WO2001085325A2

WO2001085325A2 - Parallel chemical reactor

Info

Publication number: WO2001085325A2
Application number: PCT/IB2001/000738
Authority: WO
Inventors: Yoram Palti
Original assignee: Palti Yoram Prof
Priority date: 2000-05-05
Filing date: 2001-05-01
Publication date: 2001-11-15
Also published as: WO2001085325A3; AU5058401A

Abstract

The present invention relates to chemical libraries for identifying receptor-ligand interactions. It further provides for coding and reading individual library supports for structure indentification of the attached chemical entity. Moreover, the present invention provides a method for identifying a molecule of interest in a biological or chemical library.

Description

PARALLEL CHEMICAL REACTOR

FIELD OF THE INVENTION

The present invention relates to chemical libraries for identifying receptor- ligand interactions. It further provides for coding and reading individual library supports for structure identification of the attached chemical entity.

BACKGROUND OF THE INVENTION

Numerous chemical, biochemical and biological processes involving recognition, identification, analysis, selection, isolation, synthesis, and polymerization can take place on an array (microarray) of reaction sites. These sites may be specifically addressed electrically or optically to detect the biological process. The array technology is a powerful tool to identify or process numerous elements, e.g. , in high throughput screening (HTS) or processing. Microarray assays enable massive parallel data acquisition, analysis, synthesis and frequently separation, thus making HTS possible. Parallelism greatly increases the speed of experimental progress and allow rapid screening as well as comparison of relative binding affinity or quantity of different molecules. For example, genes or gene products represented in the microarray and microarrays of complementary DNA (cDNA) sequences allow hybridization-based monitoring of gene expression. For example, devices couple an immobilized molecular recognition element, i.e., cDNA nucleic acid, to the surface of a transducer which will "transduce" a molecular recognition event into a measurable signal, pinpointing the presence of the target.

Biosensors that include high density probe immobilization are converging with microfluidic technology to assist in the elaboration of self-contained analytical biochip module systems. The key players who have entered the race to produce primarily DNA chips use techniques based essentially on immobilization chemistries, each with advantages and limitations of its own. So far, these techniques include DNA chips for nucleic acid hybridization Drmanac, et a , Science, 1993, 260:1649-1652; Gingeras, et al. , Nucleic AcidsRes., 1987, 15:5373-90; MeinkothandWahl,-4ttfl/. Biochem. , 1984, 138:267-284; and sequencing as well as identification of target DNA sequences (Merel, et a , Clin. Chem. , 1996, 42: 1285-1286; Yershov, et al , Proc. Natl. Acad. Sci. USA, 1996, 93:4913-4918). These approaches can be divided into two directions: synthesis of the probes directly onto the chip; and direct conjugation of cDNAs or cRNAs to the chip surface.

Current microarray assays focus on nucleic acid hybridization, but microarray and combinatorial chemistry technologies include parallel analysis of proteins, lipids, carbohydrates and small molecules (PCT Publication Nos. WO 99/41006, WO 96/36436, WO 96/24061, WO 98/46548, WO 99/19344, WO 98/11036, WO 97/14814, WO 95/32425). Thus, the high specificity and affinity of biomaterials to their recognition partners, e.g., enzyme-substrate, antigen-antibody, oligonucleotide-DNA, hormone-receptor, etc. permit design of highly specific and sensitive sensor systems.

In the case of microarrays involved in synthesis, the microarrays are prepared in a step wise fashion by the in situ synthesis of nucleic acids, peptides, and other biopolymers from biochemical monomer building blocks. With each round of synthesis, an additional monomer is added to growing chains until the desired length is achieved. Alternatively, pre-assembled biochemical substances, such as cDNA, which were amplified by PCR and purified, or peptides are conjugated (covalently or non-covalently) onto known chip locations using a variety of delivery technologies.

In order to enable parallel processing, each site on the array (which may include thousands of sites) must be loaded with a different specific molecule, or a series of components. Furthermore, each position should be easily addressable so that the reactions that take place on each site may be monitored. Obviously a closely packed microarray makes the above more difficult to achieve. However, technology increasingly permits higher density arrays, e.g., 10,000 entities in one cm² area.

