WO1998046550A1 - Method for the preparation of a coded chemical library - Google Patents
Method for the preparation of a coded chemical library Download PDFInfo
- Publication number
- WO1998046550A1 WO1998046550A1 PCT/GB1998/001077 GB9801077W WO9846550A1 WO 1998046550 A1 WO1998046550 A1 WO 1998046550A1 GB 9801077 W GB9801077 W GB 9801077W WO 9846550 A1 WO9846550 A1 WO 9846550A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- synthesis
- particle
- library
- code
- particles
- Prior art date
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00457—Dispensing or evacuation of the solid phase support
- B01J2219/00459—Beads
- B01J2219/00468—Beads by manipulation of individual beads
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/005—Beads
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/00502—Particles of irregular geometry
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/0054—Means for coding or tagging the apparatus or the reagents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/0054—Means for coding or tagging the apparatus or the reagents
- B01J2219/00547—Bar codes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/0059—Sequential processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00592—Split-and-pool, mix-and-divide processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00596—Solid-phase processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00718—Type of compounds synthesised
- B01J2219/0072—Organic compounds
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B70/00—Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
Definitions
- Chemical libraries are a powerful way of providing compounds for the identification of active compounds in pharmaceutical, agrochemical and related industries. Synthesis of the compounds on beads is a prefered method since it allows generation of diversity by the "split synthesis" method (Furka A., Abstr. 14th Int. Congr. Biochem., Prague, Czechoslovakia, 1988, 5, 47; Int. J. Pept. Prot. Res, 1991, 37, 487-493) and beads are convenient reaction supports which may be sequentially exposed to different reagents and washed with relative ease. Considerable research effort has taken place to find a reliable and simple method for the identification of active compounds from a library generated on beads.
- tags the bead at various stages of the synthesis, where each tag, or component of the tag, indicates the reagent(s) to which the bead has been exposed.
- tags associated with active compounds are read and the chemical structure of the active compound is inferred.
- a particularly useful approach is the use of mixtures of halogenated aromatic compounds, incorporated in trace amounts at each stage of the synthesis, to form an identifiable (by gas chromatography) 'binary code' system for ligand definition (Borchardt and Still, J. Am. Chem. Soc, 1994, 116, 373-374).
- chemical tags have certain limitations. For example, they can limit the choice of chemistry used to construct the library. Also, chemical tags can take significant amounts of time to read.
- a method for the construction of a chemical library which avoids these problems.
- This method uses a laser to inscribe a code onto a bead or synthesis particle.
- a method for the preparation of a coded chemical library which method comprises synthesising the chemical library on a plurality of synthesis particles and writing code on the synthesis particles using high-energy radiation during library synthesis, so as to provide the chemical library on a plurality of coded synthesis particles, and wherein the identity of library compounds associated with a synthesis particle is established by reference to its code.
- the code indicates the chemical reaction(s) to which the synthesis particles are to be, or have been subjected.
- a convenient advantage of the method of the invention is that initially all the particles are essentially the same which provides significant cost advantages. It may also mean that commercially available beads may be used.
- code may be written to non-rigid (eg. swellable) particles synthesis particles comprising polymers, for example polystyrene, grafted copolymers and derivatised versions thereof, and that the integrity of the code survives the rigours of library synthesis. Such rigours include the expansion and contraction of the synthesis particles.
- the code which is written at any stage is uniquely identified with a particular chemical process, or series of chemical processes, which result in the attachment of a particular structural feature to the library compounds.
- the set of codes written to a synthesis particle is directly indicative of the chemical compound attached to the bead.
- this process involves dividing or 'splitting' a pool of solid-support particles, for example resin beads, into separate vessels, then reacting the particles in each vessel each with a different reagent or building block, allowing the reactions to proceed to completion, then 'mixing' the particles from each vessel to generate a second pool of particles which is split, reacted and mixed in the same way as above.
- This process which does not involve the use of mixtures of building block reagents, is that only one compound appears on any one particular synthesis particle.
- the invention includes methods where the distribution of beads is random or directed (for example using robotic apparatus), conveniently random.
- the high energy radiation is conveniently supplied by a pulsed laser.
- the laser souce is selected to have a wavelength such that the radiation is absorbed by the bead material within a short distance of the surface and material is removed by the process of ablation.
