WO2019206779A1 - Surveillance d'une propriété d'un fluide pendant un processus d'écoulement - Google Patents

Surveillance d'une propriété d'un fluide pendant un processus d'écoulement Download PDF

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Publication number
WO2019206779A1
WO2019206779A1 PCT/EP2019/060002 EP2019060002W WO2019206779A1 WO 2019206779 A1 WO2019206779 A1 WO 2019206779A1 EP 2019060002 W EP2019060002 W EP 2019060002W WO 2019206779 A1 WO2019206779 A1 WO 2019206779A1
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WO
WIPO (PCT)
Prior art keywords
fluid
flow
unit
electromagnetic radiation
tube
Prior art date
Application number
PCT/EP2019/060002
Other languages
English (en)
Inventor
Gabriel GLOTZ
Christian KAPPE
Original Assignee
Research Center Pharmaceutical Engineering Gmbh
Karl-Franzens-Universität Graz
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 Research Center Pharmaceutical Engineering Gmbh, Karl-Franzens-Universität Graz filed Critical Research Center Pharmaceutical Engineering Gmbh
Publication of WO2019206779A1 publication Critical patent/WO2019206779A1/fr

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Classifications

    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/20—Measuring; Control or regulation
    • B01F35/21—Measuring
    • B01F35/213—Measuring of the properties of the mixtures, e.g. temperature, density or colour
    • 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
    • G01N2021/8405—Application to two-phase or mixed materials, e.g. gas dissolved in liquids

Definitions

  • the invention relates to a flow apparatus for monitoring a property of a fluid during a flow process.
  • the invention relates to a system for supplying a fluid and monitoring a property of the fluid during a flow process.
  • the invention relates to a method for monitoring a property of a fluid during a flow process.
  • Photochemical and/or photophysical processes are initiated by the absorption of a photon of electromagnetic radiation, e.g. visible or ultraviolet radiation, which leads to photometry as a technique of measuring light intensity.
  • Applications for measuring the light intensity are for example a photomultiplier tube and a photodiode.
  • techniques of photometry are used as process analytical technologies, for example for concentration measurements.
  • a flow apparatus for monitoring a property of a fluid during a flow process comprises a flow unit which comprises a fluid inlet for receiving the fluid, a fluid outlet for releasing the fluid, wherein the fluid outlet is arranged opposite to the fluid inlet, an electromagnetic radiation inlet for receiving primary electromagnetic radiation, and an electromagnetic radiation outlet for transmitting secondary electromagnetic radiation, generated by an interaction between the primary electromagnetic radiation and the fluid.
  • the flow apparatus comprises a tube extending through the flow unit from the fluid inlet to the fluid outlet, wherein the fluid is transportable through the tube from the fluid inlet to the fluid outlet.
  • the flow unit and the tube may be configured so that the flow unit and the tube are movable relative to one another, wherein in particular the flow unit may be spatially movably arranged at the tube.
  • a system for supplying a fluid and monitoring a property of the fluid during a flow process comprises a flow apparatus according to the first embodiment of the invention, and a supply apparatus configured to supply the fluid, a monitoring apparatus configured for monitoring the property of the fluid during supplying the fluid by the supply apparatus.
  • the monitoring apparatus is configured for monitoring the property of the fluid simultaneously with and during the flow process using electromagnetic radiation.
  • a method for monitoring a property of a fluid during a flow process comprises supplying a fluid to a flow apparatus according to the first embodiment of the invention, and monitoring the fluid in the flow apparatus by a monitoring apparatus.
  • the monitoring of the fluid may be done simultaneously with and during the flow process using electromagnetic radiation.
  • exemplary embodiments of the invention provide a flow apparatus, a system, and a method for monitoring main factors which are involved (and in particular relevantly involved) in a flow process of the fluid using electromagnetic radiation.
  • exemplary embodiments of the invention allow for a deeper understanding of a flow process and the components and properties of the flow process relating to fluidic medium.
  • exemplary embodiments of the invention provide a monitoring and measurement system for flow systems, which is able for monitoring an in-line analysis and which may be set and optimized by a user according to specific experimental requirements during a flow process. This may be accomplished by configuring a flow unit and a tube to be mutually spatially movable so that a user is enabled with the freedom to use the flow unit substantially anywhere where a tube is present through which a fluid (such as a fluid sample) flows.
  • a fluid such as a fluid sample
  • the term "property of the fluid” may particularly denote any measurable attribute of a fluid, in particular of a flowing fluid.
  • the property of the fluid may be any fluid attribute which is measureable by light measurements.
  • a property of a fluid may be a concentration of the fluid and its components, an absorption characteristics of the fluid, a mass transfer of the fluid, a residence time distribution of fluid particles, etc.
  • flow process may particularly denote the process or a status of a fluid in the flow apparatus, wherein the flow process may be static or in flow.
  • the apparatus and/or the system may measure a static flow or a moving flow, which depends on the behavior of the fluid inside the flow apparatus and/or the system.
  • the flow process itself takes part inside the space in which the fluid is flowing.
  • the flow process takes part inside the tube of the flow apparatus.
  • the term "movable" may particularly denote that the flow unit may change the position at the tube, such that the monitoring and/or the measurement may be conducted at an adjustable position or even at different positions at and/or along the tube.
  • the flow unit can be movably arranged along the flow path of the fluid, wherein the flow path may be located inside of the tube.
  • the flow unit may be moved manually or automatically, in particular the flow unit may be moved by a user conducting the test and/or it may be moved by an automated apparatus such as a processor-controlled electric motor.