One type of array, an electric array, consists of metal (gold, platinum, etc.) electrodes or sites, on which the reaction takes place. Each site is connected to a conductive lead that terminates, for example, in a pad that can be addressed by an electric connector. The electric connection applies electric voltage or current to permit measurement of charges in electric current at the site from a biological process, and in some instances to aid the reaction on the site. The above arrays are generally fabricated using microchip technologies, which allow manufacturing of miniaturized systems in large quantities at low cost. These technologies also allow the incorporation of electronic elements such as amplifiers, FET's or photo-diodes to aid sensing. In view of the predicted central role of microarrays in biomedical research , particularly in pharmacogenomics and pharmacoproteonomics , biochip revenues may well eventually eclipse those of computer chips. These predictions are independent of the expectation that powerful computers of the future may harness biological processes to perform logical operations.

Optical arrays, which are less common, involve sites located at the tip of optic fibers or light guides that replace the electrically conductive elements described above (see PCT Publication No. WO 99/18434).

In the case of microarrays designed for recognition, where the sites make contact with electrodes, the information generated by the reaction at the site may be either electric or optical in nature. When this information is of an electric nature (change in potential, resistance, capacity, electric current generation, etc.), it is transferred to a control and analysis system by means of the conducting leads and a connector. When the information is optical, for example, the fluorescence peptide/DNA biochips developed by Affymetrix, the information may be transferred to the control and analysis system by optic fibers, or may be remotely monitored, for example, by a CCD camera in combination with a confocal microscope . Multi-color fluorescence allows comparisons of a few samples , e . g . , normal and diseased, or diseased and treated, to be made on a single chip.

In all types of arrays loading of each of the sites with the specific designated component or series of components represents a difficult, time consuming and expensive step. Targeting of distinct molecular probes to a particular location on an array at a high density involves delicate, time consuming and precise reagent handling capabilities. Furthermore, the proximity of the different individual array elements, amplify the problem of covalent spatial allotment and their conceivable cross-contamination during their elaboration. The avoidance of the above significantly increases the cost of the process.

A variety of high accuracy placement technologies were development for this purpose. These include mechanical systems, for example, computerized x-y stages, ink-jet component spray at specific locations, various masks that prevent the reactants to reach any site except the desired one, etc. Electric systems are also available, for example, electric currents are used to direct the required constituents, for example, oligodeoxynucleotide probes, onto the activated electrodes with a concomitant increase in the hybridization speed. However, electronic activation of a single microelectrode cannot fully prevent the remaining electrodes from being reached by the specific DNA probes, with possible cross-contamination.

Random combinatorial libraries of molecules avoid the difficulties of site- specific array development by obviating the requirement for precise reagent disbursement and handling. Various combinatorial library technologies have been developed, such as, but not limited to split synthesis libraries (see PCT Publication Nos. WO92/00252, and WO 94/28028), as well as various natural product and synthetic libraries (discussed below) . However, the ease of synthesis or creation of these libraries includes a cost: their randomness may result in uncertainty about the structure of a molecule in the library. This can also be an issue in directed placement arrays as well. This problem is addressed in more detail below. These molecular arrays and libraries on solid phase supports share a more basic technical feature as well.

Both molecular arrays and combinatorial libraries on solid supports require immobilization technologies that secure the molecules, permit biological processes to occur, and preferably allow repeated use of the array or support. A common technology for immobilization of the desired specific component on the selected specific site or a support involves masking of all sites, except for the desired one, and then applying the desired component to the whole surface. The component will react and be immobilized only at the exposed site. The masking may be done, for example, by shining an IR beam only on the site of interest. The heat thus generated locally melts the mask and the site is exposed. The site should be saturated so that further binding does not occur. However, cross-contamination, i.e., binding of undesired components onto a previously exposed site can not be absolutely prevented.

Binding, as well as other reactions, may be enhanced by applying an electric potential or illuminating the sites.