- Convenient sources of radiation are for example excimer lasers operating at various wavelengths including 193 nm and 248 mm, Nd:YAG lasers used in conjunction with a so- called frequency-tripling or frequency quadrupling system and copper vapour lasers. These sources have the further advatage that a high-energy pulse of short duration is available, so there is minimal thermal damage to the material which is not removed.
- such sources will operate with a pulse duration of tens of nanoseconds with a pulse repetition rate of one pulse per 50 microseconds.
- pulses of radiation may be used but preferably the particle is marked with a single pulse of radiation. Practical considerations will include the time taken to mark beads and the cost of the laser source and the associated optics. It is noted that for marking with a single pulse, the beads may move at very high speed before there is any possibility of motion blurring of the mark. For multiple pulse marking, since the inter-pulse interval is relatively long, the beads may move only with relatively modest speed before for example the beam position must track with the bead or motion- blurring will occur. For example, motion blurring may be said to occur if the bead moves than 1 micrometre during the marking.
- the bead can have a speed of up to 50 metres per second before motion-blurring occurs. However, if 11 pulses are used then the time interval between the first and the last may be about 500 microseconds. In which case the bead speed must be less than about 2 millimetres per second. We note that even this low speed still allows several beads of typical diameter about 350 micrometres, per second to move steadily past the marking head.
- the high energy radiation may be applied for example using a mask so as to apply spatially resolved radiation to each bead.
- the pattern on the mask is indicative of the particular chemical process or processes, for example a 30x30x30 synthesis needs 90 (30+30+30) masks.
- Code may be written onto synthesis particles individually or in bulk. By individually we mean that marking is effected one particle at a time, for example by picking a particle with for example a robot and placing the particle in a writing station, or by allowing the particles to flow past a writing station.
- bulk we mean for example spread out in a 2-dimensional spread. Conveniently, the particles are scattered randomly, or in a convenient formation, onto a flat surface.
- a support such as a tray or plate, comprising a plurality of formations such as wells or indentations is used to locate the synthesis particles prior to laser treatment.
- Such articles may be manufactured using microengineering, and/or moulding techniques well known in the art.
- the wells or indentations are preferably designed so that the beads are readily located at individual loci, with no more than one bead located in each well or indentation.
- the laser may then scan the synthesis particles, or the particles are moved relative to the laser.
- the laser pulse(s) are then applied for example as the bead centre becomes aligned to the optical path of the laser.
- a recognition system may be provided so as to recognise either beads spread over a surface or beads disposed in for example wells.
- the disposition of the laser beam and beads is controlled using for example a controlled stage and focus arrangement, whereby to write code on individual beads.
- code is written on a synthesis particle more than once, this is preferably written at a differerent location on the particle.
- the surface area of the synthesis particle occupied by code is conveniently of the order of about one per cent, or about 0.2 - 5 per cent of the total surface area.
- Preferred code dimensions for particular sizes of bead may be determined by routine experimentation so as to maximise the available depth of focus.
- Code is conveniently read by an optical recognition system, such as an optical microscope. It is either read on-line using a camera or similar equipment, or off-line for example on a microscope slide.
- a chemical library synthesis particle comprising a code which has been applied using high energy radiation and which code may subsequently be used to identify the particle.
- the set may comprise any convenient number of particles such as up to 10 8 , 107, 10 6 , 10 5 , 10 4 , 10 , or 10 particles.
- a coded chemical library which comprises a plurality of coded synthesis particles, each particle comprising a code which has been applied using high-energy radiation and each particle having at least one member of the library attached thereto.
- the coded synthesis particles of the invention are conveniently manipulated using robotic apparatus as disclosed in our co-pending UK patent application no. 9707743.2, filed 17 th April 1997, the contents of which are incorporated herein by reference.
- Advantages of the use of manipulative robotic devices such as "pick-and-place" machines in combinatorial chemistry include: the ability to form an essentially complete library consisting of a single composite synthesis particle per chemistry either by selection from a larger stochastically formed set or by manipulation of particles at all stages; the ability to select a sub-library of controlled diversity for an initial screen which is designed to highlight the 'volumes of chemical space' in which compounds of interest are to be found, in particular the ability to decide not to select individual particles or sub-libraries of particles — followed by a subsequent selection of further sub-libraries surrounding the regions of interest, without further chemical synthesis processes being required. In this way, the technique significantly enhances the throughput of the overall drug discovery process.
- the chemical library may be used in screening methods to identify compounds which modulate the activity of a biological of interest.
