distribution and elimination of drug molecules and the response to chemotherapeutic agents, including newly developed, targeted anticancer drugs [12]. The role of Pgp has also been implicated in Alzheimer’s disease and chronic renal failure [13–15]. However, currently there is no selective, non-toxic fluorescent reporter compound available for the functional studies of Pgp, especially if an automated analysis of multiple samples is required. Most non-toxic reporter dyes used in ABC transporter diagnostics (e.g. Calcein-AM, Hoechst 33342, DCV or Phengreen SK- diacetate) are not selective for Pgp, and these dye assays require special conditions, making difficult to automate the diagnostic panels [2]. The TO-PRO family of dyes, identified as “cell membrane–impermeant cyanine nucleic acid stains” [16], belong to the family of cyanine monomers (see Figure 6), consisting of two positively charged and one intercalating unit. TO-PRO™-1 (TP1) has a one-carbon unit conjugating chain, while TO-PRO™-3 (TP3) has a three-carbon conjugating chain, and both compounds bind to various nucleic acids with high affinity. TO-PRO-1 These compounds become highly fluorescent upon binding to nucleic acids, and have relatively narrow emission bandwidths, thus facilitating multicolor applications in imaging and flow cytometry. The nucleic acid bound fluorescence of these dyes is determined by the length of the conjugating chain - TP1 has a green fluorescence, TP3 shows red fluorescence [17–19]. The main applications of these dyes are live/dead cell separation or direct nucleic acid analysis. TP3 is exceptionally widely used as a viability dye, and to study viruses [21], bacteria [17], or to detect peripherals of the nervous system after fixation and permeabilization [22]. The inventors have surprisingly found that certain cyanine nucleic acid stains are useful in a method according to the invention. The stain may be a monomeric cyanine nucleic acid stain, or a dimeric cyanine nucleic acid stain. BRIEF DESCRIPTION OF THE INVENTION In particular, the invention relates to a method for measuring ABC multidrug transporter activity in sample cells, said method comprising the following steps: a) providing a test sample comprising (a population of) the test sample cells and a negative control sample comprising (a population of) negative control cells; b) contacting said sample cells and said negative control cells with a compound of Formula I for at least 3 hours, particularly for at least 4 hours, preferably at least 5 hours, more preferably at least 8 hours or for a period as defined in the preferred options of the method of the invention, in particular for 16 to 24 hours; Formula I wherein in Formula I A is a substituted or unsubstituted 6 to 10 membered aromatic heterocycle having a pyridine ring wherein group is bound to the N of said pyridine of A, wherein optionally A has a fused aromatic ring, preferably a benzene ring to form a quinoline, preferably A being a pyridine or a quinoline; P136199-2417/SG wherein if A is substituted it is substituted by one or two substituents selected from the group consisting of C _1-3 alkyl (preferably methyl and ethyl) and halogen; X is O or S; R1 is ethyl, methyl or H; Q ₁ , Q ₂ , Q ₃ and Q ₄ are selected from C-H, C-CH ₃ , N-H or N-CH ₃ , wherein N is a ring atom; wherein at least 2 of Q ₁ , Q ₂ , Q ₃ and Q ₄ is C-H, preferably with the proviso that if any of Q ₁ , Q ₂ , Q ₃ and Q ₄ is N-CH ₃ , then R ₁ is H; and n is 0, 1, 2 or 3; preferably 0, 1 or 2; m is 1, 2 or 3, preferably 3; R is a tertiary amine having methyl and/or ethyl groups, preferably a trimethyl amine, OR R is a moiety having a structure of Formula I’ Formula I’, wherein Q1’, Q2’, Q3’, Q4’, X’, R1’ and A’ as well as n’ are, independently from each other, the same as defined for Q ₁ , Q ₂ , Q ₃ , Q ₄ , X, R ₁ and A as well as n, respectively, in Formula I, including any salt, in particular halogenide salt, preferably iodide salt thereof, c) measuring fluorescence in the (population of) test sample cells and in the (population of) negative control cells; d) optionally differentiating between live cells and dead cells to have the measured values refer to the live cells, (preferably by correcting the measured fluorescence intensity values by excluding fluorescence by dead cells, or by dying and dead cell, or by deducing fluorescence intensity of dead cells); e) comparing the fluorescence of sample cells to the fluorescence of the negative control cells, wherein - the lower level of fluorescence in the test sample cells compared with a higher level of fluorescence in the negative control cells indicate the presence and/or level of the ABC transporter activity or - a difference between a lower level of fluorescence of test sample cells compared to the higher level of fluorescence of the negative control cells provides a measure (or level) of the ABC transporter activity. Preferably said ABC transporter activity is a specific ABC transporter activity, i.e. ABC transporter activity of one or more, preferably one to three, more preferably one or two, in particular one ABC transporter(s). Terms given in parentheses in the Brief description of the invention (or where appropriate at other sites of the specification) are optional terms which can be included or omitted to define text versions. Preferably said specific ABC transporter activity comprises ABCB1 transporter activity, and the compound is an ABCB1 substrate. Particularly preferably as ABC multidrug transporter activity ABCB1 transporter activity is measured. In a variant embodiment the compound is an ABCG2 substrate (in a particular embodiment a PO-PRO dye) and said specific ABC transporter activity comprises ABCG2 transporter activity. P136199-2417/SG In a variant embodiment transporter activities of multiple ABC transporters are measured. In an embodiment said multiple transporter activities are measured together provided that the compound is a substrate for multiple ABC transporters and said ABC transporters are not inhibited. In a further embodiment said multiple transporter activities are measured separately in parallel test samples wherein in said parallel test samples a specific ABC transporter in inhibited and another is active and thus measured. In an embodiment ABCB1 and ABCG2 transporter activities are measured, either together or separately. In a particular embodiment the compound is a PO-PRO dye. Preferably the measured fluorescence is fluorescence intensity or the level of fluorescence is calculated based on multiple fluorescence intensity values. The compound of the invention includes any salt thereof. The compound of the invention includes any hydrate or similar variants including the formula I compound or a compound having the formula listed herein, e.g. below. In preferred embodiments the compound used is any of the compound of any of Formulae II to XIII. The invention also relates to the use of any of the compounds as defined herein for measuring ABC multidrug transporter activity, as defined above, in sample cells or in any method as defined herein. In the method of the invention the ABC multidrug transporter activity is preferably transport activity. In the method of the invention the ABC multidrug transporter activity is preferably ABCB1 transport activity. Formula I may be present in its tautomeric form of Formula Ia Formula Ia In the present invention tautomeric forms are considered as the same compound; therefore, when a compound of the type of Formula I is specified its tautomeric form illustrated by Formula Ia is contemplated. In a preferred embodimentQ2, Q3 and Q4 are C-H, and Q1 is selected from C-H, C-CH3, N-H or N-CH3, wherein N is a ring atom. In a further preferred embodiment Q2’ Q3’ and Q4’ are C-H, and Q1’ is selected from C-H, C- CH ₃ , N-H or N-CH ₃ , wherein N is a ring atom, preferably with the proviso that if Q ₁ and/or Q ₁ ’ is N-CH ₃ , then, respectively, R ₁ and/or R ₁ ’ is H. In particular, the invention relates to a preferred a method for measuring ABC multidrug transporter activity in sample cells, wherein preferably said ABC transporter activity comprises ABCB1 transporter activity, said method comprising the following steps: a) providing a test sample comprising a population of the test sample cells and a negative control sample comprising a population of negative control cells and optionally a positive control sample comprising a population of positive control cells; b) contacting said sample cells and said negative control cells with a compound of Formula I for at least 4 hours, preferably at least 5 hours, more preferably at least 8 hours or for a time period as defined in the preferred options of the method of the invention in particular 16 to 24 hours; P136199-2417/SG c) measuring fluorescence in the population of test sample cells and in the population of negative control cells and optionally in the population of positive control cells; d) optionally differentiating between live cells and dead cells to have the measured values refer to the live cells, e) comparing the fluorescence of sample cells to the intensity of the negative control cells, wherein a difference between a lower level of fluorescence of test sample cells compared to the higher level of fluorescence of the negative control cells provides a measure (or level) of ABCB1 transporter activity. Optionally the fluorescence of the positive control sample is used to check (control) whether the assay is working and/or to set the measurement range of the assay method and/or for normalization of the measurement values of the assay method. Preferably the measured fluorescence is fluorescence intensity or the level of fluorescence is calculated based on multiple fluorescence intensity values. Preferably the compound of Formula I is any of the compounds of Formulae II to XIII. In the method of the invention the compound is preferably a compound of Formula II Formula II wherein in the formula R, X, A, n and m are the same as those defined for Formula I. Preferably, A is a 6 to 10 membered aromatic heterocycle having a pyridine ring wherein group is bound to the N of said pyridine, wherein optionally A has a fused aromatic ring, preferably a benzene ring to form a quinoline, preferably A being a pyridine or a quinoline; X is O or S; n is 0, 1, 2 or 3; preferably 0, 1 or 2; m is 1, 2 or 3, preferably 3 R is a tertiary amine having methyl and/or ethyl groups, preferably a trimethyl amine, OR R is a group of Formula II’ Formula II’ wherein X’ is O or S; A’ is a 6 to 10 membered aromatic heterocycle as defined for A, independently from A, P136199-2417/SG n’ is 0, 1, 2 or 3; preferably 0, 1 or 2; wherein preferably X’, A’ and/or n’, preferably each of X’, A’ and n’ is the same as X, A and n, respectively. In a particular embodiment the compound of Formula II is described by Formula IIa which is the tautomeric form of said compound and is considered as an identical compound. Formula IIa More preferably A is a 6 to 10 membered aromatic heterocycle having a pyridine ring wherein group is bound to the N of said pyridine, wherein A has a fused aromatic ring, preferably A being a pyridine or a quinoline; R is a tertiary amine having methyl and/or ethyl groups, preferably a trimethyl amine, X is O or S; n is 0, 1 or 2; m is 3. In a preferred embodiment the compound is a compound of Formula III, Formula III wherein in Formula III, A is a (substituted or unsubstituted) 6 to 10 membered aromatic heterocycle having a pyridine ring wherein group bound to the N of said pyridine, wherein optionally A has a fused aromatic ring, preferably a benzene ring to form a quinoline, preferably A being a pyridine or a quinoline; wherein if A is substituted it is substituted by one or two substituents selected from the group consisting of methyl, ethyl and a halogen, X is O or S; R1 is ethyl, methyl or H; Q1 is selected from C-H, C-CH3, N-H or N-CH3, wherein N is a ring atom; P136199-2417/SG with the proviso that if Q ₁ is methylamine, then R ₁ is H; and n is 0, 1 or 2; Formula III may be present in its tautomeric form of Formula IIIa Formula IIIa In a particular embodiment the dye is a dimer-type dye having