  • the term “simultaneously with and during” may particularly denote that the monitoring may be done while the flow process is running, i.e. while the fluid is supplied inside the tube of the flow apparatus and further while the fluid has a static or a moving state and/or while the fluid is changing the state. Further, by conducting the monitoring simultaneously with and during the flow process an in- line monitoring and/or measurement of the property of the flow process may be achieved. In an embodiment, the monitoring is conducted by an in-line process. In the context of the present application, the term “in-line process” may particularly denote a measurement during which the fluid is not removed from the process flow, e.g. process stream, during the analysis (and which can be invasive or noninvasive).
  • the process of removing the fluid may be denoted as “off-line” process, where the fluid is analyzed outside the flow apparatus and/or the system (i.e. in particular not in situ).
  • the term “on-line” denotes a measurement during which the fluid is diverted from the flow process, and may be returned to the flow process thereafter.
  • the term “at-line” denotes a measurement where the fluid is removed, isolated from, and analyzed in close proximity to the flow process.
  • exemplary embodiments of the invention are also compatible with an on-line process or an at-line process
  • execution of the method in terms of an in-line process is particularly preferred, because this allows obtaining the desired information (in particular simultaneously with a flow process) substantially without disturbing a process flow, substantially in real time and with a small time loss.
  • the monitoring of a property of the fluid during the flow process may be performed by a monitoring apparatus configured for monitoring the property.
  • the monitoring apparatus may be located at the flow apparatus in such manner that the fluid may be monitored while the flow process takes place or is still in progress and also while the flow process is static, e.g. not in process. In other words, it may be rendered unnecessary to interrupt a flow process or to finish the supply of the fluid in order to monitor, to study or determine a property of the fluid and/or the fluid behavior.
  • it may be an advantage of the described apparatus, system and method that a property of a fluid and/ or a behavior of the fluid can be monitored or determined while the flow process is still in process.
  • the described method may provide the advantage that a reference model may be omitted and the property of the fluid and/or the behavior of the fluid may be directly determined during the flow process of the fluid.
  • the flow apparatus may be applicable with low effort and for routine in-line analysis. Further, the flow apparatus is simple and easy to use, such that a good accuracy for in-flow measurements may be achieved.
  • the system may be used as a spectrophotometer for continuous flow micro reactor systems, wherein the system may have the ability to measure in particular medium intensity light sources, which may offer an advantage over conventional photometers having low light signal intensity.
  • the free mobility between flow unit and tube offers a high flexibility in using the system.
  • the described system and the described flow apparatus may fulfil the need to determine the chemical composition of the reaction mixture at any given moment and at any given position inside the flow apparatus, in particular inside the flow reactor. This information may be used to generate feedback loops which may control the mixer/reactor performance.
  • the electromagnetic radiation inlet and the electromagnetic radiation outlet may be coplanar and may be arranged opposite to each other at the flow unit, such that the electromagnetic radiation is transmitted through the flow unit. Based on this arrangement a transmission measurement may be realized, wherein electromagnetic radiation will be transmitted from the electromagnetic radiation inlet to the electromagnetic radiation outlet only in one way. Further, the electromagnetic radiation inlet and the electromagnetic radiation outlet may be arranged at the same position at the flow unit, wherein they may be arranged coplanar at the same position. According to this arrangement the electromagnetic radiation is reflected in the flow unit. Hence, with this arrangement a measurement may be realized in which reflected or backscattered electromagnetic radiation is measured by the detection unit.
  • Electromagnetic radiation transmitted from the inlet will be reflected and/or backscattered because of an interaction with the fluid and will be therefore re- transmitted to the outlet/inlet such that the electromagnetic radiation has to pass the way from the inlet to the outlet twice or in a bidirectional manner.
  • the electromagnetic radiation inlet, the electromagnetic radiation outlet, the fluid inlet and the fluid outlet may be arranged in a specific shape at the flow unit, in particular they are arranged in a cross shape at the flow unit. More particularly, they may be arranged coplanar, i.e. within a common plane, having a cross shape.
  • a cross shape may be formed in such a manner that an angle between each respective fluid inlet, fluid outlet, electromagnetic radiation inlet, and electromagnetic radiation outlet is about 90 degrees.
  • each arm of the cross shape is formed by a respective fluid inlet, fluid outlet, electromagnetic radiation inlet, and electromagnetic radiation outlet.
  • the flow unit is movable along the tube, such that the flow unit is selectively positionable at different positions at the tube.
  • the different positions may be adjusted by a continuous movement of the flow unit along the tube or by a stepwise movement of the flow unit along the tube.
  • the flow unit may be displaced relative to the tube within a range of at least one millimeter or even at least one centimeter.
  • the flow unit may be moved independently and freely (in particular without any fixing mechanism) such that the flow unit does not need to be fixed by any means to the tube. Due to the flexible design and movability of the flow unit the flow unit may be arrangeable at any position between opposing ends of the tube.
  • the flow unit is a flow cell, wherein the flow cell may be designed with a cross mixer.
  • the flow unit may comprise a shielding cover.
  • the cover may be configured to shield the flow cell from an environmental light interfering with the fluid.
  • the cover may be made from an aluminum foil and black tape, other materials for the cover may also be possible which allow a protection from environmental light which would disturb the monitoring of the fluid property.
  • the flow unit is movable relative to the tube to thereby selectively adjust a spatial relation between the flow unit and the tube.
  • the spatial movement adjusts a spatial relation between the flow unit and/or an inlet end of the tube and/or an outlet end of the tube.
  • the flow unit is continuously and/or step-wise movable relative to the tube.
  • the movement may be conducted step- wise and/or continuously.
