EP2404155A1 - Dispositif et procédé pour l'enrichissement et la détection de cellules marquées magnétiquement dans des fluides à écoulement laminaire - Google Patents

Dispositif et procédé pour l'enrichissement et la détection de cellules marquées magnétiquement dans des fluides à écoulement laminaire

Info

Publication number
EP2404155A1
EP2404155A1 EP10707007A EP10707007A EP2404155A1 EP 2404155 A1 EP2404155 A1 EP 2404155A1 EP 10707007 A EP10707007 A EP 10707007A EP 10707007 A EP10707007 A EP 10707007A EP 2404155 A1 EP2404155 A1 EP 2404155A1
Authority
EP
European Patent Office
Prior art keywords
cells
magnetic field
magnetoresistor
detection
channel
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.)
Withdrawn
Application number
EP10707007A
Other languages
German (de)
English (en)
Inventor
Oliver Hayden
Manfred Rührig
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.)
Siemens AG
Original Assignee
Siemens AG
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 Siemens AG filed Critical Siemens AG
Publication of EP2404155A1 publication Critical patent/EP2404155A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/02—Magnetic separation acting directly on the substance being separated
    • B03C1/28—Magnetic plugs and dipsticks
    • B03C1/288—Magnetic plugs and dipsticks disposed at the outer circumference of a recipient
    • 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
    • B01L3/502761—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 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/02—Magnetic separation acting directly on the substance being separated
    • B03C1/025—High gradient magnetic separators
    • B03C1/031—Component parts; Auxiliary operations
    • B03C1/033—Component parts; Auxiliary operations characterised by the magnetic circuit
    • B03C1/0335—Component parts; Auxiliary operations characterised by the magnetic circuit using coils
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • 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
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0877—Flow chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/043—Moving fluids with specific forces or mechanical means specific forces magnetic forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C2201/00—Details of magnetic or electrostatic separation
    • B03C2201/26—Details of magnetic or electrostatic separation for use in medical applications