the formula of Formula IV Formula IV wherein Q1’, Q2’, Q3’, Q4’, X’, R1’ and A’ as well as n’ are, independently from each other, the same as defined for R Q1, Q ₂ , Q ₃ , Q ₄ , X, R ₁ and A as well as n, respectively, in Formula I, which means that the moieties and the number indicated with a comma (Q ₁ ’, Q ₂ ’, Q ₃ ’, Q ₄ ’, X’, R ₁ ’ and A’ as well as n’) in Formula IV may be the same as or may be different from those without a comma (Q ₁ , Q ₂ , Q ₃ , Q ₄ , X, R ₁ and A as well as n, respectively), however, in any case within the definition given above for Formula I or any one of Formulae given above. In a particular embodiment the moieties and the number indicated with a comma (Q ₁ ’, Q ₂ ’, Q ₃ ’, Q ₄ ’, X’, R ₁ ’ and A’ as well as n’) in Formula IV are the same as or may be different from those without a comma (Q ₁ , Q ₂ , Q ₃ , Q ₄ , X, R1 and A as well as n, respectively) in a pairwise manner (i.e. R1’ is identical with R1, Q1’ is identical with Q1, etc. and integer n is identical with n’). In a particular embodiment the dye is a dimer-type dye having the formula of Formula V Formula V P136199-2417/SG wherein in the formula X, X’, A, A’, n, n’ and m are the same as those defined for Formula IV. Preferably, A is a 6 to 10 membered aromatic heterocycle having a pyridine ring wherein group is bound to the N of said pyridine, wherein optionally A has a fused aromatic ring, preferably a benzene ring to form a quinoline, preferably A being a pyridine or a quinoline; (wherein if A is substituted it is substituted by one or two substituents selected from the group consisting of a methyl, ethyl and a halogen), X and X’ are independently selected from O or S; n and n’ are independently 0, 1, 2 or 3; preferably 0, 1 or 2; m is 1, 2 or 3, preferably 3. Preferably X and X’ are identical. Preferably n and n’ are identical. Preferably both X and X’ and n and n’ are identical. As usual, Formula V may be present in its tautomeric form. Preferably, the dye is a dimer-type dye having the formula of Formula VI Formula VI wherein in the formula X, X’, n, n’ and m are the same as those defined for Formula IV, and B and B’ are independently from each other, 6 membered heterocycle, preferably a benzene ring to form a quinoline, wherein if said B and/or B’ are substituted it is substituted by one or two substituents selected from the group consisting of a methyl, ethyl and a halogen; wherein preferably both B and B’ are unsubstituted, X and X’ are independently selected from O or S; n and n’ are independently 0, 1, 2 or 3; preferably 0, 1 or 2; P136199-2417/SG m is 1, 2 or 3, preferably 3. Preferably X and X’ are identical. Preferably n and n’ are identical. Preferably both X and X’ and n and n’ are identical. As usual, Formula VI may be present in its tautomeric form. In a preferred embodiment the dye is a dimer-type dye having the formula of Formula VII Formula VII wherein X and X’ are independently selected from O or S; n and n’ are independently 0, 1 or 2; m is 1, 2 or 3, preferably 3. Preferably X and X’ are identical. Preferably n and n’ are identical. Preferably both X and X’ and n and n’ are identical. Formula VII may be present in its tautomeric form. In a preferred embodiment of the method the negative control sample is free of the measured ABC transporter activity. In a further preferred embodiment of the method in the negative control sample the measured ABC transporter activity is inhibited. Wherein the compound is an ABCB1 substrate: In a preferred embodiment of the method the negative control sample is free of ABCB1 activity. In a preferred embodiment of the method ABCB1 activity is inhibited in the negative control sample. Wherein the compound is an ABCG2 substrate: In a preferred embodiment of the method the negative control sample is free of ABCG2 activity. P136199-2417/SG In a preferred embodiment of the method ABCG2 activity is inhibited in the negative control sample. In a preferred embodiment of the method in the samples any ABC transporter activity which is different from the measured ABC transporter activity, preferably which is different from ABCB1 activity, is inhibited. Below certain preferred options of the method of the invention are specified. In a preferred embodiment the method is carried out on a plate; in particular in step a) the control and the sample cells (preferably ABCB1-expressing cells; in certain embodiments ABCG2-expressing cells) are seeded onto plates (e.g. a 384-well or a 96-well plate). Preferably a part of the wells of the plate comprises sample cells and a part of the wells of the plate comprises control cells. In a preferred embodiment in step b) the cells are contacted with the compound for 2 to 48 h, in particular for 5 to 48 h, in particular for 5 to 24 h, or preferably for 5 to 20 hours or 5 to 16 hours or 5 to 8 hours or 8 to 48 hours or preferably 8 to 24 hours or 12 to 48 hours or 12 to 24 hours, in particular from 16 to 24 hours. In a preferred embodiment the measurement is carried out at 20 to 40 °C, preferably at 25 to 37 °C, in particularly preferred variants at 25 or 37 °C. Preferably the measurement is carried out in the presence of 2 to 10 % CO ₂ , in a particular preferred variant in 5% CO2. In a preferred embodiment the concentration of the compound is 0.2 nM to 2 µM of falls into a range as given herein; particularly preferably 500 nM TP1 or 100 nM TP1, with or without inhibitor, at 37 °C. In case an inhibitor is used it should be stable at the conditions applied during the time of the measurements, e.g. at least during the time period given for step b. Exemplary concentrations: TP1 concentrations = 0.2-2000 nM (best: 500 nM, but e.g.200 nM also works) (low concentration: 200-500 nM), TP3 concentrations = 0.2-200 nM (best: 100 nM, but e.g.25 nM also works) (low concentration: 50-200 nM). In a preferred embodiment the method comprises measuring the transport activity of the ABCB1 transporter by flow cytometer, preferably at room temperature; using a flow cytometer (preferably with plate reader). In a preferred embodiment the method comprises measuring the transport activity of the ABCB1 transporter by fluorescence microscopy. In a preferred embodiment fluorescence intensity is expressed by the MDR activity factor % (MAF%). MDR activity factor % (MAF%) is calculated as follows: 100 wherein MFIctrl and MFI0 are the median fluorescence intensity (MFI) with MFIctrl being measured in the control cells (preferably in the control sample); wherein the ABC transporter activity is inhibited with an inhibitor (inh), in this case MFI _ctrl is MFI _inh , and MFI ₀ (or MFI _test ) being the median fluorescence intensity (MFI) measured in the test sample cells or in the sample, in an embodiment without inhibitor (0). In an embodiment step d) comprises differentiating between live cells and dead cells (preferably by propidium iodide) to have the measured values refer to the live cells (and optionally correct the measured fluorescence intensity values by excluding dead cells); In a preferred embodiment a dead cell dye is used to differentiate between live and dead cell. Preferably the dead cell dye is a fluorescent dye wherein colors of the compound and the dead cell dye should be different. P136199-2417/SG In a particular embodiment the dead cell dye is selected from Zombie Violet, Zombie Green, 7AAD, TP dye series and propidium iodide, preferably the dead cell dye is propidium iodide. In a further embodiment, TP dyes are used for live/dead cell differentiation in embodiments wherein the compound is a dye different from said TP dye, e.g. TP3, used as a live/dead cell dye. There are other live/dead cell dyes available in various colors and several live/dead cell dyes can be purchased in the market. For example, dead cells can be differentiated by their different fluorescence. In a particular embodiment in case of a flow cytometry method, healthy transporting cells and dead and dying cells can be differentiated based on their fluorescence and thereby the signal of healthy cells can be selected and used (see e.g. Figure 1). The invention also relates to the use of any of the compounds as defined herein for measuring an ABC multidrug transporter activity, as defined above, in sample cells or in any method as defined herein. In a particularly preferred method cells expressing ABCB1 protein are assayed. Preferably said cells are differentiated by using inhibitors of other transporters. In a further preferred embodiment said cells are differentiated by cell sorting. In a particular embodiment a low number of ABCB1 expressing cells is assayed in the present invention. In particular embodiments as low as less than 10 ⁵ , preferably less than 10 ⁴ cells, preferably less than 5000 cell, preferably less than 2000 cells or in particular less than 1000 cells are assayed in the present invention. In the present invention compounds of Formula I, preferably compounds of Formula II and/or IV, more preferably compounds of Formula III and/or V are used in the present assay, in particular compounds of Formula II, preferably compounds of Formula III are used in the present assay. In highly preferred embodiment compounds TO-PRO-1 (TP1) and/or TO-PRO-3 (TP3) are used in the present assay. In preferred embodiments the following compounds are used in the following preferred concentrations: a compound selected from compounds of Formula II and/or IV, more preferably compounds of Formula III and/or V are used in the present assay, in particular compounds of Formula II, preferably compounds of Formula III, preferably compounds of any of Formulae VI to VII, preferably compounds of Formula VIII, preferably compounds of any of Formulae IX to XIII. Preferably the compounds according to the invention are applied in a concentration of 0.2 to 2000 nM, preferably 2 to 2000 nM, or 0.2 to 1000 nM, preferably 10 to 1000 nM, preferably in 100 to 1000 nM or in 10 to 500 nM, highly preferably in 25 to 500 nM. In a particular embodiment, live cells are differentiated from dead cells and preferably also from dying cells in the present method. In a particular embodiment live/dead markers are used. In an embodiment propidium iodide is used as a live/dead marker. In a further embodiment the compounds according to the invention, as defined above, are used as a live/dead marker. In an embodiment, the method according to the invention is carried out using a flow cytometer or fluorescence-based confocal microscopy. In a preferred embodiment, the method according to the invention is carried out using a flow cytometer, preferably a flow cytometer with a plate reader. In an alternative embodiment the assay may be carried out in a fluorescent plate reader. P136199-2417/SG In preferred embodiments of the method, in particular of the particular and preferred as well as more preferred embodiments or options mentioned above, the following preferred compounds are used in the method of the invention. In a preferred embodiment, the monomeric cyanine nucleic acid stain is of Formula VIII: Formula VIII wherein A is pyridine or quinoline; X is O or S; and n is 0, 1 or 2. In a preferred embodiment, in any of Formulae I to VIII, preferably in any of Formulae II, III or VIII, n is selected from 0 and 1 or is selected from 1 or 2. In an embodiment in any of Formulae IV to VII, preferably in any of Formulae II, III or VIII, n is selected from 0 and 1 or is selected from 1 or 2. In a preferred embodiment, the monomeric cyanine nucleic acid stain is of Formula IX: Formula IX wherein n is 0 or 1. In a preferred embodiment, the monomeric cyanine nucleic acid stain is PO-PRO ^TM -1, i.e.3-methyl-2-({1- [3-(trimethylammonio)propyl]-4(1H)-pyridinylidene}methyl)-1, 3-benzoxazol-3-ium salt (preferably diiodide, CAS number: 157199-56-9). PO-PRO-1 In a preferred embodiment, the monomeric cyanine nucleic acid stain is PO-PRO ^TM -3, i.e.3-methyl-2-((E)- 3-[1-[3-(trimethylammonio)propyl]-4(1H)-pyridinylidene]-1-pr openyl)-1,3-benzoxazol-3-ium salt (preferably diiodide, CAS number: 161016-55-3). P136199-2417/SG PO-PRO-3 In a preferred embodiment, the monomeric cyanine nucleic acid stain is of Formula X: Formula X wherein n is 0 or 1. In an