  • the measurements e.g. concentration measurements, light absorption measurements
  • the measurements may be conducted at a given and variable residence time point in the system, which has the ability to drive the flow unit, and hence the flow apparatus, through the system without the need of disassembly. Therefore, there is no need to disassemble any part in the system in order to investigate different properties of the fluid, for example events at residence time of interest, mixing of different phases, characterization of mixers (in particular micromixers), and the determination of flow characteristics of any flow mixer (or reactor). It may be hence sufficient to drive the flow unit of the flow apparatus relative to (e.g. along) the tube.
  • a provided advantage by moving the flow unit along the tube may be that the flow pattern during the measurement is not disturbed.
  • the flow unit is spatially movable along the exterior of the tube.
  • the flow unit may circumferentially surround the tube.
  • the flow unit may comprise a sleeve being slidably arranged over the tube.
  • the flow unit may be slideable along the tube and/or the flow unit may be driven up and/or down the tube. The flow unit may be moved along the exterior of the tube without disturbing the fluid inside the tube.
  • the tube is made of a material which is transparent for the primary electromagnetic radiation and the secondary electromagnetic radiation. Hence, the electromagnetic radiation is then able to pass the walls of the tube without a high loss of intensity.
  • the tube may be a PFA tube (Perfluoroalkoxy tube) which provides a good chemical resistance for the fluid to be monitored, such that any chemical composition may be used as the fluid to be monitored and the PFA tube simultaneously provide efficient transmission for the electromagnetic radiation.
  • PFA tube Perfluoroalkoxy tube
  • the monitoring apparatus comprises an emitter unit configured for emitting primary electromagnetic radiation to the flow apparatus, and a detector unit configured for detecting secondary electromagnetic radiation, generated by an interaction between the primary electromagnetic radiation and the fluid in the flow apparatus, wherein the electromagnetic radiation is received from flow apparatus, in particular from the flow unit.
  • the emitter unit and the detector unit may be attachable, in particular optically coupled, to the flow apparatus such that the primary electromagnetic radiation is guided directly through the tube and through the fluid. After the interaction with the fluid the secondary electromagnetic radiation is guided directly to the detector unit, wherein the emitter unit and the detector unit may be directly attachable, in particular optically coupled, to the tube such that a direct light path may be provided without any interfering components.
  • the emitter unit may be connected, e.g.
  • optically coupled, in particular directly, to the electromagnetic inlet of the flow unit and the detector unit may be connected, e.g. optically coupled, in particular directly, to the electromagnetic outlet of the flow unit.
  • the shape of the electromagnetic inlet and the electromagnetic outlet of the flow unit may be adapted to the shape of the emitter unit and/or to the shape of the detector unit for providing a good and sufficient coupling between the parts.
  • the emitter unit and/or the detector unit may be stacked into the electromagnetic inlet and the electromagnetic outlet, respectively.
  • the emitted primary electromagnetic radiation may be an electromagnetic radiation in a range of 300 nm to 1100 nm or in a range of 240 nm to 750 nm, more particularly it may be a substantially monochromatic radiation within one of the mentioned ranges. More generally, the electromagnetic radiation may be in a range of the visible light, infrared light, and ultraviolet light spectrum.
  • the emitter unit is a light emitting diode (LED), in particular a substantially monochromatic LED.
  • Monochromatic light may be used for the measurements, because of the narrow emission spectra of the LEDs.
  • One or more appropriate LEDs may be used as light sources for the monitoring of the fluid property.
  • the emitter unit may be configured in such a way that it is applicable to the absorption wavelength of the species of interest in the reaction mixture, e.g. the fluid or fluidic sample.
  • the emitter unit may be selected by a user based on the application. For example, for fluid concentration measurements of specific chemical species in solution, i.e. in the fluid, respective LEDs are chosen based on one or more absorption maxima of the respective chemical species.
  • the emitter unit may comprise a single LED which is connected to an LED driver module.
  • the LED diver module may be a constant current driver module which may include a feature that enables simple LED light intensity control, wherein a digital pulse width modulation signal may be provided by a control board.
  • the electromagnetic radiation emitted from the emitter unit may be split into two perpendicular beams by a beam splitter, in particular by a beam splitter cube having a 50: 50 split ratio.
  • One of the perpendicular light beams may be for a reference detector and the other one may be for the application, i.e. an interaction with fluid.
  • This configuration allows the use of the reference beam for processing detection signals, for example for the calculating of the fluid property.
  • the emitter unit may be controlled and observed.
  • the detector unit is a photodiode. The function of photodiodes is based on the photoelectric effect in order to measure light intensity.
  • a photodiode may provide a more dynamic range for applications and may ease the design and the costs of the system.
  • the detector unit may be specifically spectrally adapted to the respective emitter unit, such that the complete emitted spectral range of the emitter unit may be received by the detector unit.
  • the detector unit may be spectrally adapted to the range of the emitted electromagnetic radiation, wherein the detector unit may be spectrally adapted to at least one emitter unit or to all used emitter units.
  • at least one detector unit may be used, such that the detector arrangement may be simplified and the system may comprise a certain flexibility.
  • the sensitive wavelength of the photodiode may be in a range from 300 nm to 1100 nm.
  • the detector unit may comprise a monolithic photodiode chip coupled to a transimpedance amplifier.
  • the combination of the photodiode and a transimpedance amplifier on a single chip may eliminate problems such as leakage current errors, noise pickup, and a gain peaking as a result of stray capacitance. Further, the outlet voltage may increase linearly with light intensity.
  • the monitoring apparatus further comprises a first optical fiber (or any other light guide) configured for optically coupling the emitter unit with the flow apparatus and/or a second optical fiber (or any other light guide) configured for optically coupling the detector unit with the flow apparatus.
