WO2008052515A2 - Puce microfluidique en verre avec un émetteur à électronébulisation monolithique pour le couplage de la puce avec un spectromètre de masse - Google Patents

Puce microfluidique en verre avec un émetteur à électronébulisation monolithique pour le couplage de la puce avec un spectromètre de masse Download PDF

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Publication number
WO2008052515A2
WO2008052515A2 PCT/DE2007/001919 DE2007001919W WO2008052515A2 WO 2008052515 A2 WO2008052515 A2 WO 2008052515A2 DE 2007001919 W DE2007001919 W DE 2007001919W WO 2008052515 A2 WO2008052515 A2 WO 2008052515A2
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WO
WIPO (PCT)
Prior art keywords
microfluidic
chip
projection
chips
coupling
Prior art date
Application number
PCT/DE2007/001919
Other languages
German (de)
English (en)
Other versions
WO2008052515A3 (fr
Inventor
Detlev Belder
Ulrich Häusig
Philipp Schulze
Peter Hoffmann
Original Assignee
Studiengesellschaft Kohle Mbh
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 Studiengesellschaft Kohle Mbh filed Critical Studiengesellschaft Kohle Mbh
Publication of WO2008052515A2 publication Critical patent/WO2008052515A2/fr
Publication of WO2008052515A3 publication Critical patent/WO2008052515A3/fr

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Classifications

    • 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
    • B01L3/502715—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 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • 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
    • B01L3/502707—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 characterised by the manufacture of the container or its components
    • C—CHEMISTRY; METALLURGY
    • C03—GLASS; MINERAL OR SLAG WOOL
    • C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C15/00—Surface treatment of glass, not in the form of fibres or filaments, by etching
    • C—CHEMISTRY; METALLURGY
    • C03—GLASS; MINERAL OR SLAG WOOL
    • C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C19/00—Surface treatment of glass, not in the form of fibres or filaments, by mechanical means
    • C—CHEMISTRY; METALLURGY
    • C03—GLASS; MINERAL OR SLAG WOOL
    • C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
    • C03C23/00—Other surface treatment of glass not in the form of fibres or filaments
    • C03C23/007—Other surface treatment of glass not in the form of fibres or filaments by thermal treatment
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/0013—Miniaturised spectrometers, e.g. having smaller than usual scale, integrated conventional components
    • H01J49/0018—Microminiaturised spectrometers, e.g. chip-integrated devices, Micro-Electro-Mechanical Systems [MEMS]
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H01J49/10—Ion sources; Ion guns
    • H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
    • H01J49/165—Electrospray ionisation
    • H01J49/167—Capillaries and nozzles specially adapted therefor
    • 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
    • B01L2200/12—Specific details about manufacturing devices
    • 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
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • 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
    • B01L2300/12—Specific details about materials
    • 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
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—Drop counters; Drop formers
    • B01L3/0268—Drop counters; Drop formers using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries

