WO2011120169A1 - Dispositif microfluidique et système à élément de couplage optique évanescent - Google Patents

Dispositif microfluidique et système à élément de couplage optique évanescent Download PDF

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Publication number
WO2011120169A1
WO2011120169A1 PCT/CA2011/050176 CA2011050176W WO2011120169A1 WO 2011120169 A1 WO2011120169 A1 WO 2011120169A1 CA 2011050176 W CA2011050176 W CA 2011050176W WO 2011120169 A1 WO2011120169 A1 WO 2011120169A1
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Prior art keywords
coupling element
optical
channel
aperture
optical coupling
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PCT/CA2011/050176
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English (en)
Inventor
Jesse Greener
Eugenia Kumacheva
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The Governing Council Of The University Of Toronto
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Publication of WO2011120169A1 publication Critical patent/WO2011120169A1/fr

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    • 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
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55—Specular reflectivity
    • G01N21/552—Attenuated total reflection
    • 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
    • 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
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/648—Specially adapted constructive features of fluorimeters using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
    • 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
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0654—Lenses; Optical fibres
    • 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
    • B01L2300/0822—Slides
    • 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
    • B01L2300/00—Additional constructional details
    • B01L2300/16—Surface properties and coatings
    • B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
    • B01L2300/163—Biocompatibility
    • 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
    • G01N21/01—Arrangements or apparatus for facilitating the optical investigation
    • G01N21/03—Cuvette constructions
    • G01N2021/0346—Capillary cells; Microcells
    • 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
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N2021/3595—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using FTIR

Definitions

  • This invention relates to microfluidic devices and systems, and more particularly, the invention relates to the use of microfluidics for the optical probing of fluids and fluidic reactions.
  • Microfluidic synthesis offers new research opportunities in synthetic chemistry, owing to excellent control of reaction conditions, reduced consumption of reagents, the ability to conduct continuous multi-step reactions without exposure of reactive intermediates to ambient conditions, and the capability to carry out many reactions in a parallel manner. 1 "4 Rapid optimization of
  • formulations can be achieved by screening the effect of reaction variables, e.g., reagent concentrations, types of catalysts, or the amount of energy applied to the system. 4"8 These applications require in situ (on-chip) characterization of the concentration of reactants or products at a particular time of the reaction.
  • a microfluidic apparatus comprising a substrate having formed therein a microfluidic channel, a sealing layer adhered to the substrate, the sealing layer forming an upper surface of the microfluidic channel, an inlet and outlet for flowing a fluid in the channel, an aperture formed within a portion of the sealing layer exposing a portion of the channel, and an optical evanescent coupling element adhered within the aperture, the optical evanescent coupling element comprising a planar coupling surface, wherein the planar coupling surface contacts the substrate and seals the channel within the aperture.
  • the optical evanescent coupling element preferably comprises an attenuated total reflection crystal, surface plasmon resonance element, or diffractive optic.
  • the planar coupling surface may be functionalized with receptors, or may comprise a hydrophobic or hydrophilic surface.
  • the planar coupling surface may be coated with a material having an index of refraction that is different from a refractive index of the optical evanescent coupling element for controlling a refractive index contrast.
  • optical evanescent coupling element may be permanently adhered within the aperture.
  • optical evanescent coupling element is removably adhered within the aperture by a clamping means, where the clamping means preferably provides a force that counteracts a force applied to the planar coupling surface by a pressure within the channel, and more preferably supports a flow rate within the channel in excess of 20 ml/h.
  • the optical evanescent coupling element is preferably supported and protrudes from a base plate, and wherein the clamping means applies a clamping force to the optical evanescent coupling element through the base plate, wherein a thickness of the sealing layer is selected to contact the base plate with the sealing layer under application of the clamping force.
  • the thickness of the sealing layer substantially equals a distance over which the optical evanescent coupling element protrudes from the base plate, or is less than a distance over which the optical evanescent coupling element protrudes from the base plate, and wherein the base plate contacts the sealing layer indirectly through a compressible layer provided between the base plate and the sealing layer.
  • the clamping means may comprise a ring clamp, wherein the ring clamp applies a force between the base plate and a back side of the substrate; a vacuum clamp, wherein the base plate is held against the sealing layer a pressure gradient applied between holes extending through the sealing layer and the substrate; and a magnetic clamp, wherein electromagnetic coils or
  • permanent magnets are integrated within the substrate, and wherein the coils couple with magnetic materials or additional electromagnetic coils connected to the base plate.
