the above described bead types can be applied to assays commonly used in hts applications . such assays are conveniently categorised as one of two types . i ) the first category comprises equilibrium binding assays , in which one member of a binding pair ( the reactant ) is bound to the surface of the bead and samples containing compounds to be screened are tested for their effect upon the binding , ( either antagonistic or agonistic ) to a second member of the binding pair ( the ligand ), where the ligand carries a signal moiety , preferably a fluorescent label . in this way , the effect of the test sample on the binding reaction can be determined by measurement of the amount of labelled ligand bound to the bead through its interaction with its binding partner . examples of such equilibrium binding interactions include , but are not restricted to , receptor - ligand interactions , protein - protein binding interactions and protein - dna interactions . irrespective of the identity of the components of the interaction , all such assays are similarly characterised by having two components where one component is bound to the bead and the second component carries a signal moiety which becomes attached to the bead through the interaction of the two components . ii ) in the second category , the assay may comprise detection and measurement of a chemical or enzymatic change in the state of an assay component bound to the bead and in which the samples containing compounds to be screened are tested for their inhibitory effects , potentiation effects , agonistic , or antagonistic effects on the reaction under investigation . illustrative of such reactions are those which include the removal of a fluorescent dye - labelled moiety from a substrate coupled directly or indirectly to the bead through a covalent or non - covalent interaction , or alternatively , the covalent or non - covalent addition of a fluorescent dye - labelled moiety from a substrate in solution in the assay medium to a molecule coupled directly or indirectly to the bead by means of a covalent or non - covalent interaction . examples of such assays include , but are not restricted to , the cleavage of a fluorescent dye - labelled peptide or protein by a protease , the cleavage of fluorescent dye - labelled dna or rna molecule by a nuclease , the joining of fluorescent dye - labelled dna or rna molecules to other nucleic acid molecules by ligases , the addition of a fluorescent dye - labelled nucleotide to a dna or rna molecule by a polymerase and transfer of a fluorescent dye - labelled chemical moiety from one molecule to another by a transferase such as acetyl transferase . suitable fluorescent labels for tagging ligands or substrates are those which are : a ) spectrally distinct and distinguishable from any fluorescent dye used for bead identification , b ) detectable by a flow cytometer and , c ) capable of being attached to the ligand or substrate component of the assay by covalent or non - covalent attachment . suitable fluorescent dyes for use in labelling ligands and substrates according to the method of the invention may be selected from the general categories of fluorescent dyes listed above . preferably , derivatives of such fluorescent dyes having reactive or functional groups suitable for attachment to corresponding functional or reactive groups on biological target molecules are used . examples of such reactive fluorescent dyes are sulpho - cyanine dye nhs ester derivatives as described in u . s . pat . no . 4 , 268 , 486 ( waggoner et al ). other fluorescent reagents suitable for labelling target molecules will be well known to those skilled in the art . alternatively , labels useful for attachment to the ligands or substrates can be fluorescence energy transfer labels . examples of such energy transfer fluorescent dyes are to be found in gb pat . no . 2301833 ( waggoner et al ) which relates to fluorescent energy transfer complexes containing reactive or functional groups for covalent attachment to a target . other fluorescent energy transfer labels may be bound non - covalently to a ligand or substrate moiety , e . g . by intercalation of a dye to a dsdna molecule . examples of such dyes are disclosed in u . s . pat . no . 5 , 401 , 847 ( glazer et al . for clarity , the general principles and specific embodiments of the method according to the present invention ( termed mix / multiplex hts ), are described with reference to the following figures : with reference to fig1 , to perform the mix / multiplex hts process , sufficient individual types of carrier beads are used to allow one carrier bead type for each discrete assay to be performed in a screening unit , that is one bead type for each sample to be screened . the surfaces of beads are modified , for example by coating with a binding reagent such as an antibody , protein a , streptavidin , avidin , wheat germ agglutinin or poly - l - lysine . alternatively the bead surface may be treated by chemical modification to provide functional or reactive groups suitable for the attachment of specific assay components such as proteins , peptides , oligonucleotides , ligands and carbohydrates to the surface of the bead . suitable functional or reactive groups include hydroxyl , amino , carbonyl , carboxyl and sulphydryl groups . methods suitable for coupling reactants to the surface the bead are well known to those skilled in the art . in a further illustration of the method of this invention , reference is made to two possible but non - restrictive embodiments of the process . with reference to fig2 , beads containing different amounts of two fluorescent dyes are used as carrier beads for the assay . to set up the assay , each type of beads ( 2 , 3 , 4 ) is added to a separate well of a multiwell screening plate ( 1 ). pre - dispensed plates arrayed in this manner are then used as the basis for the screening process as described generally above . once the reaction stage of the screening process is complete , a portion , or the entire contents of each of the wells in which reactions have been conducted , are mixed together into a single container ( 6 ) and analysed by flow cytometry . in the flow cytometer , two of the available fluorescence measurement channels are used to identify the bead type to which any individual bead belongs , by determining the amounts of the two fluorescent dyes present within the bead . simultaneously , a third fluorescence channel may , be used to quantify the amount of fluorescent dye - labelled ligand or substrate bound to the surface of the bead . in performing assays according to the method of this invention , it is convenient to refer to a screening unit which will typically correspond to assay reactions performed in one multiwell plate , where a complete screen comprises from one to many multiwell plates . each bead type from 1 - n is individually added to corresponding wells 1 - n containing assay reagents , where for example in the case of a receptor based screening assay , reagents would typically comprise a receptor preparation , assay buffer and a fluorescent labelled receptor ligand . samples containing one or more compounds to be screened are added individually to the prepared wells , samples 1 - n being added to wells 1 - n . in this way , a fixed correspondence is established between each sample in the screen and the bead type carrying the reactants exposed to each individual sample containing one or more compounds under test . once the reaction stage of the assay is complete , all reactions in a screening unit are mixed together for analysis without destroying the correspondence , since on analysis by flow cytometry , both the particular bead type and the assay signal associated with it can be readily determined for any given bead in the analysed mixture . accordingly , once analysis of the mixed samples is complete , assay signals measured from beads 1 - n ( activity 1 - n ) can be correlated with samples 1 - n originally added to wells 1 - n . display of data as an x - y - z plot ( 7 ) allows identification of individual bead types according to the relative intensities of fluorescence from bead fluorescent dyes 1 ( 8 ) and 2 ( 9 ), on the x and y axes respectively and allows intensities of assay signals for each compound in the screen to be displayed separately ( 10 ). the identity of each bead type can be determined from its x - y position and therefore the z assay signal of that type can be assigned to a single well in the original multiwell plate . consequently all assay data from one mixed sample can be displayed as a data matrix ( 11 ) corresponding to the original layout of the multiwell plate and results examined to determine the activity of the compounds screened . in a second possible embodiment of the process of the invention , electronic encoding is used to identify assay carrier beads . with reference to fig3 , in this embodiment carrier beads containing semiconductor memory devices , as described in u . s . pat . no . 5 , 641 , 634 , and coated with assay reagents particular to the type of assay being performed are used in a bulk suspension ( 12 ) as described above . the bulk beads are dispensed into multiwell plates ( 13 ) using a dispensing nozzle ( 14 ) fitted with a radio - frequency generating coil ( 16 ) controlled by encoding circuitry ( 15 ). this apparatus allows beads passing through the dispensing device to be given a unique identity through action of the radio - frequency field on the semiconductor . by this means it is possible , starting with a bulk suspension of identical beads and by moving the dispensing device from well to well , to produce a multiwell plate with an uniquely coded population of beads in each well . at this stage the screening process is continued as described above with assay reagents ( 17 ) being added to the wells of the multiwell plate , followed by samples ( 18 ) containing compounds to be screened . for analysis , a modified flow cytometer ( 20 ) is used where the instrument is fitted with a second radio - frequency coil ( 22 ) set up to read information encoded on the semiconductor within beads through decoding circuitry ( 21 ). pooled beads ( 19 ) passing through the instrument are first read by the decoder and secondly by the instrument &# 39 ; s conventional fluorescence detection laser ( 23 ) and photomultiplier ( 24 ) components to give a continuous data readout of bead identity code ( 25 ) and assay fluorescence signal ( 26 ). by the use of electronic encoding as a means of bead identification , the possible number of bead types is limited only by the capacity of the semiconductor . for example a 16 bit device would allow the characterisation of 32768 different bead types and therefore mix / multiplexing of 32768 discrete screening assay reactions . secondly , beads may be prepared for an assay in bulk and coded directly before use , thereby removing the need to carry out preparations on each bead type individually . radio - frequency encoding and reading removes the requirement for multiple fluorescence channels to be used for bead identification allowing either simplification of instrumentation of use of fluorescence channels to measure additional assay information . the mix / multiplex procedure as described above allows very high throughput of individual screening assay reactions by analysis by flow cytometry in a manner which exploits the capabilities of flow cytometry instrumentation , and in particular the very fast data acquisition which can be obtained . the procedure is compatible with the wide range of different sized multiwell plates that are commonly used in hts programs . the method of this invention is preferably used in high well density , small well volume , plates such as 1536 well plates , where the assay volume / well is 10 μl or less . the amounts of beads used in each well may be varied to accommodate the requirements of different screening assays , but will preferably be in the range 0 . 01 - 10 % v / v . in respect of the assay volume , most preferably in the range 0 . 1 - 1 . 0 % v / v . at the most preferred bead concentrations and using a preferred bead size of 10 μm , a single assay well containing 10 μl of liquid would contain a number of beads in the range 10 , 000 - 100 , 000 beads / well . each bead in any individual well is identical to every other bead in the same well and is therefore an individual assay unit which can be separately measured by flow cytometry . in performing biological assays , it is common practice to perform replicate measurements in order to take account of physical or biological variations inherent to the assay process . such replicates typically take the form of duplicate or triplicate determinations of each assay which are carried out to obtain data typically expressed as a mean ± standard deviation , where the standard deviation is a statistical measure of the variation in the assay data which is used to assess the precision and accuracy of the data obtained . in conventional screening assays the assay comprises the whole well or tube in which the assay is performed , and therefore replication involves duplication of the entire assay . in contrast in bead based assays where each bead is an measurable unit , replicate measurements may be performed at the level of individual beads . therefore , while an assay well may contain 10 , 000 - 100 , 000 beads it is not necessary in the subsequent analysis to measure every bead from that well , but only to measure sufficient beads to accumulate data which meets predetermined specifications for precision and accuracy . the potential throughput of the process is illustrated by the following example . if a 1536 well plate is used as single screening unit , and it is determined that to obtain a statistically valid analysis it is necessary to measure assay results for 100 beads for each compound screened , the total number of beads to be analysed is 153 , 600 . modern flow cytometers are readily capable of performing measurements on between 1000 and 10 , 000 particles / second ; assuming analysis at an intermediate rate of 2500 beads / second yields an analysis time of 153 , 600 / 2500 = 61 . 44 seconds or approximately 1 minute to measure the 1536 discrete assays in the multiwell plate . this compares very favourably with a time of 25 . 6 minutes to read results individually in a plate reader at a speed of 1 second / well . allowing for loading of successive mixed samples on to a flow cytometer at a rate of 40 / hour gives a throughput of 1536 × 40 = 61440 assays / hour or around 500 , 000 assays in a working day . streptavidin coated bead type a ( yellow fluor ) and bead type b ( purple fluor ) were pipetted into two separate wells of a microtitre plate , such that well 1 contained bead a and well 2 contained bead b . buffer was added to well 1 and buffer containing biotin was added to well 2 . following mixing arid incubation a solution of cy - 5 labelled biotin in buffer was added to both wells . following further incubation the contents of well 1 and well 2 were combined and the mixture analysed by flow cytometry . measurement of cy - 5 fluorescence associated with each bead type showed high fluorescence for bead b indicating high cy - 5 - biotin binding in well 1 and low cy - 5 - biotin binding in well 2 , correlating with the presence in well 2 of an active competitor for binding to the streptavidin on the bead surface .