embodiment, the monomeric cyanine nucleic acid stain is BO-PRO ^TM -1, i.e. trimethyl-[3-[4-[(Z)-(3- methyl-1,3-benzothiazol-2-ylidene)methyl]pyridin-1-ium-1-yl] propyl]azanium salt (preferably diiodide, CAS number: 157199-57-0). BO-PRO-1 In an embodiment, the monomeric cyanine nucleic acid stain is BO-PRO ^TM -3, i.e. trimethyl-[3-[4-[3-(3- methyl-1,3-benzothiazol-3-ium-2-yl)prop-1-enylidene]pyridin- 1-yl]propyl]azanium salt (preferably diiodide, CAS number: BO-PRO-3 In a preferred embodiment, the monomeric cyanine nucleic acid stain is of Formula XI: Formula XI wherein n is 0 or 1. P136199-2417/SG In an embodiment, the monomeric cyanine nucleic acid stain is YO-PRO ^TM -1, i.e. trimethyl-[3-[4-[(Z)-(3- methyl-1,3-benzoxazol-2-ylidene)methyl]quinolin-1-ium-1-yl]p ropyl]azanium salt (preferably diiodide, CAS number: 152068-09-2). YO-PRO-1 In an embodiment, the monomeric cyanine nucleic acid stain is YO-PRO ^TM -3, i.e. trimethyl-[3-[4-[3-(3- methyl-1,3-benzoxazol-2-ylidene)prop-1-enyl]quinolin-1-ium-1 -yl]propyl]azanium salt (preferably diiodide, CAS number: 157199-62-7). YO-PRO-3 In a preferred embodiment, the monomeric cyanine nucleic acid stain is of Formula XII: Formula XII wherein n is 0, 1 or 2. More preferably, the monomeric cyanine nucleic acid stain is of Formula XII, wherein n is 0 or 1. In a preferred embodiment, the monomeric cyanine nucleic acid stain is TO-PRO ^TM -1, i.e.3-methyl-2-([1- [3-(trimethylammonio)propyl]-4(1H)-quinolinylidene]methyl)-1 ,3-benzothiazol-3-ium salt (preferably diiodide, CAS number: 157199-59-2). P136199-2417/SG TO-PRO-1 In a preferred embodiment, the monomeric cyanine nucleic acid stain is TO-PRO ^TM -3, i.e.3-methyl-2-((E)- 3-[1-[3-(trimethylammonio)propyl]-4(1H)-quinolinylidene]-1-p ropenyl)-1,3-benzothiazol-3-ium salt (preferably diiodide, CAS number: 157199-63-8). TO-PRO-3 In an embodiment, the monomeric cyanine nucleic acid stain is TO-PRO ^TM -5, i.e. 3-methyl-2-([5-[1- (trimethylammonio)propyl]-4(1H)-quinolinylidene]-1-pentadien yl)benzothiazolium salt (preferably diiodide, CAS number: 177027-61-1). TO-PRO-5 In a preferred embodiment, the monomeric cyanine nucleic acid stain is of Formula XIII: Formula XIII wherein n is 0 or 1, preferably 0. P136199-2417/SG In an embodiment, the monomeric cyanine nucleic acid stain is JO-PRO ^TM -1, i.e. quinolinium, 4-[(4- methyloxazolo[4,5-b]pyridin-2(4H)-ylidene)methyl]-1-[3-(trim ethylammonio)propyl]-, salt (preferably diiodide, CAS number: 305801-86-9). JO-PRO-1 In a preferred embodiment, the compound is selected from the group consisting of the following compounds: JO-PRO-1, TO-PRO-5, TO-PRO-3, TO-PRO-1, YO-PRO-3, YO-PRO-1, BO-PRO-3, BO-PRO-1, PO-PRO-3, PO-PRO-1. In some embodiments, the cyanine nucleic acid stain may be a dimeric cyanine nucleic acid stain. Examples for dimeric cyanine nucleic acid stains are POPO-1, POPO-3, BOBO-1, BOBO-3, YOYO-1, YOYO-3, TOTO-1, TOTO-3, JOJO-1, and LOLO-1. The invention also relates to the use of any of the compounds as defined herein for measuring an ABC multidrug transporter activity, as defined above, in sample cells or in any method as defined herein. In an embodiment the method of the invention is a diagnostic method. In particular, the invention relates to a diagnostic method for measuring ABC multidrug transporter activity in a biological sample (diagnostic sample) obtained from a subject (e.g. a patient), comprising sample cells, wherein said ABC transporter activity preferably comprises ABCB1 transporter activity, said method comprising the following steps: a) providing a test sample from the biological sample said test sample comprising (a population of) test sample cells and a negative control sample comprising (a population of) negative control cells; b) contacting said test sample cells and said negative control cells, preferably the test sample and the negative control sample with a compound of the invention (preferably a compound of any of Formulae I to XIII) for at least 3 hours, preferably at least 5 hours, more preferably at least 8 hours, or for a period as defined in the preferred options of the method of the invention, in particular for 16 to 24 hours; c) measuring fluorescence intensity in the (population of) test sample cells and in the (population of) negative control cells, preferably in the test sample and in the negative control; d) optionally differentiating between live cells and dead cells to have the measured values refer to the live cells as disclosed herein (by optionally carrying out said differentiating by a method as disclosed herein, e.g. by a live/dead cell dye or by difference in fluorescence), e) comparing the fluorescence (intensity) of sample cells to the fluorescence (intensity) of the negative control cells, wherein - the lower level fluorescence in the test sample cells compared with the fluorescence in the negative control cells indicates the level of said ABC transporter activity, preferably comprising ABCB1 transporter activity, or P136199-2417/SG - a difference between a lower level of fluorescence of the test sample cells compared to the level of fluorescence of the negative control cells provides level of said ABC transporter activity preferably comprising ABCB1 transporter activity f) wherein preferably if the level of said ABC transporter activity is indicative of a disease, then said subject (e.g. a patient), is considered as a subject having said disease. In a particular embodiment said ABC transporter activity is indicative of a disease when it is below a threshold level. In a particular embodiment said ABC transporter activity is indicative of a disease when it is above a threshold level. In a particular embodiment said ABC transporter activity is indicative of a disease when it is out of a normal range, e.g. when it is above a normal range or when it is below a normal range. Preferably the ABC transporter activity is ABCB1 transporter activity. Alternative embodiments in respect of different ABC activities are specified above in the particular method for measuring an ABC multidrug transporter activity. Preferably the measured fluorescence is fluorescence intensity or the level of fluorescence is calculated based on multiple fluorescence intensity values. In a preferred embodiment in step a) a positive control sample is also provided, wherein in step b) the positive control sample is also contacted with a compound of the invention and in step c) the fluorescence intensity is measured whereas the fluorescence of the positive control sample is used to check whether the assay is working and/or to set the measurement range of the assay method and/or for normalization of the measurement values of the assay method. Preferably a level of the transporter activity above a threshold level indicates an excess transporter activity typical of a disease. In an embodiment a level of the transporter activity below a threshold level indicates a low transporter activity typical of a disease. The compound of the invention can be any compound defined or listed above. For example, the compound of the invention is a compound selected from compounds of Formula II and/or IV, more preferably compounds of Formula III and/or V are used in the present assay, in particular compounds of Formula II, preferably compounds of Formula III, preferably compounds of any of Formulae VI to VII, preferably compounds of Formula VIII, preferably compounds of any of Formulae IX to XIII. In a preferred embodiment, the compound is selected from the group consisting of the following compounds: JO-PRO-1, TO-PRO-5, TO-PRO-3, TO-PRO-1, YO-PRO-3, YO-PRO-1, BO-PRO-3, BO-PRO-1, PO-PRO-3, PO-PRO-1. In some embodiments, the cyanine nucleic acid stain may be a dimeric cyanine nucleic acid stain. Examples for dimeric cyanine nucleic acid stains are POPO-1, POPO-3, BOBO-1, BOBO-3, YOYO-1, YOYO-3, TOTO-1, TOTO-3, JOJO-1, and LOLO-1. The invention also relates to the use of any of the compounds as defined herein for in a diagnostic method for measuring ABC multidrug transporter activity in a biological sample as a diagnostic sample obtained from a subject, comprising sample cells, wherein said ABC transporter activity preferably comprises ABCB1 transporter activity. P136199-2417/SG The compound includes any salt thereof. The compound includes any variant as defined above. In the method of the invention the ABC multidrug transporter activity is preferably transport activity. In the method of the invention the ABC multidrug transporter activity is preferably ABCB1 transport activity. In particular in the diagnostic method said ABC transporter activity is indicative of the disease condition. In a preferred embodiment the disease is a neoplasia, e.g. cancer. In a particular embodiment the sample cells are neoplastic cells, e.g. cancer cells. In a preferred embodiment the cells are circulating cancer cells or circulating tumor cells (CTCs). In a particular embodiment the biological sample is a blood sample. In a preferred embodiment the disease is an inflammatory disease. The inflammatory disease can be a disease selected from the group consisting of inflammatory bowel disease (IBD), Crohn-disease, rheumatoid arthritis, cancer, Alzheimer’s disease, Candida albicans infection, extracellular or intracellular bacterial infection or other inflammatory disease provided that said ABC transporter activity is indicative of the disease condition. In a particular embodiment the sample cells are inflammatory cells, e.g. leukocytes. In a preferred embodiment, functional levels of ABCB1 are determined on an individual basis in relevant lymphocyte populations during disease or drug regimens. Currently used methods (e.g. CaAM, Rhodamin123) for functional testing of ABCB1 are complicated, non-selective and not sensitive enough to provide clinically relevant data. In the case of various inflammatory diseases, such as rheumatoid arthritis, colitis ulcerosa, HIV, COVID-19, Alzheimer's disease, Candida albicans, diseases caused by bacteria (e.g. mycoplasma) or cancers (e.g. leukemia), drug treatments, e.g. steroids, NSAIDs or newly developed specific kinase inhibitors or chemotherapy drugs can significantly affect the expression of ABCB1 in the membrane of the investigated lymphocyte populations. According to a special embodiment, the sample cells are inflammatory cells, e.g. would be lymphocytes that can individually determine the functional level of ABCB1 in relevant lymphocyte populations during disease or drug treatment. In a particular embodiment the biological sample is a blood sample. Preferably coagulation is prevented in the blood sample, e.g. by an anticoagulatory agent, e.g. EDTA. In a particular embodiment the cells are red blood cells. In a particular embodiment the method is calibrated to a specific disease. Preferably the subject (preferably a patient) is an animal having a lymphatic system and/or blood, preferably a vertebrate, in particular a reptile, an amphibian, a fish, a bird, or a mammal, preferably a mammalian patient, highly preferably a human. In a particular embodiment the invention relates to a treatment method in a patient having a disease wherein the level of ABCB1 activity is abnormal, - preferably above a pre-defined threshold typical of a healthy patient, or - below a pre-defined threshold typical of a healthy patient, wherein the diagnostic method of the invention is carried out, and provided that the patient is found to have an abnormal ABCB1 activity, - preferably wherein the ABCB1 level is above a pre-defined threshold typical of a healthy patient, or - wherein the ABCB1 level is below a pre-defined threshold typical of a healthy patient, the patient is treated by a treatment appropriate in the disease. In a particular embodiment the invention relates to a method for testing a compound of interest for its ability to modifying ABC multidrug transporter activity by measuring ABC multidrug transporter activity in a biological P136199-2417/SG sample comprising test sample cells, wherein said ABC transporter activity preferably comprises ABCB1 transporter activity, said method comprising the following steps: a) providing a test sample comprising (a population of) the sample cells