  • the channel is preferably directed through one or more bends beneath the aperture. Alternatively, the channel traverses beneath the aperture in two or more locations.
  • the channel preferably contacts the planar coupling surface over at least 40% of an area of the planar coupling surface.
  • a system for measuring an optical signal from a microfluidic channel, the system comprising: an optical source, optical detector, a microfluidic device comprising: a substrate having formed therein a microfluidic channel; a sealing layer adhered to the substrate, the sealing layer forming an upper surface of the microfluidic channel; an inlet and outlet for flowing a fluid in the channel; an aperture formed within a portion of the sealing layer exposing a portion of the channel; and an optical evanescent coupling element adhered within the aperture, the optical evanescent coupling element comprising a planar coupling surface, wherein the planar coupling surface contacts the substrate and seals the channel within the aperture, and optical coupling means for directing an incident optical beam from said optical source onto said optical evanescent coupling element and for directing one of a reflected beam and fluorescence emission from said optical evanescent coupling element onto said detector.
  • the system preferably further comprises a control unit for controlling at least one of said optical source and optical detector, and also preferably comprises a wavelength selective means, wherein said controller further controls said wavelength selective means.
  • the system preferably comprises a
  • the spectrometer that is preferably a Fourier-transform infrared spectrometer, and the detector preferably comprises a non-imaging detector.
  • a method of measuring attenuated total reflection from a fluid within a microfluidic device comprising: a substrate having formed therein a microfluidic channel; a sealing layer adhered to the substrate, the sealing layer forming an upper surface of the microfluidic channel; an inlet and outlet for flowing a fluid in the channel; an aperture formed within a portion of the sealing layer exposing a portion of the channel; and an optical evanescent coupling element adhered within the aperture, the optical evanescent coupling element comprising a planar coupling surface, wherein the planar coupling surface contacts the substrate and seals the channel within the aperture; the method comprising the steps of: directing an incident optical beam onto the optical evanescent coupling element, wherein the optical beam is totally reflected by the planar coupling surface and attenuated by the fluid within the channel; and directing the reflected optical beam onto a detector and measuring a signal; determining the attenuated total reflection by relating the
  • a clamping force is preferably applied to adhere the optical evanescent coupling element within the aperture, and the clamping force is preferably provided with sufficient force to counteract a force applied to the planar coupling surface by a pressure within the channel.
  • An attenuated total reflection spectrum may be measured by varying a wavelength of the incident optical beam.
  • Additional optical measurements may be obtained by varying the angle of incidence and/or the polarization of the incident beam.
  • a method of measuring total internal reflection fluorescence from a fluid within a microfluidic device comprising: a substrate having formed therein a microfluidic channel; a sealing layer adhered to said substrate, said sealing layer forming an upper surface of said microfluidic channel; an inlet and outlet for flowing a fluid in said channel; an aperture formed within a portion of said sealing layer exposing a portion of said channel; and an optical evanescent coupling element adhered within said aperture, said optical evanescent coupling element comprising a planar coupling surface, wherein said planar coupling surface contacts said substrate and seals said channel within said aperture; said method comprising the steps of: directing an incident optical beam onto said optical evanescent coupling element, wherein said incident optical beam optically excites a fluorescent species within said channel; and directing fluorescence emission from said fluorescent species onto a detector and measuring a signal.
  • Figure 1 illustrates a microfluidic device having an aperture for housing an optical evanescent coupling element, where (a) shows an overhead view of the device, (b) shows a cross-sectional detailed view of the aperture, and (c) shows an optical evanescent coupling element housed within the aperture, thereby sealing the microfluidic channel.
  • Figure 2 provides a schematic of an ATR-FTIR system including a microfluidic device.
  • Figure 3 shows a schematic of a microfluidic device incorporating a T- junction, a reaction compartment, and an ATR characterization region.
  • a zoomed inset of the ATR-FTIR characterization region shows the geometry of the channel and the circular ATR crystal beneath it. Arrows show the direction of flow of the liquid.
  • Figure 4 is a photograph showing a top view of a fabricated microfluidic device similar to the device illustrated in Figure 2 (but features 2 fluidic inputs), where the device is shown connected to inlet and outlet tubing and interfaced with an ATR crystal apparatus.
  • Figure 5 is a side-view of an ATR crystal interfaced with a single microchannel.
  • the spectrum in (b) was acquired 10 minutes after flow was established through the device. Both spectra (a) and (b) were collected using 16 scans at 10 kHz and 4 cm "1 spectral resolution.