- a compound will be cleaved from its associated coded particle before testing; alternatively, compounds are tested whilst still attached to their particles. In both cases, there needs to be an association between the measured activity and the particle that gave rise to that activity.
- its codes are read.
- the code(s) marked on the particle are themselves directly indicative of the chemical process history. For example a code such as 12-02-09 means than the chemistry is A ⁇ -B 02 -C 0 . This is not particle number 12-02-09, rather this is the particle that underwent chemistry processes A, B and C.
- code may be read at any convenient time such as before, during and/or after chemical synthesis.
- Library compounds may be tested in a variety of assay systems. These include biochemical and in vitro assays. In general particle codes are read once the assay is complete and only beads associated with active compounds are identified and decoded. Alternatively library compounds are plated out and decoded before the assay takes place. Active compounds are then identified by reference to their position on the plate(s), for example by reference to plate number and well/locus number.
- the library may be stored with compounds removed from the synthesis particles or with compounds retained on the synthesis particles, for example in wells in microtitre plates.
- the library may be provided as stock solutions. These solutions may be used for many different assays.
- activity is detected in an assay, the location of the active compound is determined and the corresponding synthesis particle is retrieved and decoded.
- the synthesis particles are distributed in a two-dimensional assay system, for example a high density array such as on a gel or in microwells. Compounds are removed from the particles. Any active compounds give rise to zones of activity. Such an approach is disclosed for example in our zone
- Corresponding particles may be decoded, either in situ or by retrieval and transferral to a code reading station.
- the synthesis particle is preferably spheroid in shape, for example a bead, and comprises or contains a porous synthesis support suitably derivatised for the assembly of the compounds.
- a porous synthesis support suitably derivatised for the assembly of the compounds.
- porous supports such as cross-linked polystyrene.
- beads we have found the following beads to be particularly useful: higher cross-linked (5%) polystyrene, Tentagel , and CRB33 resin.
- a particular advantage of the methods of the present invention is that commercially available beads can be used.
- Convenient sizes of synthesis particles include those of about 50-500 microns, such as
- an individual code is conveniently of about 45 microns in length and and comprises marks of about 2-5 microns in diameter.
- the particles are preferably of uniform size, fine size tolerance is conveniently achieved by sieving or a similar procedure.
- the synthesis particles may swell and
- a preferred form of a code mark is a series of dots which are marked at a fixed pitch thereby defining the "clock" for the code against which the position of other dots is compared.
- a series of dots which contain the actual data to be coded,
- the code may also comprise further dots which are used to supply parity or other information to allow the code to be verified, and optionally, sufficient such information to allow errors in the particular code mark to be compensated allowing reconstruction of data from a damaged code
- a synthesis particle which comprises a synthesis support attached to a writing surface for the purpose of carrying out the method of the invention.
- the synthesis support is as described above and is conveniently for example porous cross-linked polystyrene.
- the writing surface is conveniently a rigid surface that is suitable for writing a code with a laser and resistant to library chemistry processes. Such surfaces include for example, glass.
- the writing surface and the synthesis support may be combined in a variety of different shapes and fashions. We disclose two major types, heterogeneous and pseudo-homogeneous.
- the synthesis support is attached to the writing surface to form a layered structure.
- Such structures may be spherical or spheroid (see Figure la and lb). They may be discoid (Figure lc) where the synthesis support and the writing surface may be interchangeable. They may be a layered structure ( Figure Id).
- Such layered structures are conveniently flat, but may be of alternative shapes as dictated by manufacturing convenience or other parameters.
- the synthesis support is contained within the writing surface, for example in the form of a hollow tube ( Figure le). It will be appreciated that alternative structures will be apparent to the scientist of ordinary skill.
- the laser beam may penetrate the synthesis layer to access the writing surface, or alternatively, the writing surface is on the outside of the particle and the synthesis particle is contained inside.
- the synthesis support is accessible to solvents and hence the writing surface must have one or more "holes".
- Fig le has two such holes.
- a much larger number of holes is possible.
- the writing surface may be porous.
- the shape of the structures may be selected such that unfavourable orientations cannot happen or are rare.
- the tube structures of Figure lc and le may have non-orthogonal ends so that, if writing is achieved by spreading the particles out on a flat surface, the tubes will lie with the cylindrical symmetry axis parallel to the flat surface. If writing is achieved in a flow situation, an elongated or lozenge-shaped particle may conveniently provide the required degree of orientation.