Definitions

  • the invention relates to a method for producing microfluidic glass chips with monolithically integrated electrospray emitter, and the Mikrokanalsyste- thus produced and their application in mass spectrometry and for chiplaboratories.
  • the aim of the miniaturization of chemical analysis systems on microchips is to develop integrated miniaturized analysis systems in which different work processes such as sample preparation, chemical reaction / derivatization, separation and detection are integrated on one substrate.
  • the keyword "lab-on-a-chip" is often used.
  • miniaturization such as the high analysis speed, the extremely low reagent consumption and the possibility of system integration, this is accompanied by enormous requirements for the detection of very small sample quantities.
  • chip electrophoresis The most successful chip-based analysis technology today is chip electrophoresis, which is also described in, inter alia, US Pat. No. 5,858,195.
  • the dominant detection method for chip-based analysis techniques is currently fluorescence detection because of its high sensitivity and simple technical realization.
  • fluorescence detection Because of its high sensitivity and simple technical realization.
  • detection methods is one of the biggest challenges in microfluidic analysis systems.
  • electrospray mass spectrometry ESI-MS
  • the ESI-MS has already been successfully coupled with the classical capillary electrophoresis.
  • Corresponding systems and devices are meanwhile commercially available and belong to the state of the art.
  • a disadvantage of this approach is the relatively large emitter area, as occurs at the surface. forms relatively large droplets, which not only disturbs the efficiency and stability of the electrospray process, but also contributes to the band broadening.
  • a reasonably stable electrospray can generally only be obtained by applying external pressure at the inlet of the fluidic channel.
  • the application of pressure not only complicates the technical design, but is also detrimental to the intended coupling with chip electrophoresis, as this contributes to band broadening.
  • the problem of the large emitter surface can be circumvented by coupling the microchip to a capillary, which then serves as emitter, as in classical CE-MS, see Fig. 2.
  • a capillary which then serves as emitter, as in classical CE-MS, see Fig. 2.
  • an external capillary is mechanically fitted into the fluidic channel.
  • the emitters used are fused-silica (FS) capillaries or finely drawn glass tips, as described in US Pat. No. 5,788,166 and US 2004/0229377 A1, which are attached to the chip via microbores.
  • FS fused-silica
  • the present invention relates to a method for producing a microfluidic chip of glassy material, wherein the material of an edge is removed from a carrier of glassy material with substantially straight edges, that edge has a projection and this projection then to a point is pulled out.
  • glass chips can be produced with a monolithically integrated, finely extended tip.
  • the chips are integral, i. the actual chip and the tip consist of only one part without connecting seams, including adhesive seams, abutting edges, etc.
  • an efficient electrospray is obtained which, for example, enables dead-volume-free connection of microfluidic systems such as chip electrophoresis to mass spectrometry.
  • the method described is particularly suitable for the production of chips with a monolithically integrated emitter of glass or glassy materials.
  • the invention further relates to the chips produced in this way and their use in microfluidics, electrophoresis, mass spectrometry and related techniques.
  • the invention relates to a method for producing chips with a monolithically integrated emitter, so that a complicated assembly of external emitters is eliminated.
  • glass or quartz chips (see Fig. 3A)., Which contain a microfluidic structure (1 and 2) first processed so that a protruding pin (3) is formed which contains one or more Fluidikka- channels.
  • the pin is made by micro-peeling.
  • the cone is then heated to softening and pulled out (5), see Fig. 3B, to give a very fine emitter tip (6) which is monolithically bonded to the substrate and microfluidic structure, see Fig. 3C.
  • the pin is softened by heating a heating coil (4) as sketched in Fig. 3 B.
  • a heating coil (4) as sketched in Fig. 3 B.
  • other methods of local heating may be used, such as a laser, a gas flame, or a plasma.
  • microfluidic chips are processed for electrophoresis in order to enable the dead volume-free coupling of the electrophoresis with the mass spectrometry, see FIG. 4.
  • a commercial electrophoresis chip from Micronit Microfluidics BV (Netherlands) (Fig. 5a) with T-layout and 50 ⁇ m channel width is first beveled with a diamond grinding wheel at a 45 ° angle to the separation channel (Fig. 5b).
  • This cylinder is heated with a platinum spiral and pulled out to a fine tip.
  • a glass chip with electrospray emitter is shown in Fig. 5d in size comparison to a match and in Fig. 6a and 6b are light and electron micrographs of exemplary chips with tips to see.
  • the monolithic emitter chips produced can be used for the mass spectrometric detection of various substances.
  • Fig. 7 this is exemplified by the example of ephedrine.
  • the tip of the emitter chip used here has an outer diameter of 30 ⁇ m and an inner diameter of 10 ⁇ m.
  • the sample substance 1 ⁇ g / ml ephedrine dissolved in methanol / water (50/50) and 0.001% acetic acid can be sprayed without pressure through the air gap into the MS inlet.
  • the total ion current (TIC) and the mass trace of m / z 165.95 for ephedrine over a period of 3 min are characterized by extraordinary signal stability (Figure 7a).
  • the MS spectrum of the sample substance is shown in Fig. 7b.
  • the experimental setup is analogous to the MS experiment according to Example 2.
  • an aqueous 0.1% acetic acid solution with a 25% methanol content is used as the electrolyte system.
  • each of the Sl, Bl, and MS inlets is occluded at the SO -1kV.
  • the sample mixture is separated by applying 4kV on the Sl to the OkV at the MS inlet, with a retrace voltage of 1, 75kV at each of the Sl and SO.