Definitions

  • the invention relates to a device and a method for enrichment and detection of cells in flowing media, in particular of labeled cells in complex media such as blood. 10
  • analytes can also be sorted to a limited extent according to size and magnetic moment, see N. Pamme and A. Manz, Anal. Chem., 2004, 76, 7250.
  • magnetoresistive sensor manufacturers are only offering assays for DNA and protein analysis for in vitro diagnostic use. For example, refer to the Internet addresses of magnabiosciences.com, diagnsticbioseners.com, seahawkbio.com and san.rr.com/magnesensors.
  • a magnetoresistive sensor e.g., GMR sensor
  • GMR sensor magnetoresistive sensor
  • the object of the present invention is therefore to overcome the disadvantages of the prior art and to provide an apparatus and a method for single-cell detection in the flowing medium.
  • the subject matter of the invention is an apparatus for enrichment and detection of cells, wherein at least one magnetoresistor is arranged in an outer, surrounding magnetic field below a channel in which a laminar flow of a medium flows with magnetically marked cells.
  • the invention relates to a method for enrichment and detection of magnetically labeled cells in a laminar flowing medium, wherein cells on a
  • Magnetoresistance be enriched by an external magnetic field.
  • the invention discloses the technique of obtaining an accumulation of labeled cells directly on the magnetoresistors by means of an external magnetic field so that a nearly 100% detection of the labeled cells can be achieved.
  • the flow cytometry shown here makes it almost possible to enumerate individual labeled cells with a near 100% recovery rate when the GMR component overflows dynamically in the flowing medium.
  • treacherous diseases such as cancer, it is sometimes necessary that in about 10ml of whole blood 1 to 100 cells are quantifiable.
  • Single labeled cells in a complex matrix such as blood or partially purified (typically 1: 1000 to 1: 1 000 000) while in the flowing medium are directed to the substrate surface (as close as possible to the GMR sensor)
  • the magnetic field is applied so that an amplification of the gradient of the magnetic field directly below the GMR sensors takes place so that the entry point of the magnetic field lines in the sample space is as close as possible to the GMR sensors.
  • the magnet is arranged directly below the GMR sensors.
  • the embodiment in which the magnet for the outer, the magnetoresistors surrounding magnetic field is beveled on one or both sides, so that results in a flux concentration and an increase of the magnetic field gradient.
  • Cell detection with magnetoresistors is most easily carried out with sophisticated sensors such as the AMR, GMR and / or TMR sensors, the two latter being advantageously designed as so-called spin valves.
  • the laminar flow causes the cells to be transported without turbulence in the liquid stream.
  • cells that come in contact with the surface are caused to rotate due to shear forces and the airfoil.
  • the effect is exploited to on the one hand as possible lead all labeled cells to the magnetoresistors, and on the other hand introduce the statistically distributed immunomagnetic marker on the cell surface by "rolling" close to the GMR sensors.
  • the accumulation of cells in a magnetic field gradient which is currently used only for cell separation, is suitable for specifically enriching the labeled cells from the laminar flow to the substrate surface with the magnetoresistors depending on flow rate and number of magnetic labels per cell.
  • the magnetic force and thus the shear force or holding force can be varied to the enriched cells without the transport of unlabelled cells along the microfluidic channel to prevent.
  • this measurement target is achieved by the following components of a measurement system interacting:
  • GMR sensor has a dimension equivalent to the diameter of a single cell (typically 5-40 microns), to achieve high signal-to-noise ratio and to detect signal from only one cell
  • An external magnetic gradient field is preferably used to guide stochastically distributed and labeled cells in a microfluidic channel to the substrate surface (typically the cell to GMR sensor distance will be 0-1 ⁇ m); then the signal-to-noise ratio can be increased
  • the flowing medium is advantageously laminar, since turbulence can lead to a reduction in the recovery rate of labeled cells.
  • Typical channels have a cross section of 100-1000 ⁇ m width and 100-1000 ⁇ m height. This means that a GMR sensor with cell dimensions is much smaller than the channel size.
  • the individual labeled cells are controlled in the immediate vicinity of the substrate in the flowing medium out.
  • a stochastic distribution of labeled cells on the substrate surface leads to counting losses (for example at 10 ⁇ m GMR in a 100 ⁇ m channel ⁇ 90% loss). Cells are therefore guided along, for example, ferromagnetic strips directly onto a sensor.
  • This measuring arrangement also has the advantage that in the ideal case only a single GMR sensor is necessary to count all marked cells.
  • FIG. 1 shows the two cross sections through an embodiment of a microfluidic channel according to the invention, on the left a cross section along the flow direction and on the right a cross section perpendicular to the flow direction.
  • Figure 1 shows schematically the process of cell enrichment on the substrate surface 8 with the GMR sensors.
  • FIG 1 shows a longitudinal cross section of a microfluidic channel 4 in which a laminar flow, as indicated by the arrow 5, is shown in the left part of the FIGURE. flows.
  • a laminar flow as indicated by the arrow 5
  • unlabeled cells 2 which move evenly distributed in the laminar flow.
  • a magnet 7 is arranged; the image immediately shows the accumulation of the marked cells on the bottom / substrate 8 of the channel within the magnetic field gradient 7.
  • the GMR sensors like all magnetoresistors, can also be connected to the Side walls of the channel wall and / or be arranged at the top of the channel.
  • the enrichment of cells with superparamagnetic markers 1 from a complex medium in a magnetic field 9 is shown.
  • the laminar flow 5 prevents swirling of the cells 1 and 2.
  • the cells 1,2 can roll along the substrate surface 8 and thus come into closest contact with the GMR sensors 3.
  • the strength of the magnetic field but the transport does not interfere with the labeled cells in the microfluidic channel, which can be adjusted, for example, by suitable pulsed operation and by the symmetry of the gradient field.
  • the microfluidic channel 4 can be seen in cross-section through the flow direction.
  • the field lines 9 of the magnetic field which have their origin in the GMR sensors 3 and therefore cause a gradient amplification of the magnetic field.
  • the magnet 7 has at least one bevel 6 towards the GMR sensors, but preferably 2 bevels 6 as shown.
  • Figure 2 shows the same image as Figure 1 in longitudinal cross-section and illustrates the cell rolling within the laminar flow 5.
  • the three phases of the CeIl- Rollings can be seen, first (A) the enrichment of the labeled cells 1 on the substrate surface of the bottom. 8 of the microfluidic channel 4 in the magnetic field 9, then (B) cell rolling over the sensor surface, where (C) cell detection takes place.
  • the gradient magnetic field (-100 mT with dB / dx of a few 10-100 T / m, depending on the loading of the cells with superparamagnetic particles) pulsed.
  • the detection of the labeled cells takes place in a weak measuring magnetic field of ⁇ ImT.
  • FIG. 3 shows in time sequence the strength of the magnetic field for cell enrichment, cell detection and GMR measurement.
  • the time is plotted on the X-axis, so that it can be seen that always two magnetic field strengths are applied in temporal change.
  • a method of continuous cell enrichment and cell detection may be performed by a sequence of pulsed magnetic fields.
  • FIG. 3 shows the cyclical sequence of (1) enrichment, (2) + (3) measurement for a continuous measurement, which is illustrated graphically.
  • the measurement and accumulation of the cells can thus be tracked or controlled independently of each other in the kHz range.
  • Figure 3 how at the very top with a "strong magnetic field and long pulse times" cell enrichment takes place within the microfluidic channel, below which is a graph showing that a weaker magnetic field with less pulse time is used for cell detection Graphic as with low magnetic field and short pulse time the GMR measurement is completed.
  • FIG. 4 again shows a microfluidic channel, again in cross section perpendicular to the flow direction as in FIG. 1 on the right side.
  • the measuring magnetic field can be applied vertically or in the same plane as the GMR sensors (FIG. 4).
  • the magnet (magnetic yoke) of the gradient magnetic field can be used to set a gradient in the measuring magnetic field in order to achieve a local detuning of the bridge members of the GMR measuring bridge. This detuning represents the measurement signal for the concentration of the magnetic particles in the sensor region.
  • the measuring magnetic field can additionally be time-modulated in order, for example, to obtain a time delay. using lock-in technology and suppressing the low-frequency noise (1 / f noise) to improve the signal-to-noise ratio.
  • pulsed magnetic fields are enriched and detected as shown in FIG.
  • FIG. 4 the schematic arrangement of the magnets or coils 7, 10 and 11 for enrichment and detection around the microfluidic channel 4 is shown.
  • the magnet 7 for the strong magnetic field is applied for enrichment below the GMR sensors and the coils 10 and 11 for the weak magnetic field are applied perpendicular to the GMR sensor for detection. Both fields can be controlled separately with 2 magnets, wherein preferably the weak magnetic field is applied in the sensor plane.
  • the accumulation of the cells or the applied shear force on the cells can be controlled by the magnetic field strength and the flow rate.
  • Marked cells are near the surface and can be sensitively detected with magnetoresistive components.
  • the presented method allows a large area application for multiplexing (e.g., array of GMR sensors).
  • Cell rolling can be adapted to the application by means of surface-functionalized microfluidic channels, for example functionalized with receptors (selectins), biological components (proteins, polysaccharides), or SAMs (self-assembled mono- layer) or by silanization.
  • receptors selectiveins
  • biological components proteins, polysaccharides
  • SAMs self-assembled mono- layer
  • Circulating tumor cells CTC
  • tumor stem cells inflammatory cells
  • stem cells inflammatory cells
  • bacteria or yeasts may precede the actual detection in the flowing medium.
  • the magnetic detection can be done with optical methods
  • Areas of application in the human area include:
  • Oncology regenerative medicine, infectiology, clinical diagnostics, clinical chemistry, imaging.