  • the first optical fiber and the second optical fiber may be directly optically coupled to the flow unit.
  • the first optical fiber may be directly optically coupled to the electromagnetic radiation inlet, wherein the electromagnetic radiation inlet may have a shape adapted to the shape of the optical fiber, such that a proper mechanical attachment and light transmission can be guaranteed.
  • the shape of the electromagnetic inlet may be circular or oval.
  • the second optical fiber may be directly optically coupled to the electromagnetic outlet, wherein the electromagnetic outlet may also has a shape adapted to the shape of the second optical fiber, which shape may be circular or oval.
  • the optical fibers may be attached to the respective electromagnetic inlet and outlet, without the need of any fixing mechanism. Hence, the optical fibers may simply be slid into the respective electromagnetic inlet and/or outlet.
  • the light from the LED may be split into two perpendicular light beams, wherein the second light beam (or the first light beam) may be focused on the first optical fiber using a lens. The light may be further focused on the tube comprising the fluid and may be further transmitted through the second optical fiber to the detector.
  • the emitter unit and the detector unit may be arranged opposite each other at the flow apparatus for performing a transmission measurement. On the other side the emitter unit and the detector unit may be arranged at a same position at the flow apparatus for performing a reflection or a backscattering or a fluorescence measurement. In particular, the emitter unit and the detector unit may be arranged coplanar at the flow apparatus, i.e. may be arranged coplanar at the flow unit. With the opposite arrangement of the emitter and detector unit, light from the emitter forms a direct light path through the tube and the fluid to the detector.
  • the emitter unit and the detector unit By arranging the emitter unit and the detector unit at the same position the light from the emitter unit forms a light path from the emitter unit trough the tube and into the fluid, wherein the reflected light passes back through the tube to the detector unit. In particular, the light is backscattered by the fluid to the detector. Further, by arranging the emitter unit and the detector unit at the same position a fluorescence measurement may be conducted. Fluorescence measurement, or fluorescence spectroscopy, may analyze electromagnetic radiation, in particular visible or ultraviolet light, which excites electrons in molecules of the fluid and causes them to emit light. Further, for performing a fluorescence measurement the emitter unit and the detector unit may be arranged coplanar, wherein the detector unit may be arranged with an angle of 90° to the emitter unit. Using an arrangement with an angle between the emitter unit and the detector unit may reduce the risk of transmitted or reflected incident light reaching the detector during the fluorescence measurement.
  • the supply apparatus may comprise at least one feeding unit for feeding at least one fluid (in particular multiple different fluids to be mixed) to the fluid apparatus, and a mixing unit for mixing the fluid(s) of the feeding unit.
  • An outlet of the mixing unit may be connected with the fluid apparatus.
  • the fluid from which the property will be monitored will be provided at the feeding unit, wherein the feeding unit may comprise a reservoir for the fluid for guaranteeing continuous supply of the fluid from the feeding unit to the subsequent system units.
  • the feeding unit may be able to feed at least one fluid and/or more than one fluid, for example two fluids.
  • the fed fluids may provide the composition of interest from which the fluid property should be monitored.
  • the fluids from the feeding unit may be only a part of the composition of the end fluid, wherein the fluid supplied from the feeding unit can be mixed afterwards for forming the fluid composition together with other fluids fed from the feeding unit.
  • the mixing unit may receive the fluids from the feeding unit and subsequently the mixing unit will mix the fluids for forming the respective fluid mixture from which the fluid property can be monitored.
  • the mixing unit may receive for example two fluids from the feeding unit simultaneously or the mixing unit may receive for example two fluids from the feeding unit sequentially, which means one after another.
  • the mixing unit may comprise at least two fluid inlets. After receiving the at least two fluids the mixing unit performs a mixing of the received fluids for homogenizes the fluids.
  • the mixing unit may be used to mix the fluid for guaranteeing a homogenous fluid, because the fed fluid may be comprised of different substances, e.g. analytes.
  • an outlet tube may connect the outlet of the mixing unit with the fluid apparatus.
  • the feeding unit comprises at least one outlet for supplying the mixed fluid for further processing and for monitoring to the flow apparatus.
  • the mixing unit may be a micromixer and/ or a microreactor.
  • a micromixer may be a device which (for instance based on mechanical metal parts) is used to mix fluids, wherein the micromixer may be a passive micromixer and/or an active micromixer.
  • the active micromixer may use an external energy source which may be an electric or magnetic energy source for performing the mixing of the fluids.
  • the passive micromixer does not need any power source and the fluids are guided basically by pressure.
  • the microreactor may trigger a reaction (such as a chemical reaction between different constituents of the fluid) and may, for example, be a continuous flow reactor.
  • the mixing unit may be comprise or consist of a fluid combining unit such as a T-piece, Y-piece, or X-piece and wherein at least two inlet tubes are connected to the fluid combining unit for feeding at least two fluids to the fluid combining unit, wherein the fluid combining unit may be configured for mixing the at least two fluids.
  • the T-piece may be a T-mixer which together with the tube may be used as the mixing reactor.
  • the at least two inlet tubes present at least two feeding lines from one feeding unit or at least two feeding lines from at least two feeding units, respectively.
  • the feeding unit or the feeding units supply a first fluid to the T-piece or other fluid combining unit through the first inlet tube and a second fluid to the T-piece or other fluid combining unit through the second inlet tube.
  • the T-piece may be designed as a simple form of the micro reactor which may be a so-called T-reactor. Fluids may be added and removed at the top left of the T and the top right of the T and the bottom of the T. For example at the top left of the T reactor and at the top right of the T reactor at least two fluids are supplied to the T reactor and at the bottom of the T reactor the mixed fluid may be dispensed and supplied to the flow apparatus.
