WO2010007210A1 - Procédé et appareil pour contrôler l'écoulement d'un fluide dans un système microfluidique - Google Patents

Procédé et appareil pour contrôler l'écoulement d'un fluide dans un système microfluidique Download PDF

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Publication number
WO2010007210A1
WO2010007210A1 PCT/FI2009/050557 FI2009050557W WO2010007210A1 WO 2010007210 A1 WO2010007210 A1 WO 2010007210A1 FI 2009050557 W FI2009050557 W FI 2009050557W WO 2010007210 A1 WO2010007210 A1 WO 2010007210A1
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WO
WIPO (PCT)
Prior art keywords
flow
microfluidic system
liquid
fluid flow
machine vision
Prior art date
Application number
PCT/FI2009/050557
Other languages
English (en)
Inventor
Pasi Kallio
Valtteri Heiskanen
Original Assignee
Tampereen Teknillinen Yliopisto
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 Tampereen Teknillinen Yliopisto filed Critical Tampereen Teknillinen Yliopisto
Publication of WO2010007210A1 publication Critical patent/WO2010007210A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N11/00—Investigating flow properties of materials, e.g. viscosity, plasticity; Analysing materials by determining flow properties
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N13/00—Investigating surface or boundary effects, e.g. wetting power; Investigating diffusion effects; Analysing materials by determining surface, boundary, or diffusion effects
    • G01N13/02—Investigating surface tension of liquids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01F—MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
    • G01F1/00—Measuring the volume flow or mass flow of fluid or fluent solid material wherein the fluid passes through a meter in a continuous flow
    • G01F1/66—Measuring the volume flow or mass flow of fluid or fluent solid material wherein the fluid passes through a meter in a continuous flow by measuring frequency, phase shift or propagation time of electromagnetic or other waves, e.g. using ultrasonic flowmeters
    • G01F1/661—Measuring the volume flow or mass flow of fluid or fluent solid material wherein the fluid passes through a meter in a continuous flow by measuring frequency, phase shift or propagation time of electromagnetic or other waves, e.g. using ultrasonic flowmeters using light
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01F—MEASURING VOLUME, VOLUME FLOW, MASS FLOW OR LIQUID LEVEL; METERING BY VOLUME
    • G01F1/00—Measuring the volume flow or mass flow of fluid or fluent solid material wherein the fluid passes through a meter in a continuous flow
    • G01F1/704—Measuring the volume flow or mass flow of fluid or fluent solid material wherein the fluid passes through a meter in a continuous flow using marked regions or existing inhomogeneities within the fluid stream, e.g. statistically occurring variations in a fluid parameter
    • G01F1/708—Measuring the time taken to traverse a fixed distance
    • G01F1/7086—Measuring the time taken to traverse a fixed distance using optical detecting arrangements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/84—Systems specially adapted for particular applications
    • G01N21/85—Investigating moving fluids or granular solids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01P—MEASURING LINEAR OR ANGULAR SPEED, ACCELERATION, DECELERATION, OR SHOCK; INDICATING PRESENCE, ABSENCE, OR DIRECTION, OF MOVEMENT
    • G01P5/00—Measuring speed of fluids, e.g. of air stream; Measuring speed of bodies relative to fluids, e.g. of ship, of aircraft
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N13/00—Investigating surface or boundary effects, e.g. wetting power; Investigating diffusion effects; Analysing materials by determining surface, boundary, or diffusion effects
    • G01N13/02—Investigating surface tension of liquids
    • G01N2013/0208—Investigating surface tension of liquids by measuring contact angle