While array manufacturing can be difficult and expensive, often identification of the structure of a molecule, whether the sequence of an oligonucleotide or peptide, substituents on a pharmacore, or new variations in substitutents or structure, can provide more difficult. Microsequencing techniques and nucleic acid amplification permit direct sequencing of nucleic acids and peptides. However, direct sequencing is expensive, difficult, and time consuming. Early work with "tagged" libraries used chemical tags as surrogate identifiers of the molecule. These include peptides or oligonucleotides (See PCT Publication Nos. WO 93/06121, WO 94/28028, and WO 97/00887), radioisotope-labeled compounds (see PCT Publication No. WO 97/14814), and fluorine tags (see, PCT Publication No. WO 99/19344). These strategies suffer from the possibility that the tags themselves contribute to the biological process measured in the assay.

Alternative technologies employ spectroscopic tags that uniquely identify molecules in a library. Examples of such tags include infrared/Raman spectroscopic tags (PCT

Publication No. WO 98/11036), and fluorescent labels (PCT Publication No. WO 95/32425).

Nuclear magnetic resonance spectrometry permits elucidation of fluorine and ¹³C/¹⁵N tags (PCT

Publication Nos. WO 99/19344 and WO 97/14814).

Convergence of computer data storage and microarray/molecular library technologies has recently yielded alternatives to chemical or spectroscopic identification techniques. These approaches include using silicon chips with embedded machine readable codes (PCT Publication Nos. WO 99/41006 and WO 96/24061), and matrix materials with programmable data storage or recording capacity (PCT Publication No. WO 96/36436).

However, these strategies, like addressable microarrays, depend on implementation of complex and expensive technologies. As a consequence, these techniques cannot achieve mass market potential for medical laboratory diagnostic use or routine forensic testing. There remains a need in the art for affordable technology for identification of molecular structures on arrays and combinatorial libraries. The present invention advantageously addresses these and other needs in the art.

SUMMARY OF THE INVENTION

The present invention provides a solid-support that is comprised of an immobilized molecule and a magnetically readable code. The code may be used to identify the structure of the immobilized molecule. The solid support is preferably a rod. A further embodiment of the invention includes a method of identifying molecules of interest that are immobilized on the solid support. BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 is a perspective schematic view of supports passing through a magnetic reader.

Figures 2A and 2B show a plan and an elevation of a schematic drawing of a disk-shaped support.

Figure 3 is an elevation schematic view of supports passing through a magnetic reader.

Figure 4 shows an elevation view of a flat rod support. Figure 5 shows a perspective schematic view of supports passing through a magnetic reader.

Figure 6 shows a plan view of a tape support. Figure 7 shows a perspective view of a multi-channel selector. Figures 8 A and 8B are a plan view and an elevation view of a multi-channel selector as depicted in Figure 7. Figure 9 is a schematic of a multi- valve selector apparatus.

Figure 10 is an schematic of one selection valve from Figure 9 opened to the output channel.

Figures 11, 12, and 13 show alternate embodiments for detecting binding interactions based on changes in electrical properties of the supports resulting from the binding interaction.

DETAILED DESCRIPTION

The present invention is designed to enable high throughput recognition, separation, synthesis, etc. by means of sites, similar to those on a biochip, except that they are located on individual solid supports, which optimally can be structured and connected in the form of an array chip. The invention is designed to achieve parallel processing, identification, separation etc. by using numerous sites, on which the processes take place, each of which is "free floating" and recognizable by a magnetically readable code.

The invention achieves parallel processing without carrying out numerous reactions on sites that can be identified by their geometrical location in an array, or a physical connection within the array. Instead the invention makes use of a practically infinite number of unconnected, free standing or floating sites, each having an address or an ID created by the magnetically readable code.

Let us initially assume that we have "m" Components, .... C_m that have to be recognized, isolated, polymerized, etc. by means of corresponding "m" reactants Rj ....R_m. Furthermore, we have to repeat the recognition process, etc. "i" times.