  • the mixing unit embodied as a Y-piece may be able to work in the same manner as the above described T-piece. If the mixing unit is formed of a X-piece, instead of two inlets three inlets are possible.
  • the supply apparatus further comprises at least one pump configured for pumping fluid to the supply apparatus.
  • the at least one pump may be configured for pumping the fluid from an external source, for example from the above mentioned reservoir, to the feeding unit and the pump maybe further configured for pumping the fluid from the feeding unit to the mixing unit. Therefore, kinetic energy produced by the pump for moving the fluid may be used to drive the fluid through the whole system.
  • the amount of pumps may be increased such that for each feeding unit a pump may be provided.
  • at least one pump is used for feeding the fluid to more than one feeding unit.
  • the supply apparatus comprises a pump for each feeding line, i.e. for each inlet tube which feed the fluid into the T-piece.
  • the system further comprises a processing unit, configured for controlling signals transmitted to the monitoring apparatus and to the supply apparatus, and configured for processing signals received from the monitoring apparatus.
  • the processing unit may be a processor, for instance a microprocessor or a central processing unit.
  • the processing unit may control the electromagnetic radiation, by controlling the emitter and detector unit, and the fluid, in particular the fluid speed, which is supplied through the flow apparatus.
  • the signals transmitted to the monitoring apparatus may be controlled in order to control the monitoring apparatus (especially in order to control the emitter unit and the detector unit). For example, signals may be used for electing the respective emitter unit and the respective detector unit such that the monitoring unit may be precisely adapted to the fluid to be analyzed.
  • the processing unit may comprise a signal filtering and processing board, a detector board on which the detector unit may be arranged, and a power supply board.
  • the detector board may comprise connectors for connecting with the power supply board and the detector board may comprise passive components for the gain selection of the amplifier of the for instance monolithic photodiode chip.
  • the detector board may comprise connectors for the outlet signal, e.g. micro coax connectors. In order to prevent or at least minimize an intake of environmental noise the micro coax connectors may be used for providing a shielding of the signal line with ground potential in the outer line of the cable.
  • the signal filtering and processing board may be connected to the detector board by a control board.
  • the control board may be MSP 430 Launchpad platform.
  • the signal filtering and processing board may be able for signal processing and digital gain control of different electronic components.
  • the power supply board may be able to reduce the incoming power from the respective power adapter to the appropriate voltages for the other boards in the system. Further, the power supply board may be used to drive the light source, e.g. the emitter unit, and may be used to the drive fans for cooling of integrated circuits, light emitting diodes and the power supply itself.
  • the property of the fluid is measured continuously over time and/or at different time intervals.
  • the system may be used to determine a residence time distribution (RTD) of various fluid particles in various micro reactors/micromixers.
  • RTD residence time distribution
  • a sample acquisition speed may be about 1 ms such that the length of individual fluid segments may be measured in real time.
  • This in-line continuously over time measurement may provide a real-time monitoring of fluid segment length and reactive performance with respect to the mass transfer.
  • the property of the fluid is at least one of the group comprising of a concentration of the fluid, an absorption characteristic of the fluid, a hydrolysis reaction, a mass transfer of the fluid, a calculation of energy of the activation, a mixing of different phases, and a residence time distribution.
  • concentration of the fluid may denote the concentration of each substance of which the fluid is comprised of.
  • concentration of the substance and of the water may be measured and monitored.
  • An absorption characteristic of the fluid may be the absorption characteristic of the whole composition of the fluid or it may also be the absorption characteristic of each single component, i.e. of each single substance, which the fluid may comprise.
  • a hydrolysis reaction usually describes a cleavage of chemical bonds of substances when adding water.
  • hydrolysis reaction means a reaction of cation and anion or both with water molecules due to which pH is altered and a cleavage of H-0 bond takes place.
  • a mass transfer of the fluid may denote the mass transfer of the whole fluid or the mass transfer the fluid separated into the respective mass transfers of the substances comprised in the fluid.
  • a calculation of energy of the activation may particularly denote the execution of the same experiment at different temperature values for calculating the energy of the activation for the reaction.
  • a mixing of different phases may particularly denote that each fluid which will be mixed has a different phase than the other fluid. For example by mixing at least two fluids having a different phase, a two-phase dispersion may be received.
  • a residence time distribution may particularly denote a distribution function which describes the amount of time a fluid element or particle could spend inside a reactor.
  • the RTD may be used to characterize the mixing and flow within reactors and may be used to compare the behavior of real reactors with their ideal models.
  • the method comprises moving the flow unit relative to the tube to thereby selectively adjust a user-defined spatial relation between the flow unit and the tube.
  • flow unit and tube may be movable relative to one another.
  • this relative movement may be carried out by moving the flow unit while maintaining the tube stationary.
  • the spatial movement defines a respective distance between the flow unit and the tube, in particular between the flow unit and the tube beginning and/or the tube ending.
  • Figure 1 illustrates a system for monitoring the fluid property during a flow process according to an exemplary embodiment of the invention.
  • Figure 2 schematically illustrates a signal filtering and processing board of the system according to an exemplary embodiment of the invention.
  • Figure 3 shows a flow apparatus and a mixing unit of the system according to an exemplary embodiment of the invention.
  • Figure 4 shows a fluid transported inside the tube according to an exemplary embodiment of the invention.
  • Figure 5 illustrates a diagram showing the outlet of the flow apparatus according to an exemplary embodiment of the invention.
  • Figure 6 illustrates a concentration of p-NF length/residence time according to an exemplary embodiment of the invention.