  • Figure 7 plots IR absorption spectra acquired for the solutions of PNIPAm (top spectrum) and PEG (bottom spectrum) at flow rate of the liquids of 3 mL/h. For each solution the presented spectra are the result of averaging five spectra. The concentration of each polymer solution, C p0 i, was 4 wt%,
  • Figure 7(b) plots the variation in the concentration-dependent intensity of the absorption peaks of PNIPAm (1560 cm “1 ) (open circles) and PEG (1085 cm “1 ) (solid squares). The dashed lines are the result of linear fitting.
  • Figure 8 (a) provides composite spectra acquired for the mixed aqueous solution of PNIPAm and PEG.
  • Absorption peaks of PNIPAm and PEG are shown in the spectral regions 1700-1500 cm “1 and 1200-1000 cm “1 , respectively. Arrows show the monitored peaks at 1560 cm “1 (PNIPAm) and 1085 cm “1 (PEG).
  • the ratios of flow rates of the solution of PNIPAm to the solution of PEG were 0/3 (1 ), 0.5/2.5 (2), 1/2 (3), 1 .5/1 .5 (4), 2/1 (5), 2.5/0.5 (6), 3/0 (7).
  • Spectra 1 ⁇ 7 show the change in spectral characteristics of the mixture as the concentration of PNIPAm in the solution increased and the concentration of PEG in the solution decreased.
  • Figure 9 plots in-flow absorbance of 0.48mM (1 .0 wt%) PNIPAm (open circles) and 1 .04 mM (1 .0 wt%) PEG (solid squares) solutions measured for the bands at 1560 cm “1 and 1085 cm “1 , respectively as flow rate (Q) is modulated. Spectra were collected using 16 scans at 10 kHz and 4 cm “1 spectral resolution. Error bars were obtained by determining the standard deviations in absorbance of five independent measurements for each flow rate of the liquids. Dotted lines are the results of linear fitting of the data.
  • the dotted line is the linear fit for C T x-i oo ⁇ 65.
  • the inset shows absorbance in the low concentration region (C TX - I OO ⁇ 10 mM).
  • the dotted line in the inset is the same linear fit from the main figure. Spectra were collected using 16 scans at 10 kHz and 4 cm "1 spectral resolution. Error bars were obtained by measuring the standard deviation from five independent experiments.
  • Figure 11 provides a molecular diagram for (a) the monomer NIPAm and
  • Figure 12 is a schematic of another embodiment of a microfluidic device incorporating a T-junction, a reaction compartment, and an ATR characterization region (scale bar is 1 cm).
  • Figure 13 plots (a) layered spectra acquired during the redox
  • Figure 14 plots (a) the vibrational spectrum collected on-chip showing C0 2 (2346 cm “1 ) and HC0 3 " (1365 cm “1 ) bands, where the C0 3 2" band in pH 12 aqueous phase is shown in (b) and the reappearance of C0 2 and HC0 3 " at lower pH is shown in (c).
  • the terms, “comprises” and “comprising” are to be construed as being inclusive and open ended, and not exclusive. Specifically, when used in this specification including claims, the terms, “comprises” and “comprising” and variations thereof mean the specified features, steps or components are included. These terms are not to be interpreted to exclude the presence of other features, steps or components.
  • exemplary means “serving as an example, instance, or illustration,” and should not necessarily be construed as preferred or advantageous over other configurations disclosed herein.
  • fluid means any fluid comprising a liquid component, including, but not limited to, liquids, mixtures, solvents, suspensions, colloids, and heterogeneous multi-phase systems including bubbles.
  • FIG. 1 (a) provides an overhead view of microfluidic device 10, which comprises inlet 15, outlet 20, and microfluidic channel 25.
  • Channel 25 includes a channel bend 30, which is located below an aperture 35 that locally exposes the channel to the external environment.
  • channel 25 is formed in substrate 50 and is recessed beneath a sealing layer 55 that is locally removed to form aperture 35 above the two channel segments 40 and 45 of bend 30.
  • an optical evanescent coupling element 60 is housed within aperture 35.
  • Optical evanescent coupling element 60 seals channel 25 from the external environment and enables the local optical interrogation of the channel by the evanescent field of an incident optical beam.
  • the optical coupling element is preferably an attenuated total reflection (ATR) crystal.
  • the ATR crystal may comprise a single or multi-bounce crystal.
  • optical coupling element 60 seals microfluidic channel 25 from the external environment. This is achieved by tailoring the area and geometry of aperture 35 to conform to the geometry of optical coupling element 60.