Definitions

  • the present invention relates to a method and apparatus for inspecting fluid flow in a microfluidic system.
  • Microfluidic systems are used for decreasing the size required for performing analysis or transport or distribution of liquids. Examples are so-called lab-on-a-chip devices for performing analyses in a confined "miniaturized" area where reactants may be ready for use and only a sample to be analyzed need to be injected. These devices may be easily made portable for field analysis and may be disposable. Medical tests are one important application of these devices. Devices of this type may also operate according to a predetermined sequence for injecting reactants, analytes and possible rinsing solutions to the microchannels of the device, and may be reused several times. Microfluidic systems that operate automatically are gaining importance in analytic work that requires processing a large number of samples, such as in DNA research. Examples of microfluidic systems are shown by EP 1813348, US 6192939, US 6448090, US 2003/0092172, US 2005/0220629, US 2006/0228259 and US 2007/0166199.
  • Various liquids may be injected and extracted by a pneumatic device, which may be programmed to follow the sequence.
  • a pneumatic system that is well-suited for this purpose is shown in WO 2006/117436.
  • DE10125126 shows an image processing system for detection of a reaction product on a detector surface or in a detector volume of a miniature laboratory where several parallel reaction processes take place.
  • the system is arranged to detect a change in an optically detectable property which is a response to the reaction product.
  • the system is used for analysis and for collecting reaction process data which could be processed further.
  • the flow behaviour of liquids in microchannels of a microfluidic device is a key factor for proper operation of the system.
  • the microchannels where the flow of various liquids takes place have small dimensions and contain bends and sometimes complicated circuitry for directing different flows to desired spots and for mixing different flows. It is therefore of importance that the dynamic properties of the liquid and characteristics related to the flow of the liquid can be monitored to ensure that the device is working without disturbances.
  • There is also need for testing microfluidic systems for example as response to various parameters, for example to changes in a pneumatic system that controls the propagation of different streams through the system.
  • the method is mainly characterized in that the flow is inspected by means of machine vision.
  • Machine vision involves taking several consecutive images of a flow in a microchannel or any other parts of the system (passive valves, constrictions, enlargements, connecting points etc.) and performing automatic analysis on the basis of differences between consecutive images. For example the movement of a flow front of a liquid in a microchannel (filling of the microchannel) or the movement of the tail of the liquid (evacuation of the microchannel) can be monitored by machine vision.
  • the novel system is particularly suitable for characterization of liquid plug flows, and it may be used for improving the research and development work of academic and industrial research teams working with liquid flows in microchannels.
  • the method may have one or several following functions:
  • the system is modular such that the aforementioned functions can be included in the system in any combination.
  • the developed system can be used for enhancing phases of la-on-chip products.
  • the inspection of liquid flow is important in design and characterization of microfluidic chips, in production of chips and in the use of the chips.
  • the developed method and apparatus enhances the R&D work especially in microfluidics but also in chemical microsensors, biosensors and various other detection methods by the data acquisition of fluid flows in microchannels. It can be used when designing new transparent microfluidic cartridges and chips for lab-on-chip, ⁇ TAS and point-of-care applications for example.
  • the system can be used for quality control and in chip use for chip behavior control.
  • the developed system provides versatile quantitative data about the behavior of various sample liquids (whole blood, serum, plasma, saliva, food and beverage samples, process samples, environment and waste water samples, etc), buffers, reagents, washing liquids and gas bubbles in microchannels fabricated on different materials, having different cross-sectional shapes, dimensions and surface roughness, consisting of passive valves with various geometries, and having various functional coatings e.g. dried chemistries or hydrophobic / hydrophilic valves.
  • the system can be used for the development and verification of various analytical, numerical and data- based liquid flow and fluid behavior models in microchannels.
  • Fig. 1 shows a general principle of the system.
  • the system comprises imaging means (digital camera) arranged to take consecutive images of the microfluidic device (miniaturized channel structure), a data line form the imaging means to an image and data processing unit (measurement PC) that contains an image processing algorithm and a calculation algorithm for determining a characteristic of the flow so that it can be represented in numerical form, and means of displaying the results (illustrated by a square in the figure).
  • the image and data processing unit can contain several image processing algorithms and several calculation algorithms for determining various characteristics of the flow on the basis of the image data from the same flow.
  • the system may also comprise a pressure sensor for measuring a driving pressure (positive or negative) of a pneumatic control device that is arranged to give the necessary movement energy for the liquid in the microfluidic device and to control the supply and extraction of liquids to and from the microfluidic device, respectively.
  • the pneumatic control device may have the structure according to the above-mentioned WO 2006/1 17436.
  • the pressure sensor is connected to data line to the means of displaying the results, for displaying the pressure value along with the results obtained from image processing.
  • the imaging in the system can be done using e.g. FireWire camera and macro video zoom lens.
  • a light source and in order to create uniform illumination for the target a LED based ring light is used (16 LEDs, 8 white light, 8 red light).
  • a syringe pump or an accurate pressure generation unit can be used.
  • Image data from the camera is transferred to a measurement PC.
  • the measurement PC the image data is processed using image processing algorithms. Using the algorithms, the measurement quantities such as flow rate, velocity, displacement and dynamic contact angle are calculated.
  • a pressure measurement with a proper sensor can also be included in the system.
  • the characteristics of various parts are only exemplary and do not restrict the scope of the invention.
  • any camera with a large enough image size and fast enough frame rate can be used. If channel structures are in micro-/nanoscale, the camera should be attached to a microscope. Optics with a constant focal length is recommended for the camera because of the better calibration possibilities and more accurate measurements. Image processing can be also done using various programming languages. As illumination, any light source with ability to create uniform and accurate illumination is good. Standard ring lights available in the market are acceptable, also back lights can be considered.
  • microchannels in a microfluidic system have typically cross- sectional areas less than 2 square millimeters.
  • the walls limiting the interior of the channel have great influence on the flow. Therefore, it is important to follow the behaviour of the liquid and its interaction with channel walls with great accuracy.
  • the image processing methods in the algorithms consist of arithmetic subtraction of consecutive image frames and thresholding the subtraction result to a binary image.
  • the result of the subtraction represents the moved liquid column between two image frames. From the binary image, the area and length of a blob can be calculated easily and by these, the flow rate (assuming that channel height is known), velocity and displacement can be determined. Coordinates of the front meniscus of the liquid column can also be located and by applying a circle fitting to the coordinates, dynamic contact angle can be determined.
  • Fig. 2 where the image processing steps are illustrated on the left hand side, showing original image frame (top), result of subtraction (middle) and binary image (bottom) with front meniscus coordinated located.
  • the dynamic contact angle measurement method using the circle fitting method is shown on the right hand side.
  • the measurement system gives possibility to automatically measure quantities which have been so far difficult to measure such as dynamic contact angle and instantaneous displacement or total displacement (wetted region in a channel).
  • the invention is not restricted to only measurement of these flow characterics but it can be use for the inspection of all flow phenomena mentioned in the present description or covered by the enclosed claims.