Abstract

L'invention concerne un dispositif et un procédé pour l'enrichissement et la détection de cellules dans des fluides en écoulement, en particulier de cellules marquées magnétiquement dans des fluides complexes comme par exemple le sang. À cet effet, on utilise au moins un aimant couplé à au moins une magnétorésistance.
EP10707007A 2009-03-06 2010-03-03 Dispositif et procédé pour l'enrichissement et la détection de cellules marquées magnétiquement dans des fluides à écoulement laminaire Withdrawn EP2404155A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102009012108.0A DE102009012108B4 (de) 2009-03-06 2009-03-06 Vorrichtung und Verfahren zur Anreicherung und Erfassung von Zellen in strömenden Medien
PCT/EP2010/052697 WO2010100192A1 (fr) 2009-03-06 2010-03-03 Dispositif et procédé pour l'enrichissement et la détection de cellules marquées magnétiquement dans des fluides à écoulement laminaire

Publications (1)

Publication Number Publication Date
EP2404155A1 true EP2404155A1 (fr) 2012-01-11

Family

ID=42199690

Family Applications (1)

Application Number Title Priority Date Filing Date
EP10707007A Withdrawn EP2404155A1 (fr) 2009-03-06 2010-03-03 Dispositif et procédé pour l'enrichissement et la détection de cellules marquées magnétiquement dans des fluides à écoulement laminaire

Country Status (4)