  • Optical coupling element 60 may comprise a wide variety of shapes, provided that inner surface 65 is planar and forms an upper surface for channel 25 within aperture 35.
  • the geometry of the aperture side wall 80 preferably matches that of optical coupling element 60. While it is preferable that the entire aperture is sealed by the coupling element, in some embodiments, the aperture may be sealed by the optical coupling element only for sides of the aperture where the channel crosses the aperture.
  • Figure 1 (c) illustrates an optical coupling element having vertical side walls contacting the sealing layer 55
  • optical coupling element 60 may have an angled surface. Accordingly, the slope of side wall 80 may beveled to accommodate such an angled surface.
  • a beveled side wall may be achieved by numerous methods known in the art, including micromachining, molding, and embossing. Additionally, sealing means known in the art such as o-rings may be provided within aperture 35 to further assist in the sealing of channel 25 by optical coupling element 60.
  • the optical coupling element allows for the optical evanescent probing of liquid flowing through channel 25 without distorting or altering the local fluidic environment.
  • the attenuated total reflection may be measured by directing an incident optical beam 70 from the optical source onto the optical coupling element 60 such that the incident optical beam is totally internally reflected at the interface between the coupling element while being subjected to absorption via evanescent coupling to the fluid within channel 25.
  • the reflected optical beam 75 is then directed onto the detector, the attenuated total reflection may be determined by normalizing the detected signal to a known calibration value, such as the signal obtained in the absence of the sample when the optical beam is directly incident on the detector (or reflected using a standard reflector), or the signal obtained from a reference material within the channel.
  • optical coupling element forms the upper surface of channel 25 within the aperture 35 without altering the channel dimensions, the properties of the fluid (such as Reynolds number) are unchanged by the presence of the optical coupling element. This is highly beneficial for probing in situ reaction kinetics and/or flow characteristics (in particular, this is believed to be the source of the flow rate independence of absorption intensity shown in Figure 9).
  • the optical coupling element may be coated with a thin (less than the penetration depth of the evanescent light) layer of the material from which the sealing layer is comprised, whereby the channel material is preserved in the detection region in addition to the channel dimensions.
  • the channel geometry within the aperture region may comprise a straight channel, but is preferably selected to provide a large relative surface area for optical interrogation. In Figure 1 , this is achieved with a single bend. It is to be understood that the optimization of the channel geometry may be achieved by a wide range of channel geometries.
  • the channel geometry may include a serpentine structure comprising multiple bends.
  • the channel geometry may include several closely spaced parallel channels, with bends external to the aperture region, to provide a high channel packing fraction within the aperture region.
  • Embodiments of the present invention provide the benefit of only requiring the optical probing of a microfluidic device locally, at the location of the aperture. This important benefit allows for the collection of an optical signal from a desired location with optimal signal to noise ratio.
  • the location probed may be downstream from a reaction process or reaction component of the microfluidic device, where it is desirable to collect an optical signal with high sensitivity.
  • the optical coupling element only probes a specific region on microfluidic device, the remaining areas of the microfluidic device are available for the integration of other active fluidic elements, such as fluidic injection ports or valves.
  • microfluidic device 10 shown in Figure 1 comprises only a single channel
  • the microfluidic device may comprises any number of additional fluidic components, including, but not limited to, additional inlets and outlets, mixing networks and chambers, junctions such as T-junctions and flow focusing regions, and valves.
  • additional fluidic components including, but not limited to, additional inlets and outlets, mixing networks and chambers, junctions such as T-junctions and flow focusing regions, and valves.
  • additional fluidic components including, but not limited to, additional inlets and outlets, mixing networks and chambers, junctions such as T-junctions and flow focusing regions, and valves.
  • the microfluidic device may comprise more than one aperture and optical evanescent coupling element for probing more than one location on the microfluidic device.
  • the optical coupling element 60 has an inner surface 65 that is larger in width than the width of the microfluidic channel 25. It is, however, to be understood that the optical coupling element may comprise a distal geometry that may protrude into the channel, thereby sealing the channel. In a non-limiting example, such an embodiment may be achieved with a linear channel and an optical coupling element having a shape in the form of a triangular prism, where one longitudinal vertex of the prism protrudes into and seals the channel.
  • optical coupling element 60 may be permanently adhered to microfluidic device 10 by an adhesive or other retaining mechanism.
  • optical coupling element 60 is removably adhered to microfluidic device 10 within aperture 35 by a clamping mechanism that counteracts the force of fluid flowing within the channel 25 on the inner surface 65 of optical coupling element 60. Accordingly, provided that a sufficiently high clamping force is provided, high flow rates of fluid through the channel may be achieved without leakage.