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  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Fluid Mechanics (AREA)
  • Analytical Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Electromagnetism (AREA)
  • Engineering & Computer Science (AREA)
  • Aviation & Aerospace Engineering (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)

Abstract

L'invention porte sur un procédé pour contrôler un système microfluidique, un moyen d'imagerie servant à détecter des changements d'écoulement de fluide dans un système microfluidique. L'écoulement de fluide dans le système microfluidique est contrôlé au moyen de la vision.
PCT/FI2009/050557 2008-06-23 2009-06-23 Procédé et appareil pour contrôler l'écoulement d'un fluide dans un système microfluidique WO2010007210A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FI20085628 2008-06-23
FI20085628A FI20085628L (fi) 2008-06-23 2008-06-23 Menetelmä ja laitteisto nestevirtauksen tutkimiseksi mikrofluidistisessa järjestelmässä

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WO2010007210A1 true WO2010007210A1 (fr) 2010-01-21

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GR20110100390A (el) * 2011-07-05 2013-02-25 Micro2Gen Ε.Π.Ε. Μικροσυστηματα Μικροροης Για Γενετικες Αναλυσεις Και Μοριακη Διαγνωστικη, Ολοκληρωμενο συστημα οπτικου ελεγχου, ποσοτικης και ποιοτικης μετρησης ροης σε μικροροϊκα κυκλωματα
GR20130100091A (el) * 2013-01-31 2014-09-01 Micro2Gen Μικρο-Συστηματα Μικρο-Ροης Για Γενετικους Ελεγχους Και Μοριακη Διαγνωστικη Ε.Π.Ε., Ολοκληρωμενο συστημα ανιχνευσης βιολογικων συστατικων, με οπτικο ελεγχο και χρηση μικροροϊκων κυκλωματων
WO2018200061A1 (fr) * 2017-04-26 2018-11-01 Lawrence Livermore National Security, Llc Commande automatisée de dispositifs microfluidiques basée sur un apprentissage automatique
EP3381556B1 (fr) * 2017-01-23 2020-06-17 Testo SE & Co. KGaA Procédé de caractérisation d'un transport d'un liquide transparent, dispositif de caractérisation de transport de liquide correspondant et matériel de support correspondant
RU2794420C1 (ru) * 2022-01-27 2023-04-17 федеральное государственное автономное образовательное учреждение высшего образования "Тюменский государственный университет" Устройство для измерения динамического угла смачивания в канале

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113155409B (zh) * 2021-02-10 2024-03-22 西安交通大学 一种微间隙高速流体空化观测装置