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  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Materials Engineering (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Geochemistry & Mineralogy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Dispersion Chemistry (AREA)
  • Hematology (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Mechanical Engineering (AREA)
  • Plasma & Fusion (AREA)
  • Thermal Sciences (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
  • Micromachines (AREA)

Abstract

L'invention concerne un procédé de fabrication d'une puce microfluidique à partir d'un matériau en verre. Ledit procédé consiste à retirer le matériau d'une arête d'un support de matériau en verre avec des arêtes essentiellement droites, de sorte que cette arête présente une saillie et que cette saillie est ensuite taillée en pointe. Le procédé décrit permet de fabriquer des puces en verre d'un seul tenant avec une pointe finement taillée, intégrée de manière monolithique.
PCT/DE2007/001919 2006-10-31 2007-10-24 Puce microfluidique en verre avec un émetteur à électronébulisation monolithique pour le couplage de la puce avec un spectromètre de masse WO2008052515A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE200610051877 DE102006051877A1 (de) 2006-10-31 2006-10-31 Mikrofluidische Glas-Chips mit monolithischem Elektrospray-Emitter für die Chip-MS Kopplung
DE102006051877.2 2006-10-31

Publications (2)

Publication Number Publication Date
WO2008052515A2 true WO2008052515A2 (fr) 2008-05-08
WO2008052515A3 WO2008052515A3 (fr) 2008-07-03

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PCT/DE2007/001919 WO2008052515A2 (fr) 2006-10-31 2007-10-24 Puce microfluidique en verre avec un émetteur à électronébulisation monolithique pour le couplage de la puce avec un spectromètre de masse

Country Status (2)

Country Link
DE (1) DE102006051877A1 (fr)
WO (1) WO2008052515A2 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020003209A1 (en) * 2000-01-05 2002-01-10 Wood Troy D. Conductive polymer coated nano-electrospray emitter
US20020158195A1 (en) * 2001-03-19 2002-10-31 Per Andersson Microfluidic system (MS)
DE10321472A1 (de) * 2003-05-13 2004-12-16 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Fluidik-Modul und Verfahren zu seiner Herstellung
EP1544160A2 (fr) * 2003-12-19 2005-06-22 Agilent Technologies, Inc. Micro-composant avex source electrospray et son procédé de fabrication
DE202005019822U1 (de) * 2005-12-20 2006-03-09 Agilent Technologies, Inc. (n.d.Ges.d.Staates Delaware), Palo Alto Fluidikvorvorrichtung für optische Anwendungen in Fluiden
US20070145263A1 (en) * 2005-12-23 2007-06-28 Industrial Technology Research Institute Microfluidic device and manufacturing method thereof

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5788166A (en) * 1996-08-27 1998-08-04 Cornell Research Foundation, Inc. Electrospray ionization source and method of using the same
AU6135298A (en) * 1997-01-27 1998-08-26 California Institute Of Technology Mems electrospray nozzle for mass spectroscopy
DE19947496C2 (de) * 1999-10-01 2003-05-22 Agilent Technologies Inc Mikrofluidischer Mikrochip
US7007710B2 (en) * 2003-04-21 2006-03-07 Predicant Biosciences, Inc. Microfluidic devices and methods
FR2862006B1 (fr) * 2003-11-12 2006-01-27 Univ Lille Sciences Tech Sources d'electronebulisation planaires sur le modele d'une plume de calligraphie et leur fabrication.

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020003209A1 (en) * 2000-01-05 2002-01-10 Wood Troy D. Conductive polymer coated nano-electrospray emitter
US20020158195A1 (en) * 2001-03-19 2002-10-31 Per Andersson Microfluidic system (MS)
DE10321472A1 (de) * 2003-05-13 2004-12-16 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Fluidik-Modul und Verfahren zu seiner Herstellung
EP1544160A2 (fr) * 2003-12-19 2005-06-22 Agilent Technologies, Inc. Micro-composant avex source electrospray et son procédé de fabrication
DE202005019822U1 (de) * 2005-12-20 2006-03-09 Agilent Technologies, Inc. (n.d.Ges.d.Staates Delaware), Palo Alto Fluidikvorvorrichtung für optische Anwendungen in Fluiden
US20070145263A1 (en) * 2005-12-23 2007-06-28 Industrial Technology Research Institute Microfluidic device and manufacturing method thereof

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Publication number Publication date
WO2008052515A3 (fr) 2008-07-03
DE102006051877A1 (de) 2008-05-29

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