  • Figure 7 schematically illustrates an experimental setup for a step experiment showing a water flow according to an exemplary embodiment of the invention.
  • Figure 8 schematically illustrates an experimental setup for a step experiment showing a dye flow according to an exemplary embodiment of the invention.
  • Figure 9 show experimental data obtained and compared with a behavior of a step response experiment according to an exemplary embodiment of the invention.
  • Figure 10 shows a comparison between calculated E-curves for different micro reactors using step experiments according to an exemplary embodiment of the invention.
  • Figure 11 schematically illustrates an experimental setup for a pulse experiment showing a loading of a dye according to an exemplary embodiment of the invention.
  • Figure 12 schematically illustrates an experimental setup for a pulse experiment showing an injection of a dye according to an exemplary embodiment of the invention.
  • Figure 13 illustrates an E-curve versus time for a micro reactor according to an exemplary embodiment of the invention.
  • a system 100 for supplying a fluid and monitoring a property of the fluid during a flow process according to an exemplary embodiment of the invention will be explained.
  • the system 100 comprises a flow apparatus 102, a supply apparatus 115 configured for supplying the fluid, and a monitoring apparatus 107 configured for monitoring the property of the fluid during supplying the fluid by the supply apparatus 115.
  • the monitoring apparatus 107 is configured for monitoring the property of the fluid simultaneously with and during the flow process using electromagnetic radiation.
  • An emitter unit 106 is configured for emitting primary electromagnetic radiation from the emitter unit 106 to the flow apparatus 102.
  • a detector unit 105 of the monitoring apparatus 107 is configured for detecting secondary electromagnetic radiation generated by an interaction between the primary electromagnetic radiation and the fluid in the flow apparatus 102.
  • the emitter unit 106 may be a light emitting diode (LED), and the detector unit 105 may be a photodiode.
  • the emitter unit 106 and the detector unit 105 are arranged coplanar at opposite sides of the flow apparatus 102. Further, the emitter unit 106 is optically coupled to a first optical fiber 103 which is configured for optically connecting the emitter unit 106 with the flow apparatus 102. Correspondingly, the detector unit 105 is optically coupled to a second optical fiber 104 which is configured for optically connecting the detector unit 105 with the flow apparatus 102.
  • the flow apparatus 102 comprises a flow unit 116 and a tube 101, wherein the fluid is flowing in a lumen of the tube 101.
  • the flow cell type flow unit 116 comprises a cross shape having four arms, at each arm of the cross one of the following is attachable: a fluid inlet for receiving the fluid, a fluid outlet for releasing or draining the fluid arranged opposite the fluid inlet, an electromagnetic radiation inlet for receiving emitted primary electromagnetic radiation, and an electromagnetic radiation outlet for transferring secondary electromagnetic radiation.
  • the tube 101 extends through the flow unit 116 from the fluid inlet to the fluid outlet, wherein the fluid is transportable through the tube 101 from the fluid inlet to the fluid outlet.
  • the flow unit 116 is movably (in particular slidably) arranged at the tube 101.
  • the tube 101 can be simply slid into and through the sleeve-type flow unit 116 for mounting the tube 101 carrying a fluid of interest for establishing a monitoring system.
  • the electromagnetic radiation inlet and the electromagnetic radiation outlet are arranged coplanar and opposite each other at the flow unit 116, such that the electromagnetic radiation is transmitted through the flow unit 116.
  • the flow unit 116 is movable along the tube 101. This means that the flow unit 116 is selectively positionable at different positions along the tube 101.
  • the electromagnetic radiation emitted from the emitter unit 106 may be split into two perpendicular light beams using a beam splitter 108.
  • One electromagnetic radiation beam is directed through a lens 109 (or another optical member) to the first optical fiber 103 for measuring the fluid.
  • the other electromagnetic radiation beam is directed by the beam splitter 108 to a reference detector unit 110.
  • a direct comparison between the reference electromagnetic radiation detected by the reference detector unit 110 and the detector unit 105 can be made, wherein the reference signals from the reference detector unit 110 may be used for a refined calculation of the fluid property by the processing unit 111.
  • the reference path is optional.
  • the lens 109 of the monitoring apparatus 107 is used for focusing the electromagnetic light beam into the optical fiber 103.
  • the system 100 comprises a processing unit 111 which is configured for controlling signals transmitted to the monitoring apparatus 107 and to the supply apparatus 115.
  • the processing unit 111 is configured for processing signals received from the monitoring apparatus 107.
  • the processing unit 111 comprises a signal filtering and processing board 112, a control board 113, and a power supply board 114.
  • the power supply board 114 is connected to the control board 113, to the signal filtering and processing board 112, and at least to the emitter unit 106.
  • the signal filtering and processing board 112 receives signals from the detector unit 105 and from the reference detector unit 110.
  • the control board 113 is connected to the power supply 114, to the signal filtering and processing board 112, and at least to the emitter unit 106 for controlling the respective signals from each unit/board.
  • the control board 113 is connected to the supply apparatus 115 for controlling the supplied fluid, the velocity of the fluid and the composition of the fluid.
  • the system may have maximum time scale resolution of 1 kHz, translating to a 1 ms sampling time and particular, signal intensity resolution of ⁇ 5 ADC points, wherein ADC is an analog to digital converter.
  • the system operates by measuring the electromagnetic radiation intensity at the detector unit 105 and by calculating the result in a specific manner by the processing board lll .E
  • the signal filtering and processing board 112 is used as a connection between the detector unit 105 and the control unit 113, wherein the control unit
  • the signal filtering and processing board 112 is also used for signal processing and for digital gain control.
  • the main signal processing board 112 receives a signal from the detector unit 205, which is received at an inlet signal filter 221.
