PL2886132T3 - Reagenty funkcjonalizujące tiole oraz ich zastosowania - Google Patents

Reagenty funkcjonalizujące tiole oraz ich zastosowania

Info

Publication number
PL2886132T3
PL2886132T3 PL15151649T PL15151649T PL2886132T3 PL 2886132 T3 PL2886132 T3 PL 2886132T3 PL 15151649 T PL15151649 T PL 15151649T PL 15151649 T PL15151649 T PL 15151649T PL 2886132 T3 PL2886132 T3 PL 2886132T3
Authority
PL
Poland
Prior art keywords
functionalizing reagents
thiol
thiol functionalizing
reagents
functionalizing
Prior art date
Application number
PL15151649T
Other languages
English (en)
Inventor
Andrew Graham Watts
Terrence Kantner
Amanda Mackenzie
Original Assignee
Glythera Limited
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Glythera Limited filed Critical Glythera Limited
Publication of PL2886132T3 publication Critical patent/PL2886132T3/pl

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
    • C07D213/46—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/55—Acids; Esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C07D213/80—Acids; Esters in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/26—Acyclic or carbocyclic radicals, substituted by hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/13—Labelling of peptides

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Pyridine Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Enzymes And Modification Thereof (AREA)
PL15151649T 2008-12-19 2009-12-21 Reagenty funkcjonalizujące tiole oraz ich zastosowania PL2886132T3 (pl)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US13901408P 2008-12-19 2008-12-19
GBGB0823309.0A GB0823309D0 (en) 2008-12-19 2008-12-19 Functionalising reagents and their uses
EP09795797.1A EP2373675B1 (en) 2008-12-19 2009-12-21 Thiol-functionalising reagents and their uses
EP15151649.9A EP2886132B1 (en) 2008-12-19 2009-12-21 Thiol-functionalising reagents and their uses

Publications (1)

Publication Number Publication Date
PL2886132T3 true PL2886132T3 (pl) 2018-09-28

Family

ID=40343997

Family Applications (2)

Application Number Title Priority Date Filing Date
PL15151649T PL2886132T3 (pl) 2008-12-19 2009-12-21 Reagenty funkcjonalizujące tiole oraz ich zastosowania
PL09795797T PL2373675T3 (pl) 2008-12-19 2009-12-21 Reagenty funkcjonalizujące tiole oraz ich zastosowania

Family Applications After (1)

Application Number Title Priority Date Filing Date
PL09795797T PL2373675T3 (pl) 2008-12-19 2009-12-21 Reagenty funkcjonalizujące tiole oraz ich zastosowania

Country Status (8)

Country Link
US (2) US8785595B2 (pl)
EP (2) EP2373675B1 (pl)
JP (2) JP5877712B2 (pl)
CN (2) CN102317305B (pl)
ES (2) ES2674099T3 (pl)
GB (1) GB0823309D0 (pl)
PL (2) PL2886132T3 (pl)
WO (1) WO2010070300A2 (pl)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0823309D0 (en) 2008-12-19 2009-01-28 Univ Bath Functionalising reagents and their uses
GB201007356D0 (en) 2010-04-30 2010-06-16 Leverton Licence Holdings Ltd Conjugated factor VIIa
US9445596B2 (en) 2011-08-08 2016-09-20 California Institute Of Technology Small molecule compounds for the control of nematodes
US9487551B2 (en) 2011-08-08 2016-11-08 California Institute Of Technology Small molecule compounds that control mammal-pathogenic nematodes
EP2907823A1 (en) * 2014-02-14 2015-08-19 Gene Signal International SA Polypeptide fragments of 168A-T2 and compositions comprising them for use in treating cancer
GB201419108D0 (en) * 2014-10-27 2014-12-10 Glythera Ltd Materials and methods relating to linkers for use in antibody drug conjugates
US11464810B2 (en) 2016-08-25 2022-10-11 California Institute Of Technology Ascaroside treatment of eosinophilic esophagitis
WO2020025108A1 (en) 2018-07-31 2020-02-06 Astrazeneca Ab Linkers and conjugates
WO2020236621A1 (en) 2019-05-17 2020-11-26 California Institute Of Technology Ascaroside derivatives and methods of use
CN115998707A (zh) * 2021-10-21 2023-04-25 福州大学 一种聚二硫多肽纳米粒及其制备方法和多肽药物口服制剂
CN115181091A (zh) * 2022-06-21 2022-10-14 江苏联环药业股份有限公司 一种贝他斯汀的制备方法
CN121800880B (zh) * 2026-03-06 2026-06-16 天府锦城实验室(前沿医学中心) 一种多价糖肽及其制备方法和用途