having said ABC transporter activity, and a negative control sample (here: reference sample) comprising (a population of) negative control cells (here: reference cells); b) contacting said test sample cells, preferably the test sample and the negative control sample with a compound of the invention as well as with the compound of interest for at least 3 hours, preferably at least 5 hours, more preferably at least 8 hours or a period as defined in the preferred options of the method of the invention, in particular for 16 to 24 hours; c) measuring fluorescence intensity in the (population of) test sample cells and in the (population of) negative control cells, both in the presence and absence of the compound of interest, preferably in the test sample and in the negative control; d) optionally differentiating between live cells and dead cells to have the measured values refer to the live cells as disclosed herein, e) comparing the fluorescence of test sample cells to the fluorescence of the negative control cells, both in the presence or absence of the compound of interest, f) measuring the ABC transporter activity in the presence and absence of the compound of interest, wherein - if the ABC transporter activity in the test sample cells is modified by the compound of interest then said compound of interest is considered an ABC (preferably ABCB1) transporter activity modifier. If the ABC transporter activity in the test sample cells is reduced by the compound of interest then said compound of interest is considered an ABC (preferably ABCB1) transporter inhibitor. If the ABC transporter activity in the test sample cells is increased by the compound of interest then said compound of interest is considered an ABC (preferably ABCB1) transporter activator. Preferably the measured fluorescence is fluorescence intensity or the level of fluorescence is calculated based on multiple fluorescence intensity values. In a particular embodiment the method for testing a compound of interest is a screening method wherein multiple compounds of interest are tested in parallel. In a particular embodiment the invention relates to an assay kit comprising - a compound of the invention, - negative control cells, and/or - means to (prepare, e.g. with inhibitor to) provide negative control cells, - optionally a positive control, - optionally appropriate buffers and reagents. In a preferred embodiment the assay kit is formulated in a plate format, preferably a plate applicable with fluorescence detection, preferably with a flow cytometer. The invention also relates to the use of any of the compounds as defined herein or a kit as defined herein for testing a compound of interest for its ability to modify ABC multidrug transporter activity by measuring ABC multidrug transporter activity, as defined above, in a test sample comprising test sample cells or in any method as defined herein. P136199-2417/SG DEFINITIONS “ABC transporter” as used herein stands for ATP-binding cassette transporters which are a superfamily of membrane transporters that utilize the energy of adenosine triphosphate (ATP) hydrolysis to transport entities, in the context of the present invention molecules, across membranes. Denominations and subfamilies of ABC transporters are used herein as assigned by the HUGO Gene Nomenclature Committee (HGNC). Membrane transporters of the “ABCB family” belong to the B subfamily of ABC transporters, which comprises both full transporters and half transporters which is unique among the ABC transporter families. ABCB1 (MDR1, Pgp) is overexpressed in certain tumor cells which exhibit multi-drug resistance. Normally it is expressed in the blood brain barrier and liver. “ABC transporter activity”, i.e. the “activity” of an ABC transporter protein refers to any activity exerted by said transporter protein including e.g. its biological function, transport activity, i.e. transport of a drug through the membrane carrying said protein, or ATP-ase activity, as far as it is an indicator of transport activity, like substrate stimulated ATP-ase activity. A "substrate” of an ABC transporter protein is a compound that can be extruded from the cell through an ABC transporter mediated active transport mechanism. An “activator” substance increases activity as defined herein, whereas an “inhibitor” substance decreases activity of the said ABC multidrug transporter. An inhibitor can be, for example, an inhibitor of the transport process or a good substrate applied in excess of the amount of the compound of interest present (competitive inhibitor). The term “test sample” refers to a composition of matter or materials comprising cells in which the ABC transporter activity is or is to be examined or assessed. In an embodiment said test sample is prepared from a biological sample obtained from a living organism, including compositions which are processed e.g. completed with appropriate agents and/or cultured from the originally collected sample. In another embodiment the test sample is artificial, e.g. is prepared from a biological sample taken from a culture in a production method or is any laboratory sample in which the ABC transporter activity, preferably ABCB1 transporter activity is to be measured. The living organism, from which the sample is taken is preferably a multi-cellular plant or animal. In a preferred embodiment the animal is an arthropod, e.g. an insect or, preferably, a vertebrate animal, e.g. a fish, an amphibian, reptile, a bird or a mammal. In a more preferred embodiment the animal is a mammal, in a highly preferred embodiment is a human. The plant is typically an economically important plant for example those listed in [31. Bennett, B.C. 2007. Chapter 3. Twenty-five Important Plant Families. B.C. Bennett, editor. UNESCO Encyclopedia of Life Support Systems. http://eolss.net.] but not limited thereto. The “biological sample” may be obtained from tissue, bodily fluid, or microorganisms collected from a subject. In case of vertebrates sample sources include, but are not limited to, sputum (processed or unprocessed), bronchial alveolar lavage (BAL), bronchial wash (BW), blood, whole blood, bodily fluids, cerebrospinal fluid (CSF), lymphatic fluid, urine, plasma, serum, provided that it comprises cells, or a tissue (e.g., biopsy material). Preferably the biological sample is obtained for the purpose of diagnosis. A “test sample”, is one in which the cells, in which said ABC transporter activity to be measured is present. A test sample may be obtained from a biological sample by sampling or preparation. A “control sample” is a sample in which control cells are present. Control cells may be negative control cells which are cells from which said ABC transporter activity is missing, cells having an ABC transporter activity below a threshold level or having a baseline ABC transporter activity or cells in which said ABC transporter P136199-2417/SG activity is inhibited. Preferably the threshold level and/or the baseline level is pre-determined in a previous experiment or set to a value which is in the lower range of the expected measurement range. In a variant of negative control cells the ABC transporter activity is inhibited. A level of fluorescence is understood herein as a value or set of values obtained from a sample and which is indicative of an ABC activity level. The level of fluorescence in negative control cells is indicative of the fact that the ABC transporter activity to be measured can be considered as missing (level typical of missing ABC transporter activity) and/or is at a baseline level and/or provides a background. This may be assessed or measured e.g. when a negative control cell population is applied and the cells of the population are selected from the following types of cells: - cells which do not express the ABC transporter protein, - cells which express the ABC transporter protein under a pre-determined threshold value, - cells in which the expression of the ABC transporter protein is silenced, - cells which express a mutant ABC transporter protein which is not capable of transporting the fluorescein derivative of the invention (either in ester or in hydroxy form) and/or - cells in which the activity of the ABC transporter protein is inhibited. Thus, the negative control level is a reference level used to calculate the value typical of the ABC activity level given. It follows that the “missing ABC transporter activity” is a consideration for the measurement and is to be understood that it is considered as missing in the method given. Control sample may be a positive control sample wherein the control cells are positive control cells with a known or pre-determined level, preferably high level of ABC transporter activity. High level is understood that it is in the upper range of the expected measurement range. Measured fluorescence of the positive control sample may be used to check whether the assay is working and/or to set the measurement range of the assay method and/or for normalization of the measurement values of the assay method. A biological sample obtained from an animal, preferably a vertebrate, preferably a mammalian or a human comprising cells in which the ABC transporter activity is or is to be examined or assessed for diagnostic purposes is a diagnostic sample. “Measuring”, as understood herein, comprises obtaining information characterizing a physical phenomenon, e.g. a process or object, which information can be understood and/or interpreted by a human subject. Measuring a value, e.g. a level of a compound or the rate of a process is understood to cover quantitative or even analytically precise determinations, preferably from multiple samples, including calculations and optionally also statistical analysis and to cover less precise determination, e.g. quantitative determination without statistical analysis or semi-quantitative determinations or even determinations with a few result values (e.g. low, medium, high or yes or no /present or not present). Preferably measuring means quantitative determination or measurement with calculation, i.e. “quantitative measuring”. In the present invention preferably the level of activity, preferably transport activity of an ABC transporter protein is assessed or measured. “Comparing” two levels is understood herein to include a comparison to establish which is higher or lower, or establishing a difference or establishing a ratio of the levels, or values derived from the levels, optionally completed with other mathematical procedures (calculation) as the measurement method requires. In an embodiment comparing comprises subtracting two levels, e.g. subtracting two normalized or baseline-corrected level. In an embodiment comparing comprises a mathematical procedure, e.g. transformation carried out on both levels, e.g. calculating logarithm, or other function. In an embodiment comparing comprises making statistics and P136199-2417/SG calculating errors and/or means or averages which is/are considered, and/or assessment of statistics assessment of statistical significance. A threshold may be an upper limit or a lower limit of a normal range or a typical range which is defined for the purpose of the measurement given. A “subject” is an animal or preferably a vertebrate, highly preferably mammalian or human individual. A “patient” is a subject under medical care, preferably observation, diagnosis, treatment or prevention. A patient may be healthy or may suffer in a disease. A “normal range” of values measured in connection with a cohort or a population of subjects is a range of values having some or any advantage for subjects characterized thereby over values falling outside the range and being typical for other subjects. Preferably a “normal range” is a range of values typical of healthy subjects. In particular the value is a level of ABC transporter activity, typically a level measured by a method provided herein. A “normal level” is a normal range which is relatively narrow or a single value. In a broader sense normal range and normal level are used interchangeably. A “group” (or “moiety”) is used herein as a part of a molecule which can be derived in principle by