  • the reference signal from the reference detector unit 210 is received at a reference signal filter 222.
  • the signal filters 221, 222 are active filters having a cut off frequency at for example 1 kHz and the filters are used for filtering the signals and for providing a clean outlet signal with low impedance to a subsequent amplifier 223. Both signals are transmitted to the amplifier 223, wherein the amplifier may be a PGA205 zero drift programmable gain instrumentation amplifier.
  • This amplifier is used in a subtracting configuration for subtracting the signals from the detector unit 205 and from the reference detector unit 210 and further for providing a low impedance outlet signal to the control board 113 (to the MSP430), thus reducing noise pickup in the signal path.
  • the amplifier 223 can have an additional feature of adjusting 224 the outlet offset voltage which in turn will provide the user with the ability to adjust the outlet of the system to zero blank measurements.
  • the digital gain control of the amplifier 223 may be enabled and the gain may be controlled by digital signals directly from the control board 113 (directly from the MSP430 Launchpad).
  • the supply apparatus 115 comprises a feeding unit 338, in particular two feeding units 338, for feeding at least one fluid by each feeding unit 338 to the fluid apparatus 102.
  • the mixing unit 335 comprises an outlet which is connected to the fluid apparatus 102, wherein an outlet tube connects the mixing unit 335 to the fluid apparatus 102 at the outlet.
  • the flow unit 116 comprises an electromagnetic radiation inlet 332, an electromagnetic radiation outlet 334, a fluid inlet 333, and a fluid outlet 331, wherein the tube 101 extends through the fluid inlet 333 to the fluid outlet 331.
  • the electromagnetic radiation inlet 332, the electromagnetic radiation outlet 334, the fluid inlet 333 and the fluid outlet 331 are arranged in a specific shape at the flow unit 116, in particular they are arranged in a cross shape at the flow unit 116.
  • a cross shape may be formed in such a manner that an angle between each respective fluid inlet 333, fluid outlet 331, electromagnetic radiation inlet 332, and electromagnetic radiation outlet 334 is about 90 degrees.
  • the mixing unit 335 is a T-piece.
  • Two inlet tubes 336, 337 are connected to the T-piece for feeding two fluids to the T-piece.
  • the T-piece is functioning as micro mixer/micro reactor. However, also other mixers, micro mixers, and micro reactors may be applicable.
  • the flow unit 116 is spatially movable along the tube 101, wherein arrows in Fig. 3 indicate the movement direction.
  • the flow unit 116 can be moved from a front end of the tube 101 (wherein the front end of the tube 101 is located at the mixing unit 335) to the opposing end of the tube 101.
  • the flow unit 116 can be freely moved forwardly and backwardly along the tube 101.
  • a user may slide the flow unit 116 (for example a flow cell) in predetermined space intervals over the transparent tube 101, wherein the monitoring apparatus 107 records a number of samples.
  • FIG. 4 an outlet stream of a hydrolysis reaction is shown.
  • the outlet stream is illustrated as different fluid segments 440.
  • the segments 440 represent p-nitro phenol anion transferred into a basic solution.
  • a DCM methylene chloride
  • p-NFA dissolved p-NFA
  • FIG. 5 experimental data from the outlet as displayed in Fig. 4 was recorded.
  • the diagram shows the recorded data points on the x-axis and the obtained data as an ADC value which is converted to p-NF concentration. From the obtained data one could calculate the order of the reaction and rate constant. By performing the same experiment at different temperatures one could calculate the energy of actuation for the reaction.
  • Fig. 6 the converted p-NF concentration, averaged from the data of Fig. 5, is shown versus the length/resident time. As can be seen at the beginning of the tube the concentration of p-NF is low at the beginning of the mixing point. The concentration increases unit at a length of 40 cm the p-NF concentration of 1.00 mol/L is reached.
  • FIG. 7 another mixing unit 335, in particular another micro reactor 335, is used instead of the above-described T-reactor.
  • the micromixer 335 is connected via a tube to a six way valve.
  • One feed is a 1 mM solution of RB dye in water
  • the second feed is pure water. Both feeds were pumped with the same flow rate (0.25, 0.50, 0.75 or 1.00 mL/min).
  • the figure shows the experimental setup for the step experiment, wherein the water flow is enabled.
  • the solvent is feed with no tracer and is instantly exchanged for the maximum tracer concentration.
  • the feeding unit 770 two pumps 771 are connected which are configured for pumping fluid to the feeding unit 770 (supply apparatus).
  • the pumps may be continuous syringe pumps.
  • One pump 771 is pumping a dye 772 and the other pump 771 is pumping water 773 to the feeding unit 770.
  • a timing of the measurements was set for all experiments to 1 ms.
  • the six way valve in Fig. 7 enables a water 773 flow to the mixing unit 335.
  • Fig. 8 the experimental setup for the step experiment is shown.
  • the setup according to Fig. 8 is the same as described with Fig. 7.
  • the difference to Fig. 7 is that the dye flow is enabled by the six way valve, wherein the dye is fed to the mixing unit 335.
  • the mixing unit 335 receives a specific amount of dye and water after one another and the mixing unit 335 can mix the dye and the water.
  • the comparison between the obtained curve 991 from then step response experiment and the ideal behavior 990 of a step response using a 1.6 mm tube and a liquid flow rate of 0.5 mL/min is shown.
  • the ADC value is displayed, which ADC value can be translated to the concentration by having an appropriate response factor.
  • the obtained measurement curve 991 nearly fits the ideal curve 990 of a step response.
  • the diagram shows exit age distribution of several micro reactors 1010 to 1014.
  • the exit age distribution represents the resident time distribution of the fluid.