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8308235D0 (en) 1983-03-25 1983-05-05 Celltech Ltd Polypeptides
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4719272A (en) * 1984-06-27 1988-01-12 National Starch And Chemical Corporation Monomeric cationic glycoside derivatives
CA1236454A (en) * 1984-06-27 1988-05-10 John J. Tsai Monomeric cationic glycoside derivatives
JPS61134325A (ja) 1984-12-04 1986-06-21 Teijin Ltd ハイブリツド抗体遺伝子の発現方法
GB8607679D0 (en) 1986-03-27 1986-04-30 Winter G P Recombinant dna product
EP0298101A1 (en) * 1987-01-15 1989-01-11 Celltech Limited Thiol-reactive cross-linking reagents
DE3942355A1 (de) * 1989-12-21 1991-06-27 Boehringer Mannheim Gmbh N- und o-substituierte aminophenolderivate, zwischenprodukte zu deren herstellung, deren verwendung als hydrolasesubstrate, ein entsprechendes bestimmungsverfahren und hierfuer geeignetes diagnostisches mittel
AU1674292A (en) * 1991-03-15 1992-10-21 Synergen, Inc. Pegylation of polypeptides
ATE199392T1 (de) 1992-12-04 2001-03-15 Medical Res Council Multivalente und multispezifische bindungsproteine, deren herstellung und verwendung
US5446090A (en) * 1993-11-12 1995-08-29 Shearwater Polymers, Inc. Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules
US6309646B1 (en) * 1996-05-09 2001-10-30 The Henry M. Jackson Foundation For The Advancement Of Military Medicine Protein-polysaccharide conjugate vaccines and other immunological reagents prepared using homobifunctional and heterobifunctional vinylsulfones, and processes for preparing the conjugates
US6602498B2 (en) * 2000-02-22 2003-08-05 Shearwater Corporation N-maleimidyl polymer derivatives
EP1438387A4 (en) 2001-09-14 2004-10-13 Momenta Pharmaceuticals Inc METHODS OF MAKING GLYCOMOLECULES WITH IMPROVED ACTIVITY, AND USES THEREOF
US20040214228A9 (en) 2001-09-14 2004-10-28 Ganesh Venkataraman Methods of evaluating glycomolecules for enhanced activities
PT3025726T (pt) * 2002-01-18 2020-01-09 Biogen Ma Inc Compostos do polímero polialquileno e utilizações dos mesmos
JP4764630B2 (ja) * 2002-09-09 2011-09-07 ネクター セラピューティックス 水溶性ポリマーアルカナール
JP2004262781A (ja) * 2003-02-28 2004-09-24 Noguchi Inst 蛍光糖鎖プローブ
US20050074895A1 (en) 2003-09-05 2005-04-07 Bio-Rad Laboratories, Inc. Alkyl-substituted vinyl pyridines for mass-coded tagging of proteins
ES2360607T3 (es) * 2005-07-11 2011-06-07 MERCK SHARP & DOHME CORP. Procedimiento de fabricación de antagonistas del receptor de taquiquinina de hidroisoindolina.
GB0823309D0 (en) 2008-12-19 2009-01-28 Univ Bath Functionalising reagents and their uses
US9209965B2 (en) 2014-01-14 2015-12-08 Microsemi Semiconductor Ulc Network interface with clock recovery module on line card

Also Published As

Publication number Publication date
WO2010070300A3 (en) 2010-10-14
JP6240122B2 (ja) 2017-11-29
EP2886132A1 (en) 2015-06-24
HK1210026A1 (en) 2016-04-15
GB0823309D0 (en) 2009-01-28
US20120101254A1 (en) 2012-04-26
JP5877712B2 (ja) 2016-03-08
US9212148B2 (en) 2015-12-15
ES2556328T3 (es) 2016-01-15
PL2373675T3 (pl) 2016-03-31
CN102317305B (zh) 2016-03-23
US8785595B2 (en) 2014-07-22
CN104558098A (zh) 2015-04-29
CN104558098B (zh) 2020-06-30
ES2674099T3 (es) 2018-06-27
CN102317305A (zh) 2012-01-11
EP2373675B1 (en) 2015-10-21
HK1165435A1 (zh) 2012-10-05
EP2373675A2 (en) 2011-10-12
JP2012512858A (ja) 2012-06-07
EP2886132B1 (en) 2018-04-04
US20140364586A1 (en) 2014-12-11
WO2010070300A2 (en) 2010-06-24
JP2015221812A (ja) 2015-12-10

Similar Documents

Publication Publication Date Title
EP2217371A4 (en) CATALYSTS AND RELATED METHODS
PT2537529T (pt) Anticorpos inibidores de loxl2 e suas utilizações
BRPI0907231A2 (pt) pirrolpirimidinas e pirrolpiridinas
EP2365879C0 (en) MICROFLUIDIC DEVICE
EP1982167A4 (en) BIOSENSOR
HRP20171011T1 (hr) ANTI-eMET ANTITIJELO
BRPI0907237A2 (pt) Anticorpo anti-cldn6
EP2263087A4 (en) MARKED REACTANDS AND ITS USE
BRPI0812509A2 (pt) Aparelho reformador e método
BRPI0822296A2 (pt) Transponder e livreto
EP2020311A4 (en) TIRE
EP2372732A4 (en) WAKED ACCUMULATOR
EP2373413A4 (en) DEGRADATION CATALYST AND METHOD
EP2101179A4 (en) ANALYSIS DEVICE
EP1974955A4 (en) TIRE
EP2089722A4 (en) BIOMARKERS
EP2129285A4 (en) Analyte sensor
EP2208072A4 (en) FORECAST PROCEDURES
DE502007005526D1 (de) Pipettiervorrichtung
BRPI0914098A2 (pt) biosensor
EP2280284A4 (en) Biosensor
BRPI0817427A2 (pt) Anticorpo anti-bst2
EP2006664A4 (en) Analyzing apparatus
DK2325662T3 (da) Multi-indlæsnings- og multi-udlæsningsanalysator
EP2307141A4 (en) MICROFLUIDIC DEVICE