The sites in the invention, on which the reactions are to take place, are a part of independent solid support units, e.g., in the form of miniature rods, beads, plates, etc. (See Figures 1, 2 and 5). The supports may be constructed from materials similar to those currently used in biochip sites (silicon, polyamide, gold or platinum plating, etc.), although other materials may also be used. To enhance the binding of specific molecules to the supports, binding sites on the supports may be created by chemical treatment, derivitization by coating the linker molecules, e.g., as is conventionally done in biochip arrays. Alternatively, depending on the support material, no modification may be necessary to permit irreversible immobilization of the molecule. However, while in the biochip all sites are coated by the same linker groups, as will be illustrated, in the invention the linker group may be optimally matched to each molecule.

The size of the supports may be comparable to the size of the sites on microarrays, the main limitation on the support size being the minimal possible size of the magnetic ID and/or the amount of reactant. The amount of information that needs to be put in the ID depends on the total number of different sites. Currently arrays with 64 (6 bit) to 32,000 (12 bit) sites are common. High density of information is achieved using magnetic coding, such as with magnetic tapes or memories. These technologies routinely permit densities of an 8 to 12 bit word per 1-10 square micrometers, and the available densities are growing. Engraving, etching, marking the surface by miniature optical signs, as in optical discs, or coating silicone by microelectronics technologies, etc., may also be done in combination with the magnetic code, if desired. Using microelectronics technology, one may achieve resolutions of better than 1 micrometer. Thus, for example, cylindrical rods, 10-100 micrometers long and 5-50 micrometer in diameter have sufficient areas to serve as sites and contain all the necessary information. Flat rods (Figures 4 and 5) in the form of plates, beads-etc. can also have dimensions in the 10 micrometer range. Note however, that in contrast to arrays where miniature size and close packing is highly important, the size and packing requirements of the supports is much more relaxed in cases where the quantity of the materials to be tested, identified, etc. is not highly restricted, and the support size may be increased to the mm range.

In a preferred embodiment, supports, particularly linear supports such as tapes and rods, have large enough dimensions to permit facile mechanical selection and manipulation, and decoding (reading the magnetic code) with standard, inexpensive magnetic readers, i.e., using available technology currently employed in audiotape players, magnetic key readers, and the like. Thus, the invention advantageously permits high throughput using inexpensive technology.

Each rod will have a magnetic identification, ID (4 as shown in Figure 1 and 32 as shown in Figure 2) for example, a binary number or alphanumeric code of these technologies make the immobilization of identifiable molecules simple and efficient.

The support activation process is as follows: "i" or more supports with an identical ID, for example S_l5 are selected, coated with an appropriate linkers (if desired) and then with the appropriate molecule, in this case M Coating may be achieved by dipping in the appropriate solution, spraying, electroplating, subjecting the sites to an electric potential, electric current of a selected characteristics, illumination, etc. The coated supports are stored for further use. The process is repeated for supports coded S₂ and coated by M₂, and so on. Note that in the currently available technologies, in practice all the linkers are identical. In contrast, here different linkers may be easily used to optimize the conditions for different molecules. Also, the danger of "contamination", i.e., the partial or complete coating of a site by a wrong molecule, is virtually nil as no reactant or type of linker, others than the one intended for use with a particular support, are in the system when the molecules are immobilized on the support.

A "linker" is a moiety, molecule, or group of molecules attached to a solid support. Typically a linker may be bi-functional, wherein the linker has a functional group at each end capable of attaching to a monomer or oligomer, and to a solid support or substrate.

Various reactants or ligands can be attached to the support. These include oligonucleotides, peptides, peptideomimetics, pharmacores, and the like. An "oligonucleotide" refers to the phosphate ester polymeric form of ribonucleosides

(adenosine, guanosine, uridine or cytidine; "RNA molecules") or deoxyribonucleosides (deoxyadenosine, deoxyguanosine, deoxythymidine, or deoxycytidine; "DNA molecules"), or any phosphoester analogs thereof, such as phosphorothioates and thioesters, in either single stranded form, or a double-stranded helix, as well as "protein nucleic acids" (PNA) formed by conjugating bases to an amino acid backbone. This also includes nucleic acids containing modified bases, for example thio-uracil, thio-guanine and fluoro-uracil. The oligonucleotides may also be modified by many means known in the art.