Country Link
US (1) US9522401B2 (fr)
EP (1) EP2404155A1 (fr)
DE (1) DE102009012108B4 (fr)
WO (1) WO2010100192A1 (fr)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102010043276A1 (de) * 2010-11-03 2012-05-03 Siemens Aktiengesellschaft Magnetische Zelldetektion
DE102011004805A1 (de) * 2011-02-28 2012-08-30 Siemens Aktiengesellschaft Miniaturisierte magnetische Durchflusszytometrie
DE102011004806A1 (de) * 2011-02-28 2012-08-30 Siemens Aktiengesellschaft Magnetische Durchflusszytometrie für hohen Probendurchsatz
DE102011077905A1 (de) * 2011-06-21 2012-12-27 Siemens Aktiengesellschaft Hintergrundfreie magnetische Durchflusszytometrie
DE102011080945A1 (de) * 2011-08-15 2013-02-21 Siemens Aktiengesellschaft Dynamische Zustandsbestimmung von Analyten mittels magnetischer Durchflussmessung
DE102012210598A1 (de) 2012-06-22 2013-12-24 Siemens Aktiengesellschaft Verfahren und Anordnung zur Detektion von Zellen in einer Zellsuspension
DE102012211626A1 (de) * 2012-07-04 2014-01-09 Siemens Aktiengesellschaft Anordnung zur Quantifizierung von Zellen einer Zellsuspension
DE102014205949A1 (de) * 2014-03-31 2015-10-01 Siemens Aktiengesellschaft Durchflusskammer für einen Durchflusszytometer sowie Durchflusszytometer
DE102015225847A1 (de) * 2015-12-18 2017-06-22 Robert Bosch Gmbh Detektionsvorrichtung und Verfahren zum Detektieren zumindest eines an zumindest ein Bindepartikel gebundenen Partikels in einer Flüssigkeit
US11112468B2 (en) * 2019-04-12 2021-09-07 Western Digital Technologies, Inc. Magnetoresistive sensor array for molecule detection and related detection schemes
CN113720667B (zh) * 2021-09-02 2022-09-06 苏州幻宝安全与环境工程有限公司 一种环境监测用水样品处理系统及方法

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5475304A (en) * 1993-10-01 1995-12-12 The United States Of America As Represented By The Secretary Of The Navy Magnetoresistive linear displacement sensor, angular displacement sensor, and variable resistor using a moving domain wall
DE19706617C1 (de) 1997-02-20 1998-04-30 Mueller Ruchholtz Wolfgang Pro Verfahren zur Zählung mikroskopischer Objekte
US6337215B1 (en) * 1997-12-01 2002-01-08 International Business Machines Corporation Magnetic particles having two antiparallel ferromagnetic layers and attached affinity recognition molecules
US6623984B1 (en) * 2000-11-01 2003-09-23 The Cleveland Clinic Foundation MEMS-based integrated magnetic particle identification system
US6736978B1 (en) * 2000-12-13 2004-05-18 Iowa State University Research Foundation, Inc. Method and apparatus for magnetoresistive monitoring of analytes in flow streams
US20040219695A1 (en) * 2002-01-19 2004-11-04 Fox John Stewart High sensitivity detection of and manipulation of biomolecules and cells with magnetic particles
US20080024118A1 (en) * 2004-05-24 2008-01-31 Koninklijke Philips Electronics, N.V. Magneto-Resistive Sensor for High Sensitivity Depth Probing
JP5311445B2 (ja) * 2005-01-31 2013-10-09 コーニンクレッカ フィリップス エヌ ヴェ 高速かつ高感度バイオセンシング
US7300631B2 (en) * 2005-05-02 2007-11-27 Bioscale, Inc. Method and apparatus for detection of analyte using a flexural plate wave device and magnetic particles
US8512559B2 (en) * 2005-11-18 2013-08-20 Intel Corporation Device, method, and system for separation and detection of biomolecules and cells
WO2008001261A2 (fr) * 2006-06-28 2008-01-03 Koninklijke Philips Electronics N. V. Dispositif détecteur magnétique et procédé permettant de détecter des particules magnétiques
JP2009543088A (ja) 2006-07-11 2009-12-03 コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ 磁気センサ素子
ATE472372T1 (de) 2006-10-26 2010-07-15 Imec Handhabung von magnetischen oder magnetisierbaren objekten unter verwendung von kombinierter magnetophorese und dielektrophorese
ATE471516T1 (de) 2007-02-23 2010-07-15 Koninkl Philips Electronics Nv Sensorvorrichtung und verfahren zum detektieren magnetischer partikel
DE102007057667A1 (de) * 2007-11-30 2009-09-03 Siemens Ag Vorrichtung zur Detektion von Partikeln in einem Fluid
US20130004982A1 (en) * 2011-06-29 2013-01-03 The Regents Of The University Of California Method and apparatus for magnetic flow cytometry