removing another part, like a hydrogen atom. As used herein, the term “alkyl” alone or in combinations means a straight or branched-chain (if appropriate) hydrocarbon group containing preferably from 1 to 4 carbon atom(s) (“C1-4”) or preferably 1 to 3 or 1 to 2 carbon atoms (i.e. “C1-3” or “C1-2” alkyl groups, respectively), such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl and t-butyl. An “alkenyl” as used herein, alone or in combinations, means a straight or branched-chain unsaturated hydrocarbon group containing at least one carbon–carbon double bond. An alkenyl group with conjugated double bonds has an alternating double and single bonds forming a delocalized and pi electron system excitable by light, preferably by visible light. A “heterocyclic” ring as used herein is a cyclic moiety that has, besides carbon atom(s), atoms of at least one non-carbon element as member(s) of its ring(s). A heterocycle may comprise multiple rings, preferably two rings, and it may comprise an aromatic heterocycle and, fused to the aromatic heterocycle another ring which may or may not be aromatic; i.e. if it is not aromatic it may form a cyclic substituent of the aromatic heterocycle. In a preferred embodiment, if the heteroaryl comprises multiple, in particular two fused rings, both rings are aromatic. Preferably the ring(s) of the heterocyclic moiety is/are 5 to 6 membered ring(s). An “N-heterocyclic” ring as used herein is a heterocyclic ring comprising at least one N as a ring-forming heteroatom. The “N-heterocyclic” ring may comprise other heteroatoms, typically N, S and O atoms as well. An “aromatic” moiety as used herein can be described as a planar cyclic moiety (a ring) wherein the single bonds (called σ-bonds) between the ring-forming atoms are formed from overlap of hybridized atomic sp2-orbitals in line between the carbon nuclei, wherein a system of delocalized π-bonds are formed from overlap of atomic p-orbitals of each of the ring forming atoms above and below the plane of the ring and wherein the number of π electrons, which is provided by the ring-forming atoms, participates in according to molecular orbital theory, must be equal to 4n + 2 (Hückel’s rule), in which n = 1, 2, 3, etc., preferably 1 or 2, for a single ring with six π electrons, n = 1. The ring-forming atoms typically provide one or two π electrons to the delocalized π electron system. As used herein, the term “fused ring” means that the ring is fused with at least one other ring to form a group of a compound which comprises two or more rings wherein a single bond between two member atoms of the rings is, together with said two members, common in, i.e. shared by the two rings. P136199-2417/SG A “substituted” moiety comprises a substituent selected from the groups and moieties as defined herein; however a substituent is preferably smaller, i.e. shorter, i.e. consists of not more, preferably less atoms than the moiety which is/are substituted thereby. In the present invention, “optionally substituted”, i.e. “unsubstituted or substituted” means that it may be substituted with any substituent. As used herein the singular forms “a”, “an” and if context allows “the” include plural forms as well unless the context dictates otherwise. Thus, the meaning of “a” or “an” if the context allows includes the meaning “one or more”. The term “comprises” or “comprising” or “including” are to be construed here as having a non-exhaustive meaning and allow the addition or involvement of further features or method steps or components to anything which comprises the listed features or method steps or components. The expression “consisting essentially of” or “comprising substantially” is to be understood as consisting of mandatory features or method steps or components listed in a list e.g. in a claim whereas allowing to contain additionally other features or method steps or components which do not materially affect the essential characteristics of the use, method, composition or other subject matter. It is to be understood that “comprises” or “comprising” or “including” can be replaced herein by “consisting essentially of” or “comprising substantially” if so required without addition of new matter. Selection from a list, for example the term “selected from” can be replaced by “selected from a group consisting of” if practice so requires and, unless expressly stated otherwise, includes selecting one or more item(s) from the list. BRIEF DESCRIPTION OF THE FIGURES Figure 1. Uptake of TP dyes in human cells - effects of ABCG2, ABCB1 and ABCC1 expression in various cell types, measured by flow cytometry. Panel a. Uptake of 500 nM TP1 or 100 nM TP3 in PLB-985 control and ABCB1-expressing cells was measured after incubation for 24 h, at 37°C. TP3 fluorescence was measured by Attune NxT flow cytometer with red laser (638 nm) in the RL1 channel (emission filter: 670/14 nm). Dead cells were identified based on PI staining (488 nm blue laser, emission filter: 695/40 nm). TP1 signal was measured by Attune NxT flow cytometer with blue laser (488 nm) in the BL1 channel (emission filter: 530/30 nm). Dead cells were identified based on TP3 staining (added immediately before measurement). Experiments were repeated at least three times, the result of one representative experiment is shown. Panel b. MDR activity factors (see Methods) calculated by measuring inhibitor-sensitive TP1 or TP3 accumulation in various human cells, expressing ABCG2, ABCB1 or ABCC1. Upper row: TP1 measurements, lower row: TP3 measurements. The specific inhibitors used were 2.5 μM KO143, ABCB1 by 250 nM TQ, and ABCC1 by 10 μM IM. +/- SD values are indicated. Statistical analysis was performed by Student’s t-test. * p < 0.05 ***p < 0.001 ****p < 0.0001. (n=3) Figure 2. Concentration dependence of TP1 (Panel a) or TP3 (Panel b) dye uptake in PLB-985 and A431 control cells and in those overexpressing ABCB1. The CTRL (■) and ABCB1-expressing (×) cells were incubated with increasing concentrations of the dyes at 37 °C, for 24 h. The rhombuses (◊: CTRL) and the triangles (▲: ABCB1) demonstrate TP1 or TP3 accumulation in the presence of 250 nM TQ, a specific ABCB1 inhibitor. Dead cells were identified based on rapid TP3 dye (for TP1) or PI staining (for TP3). +/- SD values are indicated (n=3). P136199-2417/SG Figure 3. Flow cytometry detection of TP1 (Panel a) or TP3 (Panel b) accumulation in human PLB-985 cells: recognition and separation of control PLB-985 cells and PLB-985 cells expressing the ABCB1 transporter, respectively. Comparison to cell recognition by DCV accumulation. Control PLB-985 cells and PLB-985 cells expressing wild-type ABCB1 were mixed in various ratios, from 0.2% to 99.8%, respectively. TP1 accumulation was measured after incubation with 500 nM TP1 for 24 h at 37 °C. DCV accumulation was measured after the addition of 1 µM DCV (incubation for 1 h, at 37 °C). TP3 accumulation was measured after incubation with 200 nM TP1 for 24 h at 37 °C. Calcein accumulation was measured after the addition of 250 nM Calcein AM (incubation for 15 min at 37 °C). Figure 4. TP sensitivity assay in MES-SA cell line. Uptake of 500 nM TP1 (upper row) or 100 nM TP3 (lower row, dark gray) in control and different ABCB1-expressed MESSA cells were measured after 24 h incubation at 37 °C. Calcein accumulation (light gray) was measured in control and ABCB1 expressing MES-SA cells, after the addition of 250 nM Calcein-AM. MAF values were calculated as described in Methods. In all cases Tariquidar (TQ, 250 nM) was applied as selective inhibitor of ABCB1. Linear regression coefficient (r ² ) was calculated by excel. Determination of cell surface expression of ABCB1 was performed by UIC2 antibody labelling. ABCB1 expressions were estimated relative to that in the CTRL cells. (+/- SD values are indicated, n=3). Figure 5. Fluorescent TP1 or TP3 accumulation in human A431 cells, examined by confocal microscopy. Effects of ABCB1 protein expression and the specific inhibition of the transporter function by Tariquidar. Cellular fluorescence was followed by confocal microscopy. TP1 fluorescence (green) or TP3 fluorescence (red) was examined after 24 h of the addition of 500 nM TP1 or 200 nM TP3 to the medium, either in the absence or presence of the transporter inhibitor (250 nM Tariquidar for ABCB1). The nuclei were counterstained with DAPI. Figure 6. A, Important information about monomeric cyanine nucleic acid stains. B, and C, Chemical structure of TO-PRO-1 and TO-PRO-3. Figure 7. Time dependent accumulation of TP3 dye in PLB-985 cells overexpressing ABCB1. The CTRL (■) and ABCB1 (×) cells were incubated with 25 nM or 100 nM TP30-24 h, 37 °C. The rhombuses (◊ :CTRL) and triangles (▲:ABCB1) demonstrate TP3 accumulation in the presence of 250 nM TQ, a specific ABCB1 inhibitor. Dead cells were identified based on PI staining. +/- SD values are indicated. (n=3) Figure 8. Supplementary Fig 3. TP1 or TP3 toxicity assays. A, Effect of TP1 or TP3 accumulation on cell growth in PLB-985 cells and PLB-ABCB1 cells. Cell growth was measured after 500 nM TP1 or 100 nM TP3 treatment for 24 h at 37°C. B, C, Cytotoxic effects of TP1 or TP3 treatment in PLB-985 (B) and A431 (C) cells. The cells were pre-treated with the increasing concentrations of TP1 or TP3 for 24 h at 37 °C, then washed and cultured for 72 hours. Dead cells were identified based on TP3 or PI staining. +/- SD values are indicated (n=3). Figure 9. Flow cytometry detection of TP1 or TP3 accumulation in human PLB-985 cells. Recognition and separation of control PLB-985 cells and PLB-985 cells expressing the ABCB1 transporter by cell sorting. Control PLB-985 cells and PLB-985 cells expressing ABCB1 were mixed in 99:1 or 1:99 ratios. Cells were incubated with 500 nM TP1 or 100 nM TP3 24 h, 37°C. The mixed cell culture was sorted by FACSAriaIII with blue laser (488 nm) in the FITC channel (emission filter: 525/40nm) and with red laser (633 nm) in the APC channel (emission filter: 660/20 nm). After cell sorting, the purity of populations was controlled by DCV accumulation (TP1) or Calcein accumulation (TP3). Figure 10. Co-localisation of TP1 staining with Mitotracker Red, a mitochondrion-specific marker in A431 CTRL cells. TP1 fluorescence (green) was examined after 24 h of the addition of 500 nM TP1 to the medium, either in the absence or presence of 0.25 μM Tariquidar. After 24 h, the cells were co-stained with Mitotracker Red (red). P136199-2417/SG Merging the red and green signals shows a yellow color in overlapping regions. The TP1 staining co-localised – especially after the addition of TQ - mostly (as punctate structures) with the mitochondria. The inset shows higher magnification of the specific area. Figure 11. Flow cytometry analysis of cell surface membrane expression of ABCB1 in PLB-985 and A431 cells, detected by the phycoerythrin direct labelled UIC2 antibody. Figure 12. MDR activity factors (see Methods in Examples) calculated by measuring inhibitor-sensitive TP1 or TP3 accumulation in various human cells, expressing ABCG2, ABCB1 or ABCC1. Upper row: YP1 measurements, lower row: PP1 measurements. The specific inhibitors used were ABCG2 by 2.5 μM KO143, ABCB1 by 250 nM TQ, and ABCC1 by 10 μM IM. +/- SD values are indicated. Statistical analysis was performed by Student’s t-test. * p < 0.05 ***p < 0.001 ****p < 0.0001. (n=3) Figure 13. Concentration dependence of YP1 (Panel A) or PP1 (Panel B) dye uptake in PLB-985 and A431 control cells and in those overexpressing ABCB1. The CTRL (■) and ABCB1-expressing (×) cells were incubated with increasing concentrations of the dyes at 37 °C, for 24 h. The rhombuses (◊ :CTRL) and the triangles (▲:ABCB1) demonstrate YP1 or PP1 accumulation in the presence of 250 nM TQ, a specific ABCB1 inhibitor. +/- SD values are indicated (n=3). Figure 14. White blood cell pre-experiment TP1, TP3, PP1 and CaAM. After white blood cell isolation, 250 nM Calcein-AM (CaAM) uptake was measured after 15 min and 1 µM TP3, 1 µM TP1 or 1 µM PP1 cyanine dyes uptake after 24 h. The specific ABCB1 inhibitor was 250 nM TQ. The fluorescence signals were measured by Attune NxT flow cytometer with violet (405 nm), blue (488 nm) and red (638 nm) lasers. PO-PRO-1 signal was detected in VL1 channel (emission filter: 440/50 nm), TO-PRO-1, Calcein and CD4-FITC signals were detected in the BL1 channel (emission filter: 530/30 nm), CD8-PE signal was detected in the BL2 channel (emission filter: 590/40 nm), the TO-PRO-3 and CD3-APC signals were detected in RL1 channel (emission filter: 670/14 nm). Red lines are represented dyes, blue lines are represented dyes with inhibitor. Panel A. 1. uptake of 1 µM PP1 and 250 nM CaAM in lymphocytes, 2. 