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07175934A (ja) * 1993-12-17 1995-07-14 Tokyo Gas Co Ltd 流体の画像処理解析装置
US6581438B1 (en) * 2002-01-31 2003-06-24 Sandia Corporation Capillary test specimen, system, and methods for in-situ visualization of capillary flow and fillet formation
US6653651B1 (en) * 1998-12-09 2003-11-25 Carl D. Meinhart Micron resolution particle image velocimeter
DE102005036106A1 (de) * 2004-10-30 2006-05-04 Korea Institute Of Science And Technology (Kist) Verfahren und Vorrichtung zum Bestimmen des Geschwindigkeitsprofils einer verdünnten Suspension in einem Mikrofluidik-Kanal
US7210937B1 (en) * 2002-05-23 2007-05-01 Surya Raghu Method and apparatus for microfluidics education
US20080041722A1 (en) * 2005-04-22 2008-02-21 Pal Ormos Method and device for controlling electoosmotic flow by using light

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07175934A (ja) * 1993-12-17 1995-07-14 Tokyo Gas Co Ltd 流体の画像処理解析装置
US6653651B1 (en) * 1998-12-09 2003-11-25 Carl D. Meinhart Micron resolution particle image velocimeter
US6581438B1 (en) * 2002-01-31 2003-06-24 Sandia Corporation Capillary test specimen, system, and methods for in-situ visualization of capillary flow and fillet formation
US7210937B1 (en) * 2002-05-23 2007-05-01 Surya Raghu Method and apparatus for microfluidics education
DE102005036106A1 (de) * 2004-10-30 2006-05-04 Korea Institute Of Science And Technology (Kist) Verfahren und Vorrichtung zum Bestimmen des Geschwindigkeitsprofils einer verdünnten Suspension in einem Mikrofluidik-Kanal
US20080041722A1 (en) * 2005-04-22 2008-02-21 Pal Ormos Method and device for controlling electoosmotic flow by using light

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
CHAN, WK. ET AL.: "Surface-tension-driven liquid-liquid displacement in a capillary", JOURNAL OF MICROMECHANICS AND MICROENGINEERING, vol. 15, 2005, pages 1722 - 1728 *
CHEN, JM. ET AL.: "Analysis and experiment of capillary valves for microfluidics on a rotating disk", MICROFLUID NANOFLUID, vol. 4, 2008, pages 427 - 437 *
CHEN, JM. ET AL.: "Analysis and measurement of mixing in pressure-driven microchannel flow", MICROFLUID NANOFLUID, vol. 2, 2006, pages 455 - 469 *
CHO, H. ET AL.: "Capillary passive valve in microfluidic systems", TECHNICAL PROCEEDINGS OF THE 2004 NSTI NANOTECHNOLOGY CONFERENCE AND TRADE SHOW, vol. 1, - 2004, pages 263 - 266 *
WANG, C. ET AL.: "Interface control of pressure-driven two-fluid flow in microchannels using electroosmosis", JOURNAL OF MICROMECHANICS AND MICROENGINEERING, vol. 15, 2005, pages 2289 - 2297 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GR20110100390A (el) * 2011-07-05 2013-02-25 Micro2Gen Ε.Π.Ε. Μικροσυστηματα Μικροροης Για Γενετικες Αναλυσεις Και Μοριακη Διαγνωστικη, Ολοκληρωμενο συστημα οπτικου ελεγχου, ποσοτικης και ποιοτικης μετρησης ροης σε μικροροϊκα κυκλωματα
GR20130100091A (el) * 2013-01-31 2014-09-01 Micro2Gen Μικρο-Συστηματα Μικρο-Ροης Για Γενετικους Ελεγχους Και Μοριακη Διαγνωστικη Ε.Π.Ε., Ολοκληρωμενο συστημα ανιχνευσης βιολογικων συστατικων, με οπτικο ελεγχο και χρηση μικροροϊκων κυκλωματων
EP3381556B1 (fr) * 2017-01-23 2020-06-17 Testo SE & Co. KGaA Procédé de caractérisation d'un transport d'un liquide transparent, dispositif de caractérisation de transport de liquide correspondant et matériel de support correspondant
WO2018200061A1 (fr) * 2017-04-26 2018-11-01 Lawrence Livermore National Security, Llc Commande automatisée de dispositifs microfluidiques basée sur un apprentissage automatique
US10408852B2 (en) 2017-04-26 2019-09-10 Lawrence Livermore National Security, Llc Automated control of microfluidic devices based on machine learning
US11061042B2 (en) 2017-04-26 2021-07-13 Lawrence Livermore National Security, Llc Automated control of microfluidic devices based on machine learning
RU2794420C1 (ru) * 2022-01-27 2023-04-17 федеральное государственное автономное образовательное учреждение высшего образования "Тюменский государственный университет" Устройство для измерения динамического угла смачивания в канале

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Publication number Publication date
FI20085628L (fi) 2009-12-24
FI20085628A0 (fi) 2008-06-23

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