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
MATHIAS REISBECK ET AL: "Magnetic fingerprints of rolling cells for quantitative flow cytometry in whole blood", SCIENTIFIC REPORTS, vol. 6, 6 September 2016 (2016-09-06), pages 32838, XP055340593, DOI: 10.1038/srep32838 *
MICHAEL HELOU ET AL: "Time-of-flight magnetic flow cytometry in whole blood with integrated sample preparation", LAB ON A CHIP, vol. 13, no. 6, 1 January 2013 (2013-01-01), pages 1035, XP055074753, ISSN: 1473-0197, DOI: 10.1039/c3lc41310a *
See also references of WO2010100192A1 *

Also Published As

Publication number Publication date
US20110315635A1 (en) 2011-12-29
WO2010100192A1 (fr) 2010-09-10
DE102009012108B4 (de) 2015-07-16
DE102009012108A1 (de) 2011-01-20
US9522401B2 (en) 2016-12-20

Similar Documents

Publication Publication Date Title
DE102009012108B4 (de) Vorrichtung und Verfahren zur Anreicherung und Erfassung von Zellen in strömenden Medien
EP2212673B1 (fr) Dispositif de détection magnétique de particules individuelles dans un canal microfluidique
DE102009047801B4 (de) Durchflusskammer mit Zellleiteinrichtung
DE112011102234B4 (de) Erkennung magnetischer Nanopartikel durch eine Membran hindurch
WO2013000853A1 (fr) Procédé et appareil pour cytométrie à flux magnétique
EP2906949B1 (fr) Contrôle d'un analyte et détermination de la concentration d'un analyte à l'aide de billes magnétisables
WO2020011793A1 (fr) Système de détection de fluide
DE102011076051A1 (de) Magnetophoretische Analytselektion und -anreicherung
DE102012210457B4 (de) Verfahren und Anordnung zur partiellen Markierung und anschließenden Quantifizierung von Zellen einer Zellsuspension
DE102017130033B4 (de) Detektionsvorrichtung und Verfahren zur Detektion von magnetischen Partikeln in Schmierstoffen
DE102006037739B4 (de) Vorrichtung zur Durchführung eines Analyseverfahrens, insbesondere zur Erkennung biochemischer Moleküle, und mit dieser Vorrichtung ausführbare Analyseverfahren
EP2501475B1 (fr) Système et procédé pour la détection de molécules d'analyte contenues dans des échantillons liquides
EP2668500B1 (fr) Cytométrie de flux magnétique miniaturisée
DE102013219114A1 (de) Multiplexverfahren für eine magnetische Durchflusszytometrie
WO2012059414A1 (fr) Détection magnétique de cellules
EP2841940A1 (fr) Procédé et dispositif de détection de cellules dans une suspension cellulaire
DE102012210077A1 (de) Verfahren und Anordnung zur Markierung von Zellen in einer Zellsuspension
WO2011104312A1 (fr) Amélioration de la limite de détectabilité d'échantillons à marquage magnétique
DE19706617C1 (de) Verfahren zur Zählung mikroskopischer Objekte
EP2726844A1 (fr) Détection d'analytes individuels à l'aide d'une mesure magnétique d'écoulement
WO2012052392A1 (fr) Cytométrie en flux magnétique
EP1198712A2 (fr) Procede et dispositif pour representer des particules biologiquement activees faisant varier l'inductance
DE102008013997A1 (de) Verfahren zum quantitativen Nachweis von Analyten in flüssigem Medium
DE102007015543A1 (de) Verfahren und Anordnung zur Detektion biologischer Reaktionsprodukte
WO2015185391A1 (fr) Procédé de mesure de forces de liaison entre des cellules et des ligands dans des solutions troubles

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20110829

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR

DAX Request for extension of the european patent (deleted)
RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: SIEMENS AKTIENGESELLSCHAFT

17Q First examination report despatched

Effective date: 20170207

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: SIEMENS AKTIENGESELLSCHAFT

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20170620