Non-limiting examples of such modifications include, substitution of one or more of the naturally occurring nucleotides with an analog, and internucleotide modifications such as, for example, those with uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoroamidates, carbamates, etc.) and with charged linkages (e.g., phosphorothioates, phosphorodithioates, etc.). Polynucleotides may contain one or more additional covalently linked moieties, such as, for example, proteins (e.g., nucleases, toxins, antibodies, signal peptides, poly-L-lysine, etc.), intercalators (e.g., acridine, psoralen, etc.), chelators (e.g., metals, radioactive metals, iron, oxidative metals, etc.), and alkylators. The polynucleotides may be derivatized by formation of a methyl or ethyl phosphotriester or an alkyl phosphoramidate linkage.

A "peptide" is a chain of chemical building blocks called amino acids that are linked together by chemical bonds called peptide bonds. Peptidomimetics are compounds structurally mimic peptides but lack the peptide bond.

Synthetic or Combinatorial libraries (Needels et al, Proc. Natl. Acad. Sci. ,USA 90:10700-4, 1993; Ohlmeyer et al, Proc. Natl. Acad. Sci. USA 90:10922-10926, 1993; Lam et al, International Patent Publication No. WO 92/00252; Kocis et al, International Patent Publication No. WO 9428028) and the like can be used to prepare support libraries. Numerous means are currently used for random and directed synthesis of saccharide, peptide, and nucleic acid based compounds. Synthetic compound libraries are commercially available from Maybridge Chemical Co. (Trevillet, Cornwall, UK),

Comgenex (Princeton, NJ), Brandon Associates (Merrimack, NH), and Microsource (New Milford, CT). A rare chemical library is available from Aldrich (Milwaukee, WI). Alternatively, libraries of natural compounds in the form of bacterial, fungal, plant and animal extracts are available from e.g. Pan Laboratories (Bothell, WA) or MycoSearch (NC), or are readily producible. Additionally, natural and synthetically produced libraries and compounds are readily modified through conventional chemical, physical, and biochemical means (Blondelle et al, Tib Tech, 14:60, 1996). The above is repeated for all specimens up to M_m, each group being stored separately.

One, or more if quantitative evaluation is required, a support of each group is selected and placed in a test or separation pool or vehicle (library of supports), for example, in a small volume of liquid or gas, positioned along a sticky band or ribbon in an appropriate density, etc. For separation purposes, the supports may be bonded to a separation column through which the components can be made to flow, or bonded to a tape or ribbon, etc. The system is now ready for use.

Assuming that the components to be tested, identified, separated, polymerized, etc. are in a liquid, this liquid is contacted with the supports Sj .... S_m, and the conditions are adjusted such that the specific process can take place. Alternatively the components are made to flow through a separation column comprising the supports, or if the supports are placed in a selected orientation, on a ribbon or a similar substrate, the ribbon is passed through the liquid, gas, etc that contains the components (Figure 6), thus allowing the desired process to take place. If desired, the ribbon could be a magnetic tape, where the ID No. is magnetically recorded on the tape adjacent to the rods. In a preferred embodiment, the supports are geometric rods arranged to create a temporary array. Indicators (for example pH indicators) that provide information regarding the state of the reaction and when the reaction is complete, may be added to the system. When the reaction terminates, the "activated supports" on which the process of interest has occurred are passed by the sensors of the system (1 and 6 as shown in Figures 1 and 3). This can be done by passing the band along the sensors or forcing the fluid that contains the supports, to flow in a channel running along the sensors. In the case of a separation column, the supports are released from the column by mechanical forces such as agitation, by chemical destruction of the adhesive, etc. and then passed through the sensing system as above, and/or the separation system described below.

In the instance where the supports are in the shape of cylinders or plates, the flow channel may have a cross-section that matches them (5 as shown in Figures 1 and 5) such that they flow at a specific selected orientation. The dimensions of the channel are such that the supports move in single file and the flow rate and support spacing in the fluid are regulated such that only one support passes the sensors at a time to prevent interference between reading the codes on the different rods. Alternatively, the rods may be placed, at a proper orientation, on an adhesive band (88 as shown in Figure 6) and the band passed along the sensors (1 and 6 as shown in Figure 1). It is important to note that magnetic and some other readers preferably require proper orientation of the magnetic coded particle in order to get a optimal reading and to prevent cross-talk. However, because of the possibility to provide a relatively large separation of the "words" in our case the danger of cross-talk is minimal. Furthermore, this arrangement also makes the system less sensitive to the orientation of the rods or to their distance from the readers. The walls of the channel are to be made out of materials "transparent" to the appropriate signals or energy. In the case of magnetic coding, the walls are to be made as thin as possible to allow close proximity of the sensors to the rods (preferably on the order of tens of micrometers).