  • Various clamping mechanisms may be employed to achieve the desired retaining force. Preferred clamping mechanisms include, but are not limited to, ring clamps, an external lever clamp, magnetic clamping, and vacuum clamping.
  • optical coupling element is housed in or on a support having a base plate, in which the base plate has a bottom surface that is parallel to the inner surface 65 of the optical coupling element.
  • the base plate thus provides a broad surface over which pressure can be applied to the optical coupling element.
  • the optical coupling element protrudes over a short (e.g. sub-millimeter) offset distance from the base plate, and the thickness of the sealing layer 55 is chosen to be equal to the offset distance. This enables the base plate surface to contact the outer surface of the sealing layer when the coupling element is secured within the aperture.
  • the thickness of sealing layer 55 may be chosen to be less than the offset distance, and an additional compressible layer may be included between the base plate and sealing layer 55 in order to obtain a consistent and reliable seal.
  • Materials that can be used to form substrate 50 housing the channels and sealing layer 55 include elastomers, but are preferably, materials with sufficient hardness to resist the distortion of the microfluidic channel when optical coupling element 60 is clamped to microfluidic device 10, such as, hard plastics, metals, ceramics, glasses.
  • substrate 50 may be imprinted with the fluidic features and can form a bond between the imprinted and sealing 55 layers.
  • Imprinting can be accomplished by techniques including, but not limited to, hot embossing, injection molding, laser ablation and end milling.
  • Bonding to a sealing layer has been achieved by low temperature bonding after exposure of the imprinted layer and/or the sealing layer to liquid-phase solvents or plasma gas, as described in J. Greener, W. Li, J. Ren, D. Voicu, V. Pakharenko, T. Tang and E. Kumacheva, Lab Chip, 2010, 10, 522-524, which is incorporated herein by reference in its entirety.
  • Other methods include exposure of imprinted layer and/or sealing layer to solvent vapours or UV light to achieve surface activation and subsequent low-temperature bonding or purely thermal bonding at temperatures very close to the glass transition temperature of the thermoplastic materials.
  • the optical properties of microfluidic device 10 and the optical coupling element 60 are preferably selected such that light reflected back to the detector has minimized interaction with material. This may be accomplished by reducing the difference between the index of refraction of the optical coupling element and substrate 50, and/or modifying the angle of incidence of light incident on optical coupling element 60, such that light passing into substrate 50 as opposed to light passing into liquid filled microchannels, escapes from the microfluidic device and does not propagate to the detector.
  • this may be achieved by increasing the index of refraction contrast and/or modifying the angle of incidence of light incident on optical coupling element 60 such that light passing into substrate 50 (as opposed to light passing into liquid filled microchannels) is reflected to the detector with as little interaction with material as possible.
  • the index contrast may be tailored by applying a coating to either the optical coupling element or the microfluidic device material.
  • the apparatus shown in Figure 1 forms a component of a measurement system such as an attenuated total reflection measurement system that further comprises an optical source 100, optical detector 1 10, and preferably further includes a control unit 120 as shown in Figure 2 for processing signals detected by the optical detector.
  • the system also includes optical elements for directing the incident beam from the source to the optical coupling element (not shown), and optical components for receiving a reflected or emitted beam and directing the reflected or emitted beam to the detector (not shown).
  • Exemplary but non-limited optical components include lenses, mirrors, and fiber optics.
  • the system comprises a total internal reflection fluorescence system, in which incident light excites a fluorescent species within the channel, and the emitted fluorescence is collected and directed to the detector.
  • the system may further comprise a spectral device for the measurement of an optical spectrum .
  • exemplary yet non-limiting spectral devices include monochromators, diffraction gratings, and scanning interferometers.
  • Control 120 unit may include a processor, and may comprise an internal processor within a spectroscopy system or may additionally or alternatively comprise an external computer.
  • the optical beam is may be delivered to and from the optical coupling element 60 by optical fibers (not shown).
  • optical detector 1 10 is a single detector that integrates the net signal from the received optical beam.
  • the system comprises a spectrometer-ATR system 130, such as an ATR-FTIR (Fourier Transform Infrared Spectrometer) in which the optical source 100, optical detector 1 10 and control unit 120 comprise an FTIR system 130.
  • a spectrometer-ATR system 130 such as an ATR-FTIR (Fourier Transform Infrared Spectrometer) in which the optical source 100, optical detector 1 10 and control unit 120 comprise an FTIR system 130.