250 nM TQ inhibited transport of 1 µM PP1 and 250 nM CaAM in lymphocytes, 3-6. figs 1 µM TP3 (3.), 1 µM TP1 (4.), 1 µM PP1 (5.) or Calcein-AM (6.) transport activity in lymphocytes. Cyanine dyes were more sensitive to the presence of ABCB1 than Calcein, which may be explained by the high expression of ABCC1 on lymphocytes. Panel B. In addition to PO-PRO-1 uptake, CD3, CD4, and CD8 labeling were used to identify major lymphocyte types. In most cases, additional subtypes need to be identified. DETAILED DESCRIPTION OF THE INVENTION The multidrug transporter ABCB1 (MDR1, Pgp) plays an important role in the absorption, distribution, metabolism and elimination of a wide range of pharmaceutical compounds. Functional investigation of the ABCB1 expression is also essential in many diseases, including drug-resistant cancer, inflammatory conditions or Alzheimer’s disease. The present inventors have examined the potential interaction of the ABCB1 multidrug transporter with a group of commercially available viability dyes. When the cell membrane becomes permeable in the dead cells, these dyes accumulate in the cell nuclei and become fluorescent upon binding to nucleic acids which property renders them excellent viability markers. Importantly, these markers are considered not to penetrate into intact cells [16]. Here the inventors surprisingly found that TO-PRO™-1 (TP1) or TO-PRO™-3 (TP3), previously known as non cell penetrable dyes, slowly accumulated in the cells and their accumulation is strongly reduced by ABCB1-dependent dye extrusion. TP1/3 dye accumulation is not affected by the presence of ABCC1 or ABCG2, P136199-2417/SG while, surprisingly, increased to the level found in the ABCB1-negative cells by a specific P-glycoprotein inhibitor, Tariquidar. Thereby, the present inventors have found that these TP compounds can be used as highly sensitive, selective, non-toxic and stable dyes in various applications. Starting from these compounds the present inventors have tested a number of structurally related compounds and found further compound applicable in the assay whereby identified a scope of compounds useful in the assay method of the invention. Slow accumulation is also an advantage as it provides ample time to detect even a low level of ABC, preferably ABCB1 activity. In the present invention it is possible to measure ABCB1 activity in a simple way without the need of highly complex instrumentation. The assay can be carried out in a plate format. The assay also can be carried out in a high throughput format. In an embodiment the assay is carried out by flow cytometry, especially in microplate-based high- throughput assays, to examine the functional expression and properties of the ABCB1 multidrug transporter. The assay also can be carried out in a plate format with a fluorescence reader provided that it is sufficiently sensitive. In addition, the present inventors have demonstrated the applicability of the TP dyes to efficiently select and separate even a very low number of Pgp-expressing intact cells. The present inventors have initially found that the TP dyes slowly penetrate the membranes of intact cells, and inside the cells they are trapped by binding to nucleic acids and become fluorescent. As preferred embodiments, TP1 and TP3 have been shown to be compounds which are non-toxic to the cells and their fluorescence is stable for use in flow cytometry. Moreover, these dyes are actively extruded by the ABCB1/Pgp transporter, and not by the ABCC1 or ABCG2 multidrug pumps. Even if in certain case other transporters transport the compounds (like ABCG2 in certain embodiments) they can be inhibited, preferably specifically. In fact, certain compounds of the invention structurally related to TP1 and TP3, are transported to certain extent by other transporters like ABCG2 and they are to be, preferably specifically, inhibited. Following compound (e.g. TP) accumulation by cellular fluorescence and the concomitant use of PgP inhibitors makes this assay a simple, versatile, and sensitive tool for a selective functional evaluation of the ABCB1/Pgp transporter in human cells. Potential applications for efficient sorting of Pgp expressing cells, and the use of this method in high-throughput studies are also presented. ABCB1 (also indicated as glycoprotein P or Pgp) is an ATP dependent plasma membrane efflux pump which plays a crucial physiological role in protecting tissues from toxic xenobiotics and endogenous metabolites. ABCB1/Pgp is also an important factor in cancer multidrug resistance, potentially protecting the transporter- expressing tumor cells from targeted chemotherapeutic agents. Several ABCB1 substrates have already been identified, and these are structurally unrelated hydrophobic and/or amphipathic compounds, including anticancer agents, peptides or lipid-like compounds. Some of the transported substrate compounds of ABC multidrug transporters are fluorescent and these are widely used for functional assays. Intracellular cleavage of some compounds, when the dyes become fluorescent only after cellular cleavage and are trapped by a low efflux rate (e.g. Calcein-AM or PhenGreen SK diacetate), are certainly useful for multidrug transporter activity detection (see [2,24]). Several nucleic acid staining dyes, including Hoechst33342, DCV, become highly fluorescent only after binding to intracellular DNA or RNA, thus this intracellular trapping can also be efficiently used for monitoring an active dye extrusion by the transporters [4]. However, these reporter dyes are mostly non-selective and, because of the relatively short-term responses, are P136199-2417/SG not suitable for high-throughput, microplate-based flow cytometry measurements. In this work the present inventors’ aim was to identify novel ABCB1 substrate dyes. The present dyes have unexpectedly proven to be both specific and fluorescent, being suitable for HTS or microplate-based as well as flow-cytometry measurements. TP1 and TP3 are widely applied as viability dyes, as in short time incubations they do not permeate into intact cells and can be used for recognizing dead cells with leaky membranes, or fixed and permeabilized cells, through their binding to nucleic acids. The present inventors have shown that, surprisingly, these compounds slowly penetrate and accumulate in intact human cells, while the membrane expression of the ABCB1/Pgp transporter greatly reduces this accumulation. Importantly, the addition of specific ABCB1/Pgp inhibitors prevent this dye extrusion and the expression of the ABCG2 or the ABCC1 multidrug transporter does not reduce cellular TP1 or TP3 accumulation. The dye penetration and transporter extrusion are time- and concentration-dependent, and the accumulation of TP1 or TP3 is not toxic to the cells. Moreover, TP1 or TP3 extrusion by ABCB1/Pgp correlates with the membrane expression level or by the activity of the ABCB1 transporter, measured by monoclonal antibody staining and/or the Calcein assay. The transport activity was measured by flow cytometer equipped with a violet (405 nm,) a blue (488 nm) and red (633 nm) lasers. The wavelength values of the laser are to be set to the dye properties as described in the Molecular Probes Handbook, Chapter 8.1 [16]. Long-term (more than 4 hours and up to 24 hours) accumulation and fluorescence of TP1 and TP3 in various live cell types have been shown by using microplate-based flow cytometry. Cellular fluorescence after TP1 and/or TP3 incubation proved to be well measurable in the PLB-985 control cells, while there is very little accumulation in the PLB-985-MDR1 cells expressing ABCB1. However, this latter accumulation is greatly increased upon the addition of specific inhibitor, Tariquidar. The measurements have shown that only ABCB1/Pgp expressing cell lines were capable of extruding either TP1 or TP3. Due to the slow accumulation and low toxicity of TP1 or TP3, the differences in the long-term accumulation can be precisely measured in a microplate-based system which is a highly unexpected advantage and is in contrast to previously applied dye accumulation assays. Moreover, in the fluorescence-based TP1 or TP3 accumulation assays the sorting and selection of low number of cells expressing the ABCB1 protein could be achieved. Based on the difference in TP1 or TP3 accumulation, cell populations representing even less than 1% of the total cell mixture could be visualized and separated by flow cytometry. In a simple 96-well based cell format the assays of the invention have proved to be similarly efficient for the recognition and separation of ABCB1/Pgp expressing cells, as the previously applied, less convenient and less selective fluorescence-based assays. In a set of experiments, the TP-based functional assays showed good correlation with the variable expression levels of the ABCB1/Pgp. The MDR activity (MAF) values were calculated by the inhibitor sensitive increase in cellular fluorescence for both the TPs and Calcein AM. The MAF values obtained by measuring Calcein accumulation, the gold standard for such assays were less sensitive to the actual expression levels (probably because even low ABCB1 expression levels caused a high inhibition of Calcein AM uptake). The present assays have shown a good performance in these measurements as well. In fluorescence-based confocal microscopy studies with TP1 or TP3, upon the addition of the specific ABCB1 inhibitor, Tariquidar, cellular fluorescence in the ABCB1 expressing cells was greatly increased, while TP1 or TP3 in the live cell preparations did not show a high level of nuclear staining (expected based on studies in permeabilized cells). While TP3 is not stable the rest of the dyes are suitable in this type of assays, too. P136199-2417/SG It can be concluded that even very low numbers of ABCB1 transporter-positive live cells can be distinguished and sorted out from mixed cell populations, and the assay is applicable for high-throughput studies in a stable microplate-based system. TP1 and TP3 have proved particularly useful. However, other dyes of related structure are also useful in the assay of the invention. The present inventors have also analyzed the applicability of various cyanine, TO-based monomeric and dimeric dyes, like PO-PRO™-1 (PP1) Iodide and YO-PRO™-1 (YP1) for ABCB1 transport assays, as well as dimeric dyes. In microplate-based accumulation measurements with PP1 and YP1 fluorescence was measured at room temperature using a flow cytometer with plate reader. The three key multidrug transporters, ABCG2, ABCB1, and ABCC1 have also been tested in the cells on dye accumulation. After a relatively long-term incubation (24 hours at 37°C), both YP1 and PP1 significantly penetrate into the living cells which do not express ABCB1/Pgp. This YP1 accumulation occurs even in cells which express ABCC1 or ABCG2, while the presence of ABCB1 practically eliminated this accumulation. Accumulation of PP1 corresponding to the control was observed only in ABCC1 cells, thus PP1 appears to be a weak substrate for ABCG2. The best conditions for assessing ABCB1/Pgp activity, in 24-hour incubation periods at 37 ^o C, the optimum concentrations to be used are 500 nM for YP1 and 1µM for PP1. Compared to monomeric cyanine dyes, the nucleic acid binding affinity of dimers is orders of magnitude higher. Moreover, the dimers are fluorescent in the presence of a nucleic acid only. It is contemplated that the methodology presented in the case of monomers is also valid for dimers. Due to the increased cationic property, the applicable concentration may be different and a careful setting of the dye:cell ratio may be necessary. The key application of the accumulation assay of