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 PDFInfo
- 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
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compounds
- chip
- biological
- transport
- chemical
- Prior art date
Links
- 239000000126 substance Substances 0.000 title claims abstract description 24
- 230000031018 biological processes and functions Effects 0.000 title claims abstract description 6
- 238000000034 method Methods 0.000 title description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 45
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 17
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 15
- 238000004458 analytical method Methods 0.000 claims abstract description 14
- 238000003556 assay Methods 0.000 claims abstract description 14
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 11
- 238000010626 work up procedure Methods 0.000 claims abstract description 10
- 239000002994 raw material Substances 0.000 claims abstract description 9
- 238000004166 bioassay Methods 0.000 claims abstract description 7
- 230000003851 biochemical process Effects 0.000 claims abstract description 5
- 230000004060 metabolic process Effects 0.000 claims abstract description 5
- 230000001988 toxicity Effects 0.000 claims abstract description 4
- 231100000419 toxicity Toxicity 0.000 claims abstract description 4
- 238000004519 manufacturing process Methods 0.000 claims abstract description 3
- 238000005259 measurement Methods 0.000 claims abstract description 3
- 238000005457 optimization Methods 0.000 claims description 14
- 230000004071 biological effect Effects 0.000 claims description 10
- 239000000463 material Substances 0.000 claims description 4
- 230000005684 electric field Effects 0.000 claims description 3
- 239000011521 glass Substances 0.000 claims description 3
- 229910010272 inorganic material Inorganic materials 0.000 claims description 3
- 239000011147 inorganic material Substances 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 239000004033 plastic Substances 0.000 claims description 3
- 239000005060 rubber Substances 0.000 claims description 3
- 230000009141 biological interaction Effects 0.000 claims description 2
- 238000004590 computer program Methods 0.000 claims description 2
- 230000000704 physical effect Effects 0.000 claims description 2
- 239000004065 semiconductor Substances 0.000 claims description 2
- 230000003993 interaction Effects 0.000 abstract description 6
- 238000006243 chemical reaction Methods 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- 150000003384 small molecules Chemical class 0.000 description 7
- 239000003814 drug Substances 0.000 description 6
- 238000004617 QSAR study Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000002253 acid Substances 0.000 description 2
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000007876 drug discovery Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002493 microarray Methods 0.000 description 2
- 241001598984 Bromius obscurus Species 0.000 description 1
- 241000233855 Orchidaceae Species 0.000 description 1
- 108010026552 Proteome Proteins 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000012988 high-throughput synthesis Methods 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001948 isotopic labelling Methods 0.000 description 1
- 238000002032 lab-on-a-chip Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000011325 microbead Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000004801 process automation Methods 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000010916 retrosynthetic analysis Methods 0.000 description 1
- -1 small molecule compound Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 238000002723 toxicity assay Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000000539 two dimensional gel electrophoresis Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
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)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Clinical Laboratory Science (AREA)
- Engineering & Computer Science (AREA)
- Structural Engineering (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Investigating Or Analysing Biological Materials (AREA)
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 |
|---|---|---|---|
| HUP0202551 | 2002-08-01 | ||
| HU0202551A HUP0202551A2 (hu) | 2002-08-01 | 2002-08-01 | Kémiai, biokémiai és biológiai folyamatok miniatürizálására szolgáló hibrid lapka (chip) és eljárás annak alkalmazására |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2004012856A1 true WO2004012856A1 (en) | 2004-02-12 |
Family
ID=89980671
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/HU2003/000063 WO2004012856A1 (en) | 2002-08-01 | 2003-07-30 | Hybrid chip for the miniaturization of chemical, biomedical, and biological processes and method of application |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU2003249102A1 (enrdf_load_stackoverflow) |
| HU (1) | HUP0202551A2 (enrdf_load_stackoverflow) |
| WO (1) | WO2004012856A1 (enrdf_load_stackoverflow) |
Citations (4)
| 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 |
-
2002
- 2002-08-01 HU HU0202551A patent/HUP0202551A2/hu unknown
-
2003
- 2003-07-30 WO PCT/HU2003/000063 patent/WO2004012856A1/en not_active Application Discontinuation
- 2003-07-30 AU AU2003249102A patent/AU2003249102A1/en not_active Abandoned
Patent Citations (4)
| 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 (enrdf_load_stackoverflow) | 2002-10-28 |
| AU2003249102A1 (en) | 2004-02-23 |
| HUP0202551A2 (hu) | 2004-03-29 |
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