  • Attenuated Total Reflection Fourier Transform Infrared spectroscopy is a well-established analytical tool applicable to spectral
  • c is the analyte concentration (M)
  • / is the path length (cm)
  • ⁇ is the wavelength-dependant molar extinction coefficient (M ⁇ 1 cm "1 ).
  • ATR-FTIR path length for ATR-FTIR is typically only a few microns in the mid-IR spectral range, with its exact value being determined by the wavelength of light, the angle of incidence and the indices of refraction of the ATR crystal and the medium being probed.
  • ATR overcomes the major limitation of conventional transmission FTIR: the dramatic reduction of transmission for strongly absorbing carrier-phase liquids (e.g., water) for path lengths exceeding 10-20 ⁇ .
  • carrier-phase liquids e.g., water
  • ATR-FTIR path length e.g., by using a lower index of refraction ATR crystal, by interfacing a larger, multiple reflection, ATR crystal with the microfluidic device (thereby probing a longer segment of the microchannel), and by implementing a purge gas or vacuum system to reduce interference from water vapour and C0 2 along the optical path within the spectrometer.
  • optical coupling element may support alternative detection methods.
  • optical coupling element 60 may alternatively be a surface plasmon resonance crystal.
  • optical coupling element 60 may be a diffractive optical element.
  • an optical beam incident on optical coupling element 60 may comprise additional frequencies of light that are selected to pass through the coupling element (for example, frequencies in the UV/Vis/NIR range), whereby such additional frequencies may be useful in probing different properties of the material(s) in the channel (i.e., vibrational vs. electronic) and/or at different penetration depths due to the frequency-dependence of the evanescent field depth.
  • additional frequencies of light for example, frequencies in the UV/Vis/NIR range
  • an internal surface of optical coupling element 60 namely the surface in fluidic contact with liquid contained within channel 25, may further comprise an activated or functionalized surface layer.
  • the internal surface may be activated with a species or
  • the internal surface may be functionalized with a receptor such as, but not limited to, an antibody, nucleic acid probe, or aptamer.
  • Example 1 Microfluidic System with Integrated ATR Probe
  • FIGs 3 and 4 An exemplary yet non-limiting embodiment is shown in Figures 3 and 4, which provide a schematic and a photograph (top view), respectively, of a microfluidic device 200 with a built-in ATR-probe.
  • the device consists of inlets 205 and 210 for the supply of a one-phase liquid medium, or multiple miscible or immiscible liquid phases, a mixing and/or reaction compartment 215, the ATR probe zone 220, and outlet 240.
  • Exemplary designs of the inlets include a T-junction (shown at 225) or a flow-focusing geometry, as shown in Figures 3 and 4, respectively, so that droplets or bubbles can be introduced in the microfluidic device.
  • the microchannel 250 in the ATR zone 220 includes a serpentine geometry in order to maximise the area of interface between the crystal and the liquid phase (approximately 45% surface coverage of the crystal versus 15% for a straight channel).
  • the entire microfluidic device 200 may be fabricated by an imprinting process in which the fluidic features are imprinted in a cycloolefin polymer (COP) sheet by hot embossing using imprint templates fabricated from photoresist on a metal base as described in co-pending Patent Cooperation Treaty Application No. PCT/CA2010/000144, titled "Method of Producing a Stamp for Hot
  • Figure 5 shows a schematic (not to scale) of the ATR region including microfluidic channel 300, which is formed within the device substrate 305, and passing over the ATR crystal 315. Note that for simplicity, only a single channel is shown and additional channels within the serpentine geometry are not shown.
  • a planar (non-patterned) sealing sheet 320 encloses the microchannel everywhere, except at a circular hole forming an aperture having a diameter equal to that of the ATR crystal (which was 1 .8 mm in the present example).
  • the patterned COP sheet was sealed with either a non-patterned COP sealing sheet using low-temperature thermal bonding or with an adhesive film (HDCIear, Henkel Corp.).
  • the ATR crystal was aligned with the bottom wall of the microchannel, thereby sealing the bottom-side of the microfluidic device.
  • a thin compressible rubbery mat 325 (thickness 100 mm), located between the sealed device and the ATR base-plate 330 assembly, was optionally used to conform to the space between the sealing layer and the ATR base-plate.
  • the ATR crystal 315 was clamped to the device, sealing the channel 300, by a ring clamp 335 containing an internal thread matching an external thread of the ATR base plate 330.