At least two types of sensors (1 and 6 as shown in Figure 1) should be used by the system. Ones type or set of types is designed to read the ID, for example magnetic information readers like those in tape recorders, magnetic disks, etc., while the others are designed to simultaneously observe the process of interest, i.e., a reaction between the components and the molecules. Some of the most common detection systems are the emission of fluorescent light, color formation, and other optical changes, including opacity changes and masking of symbols, etc. In all such cases optic readers are designed to read the signals from the supports, e.g., flowing through the reader or arranged in a temporary array. Note that the readers can identify the presence of a process and also its quantity or magnitude.

Binding reactions of target molecules to ligands on supports are readily observed by labeling the target molecule. A "label" is any molecule, or a portion thereof, that is detectable, or measurable, for example, by optical detection. In addition, the label associates with a molecule or cell or with a particular marker or characteristic of the molecule or cell, or is itself detectable, to permit identification of the molecule or cell, or the presence or absence of a characteristic of the molecule or cell. In the case of molecules such as polynucleotides such characteristics include size, molecular weight, the presence or absence of particular constituents or moeties (such as particular nucleotide sequences or restrictions sites). In the case of cells, characteristics which may be marked by a label includes antibodies, proteins and sugar moieties, receptors, polynucleotides, and fragments thereof. The label is typically a dye, fluorescent, ultraviolet, or chemiluminescent agent, chromophore, or radio-label, any of which may be detected with or without some kind of stimulatory event, e.g., fluoresce with or without a reagent. Typical labels for molecule- based embodiments include Cy3, Cy5, fluoroscein, phycoeryfhing. etc. In one cell-based embodiment, the label is a protein that is optically detectable without a device, e.g. a laser, to stimulate the label, such as horseradish peroxidase (HRP). A protein label can be expressed in the cell that is to be detected, and such expression may be indicative of the presence of the protein or it can indicate the presence of another protein that may or may not be coexpressed with the label. A label may also include any substance on or in a cell that causes a detectable reaction, for example by acting as a starting material, reactant or a catalyst for a reaction which produces a detectable product. Cells may be sorted, for example, based on the presence of the substance, or on the ability of the cell to produce the detectable product when the label substance is provided.

When the "products" of the process are changes in the electric characteristics of the supports, sensors may detect the changes in the capacity, the impedance, or any electric potential or current generated by the reaction, using electrodes (81 as shown in Figure 11) and leads (82 as shown in Figures 11 and 12) positioned outside the channel, embedded in the walls of the channel or in the fluid inside the channel as in Fig. 11. Alternatively, plates etc. (83 as shown in Figure 12) that serve as capacitance sensors as in some cell sorters, or wire coils (80 as shown in Figure 13) that serve to measure current or flow of charged particles, etc. may be placed around the tube. The information detected by the sensors is transferred to the control unit that matches the output of the ID readers for selected supports, interprets the results, and outputs the reaction product reading values for each identified rod. The system can also output the identification as well as the quantity of the various components that are being tested. Obviously more than one ID reader and reaction reader can be used to increase the versatility and/or the reliability of the system.

Within the above framework the system may perform like a cell sorter, i.e., not only identify a molecule that undergoes a process with a component type, but also serve to separate the supports that have undergone the process from those that have not. The separation may be achieved as follows. The supports that pass the readers are identified and each support directed into a separate channel and collection site, as is commonly done in commercially available cell sorters, etc. The direction of the supports to the appropriate channels may be done, for example, by flow selector switch (69 as shown in Figure 8) that, under electronic control and support sensors as in Figure 9, switches the flow from the main channel (66 in Figures 7 and 8) into different channels (65 in Figures 7 and 8). This may be accomplished, for example, by rotation of the selector around axis (75 as shown in Figure 7). The supports thus separated and collected may be processed as desired, for example, the individual components may be released from the supports and thus their separation- purification and collection completed.

