WO2004012856A1 - Hybrid chip for the miniaturization of chemical, biomedical, and biological processes and method of application - Google Patents

Hybrid chip for the miniaturization of chemical, biomedical, and biological processes and method of application Download PDF

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Publication number
WO2004012856A1
WO2004012856A1 PCT/HU2003/000063 HU0300063W WO2004012856A1 WO 2004012856 A1 WO2004012856 A1 WO 2004012856A1 HU 0300063 W HU0300063 W HU 0300063W WO 2004012856 A1 WO2004012856 A1 WO 2004012856A1
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WO
WIPO (PCT)
Prior art keywords
compounds
chip
biological
transport
chemical
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/HU2003/000063
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English (en)
French (fr)
Inventor
Ferenc Darvas
László ÜRGE
György Dormán
Tamás KARANCSI
Lajos GÖDÖRHÁZY
Dániel SZALAY
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
AMRI Hungary Zrt
Original Assignee
Comgenex RT
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Filing date
Publication date
Application filed by Comgenex RT filed Critical Comgenex RT
Priority to AU2003249102A priority Critical patent/AU2003249102A1/en
Publication of WO2004012856A1 publication Critical patent/WO2004012856A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B50/00—Methods of creating libraries, e.g. combinatorial synthesis
    • C40B50/08—Liquid phase synthesis, i.e. wherein all library building blocks are in liquid phase or in solution during library creation; Particular methods of cleavage from the liquid support
    • 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
    • B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B30/00—Methods of screening libraries
    • C40B30/10—Methods of screening libraries by measuring physical properties, e.g. mass
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
    • 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
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00418—Means for dispensing and evacuation of reagents using pressure
    • 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
    • B01J2219/00599—Solution-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
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00686—Automatic
    • B01J2219/00689—Automatic using computers
    • 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
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00695—Synthesis control routines, e.g. using computer programs
    • 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
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/007—Simulation or vitual synthesis
    • 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
    • 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
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00819—Materials of construction
    • B01J2219/00822—Metal
    • 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
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/00851—Additional features
    • B01J2219/00871—Modular assembly
    • 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
    • B01J2219/00781—Aspects relating to microreactors
    • B01J2219/0095—Control aspects
    • B01J2219/00986—Microprocessor
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/02—Identification, exchange or storage of information

Definitions

  • the four main elements of lead optimization are: (1 ) synthesis and work-up of compounds, (2) chemical analysis of the compounds, (3) biological assay of the compounds and (4) establishing the quantitative structure-activity relationships (QSAR) between the compounds, which allows the structure of compounds to be modified or affected in a new iterative cycle.
  • the advantages afforded by these systems include the low amounts of reagents needed, the low cost involved, and the ability to apply reliable, parallel, process automation and unique detection techniques (Sundberg, S.A., Curr. Opin. Biotechnol, 2000, 1 1 , pp. 47-53).
  • the CellChip system was developed by Cellomics (Pittsburgh, PA, USA) and ACLARA (Mountain View, CA, USA) for assay using live cell cultures.
  • a mono or multi-layer hybrid sheet is particularly suitable for producing compounds, and especially biologically active materials (i.e. drugs or pesticides), for optimizing the chemical structure of materials, and for miniaturizing biological processes.
  • This chip should include units that are directly connected to one another, preferably via a micron-sized channel network, and should perform the following functions: (1 ) the synthesis and work-up of compounds, (2) analysis of the compounds, (3) interaction studies on the compounds, preferably biological, biological utilization, metabolism or toxicity assays with biomolecules, cells, and tissue samples obtained from or related to live organisms, and (4) the establishment of quantitative structure-activity relationships (QSAR) for the compounds. which allows the structure of compounds to be modified or affected in a new iterative cycle.
  • QSAR quantitative structure-activity relationships
  • this invention involves a small hybrid sheet (chip), used to miniaturize chemical, biochemical, and biological processes, characterized by that it consists of mono or multilayer sheet (chip) comprising the following directly connected units:
  • a unit used for the execution of biological assays of compounds and the transport of raw materials, reagents, and final products and preferably, an electronic unit, more preferably a semi conductor chip into which the following have been burnt:
  • This invention also includes the manner of application of the small hybrid sheet (chip) described above; namely, the production, analysis and assay of biologically active compounds, and the measurement of their metabolism, toxicity, and any other adaptable biological interaction.
  • reaction chain is formed with a wide selection of substituents (from the reagent set) for structural diversity, so that structural optimization may also be executed primarily at these diversity points when the system is running.
  • a reaction chip which has a micro channel system consisting of an eight- point hole converging at a star point
  • the change in color of bromo-phenol blue indicator will indicate how the reaction is progressing.
  • 0.1 DL of acid and base enter the reactor channel, equally divided between the two feeding channels, establishing an electrokinetic difference in the electric field intensity (0.25-0.5 kV/cm) between the reactor channel and the two feeding channels.
  • the change of color of the bromo-phenol blue indicator to yellow, corresponding to a neutral pH indicates that the reaction has run to a full and immediate completion.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Structural Engineering (AREA)
  • Engineering & Computer Science (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
PCT/HU2003/000063 2002-08-01 2003-07-30 Hybrid chip for the miniaturization of chemical, biomedical, and biological processes and method of application Ceased WO2004012856A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003249102A AU2003249102A1 (en) 2002-08-01 2003-07-30 Hybrid chip for the miniaturization of chemical, biomedical, and biological processes and method of application

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HU0202551A HUP0202551A2 (hu) 2002-08-01 2002-08-01 Kémiai, biokémiai és biológiai folyamatok miniatürizálására szolgáló hibrid lapka (chip) és eljárás annak alkalmazására
HUP0202551 2002-08-01

Publications (1)

Publication Number Publication Date
WO2004012856A1 true WO2004012856A1 (en) 2004-02-12

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PCT/HU2003/000063 Ceased WO2004012856A1 (en) 2002-08-01 2003-07-30 Hybrid chip for the miniaturization of chemical, biomedical, and biological processes and method of application

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AU (1) AU2003249102A1 (enExample)
HU (1) HUP0202551A2 (enExample)
WO (1) WO2004012856A1 (enExample)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996008781A1 (en) * 1994-09-16 1996-03-21 3-Dimensional Pharmaceuticals, Inc. System and method of automatically generating chemical compounds with desired properties
US5580523A (en) * 1994-04-01 1996-12-03 Bard; Allen J. Integrated chemical synthesizers
WO2000062919A1 (de) * 1999-04-16 2000-10-26 Norbert Schwesinger Modulares chemisches mikrosystem
WO2001097152A2 (en) * 2000-06-10 2001-12-20 Hte Aktiengesellschaft The High Throughput Experimentation Company Computer-aided optimization of substance libraries

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5580523A (en) * 1994-04-01 1996-12-03 Bard; Allen J. Integrated chemical synthesizers
WO1996008781A1 (en) * 1994-09-16 1996-03-21 3-Dimensional Pharmaceuticals, Inc. System and method of automatically generating chemical compounds with desired properties
WO2000062919A1 (de) * 1999-04-16 2000-10-26 Norbert Schwesinger Modulares chemisches mikrosystem
WO2001097152A2 (en) * 2000-06-10 2001-12-20 Hte Aktiengesellschaft The High Throughput Experimentation Company Computer-aided optimization of substance libraries

Also Published As

Publication number Publication date
HU0202551D0 (enExample) 2002-10-28
HUP0202551A2 (hu) 2004-03-29
AU2003249102A1 (en) 2004-02-23

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