- the heterogeneous particle may also contain features that ensure that the two layers do not come apart during the process. Such features may be for example lips (Figure 2a) or pegs ( Figure 2b).
- the synthesis support and the writing surface may be fabricated with a support structure, for example a support layer.
- This support structure may provide rigidity, a means of adhering the synthesis support to the writing surface, or may facilitate manufacture.
- a pseudohomogeneous particle for use in the methods of the invention.
- This comprises an assembly of synthesis material and writing material such the code is written on the synthesis and/or writing material.
- the writing material contributes structural integrity.
- the pseudo-homogeneous particle is for example a macro-porous structure, for example a bead, in the macro-pores of which is contained a (micro) porous synthesis support.
- the macro-porous structure is a controlled-pore glass bead.
- the (micro) porous synthesis support is preferably polystyrene, a grafted copolymer or a derivatised version thereof. Polymerisation is conveniently effected under swelling conditions.
- Synthesis of chemical libraries of the invention may comprise any convenient number of individual reaction steps. This number is limited only by practical considerations. For example there may be up to 10, 9, 8, 7, 6, 5, 4 , 3, or 2 reaction steps. At present there are typically about 2-4 reaction steps, such as 3 reaction steps.
- the chemical libraries may comprise any convenient number of individual members, for example tens to hundreds to thousands to millions etc., of suitable compounds, for example peptides, peptoids and other oligomeric compounds (cyclic or linear), and template- based smaller molecules, for example benzodiazepines, hydantoins, biaryls, carbacyclic and polycyclic compounds (eg.
- naphthalenes phenothiazines, acridines, steroids etc.
- carbohydrate and amino acids derivatives dihydropyridines, benzhydryls and heterocycles (eg. triazines, indoles, thiazolidines etc.).
- triazines triazines, indoles, thiazolidines etc.
- Preferred compounds are chemical compounds of low molecular weight and potential therapeutic agents. They are for example of less than about 1000 daltons, such as less than 800, 600 or 400 daltons.
- Any convenient biological of interest such as a receptor, enzyme or the like may be contacted with the chemical library as above in an assay or test system apparent to the scientist of ordinary skill.
- Figure 1 shows synthesis particle structures comprising a synthesis support and a writing surface.
- Figure la shows spherical structures
- Figure lb shows spheroid structures
- Figure 1 c shows discoid structures
- Figure 1 d shows flat layered structures
- Figure le shows hollow tube structures.
- Figure 2 shows two ways in which the synthesis support and writing surfaces of a synthesis particle way be tethered.
- Figure 2a shows the use of lips and
- Figure 2b shows the use of pegs.
- FIG. 3 shows Tentagel beads with code marked by laser
- Figure 4 shows a plurality of Tentagel beads with code marked by laser
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98917351A EP0975562A1 (en) | 1997-04-17 | 1998-04-14 | Method for the preparation of a coded chemical library |
AU70596/98A AU7059698A (en) | 1997-04-17 | 1998-04-14 | Method for the preparation of a coded chemical library |
JP54362098A JP2002501489A (en) | 1997-04-17 | 1998-04-14 | Preparation method of chemical library with code |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9707742.4A GB9707742D0 (en) | 1997-04-17 | 1997-04-17 | Methods |
GB9707742.4 | 1997-04-17 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09402927 A-371-Of-International | 2000-02-23 | ||
US10/141,833 Continuation US20020177169A1 (en) | 1997-04-17 | 2002-05-08 | Method for the preparation of a coded chemical library |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1998046550A1 true WO1998046550A1 (en) | 1998-10-22 |
Family
ID=10810907
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB1998/001077 WO1998046550A1 (en) | 1997-04-17 | 1998-04-14 | Method for the preparation of a coded chemical library |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0975562A1 (en) |
JP (1) | JP2002501489A (en) |
AU (1) | AU7059698A (en) |
GB (1) | GB9707742D0 (en) |