the invention in intact cells preferably is based on flow cytometry and not by direct cellular imaging methods. As experimentally shown below the intracellular binding of TP1 or TP3 in the live cell preparations by fluorescence microscopy, this method did not show a high level of nuclear staining (expected based on studies in permeabilized cells), and fluorescence was observed in various cellular organelles containing nucleic acids. Thus, intracellular membranes in live cells may have variable permeabilities for the TP dyes, complicating the quantitative evaluation of cellular dye accumulation. The present inventors note here that vesicular TP dye transport studies by the ABC transporters could not be efficiently performed, as TP fluorescence would require nucleic acid trapping in the membrane vesicles. However, this long-time assay may have various variants. Flow cytometry may be completed with a plate format. A fluorescent plate reader would result in a single fluorescent value per well and may be a less precise method, however, with careful setting and possibly optimization may work out and result is a very simple way to test samples. Use with fluorescent microscopy may require careful setting and may be a more cumbersome way. The plate variants could allow high throughput version. Thereby several samples can be assayed in parallel. This can well be utilized in a number of fields. In research study of several parallel samples may provide valuable information. In diagnostic application samples from several patients or several samples of the same patient may be tested. P136199-2417/SG In screening applications the parallel screening of several compounds may render the method highly effective. However, the person skilled in the art will recognize that the compounds of Formula II and Formula IIa, respectively, are tautomers and are to be considered as the same compounds. As a summary, here the present inventors document an application of dyes of the invention e.g. TP1 or TP3, previously applied as non cell membrane permeable viability dyes, for an efficient functional detection of the ABCB1/Pgp transporter in intact live cells by flow cytometry. The dye uptake assays, complemented with the use of selective transporter inhibitors, provide new, highly sensitive, extremely stable, microplate-based, potentially high-throughput tools to examine the functional properties of certain ABC-transporters, in particular the ABCB1 multidrug transporter, and to efficiently select and sort transporter expressing cells. Below the invention is further illustrated by way of non-limiting examples. EXAMPLES EXAMPLE 1 Methods Materials TO-PRO™-1 Iodide and TO-PRO™-3 Iodide were purchased from Thermo Fischer Scientific (Waltham, MA, USA). KO143 was obtained from Tocris Bioscience (Bristol,UK). Indometacine (IM) was purchased from Sigma-Aldrich-Merck (St. Louis, USA). Tariquidar (TQ) was a kind gift from Dr. S. Bates (NCI, NIH). Calcein AM (Ca-AM) and Vybrant™ DyeCycle™ Violet Stain (DCV) were bought from Thermo Fischer Scientific (Waltham, MA, US). The DAPI, Mitotracker Green and Lysotracker Green used to make microscopic images are from Thermo Fischer Scientific (Waltham, MA, USA). Components of phosphate buffered saline were obtained VWR (Radnor, Pennsylvania, USA). All other materials, if unless otherwise were purchased from Thermo Fischer Scientific (Waltham, MA, USA). Cell lines PLB-985 myelomonocytic and A431 skin derived epidermoid carcinoma cell lines, stably expressing the ABCG2 or the ABCB1 protein were generated by using a retroviral transduction system [2,25–27]. HEK-293 human embryonic kidney and HL-60 human promyelocytic leukemia cell lines stably expressing ABCC1 were also generated by retroviral transduction (HEK-293-ABCC1) or drug selection (HL60-ABCC1) [28]. The present inventors have also examined MES-SA (human sarcoma) cells, a gift from G. Szakács, stably expressing the ABCB1-Pgp protein at variable levels [29]. Flow cytometry The transport activity of the ABC transporters was measured by Attune NxT flow cytometer (Thermo Fischer Scientific Waltham, MA, US) equipped with a violet (405 nm,) a blue (488 nm) and red (638 nm) lasers. The Calcein and TO-PRO-1 signal was detected in the BL1 channel (emission filter: 530/30 nm), TO-PRO-3 signal was detected in the RL1 channel (emission filter: 670/214 nm), the DCV signal was detected in VL1 channel (emission filter: 440/50 nm). The live/dead marker was propidium-iodide (PI), which was detected in the BL3 channel (emission filter: 695/40 nm). Microplate-based TO-PRO-1 or TO-PRO-3 accumulation measurements by flow cytometry For the microplate-based TP1 or TP3 accumulation measurements control and ABCB1-expressing A431 cells were seeded (3 × 10 ⁴ cells in 100 µL final volume/well) onto 96-well plates and cultured for 24 h at 37 °C, P136199-2417/SG 5% CO ₂ . The treatment was next day. The control and ABCB1-expressing PLB-985 cells were seeded (3 × 10 ⁴ cells in 100 µL final volume/well) onto 96-well plates, and treated. At the end of the 24-hour treatment period (except for time dependence), we supplemented the cells with 100μL of complete medium containing 5μg/mL propidium iodide (PI). Finally, fluorescence was measured at room temperature using an Attune Nxt flow cytometer with plate reader. All experiments were performed at least three times. For assessing transporter inhibition, the ABCG2 transporter function was inhibited by 2.5 μM KO143, ABCB1 by 250 nM TQ, and ABCC1 by 10 μM IM. The cells (3×10 ⁴ ) were incubated with 500 nM TP1 or 100 nM TP3 with or without inhibitors, 24 hours at 37 °C. In order to follow for the microplate-based time-dependent accumulation of TP1 or TP3, control and ABCB1-expressing PLB-985 cells were incubated in the culture medium with various concentrations of TP1 or TP3, with or without transporter inhibitor, at 37 °C, for 15 minutes-24 hours. For assessing the TP1 or TP3 concentration dependence PLB-985 or A431 cells, expressing the ABCB1 transporter, were incubated in culture media with 0.2- 2000 nM of TP1 or 0.2–200 nM of TP3 at 37 °C for 24 hours. In order to follow the time-dependent accumulation of TP1 or TP3 the control and ABCB1-expressing PLB- 985 were incubated with 500 nM TP1 or 100 nM TP3 with or without inhibitors, 0-24 hours at 37 °C. Calcein Assay The cellular accumulation of the fluorescent free Calcein in control and ABCB1-expressing cell lines was measured by the Calcein assay. The cells were incubated with 250 nM Calcein AM with or without 250 nM Tariquidar (TQ), as specific ABCB1 transporter inhibitor, in DPBS for 15 minutes at 37 °C. Dye uptake was stopped by the addition of 250 μL ice-cold DPBS, and the cells were kept on ice until the measurements. DCV assay The transport activity of control and ABCB1-expressing cell lines was measured by the DCV assay [30]. The cells were incubated with 1 μM DCV with or without 250 nM TQ in DPBS for 1hour at 37 °C. Dye uptake was stopped by the addition of 100 μL ice-cold DPBS, the cells were kept on ice until the measurements. Flow cytometry data analysis Data analysis was performed using the Attune Acoustic Focusing Cytometer v3.2.1. Software (Applied Biosystems, Life Technologies, Carlsbad, CA, USA). Results were expressed as median ± standard deviation. The MDR activity factor % (MAF%—see refs [23,24]) was calculated as follows: MAF% = (((MFI _inh -MFI ₀ )/MFI _inh ) ×100), wherein MFIinh and MFI0 are the median fluorescence intensity (MFI) with (inh) or without (0) inhibitor. Confocal microscopy images For confocal microscopy the control and ABCB1-expressing A431 cells (5×10 ⁵ ) were treated with 200 nM TP3 or 500 nM TP1 with or without 250 nM TQ. At the end of the 24-hour incubation, the cells were treated with 4 µM DAPI, 200nM Mitotracker Green or 1 µM Lysotracker Green. The images were acquired by a Zeiss LSCM 710 microscope using a 63× NA = 1.4 Plan Apo objective. Images were captured and analyzed by Zen2 (Blue edition) Software. Results The present inventors have examined the potential interactions of ABC multidrug transporters with TO- PRO™-1 and TO-PRO™-3 nucleic acid staining fluorescent dyes. These compounds are considered as membrane- impermeable, when used in short-term (maximum few hours) incubations. When the cell membrane becomes permeable in the dead cells, both of these dyes accumulate in the cell nuclei and become fluorescent upon binding P136199-2417/SG to nucleic acids. Therefore, these compounds are widely used as viability markers in flow cytometry or for visualizing the cell nuclei after fixation and permeabilization of the cells. TP1 or TP3 accumulation in live cells - effects of ABC transporters First, we measured the long-term (more than 4 hours and up to 24 hours) accumulation and fluorescence of TP1 and TP3 in various live cell types, by using microplate-based flow cytometry. Then we examined the effects of the presence of the three key multidrug transporters, ABCG2, ABCB1, and ABCC1 in the cells on dye accumulation. In these assays we co-stained the cells with propidium iodide (PI), to exclude dead cells. As shown in Figure 1, after a relatively long-term incubation (24 hours at 37 °C), both TP1 and TP3 significantly penetrate into the living cells which do not express ABCB1/Pgp. This accumulation occurs even in cells which expressing ABCC1 or ABCG2, while the presence of ABCB1 practically eliminated this accumulation. As documented in Panel A, cellular fluorescence after TP1 and/or TP3 incubation is well measurable in the PLB-985 control cells, while there is very little accumulation in the PLB-985-MDR1 cells. As indicated by the graphs in the lower row of Panel A, this latter accumulation is greatly increased, up to the level seen in the control cells, upon the addition of ABCB1/Pgp inhibitor, Tariquidar. Figure 1, Panel B demonstrates the quantitation of the inhibition of TP1 (upper row) or TP3 (lower row) accumulations, respectively, in cell types expressing various ABC multidrug transporters. The calculated MDR activity factors show the relative efficiency of inhibiting dye accumulation by the respective ABC transporters, as compared to those seen by the addition of their selective inhibitors (see Methods and refs [23,24]). These measurements clearly show that only ABCB1/Pgp expressing cell lines are capable of extruding either TP1 or TP3, thus reducing cellular fluorescence in an inhibitor-sensitive manner. In order to establish optimum conditions for assessing cellular TP uptake and ABCB1 function, we have analyzed the time-dependence of the TP uptake in various cell types (see Figure 7). As shown, when TP uptake was measured in the PLB-985 cells (in the presence of 200 nM or 500 nM TP1 in the culture media), the increase in cellular TP fluorescence at 37 °C saturated after about 16 hours. A similar saturation of cellular fluorescence was observed when 25 nM or 100 nM TP3 was applied. Similar time-dependent saturation curves were obtained in PLB-985 cell lines (see Figure 7). As shown in Fig 2, in the PLB-985 and A431 cells at low (200-500 nM of TP1 or 50-200 nM of TP3) concentrations, the presence of the ABCB1 protein in the cell membrane caused a major difference in the amount of the accumulated TP fluorescence. At increasing TP concentrations, the difference in cellular fluorescence caused by the ABCB1 protein still increased, while the ratio of the fluorescence in the absence and presence of ABCB1, respectively, did not increase. Based on these experiments, the suggested best conditions for assessing ABCB1/Pgp activity, in 24-hour incubation periods at 37 °C, the optimum concentrations to be used are 500 nM for TP1 or 100 nM for TP3. In contrast to previously applied dye accumulation assays, due to the slow accumulation and low toxicity of TP1 or TP3, the differences in the long-term accumulation can be properly measured in a microplate-based system (see Figure 8). Therefore, in the present inventors’ further experiments they used a TP1 concentration of 500 nM, or a TP3 concentration of 100 nM, and 24-hour incubation at 37 °C in 96-well microplates, providing optimum conditions for the functional ABCB1/Pgp assays. In the following