When the selection is to be made to numerous groups the selection apparatus described in Figures 9 and 10 can be used. Here along the flow path (66 in Figure 10) one can construct as many junctions with selector valves (64 in Figures 9 and 10) as necessary. The system keeps track of the position of each identified support by a series of photo- detectors, or other detectors that can monitor the position of the supports (63 in Figures 9 and 10) positioned along the flow path. At each junction there is a selector valve that by turning on its axis can direct the flow of the supports (61 as shown in Figures 9 and 10) into one of the following directions: straight ahead along the flow channel (62 and 67 in Figures 9 and 10) into the selected collection channel (68 in Figure 10). The valve rotation and the duration of the time the flow is directed into the collection channel are adjusted such that before the next coming support, as monitored by the photo-electric sensors, arrives at the junction the valves are returned to their original position.

The system can serve also as a new type of separation system or "affinity chromatography column" in which the bonded components together with the high affinity particles may be recognized, separated, and collected. An important advantage of the invention over affinity columns or affinity chromatography, etc. is the ability to recognize and separate a much larger repertoire of components.

The present invention is not to be limited in scope by the specific embodiments described herein. Indeed, various modifications of the invention in addition to those described herein will become apparent to those skilled in the art from the foregoing description and the accompanying figures. Such modifications are intended to fall within the scope of the appended claims. Various patents, patent applications, and publications cited herein are incorporated by reference in their entireties for all purposes.

Claims

WHAT IS CLAIMED;

1. A solid support comprising an immobilized molecule and a magnetically-readable code that identifies the structure of the molecule.

2. The solid support of claim 1, which is a magnetic tape.

3. The solid support of claim 1 , which is a rod.

4. The solid support of claim 3, wherein the magnetic code is readable from either end of the rode.

5. The solid support of claim 3, wherein the rod has a regular geometric shape perpendicular to its axis, whereby rods of like shape and dimension can be arranged or packed in parallel to create a surface from the ends of the packed rods.

6. The solid support of claim 5, wherein the molecule is immobilized at an end of the rod.

7. The solid support of claim 5, wherein the geometric shape is selected from the group consisting of an equilateral triangle, an isosceles triangle, a square, a rectangle, a rhombus, a parallelogram, a regular trapezoid, an irregular trapezoid, a quadrilateral, and a regular hexagon.

8. The solid support of claim 1, wherein the molecule is selected from the group consisting of a nucleic acid, a peptide, a peptide mimetic, a pharmacore, and a carbohydrate.

9. The solid support of claim 1, wherein the code is an alphanumeric code.

10. The solid support of claim 1, wherein support material is selected from the group consisting of an organic polymer, silica, glass, a metal, and a semiconductor.

11. A library of a plurality of solid supports of claim 1 comprising different molecules.

12. A library of a plurality of solid supports of claim 3 comprising different molecules.

13. A library of a plurality of solid supports of claim 6 comprising different molecules.

14. The library of claim 13 arranged in a parallel array, wherein all of the ends containing the immobilized molecule are oriented in a same direction.

15. A method for identifying a molecule of interest, which method comprises identifying the structure of a molecule immobilized on a solid support from a library of claim 11 selected on the basis of observing a chemical, biochemical, or biological process involving the molecule on the solid support.

16. A method for identifying a molecule of interest, which method comprises identifying the structure of a molecule immobilized on a solid support from a library of claim 12 selected on the basis of observing a chemical, biochemical, or biological process involving the molecule on the solid support.

17. A method for identifying a molecule of interest, which method comprises identifying the structure of a molecule immobilized on a solid support from a library of claim 13 selected on the basis of observing a chemical, biochemical, or biological process involving the molecule on the solid support.

18. A method for identifying a molecule of interest, which method comprises identifying the structure of a molecule immobilized on a solid support from a library of claim 14 selected on the basis of observing a chemical, biochemical, or biological process involving the molecule on the solid support.