WO (1) | WO1998046550A1 (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2349641A (en) * | 1998-07-02 | 2000-11-08 | Univ Hertfordshire | Use of coded particles in combinatorial chemistry |
US6319668B1 (en) | 1995-04-25 | 2001-11-20 | Discovery Partners International | Method for tagging and screening molecules |
US6340588B1 (en) | 1995-04-25 | 2002-01-22 | Discovery Partners International, Inc. | Matrices with memories |
US6352854B1 (en) | 1995-04-25 | 2002-03-05 | Discovery Partners International, Inc. | Remotely programmable matrices with memories |
US6372428B1 (en) | 1995-04-25 | 2002-04-16 | Discovery Partners International, Inc. | Remotely programmable matrices with memories |
GB2364704B (en) * | 1999-04-15 | 2004-07-14 | Virtual Arrays Inc | Combinatorial chemical library supports having indicia at coding positions and methods of use |
US6908737B2 (en) | 1999-04-15 | 2005-06-21 | Vitra Bioscience, Inc. | Systems and methods of conducting multiplexed experiments |
US7253435B2 (en) | 1999-04-15 | 2007-08-07 | Millipore Corporation | Particles with light-polarizing codes |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04267191A (en) * | 1991-02-22 | 1992-09-22 | Dainippon Ink & Chem Inc | Laser marking and resin composition therefor |
GB2289150A (en) * | 1994-04-25 | 1995-11-08 | Univ Hertfordshire | Coded items for labelling objects |
WO1996024061A1 (en) * | 1995-02-02 | 1996-08-08 | Ontogen Corporation | Methods and apparatus for synthesizing labeled combinatorial chemical libraries |
GB2306484A (en) * | 1995-10-26 | 1997-05-07 | Univ Hertfordshire | Solid support particle marked with a machine-readable code for use in Combinatorial Chemistry Techniques |
WO1997032892A1 (en) * | 1996-03-07 | 1997-09-12 | Imperial College Of Science Technology And Medicine | A composite for combinatorial organic synthesis |
-
1997
- 1997-04-17 GB GBGB9707742.4A patent/GB9707742D0/en active Pending
-
1998
- 1998-04-14 AU AU70596/98A patent/AU7059698A/en not_active Abandoned
- 1998-04-14 JP JP54362098A patent/JP2002501489A/en active Pending
- 1998-04-14 EP EP98917351A patent/EP0975562A1/en not_active Withdrawn
- 1998-04-14 WO PCT/GB1998/001077 patent/WO1998046550A1/en active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04267191A (en) * | 1991-02-22 | 1992-09-22 | Dainippon Ink & Chem Inc | Laser marking and resin composition therefor |
GB2289150A (en) * | 1994-04-25 | 1995-11-08 | Univ Hertfordshire | Coded items for labelling objects |
WO1996024061A1 (en) * | 1995-02-02 | 1996-08-08 | Ontogen Corporation | Methods and apparatus for synthesizing labeled combinatorial chemical libraries |
GB2306484A (en) * | 1995-10-26 | 1997-05-07 | Univ Hertfordshire | Solid support particle marked with a machine-readable code for use in Combinatorial Chemistry Techniques |
WO1997032892A1 (en) * | 1996-03-07 | 1997-09-12 | Imperial College Of Science Technology And Medicine | A composite for combinatorial organic synthesis |
Non-Patent Citations (1)
Title |
---|
DATABASE WPI Section Ch Week 9244, Derwent World Patents Index; Class A13, AN 92-363307, XP002071052 * |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6319668B1 (en) | 1995-04-25 | 2001-11-20 | Discovery Partners International | Method for tagging and screening molecules |
US6340588B1 (en) | 1995-04-25 | 2002-01-22 | Discovery Partners International, Inc. | Matrices with memories |
US6352854B1 (en) | 1995-04-25 | 2002-03-05 | Discovery Partners International, Inc. | Remotely programmable matrices with memories |
US6372428B1 (en) | 1995-04-25 | 2002-04-16 | Discovery Partners International, Inc. | Remotely programmable matrices with memories |
GB2349641A (en) * | 1998-07-02 | 2000-11-08 | Univ Hertfordshire | Use of coded particles in combinatorial chemistry |
GB2364704B (en) * | 1999-04-15 | 2004-07-14 | Virtual Arrays Inc | Combinatorial chemical library supports having indicia at coding positions and methods of use |
US6908737B2 (en) | 1999-04-15 | 2005-06-21 | Vitra Bioscience, Inc. | Systems and methods of conducting multiplexed experiments |
US7253435B2 (en) | 1999-04-15 | 2007-08-07 | Millipore Corporation | Particles with light-polarizing codes |
Also Published As
Publication number | Publication date |
---|---|
GB9707742D0 (en) | 1997-06-04 |
JP2002501489A (en) | 2002-01-15 |
EP0975562A1 (en) | 2000-02-02 |
AU7059698A (en) | 1998-11-11 |
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