experiments the present inventors examined the potential applicability of the fluorescence- based TP1 or TP3 accumulation assays for the sorting and selection of low number of cells expressing the ABCB1 P136199-2417/SG protein. They compared the TP-based assays in this regard to the established DCV and the Calcein AM assays, previously used for similar purposes. As documented in Fig 3, and in Figure 9, based on the difference in TP1 or TP3 accumulation, cell populations representing even less than 1% of the total cell mixture, could be visualized and separated by flow cytometry. These experiments show that the relatively simple and optimized, 96-well based TP assays are similarly efficient for the recognition and separation of ABCB1/Pgp expressing cells, as the previously applied, less convenient and less selective fluorescence-based assays. In their following experiments the present inventors have examined how the TP-based functional assays correlate with the variable expression levels of the ABCB1/Pgp. In order to explore this question, they have used MES-SA cells with no, or increasing levels of ABCB1 expression. As shown in Figure 4, control and ABCB1- expressing MES-SA cells were incubated with 500 nM TP1 or 100 nM TP3 for 24 h at 37 °C, or with 250 nM CaAM, for 15 min at 37 °C. The MDR activity (MAF) values were calculated by the inhibitor sensitive increase in cellular fluorescence for both the TPs and Calcein AM. Interestingly, the MAF values obtained by measuring Calcein accumulation were less sensitive to the actual expression levels, probably because even low ABCB1 expression levels caused a maximum inhibition of Calcein AM uptake. The best correlation with the low levels of ABCB1 in the MES-SA cell membranes, measured by specific monoclonal antibody binding, was shown by the TP1 uptake. TP3 accumulation was somewhat less sensitive to the low levels of ABCB1 expression, giving high MAF values even at low membrane protein levels. In addition to the flow cytometry studies the present inventors have also examined TP1 and TP3 accumulation in control A431 cells and in A431 cells expressing ABCB1, by using fluorescence-based confocal microscopy. In these experiments, to label the nuclei of the cells, they also included the staining of live A431 cells with DAPI. As shown in Figure 5, in a representative confocal microscopy study, the control A431 cells showed an intensive green or red signal due to dye accumulation in cell organelles, while the A431-ABCB1 cells practically did not accumulate TP1 or TP3. Upon the addition of the specific ABCB1 inhibitor, Tariquidar, cellular fluorescence in the ABCB1 expressing cells was greatly increased, while there was no significant change in the fluorescence level in the control cells. Interestingly, TP1 or TP3 in the live cell preparations did not show a high level of nuclear staining (expected based on studies in permeabilized cells), while fluorescence was observed in cellular organelles containing nucleic acids (see Figure 10). EXAMPLE 2 Materials PO-PRO™-1 Iodide and YO-PRO™-1 Iodide were purchased from Thermo Fischer Scientific (Waltham, MA, USA). Cell lines PLB-985 myelomonocytic and A431 skin derived epidermoid carcinoma cell lines, stably expressing the ABCG2 or the ABCB1 protein were generated by using a retroviral transduction system [2,25–27]. HEK-293 human embryonic kidney and HL-60 human promyelocytic leukemia cell lines stably expressing ABCC1 were also generated by retroviral transduction (HEK-293-ABCC1) or drug selection (HL60-ABCC1) [28]. P136199-2417/SG Flow cytometry The transport activity of the ABC transporters was measured by Attune NxT flow cytometer (Thermo Fischer Scientific Waltham, MA, US) equipped with a violet (405 nm,) a blue (488 nm) and red (638 nm) lasers. YO-PRO-1 signal was detected in the BL1 channel (emission filter: 530/30 nm), the PO-PRO-1 signal was detected in VL1 channel (emission filter: 440/50 nm). Microplate-based YO-PRO-1 or PO-PRO-1 accumulation measurements by flow cytometry For the microplate-based YP1 or PP1 accumulation measurements control and ABCB1-expressing A431 cells were seeded (3 × 10 ⁴ cells in 100 µL final volume/well) onto 96-well plates and cultured for 24 h at 37 °C, 5% CO ₂ . The treatment was next day. The control and ABCB1-expressing PLB-985 cells were seeded (3 × 10 ⁴ cells in 100 µL final volume/well) onto 96-well plates, and treated. At the end of the 24-hour treatment period (except for time dependence), we supplemented the cells with 100μL of complete medium. Finally, fluorescence was measured at room temperature using an Attune Nxt flow cytometer with plate reader. All experiments were performed at least three times. For assessing transporter inhibition, the ABCG2 transporter function was inhibited by 2.5μM KO143, ABCB1 by 250 nM TQ, and ABCC1 by 10 μM IM. The cells (3×10 ⁴ ) were incubated with 500 nM YP1 or 500 nM PP1 with or without inhibitors, 24 hours at 37 °C. In order to follow for the microplate-based time- dependent accumulation of YP1 or PP1, control and ABCB1-expressing PLB-985 cells were incubated in the culture medium with various concentrations of YP1 or PP1, with or without transporter inhibitor, at 37 °C, for 15 minutes-24 hours. For assessing the YP1 or PP1 concentration dependence PLB-985 or A431 cells, expressing the ABCB1 transporter, were incubated in culture media with 0.2- 2000 nM YP1 or PP1 at 37 °C for 24 hours. Flow cytometry data analysis Data analysis was performed using the Attune Acoustic Focusing Cytometer v3.2.1. Software (Applied Biosystems, Life Technologies, Carlsbad, CA, USA). Results were expressed as median ± standard deviation. The MDR activity factor % (MAF%—see refs [23,24]) was calculated as follows: MAF% = (((MFIinh-MFI0)/MFIinh) ×100), wherein MFI _inh and MFI ₀ are the median fluorescence intensity (MFI) with (inh) or without (0) inhibitor. Results In this study we have examined the potential interactions of ABC multidrug transporters with PO-PRO™- 1 and YO-PRO™-1 nucleic acid staining fluorescent dyes. These compounds are considered as membrane- impermeable, when used in short-term (maximum few hours) incubations. When the cell membrane becomes permeable in the dead cells, both of these dyes accumulate in the cell nuclei and become fluorescent upon binding to nucleic acids. Therefore, these compounds are widely used as viability markers in flow cytometry or for visualizing the cell nuclei after fixation and permeabilization of the cells. YP1 or PP1 accumulation in live cells - effects of ABC transporters First, we examined the effects of the presence of the three key multidrug transporters, ABCG2, ABCB1, and ABCC1 in the cells on dye accumulation. Figure 12 demonstrates the quantitation of the inhibition of YP1 (upper row) or PP1 (lower row) accumulations, respectively, in cell types expressing various ABC multidrug transporters. The calculated MDR activity factors show the relative efficiency of inhibiting dye accumulation by the respective ABC transporters, as compared to those seen by the addition of their selective inhibitors (see Methods and refs [23,24]). As shown in Figure 12, after a relatively long-term incubation (24 hours at 37 °C), both YP1 and PP1 significantly penetrate P136199-2417/SG into the living cells which do not express ABCB1/Pgp. This YP1 accumulation occurs even in cells which expressing ABCC1 or ABCG2, while the presence of ABCB1 practically eliminated this accumulation. Accumulation of PP1 corresponding to the control was observed only in ABCC1 cells, PP1 appears to be a weak substrate for ABCG2. These measurements clearly show that only ABCB1/Pgp expressing cell lines are capable of extruding either YP1 or PP1, thus reducing cellular fluorescence in an inhibitor-sensitive manner. As shown in Fig 13, in the PLB-985 and A431 cells at low (200-500 nM of TP1 or 50-200 nM of TP3) concentrations, the presence of the ABCB1 protein in the cell membrane caused a major difference in the amount of the accumulated TP fluorescence. At increasing TP concentrations, the difference in cellular fluorescence caused by the ABCB1 protein still increased, while the ratio of the fluorescence in the absence and presence of ABCB1, respectively, did not increase. Based on these experiments, the suggested best conditions for assessing ABCB1/Pgp activity, in 24-hour incubation periods at 37 °C, the optimum concentrations to be used are 500nM for YP1 or 1µM for PP1. EXAMPLE 3 Experiments with lymphocytes Whole blood samples were obtained in Vacuette tubes containing EDTA.1mL human blood was diluted in 1mL phosphate buffered saline (PBS) which is carefully layered on 2 ml of FICOLL reagent. The cells were centrifuged at 400×g for 40 min and the mononuclear blood cells (PMBC) was aspirated in 1mL PBS and washed 3 times. The PMBC cells were resuspended in 1mL RPMI cell culture media. The cells were seeded onto 24-well plates and treated with the appropriate cyanine dye with or without inhibitor for 24 h at 37 °C, 5% CO2. At the end of the 24-hour treatment period, we labeled the cells with CD antibodies, according to description of the product, and supplemented the cells with 500μL of PBS. Finally, fluorescence was measured at room temperature using tube system of flow cytometer. All experiments were performed at least three times. We recommend the use of a general PMBC stain (e.g. CD45, DraQ5) or No-Wash No-Lyse filter to remove any red blood cell. Evaluation by comparing the with or without inhibitor histogram curves of the cyanine dyes are on PMBC subpopulation, by comparing the quadrant ratio, signal intensity values or MAF% values. As shown in the preliminary data, CaAM cannot accurately distinguish between lymphocyte populations expressing ABCB1 differently, while cyanine dyes (in this case TP1) show the differences much more sensitively. EXAMPLE 4 Experiments with dimeric cyanine dyes Compared to monomeric cyanine dyes, the nucleic acid binding affinity of dimers is orders of magnitude higher, due to the fact that the positively charged side chains of two monomers are covalently linked to form a dimer containing 4 positive charges. In addition to excellent binding properties, the dimers are practically non- fluorescent in the absence of nucleic acid. However, the shift to the red range that occurs with the change of the dye:DNA ratio is amplified in the case of dimers. Based on these data, we believe that the methodology presented in the case of monomers is also valid for dimers. However, due to the increased cationic property, there may be differences in concentration, as well as the inaccurate setting of the dye:cell ratio may give a fluorescent signal appearing in other channels, so the examination of other channels of the same laser excitation may encounter difficulties. P136199-2417/SG PLB-985 myelomonocytic and A431 skin derived epidermoid carcinoma cell lines, stably expressing the ABCG2 or the ABCB1 protein were generated by using a retroviral transduction system [2,25–27]. HEK-293 human embryonic kidney and HL-60 human promyelocytic leukemia cell lines stably expressing ABCC1 were also generated by retroviral transduction (HEK-293-ABCC1) or drug selection (HL60-ABCC1) [28]. Flow cytometry The transport activity of the ABC transporters was measured by Attune NxT flow cytometer (Thermo Fischer Scientific Waltham, MA, US) equipped with a violet (405nm,) a blue (488nm), yellow (561nm) and red (637nm) lasers. Table 1: Spectral parameters of cyanine dimer nucleic acid stains in the cells Microplate-based YO-PRO-1 or PO-PRO-1 accumulation measurements by flow cytometry For the microplate-based cyanine dimer dyes accumulation measurements control and ABCB1-expressing A431 cells were seeded (3 × 10 ⁴ cells in 100 µL final volume/well) onto 96-well plates and cultured for 24 h at 37 °C, 5% CO2. The treatment was next day. The control and ABCB1-expressing PLB-985 cells were seeded (3 × 10 ⁴ cells in 100 µL final volume/well) onto 96-well plates, and treated. At the end of the 24-hour treatment period (except for time dependence), we supplemented the cells with 100μL of complete medium. 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