  • the clamp enabled the application of sufficient pressure to the ATR crystal to provide a robust seal, allowing for high flow rates
  • the thickness of the sealing sheet 320 is less than the protrusion distance of the ATR crystal from the base plate, and by including the
  • the base plate was supported under pressure by the compression of the compressible layer between the base plate and the sealing sheet.
  • clamping mechanisms may be used to apply pressure between the ATR crystal and the microfluidic device.
  • an external lever may be employed, or holes may be introduced through the microfluidic device for vacuum clamping to secure the base plate (holes may further extend through the base plate for the application of a vacuum clamping force by an external member).
  • magnetic clamping may be incorporated by integrating electromagnetic coils into the microfluidic device that couple with magnetic materials or electromagnetic coils on or near the base plate.
  • a threaded connector could be integrated into the microfluidic device, into which the ATR base plate could be threaded.
  • ATR crystal accessory (PIKE Tech.) attached to Vertex 70 FTIR spectrometer (Bruker Inc.). Opus 6.5 software was used for data acquisition, manipulation and analysis. Following thermo-embossing, the imprinted polymer sheets were sealed by low-temperature bonding or with an adhesive film. In the case of sealing via adhesive film, it was ensured that the exposed adhesive coating in the channel did not leach into the solution phase during the timeframe of the experiments (ca. 10 minutes) by monitoring the ATR-FTIR spectra acquired from the flowing solution in the microchannels.
  • the spectrum in (b) was acquired 10 minutes after flow was established through the device.
  • Both spectra (a) and (b) were collected using 16 scans at 10 kHz and 4 cm "1 spectral resolution. The strongest and most isolated absorbance peak (1730 cm "1 ) was used to determine the presence of dislodged or dissolved adhesive. No signal from the adhesive could be detected in the TX-100 solutions acquired for this work.
  • Figure 7 is a typical spectrum of a TX-100 solution flowing through the MF device which was sealed with an adhesive film.
  • TX-100 Triton X-100
  • Figure 7(b) shows the variation in intensity of the COC absorption peak (for PEG) and the NH absorption peak (for PNIPAm) for solutions with varying polymer concentrations, C p0 i.
  • the graphs presented in Figure 7(b) can be used as calibration graphs, so that the concentration of PEG or PNIPAm is determined from measured absorbance values.
  • molar extinction coefficients can be determined by replacing A/c in eqn (1 ) with the slopes of the calibration graph in Figure 7(b) (with concentration units changed to mM).
  • FIG. 8(a) shows IR spectra acquired for the mixed polymer solutions with varying concentrations of PNIPAm and PEG. Two monitored peaks are indicated with arrows. Spectra 1 ⁇ 7 show, as expected, that progressive growth in the intensity of absorption of PNIPAm was accompanied by the reduction in absorbance of PEG.
  • Figure 8(b) shows the variation in absorbances of PNIPAm and PEG (corresponding to the spectra in Figure 8(a)), with the polymer concentrations in the mixture, C PE G,m and C PN iPAm,m- For each polymer, the relationship between absorbance and polymer concentration remained linear. Furthermore, for each polymer in the mixed solution, the slopes of the variation of absorbance vs.
  • D and A are the length and cross-sectional area, respectively, of microchannel in which the reaction takes place and Q (mL/s) is the volumetric flow rate of the liquid.
  • the ATR-FTIR is a technique inherently sensitive to the adsorption of solutes to the surface of the ATR crystal
  • the applicability of the described method to the differentiation of adsorbed and dissolved molecules was examined. This was achieved by monitoring the concentration-dependent absorbance of the aqueous solution of a non-ionic surfactant Triton X-100 (TX- 100).
  • Figure 10(a) shows the absorption spectrum in the region of 1400-900 cm “1 .
  • Figure 10(b) focuses on the dominant band at 1 100 cm “1 and plots the variation of its absorbance vs.
  • Example 2 Monitoring of In-Situ Polymerization
  • embodiments of the present disclosure are adapted for the in-situ (on-chip) monitoring of the kinetics of polymerization reaction, where the optical monitoring was performed using infrared (IR) spectroscopy.
  • the present study involved an exemplary polymerization reaction of /V-isopropylamide in water, which was initiated by ammonium persulfate (APS) and ⁇ , ⁇ , ⁇ ', ⁇ '- tetramethylethylenediamine (TEMED) to form poly-NIPAm.
  • APS ammonium persulfate
  • TEMED ⁇ , ⁇ , ⁇ ', ⁇ '- tetramethylethylenediamine
  • the results presented below demonstrate the ability to rapidly examine the effect of the concentration of APS, TEMED and NIPAm and the effect of pH of the solution on the kinetics of polymerization.
  • Figure 1 1 in which a molecular diagram is provided for (a) the monomer NIPAm and (b) the
  • Figure 12 show schematic of the microfluidic device 400 that incorporates a mixing region 410, reaction region 420 and detection region 430.
  • Inlets 435- 450 carry reagents APS, TEMED, NIPAm and water (for dilutions). Reaction time was controlled by modulating the total volumetric flow rate of the reagent streams while keeping their flow rate ratios constant.
  • ATR-FTIR spectra that were acquired in detection region 430 after different times on chip are show in Figure 13(a).
  • C0 2 carbon dioxide
  • water water
  • HC0 3 ⁇ bi-carbonate
  • C0 3 2 ⁇ carbonate
  • H 2 C0 3 carbonic acid
  • the present example demonstrates the ability to differentiate between these states using an integrated ATR-FTIR microfluidic apparatus.
  • Figure 14(a) shows the bands associated with aqueous CO 2 (2343 cm “1 ) and the distinctive asymmetric bicarbonate band (1365 cm “1 ).

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Abstract

La présente invention concerne un dispositif microfluidique conçu pour mesurer localement une réflexion totale atténuée à partir d'un canal microfluidique. Le dispositif comprend un substrat dans lequel un canal microfluidique est formé et rendu étanche au moyen d'une couche d'étanchéité collée au substrat. Il comprend en outre une entrée et une sortie fluidiques. Une partie de la couche d'étanchéité est retirée, ce qui expose le canal et forme une ouverture, partie à laquelle est fixée une surface de couplage d'un élément de couplage optique évanescent. La surface de couplage rend le canal étanche à l'intérieur de l'ouverture et permet le sondage optique d'un fluide à l'intérieur du canal au moyen du champ évanescent d'un faisceau optique réfléchi par la surface de couplage. Le dispositif est de préférence utilisé dans un système comprenant un spectromètre destiné à la mesure d'un spectre de réflexion totale atténuée.
PCT/CA2011/050176 2010-03-31 2011-03-31 Dispositif microfluidique et système à élément de couplage optique évanescent WO2011120169A1 (fr)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022177940A1 (fr) * 2021-02-16 2022-08-25 Si-Ware Systems Dispositif intégré de détection spectrale d'ondes évanescentes
WO2023069453A1 (fr) * 2021-10-18 2023-04-27 The Board Of Trustees Of The Leland Stanford Junior University Procédés de quantification de l'hydratation du dioxyde de carbone dans des solutions aqueuses
US11953377B2 (en) 2021-02-16 2024-04-09 Si-Ware Systems Integrated evanescent wave spectral sensing device
US12005444B2 (en) 2018-07-09 2024-06-11 Presens Precision Sensing Gmbh System for analysis of a fluid sample

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009112038A2 (fr) * 2008-03-14 2009-09-17 Scandinavian Micro Biodevices Aps Système microfluidique et procédé de réalisation d'un test
US20090261086A1 (en) * 2008-03-21 2009-10-22 Neil Reginald Beer Laser Heating of Aqueous Samples on a Micro-Optical-Electro-Mechanical System
US20090285719A1 (en) * 2006-06-26 2009-11-19 Life Technologies Corporation Compressible Transparent Sealing for Open Microplates

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090285719A1 (en) * 2006-06-26 2009-11-19 Life Technologies Corporation Compressible Transparent Sealing for Open Microplates
WO2009112038A2 (fr) * 2008-03-14 2009-09-17 Scandinavian Micro Biodevices Aps Système microfluidique et procédé de réalisation d'un test
US20090261086A1 (en) * 2008-03-21 2009-10-22 Neil Reginald Beer Laser Heating of Aqueous Samples on a Micro-Optical-Electro-Mechanical System

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12005444B2 (en) 2018-07-09 2024-06-11 Presens Precision Sensing Gmbh System for analysis of a fluid sample
WO2022177940A1 (fr) * 2021-02-16 2022-08-25 Si-Ware Systems Dispositif intégré de détection spectrale d'ondes évanescentes
US11953377B2 (en) 2021-02-16 2024-04-09 Si-Ware Systems Integrated evanescent wave spectral sensing device
WO2023069453A1 (fr) * 2021-10-18 2023-04-27 The Board Of Trustees Of The Leland Stanford Junior University Procédés de quantification de l'hydratation du dioxyde de carbone dans des solutions aqueuses

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