  • the exit age distribution was calculated by the concentration response of the step change from water to dye solution conducted with different micro reactors lOlOto 1014.
  • the system is able to determine for different micro reactors 1010 to 1014 a respective resident time distribution, such that the behavior of different micro reactors can be monitored by the described system 100.
  • Fig. 11 the experimental setup for the pulse experiment, in particular a loading of the fluid, is shown.
  • pulse experimental setup a small volume pulse of concentrated tracer solution is injected into the micro reactor 335.
  • a 13 pL loop is loaded with 1 mM solution of RB dye using the syringe.
  • the micro reactor 335 is connected to the six way valve by a tube.
  • the flow rate was set to .25, 0.50, 0.75 or 1.00 mL/min.
  • a recording of the data was started immediately upon switching the six way valve whereupon a 13 pL pulse of the dye was injected into the micro reactor335.
  • the injection status is shown in Fig. 12. The timing of the measurements depends on the evaluated micro reactor 335 and the used flow rate.
  • the recording time was set to every 10 ms and for flow rates of 0.75 and 1.00 mL/min the timing was set to 1 ms.
  • the used micro reactor 335 is a Dolomite micro reactor (250 pl_ glass micro reactor), wherein the graph shows the resident time distribution (E) for different flow rates during the pulse experiment.
  • Curve 1310 displays the micro reactor at a flow rate of 1 mL/min, curve 1311 at a flow rate of 0.75 mL/min, curve 1312 at a flow rate of 0.5 mL/min, and curve 1313 at a flow rate of 0.25 mL/min.
  • the obtained means residence time distribution corresponds to the theoretically determined residence time distribution for different flow. Therefore, the described system 100 can be used for determining the behavior of different micro mixers in a pulse experiment setup as well as in a step experiment setup.

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Abstract

L'invention concerne un système de surveillance d'une propriété d'un fluide pendant un processus d'écoulement, le système comprenant un appareil d'écoulement, un appareil d'alimentation conçu pour fournir le fluide, et un appareil de surveillance configuré pour surveiller la propriété du fluide pendant l'alimentation du fluide par l'appareil d'alimentation. L'appareil d'écoulement comprend une unité d'écoulement qui est disposée de façon mobile au niveau d'un tube de l'appareil d'écoulement, le fluide s'écoulant à travers le tube.
PCT/EP2019/060002 2018-04-26 2019-04-17 Surveillance d'une propriété d'un fluide pendant un processus d'écoulement WO2019206779A1 (fr)

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Application Number Priority Date Filing Date Title
GBGB1806797.5A GB201806797D0 (en) 2018-04-26 2018-04-26 Monitoring a property of a fluid during a flow process with a flow unit and a tube being movable relative to one another
GB1806797.5 2018-04-26

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WO2019206779A1 true WO2019206779A1 (fr) 2019-10-31

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Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4312341A (en) * 1979-12-13 1982-01-26 Baxter Travenol Laboratories, Inc. Bubble detector
US4816695A (en) * 1987-08-31 1989-03-28 Lavin Thomas N Optical fluid detector
WO2000028322A1 (fr) * 1998-11-06 2000-05-18 Medtronic Avecor Cardiovascular, Inc. Appareil et procede permettant de determiner des parametres sanguins
DE19905983A1 (de) * 1999-02-12 2000-10-05 J & M Analytische Mess & Regeltechnik Gmbh Kapillarenhalter
WO2002084258A1 (fr) * 2001-04-12 2002-10-24 Mwg Biotech Ag Dispositif de surveillance d'un flux de produits chimiques
WO2003034045A1 (fr) * 2001-10-16 2003-04-24 Abb Bomem Inc. Analyse optique en ligne d'une substance a travers une section de conduite d'une ligne de processus
GB2460265A (en) * 2008-05-23 2009-11-25 Univ Dublin City Detection assembly
WO2012062829A1 (fr) * 2010-11-12 2012-05-18 Endress+Hauser Conducta Gesellschaft Für Mess- Und Regeltechnik Mbh+Co. Kg Capteur uv miniature utilisant une cellule d'écoulement jetable
US20130187067A1 (en) * 2010-07-26 2013-07-25 Endress+Hauser Conducta Gesellschaft Fur Mess-und Regeltechaft Fur Mess-und Regeltechnik mbH+Co.KG Optical Measuring System
JP2014209063A (ja) * 2013-04-16 2014-11-06 横河電機株式会社 分光分析装置

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4312341A (en) * 1979-12-13 1982-01-26 Baxter Travenol Laboratories, Inc. Bubble detector
US4816695A (en) * 1987-08-31 1989-03-28 Lavin Thomas N Optical fluid detector
WO2000028322A1 (fr) * 1998-11-06 2000-05-18 Medtronic Avecor Cardiovascular, Inc. Appareil et procede permettant de determiner des parametres sanguins
DE19905983A1 (de) * 1999-02-12 2000-10-05 J & M Analytische Mess & Regeltechnik Gmbh Kapillarenhalter
WO2002084258A1 (fr) * 2001-04-12 2002-10-24 Mwg Biotech Ag Dispositif de surveillance d'un flux de produits chimiques
WO2003034045A1 (fr) * 2001-10-16 2003-04-24 Abb Bomem Inc. Analyse optique en ligne d'une substance a travers une section de conduite d'une ligne de processus
GB2460265A (en) * 2008-05-23 2009-11-25 Univ Dublin City Detection assembly
US20130187067A1 (en) * 2010-07-26 2013-07-25 Endress+Hauser Conducta Gesellschaft Fur Mess-und Regeltechaft Fur Mess-und Regeltechnik mbH+Co.KG Optical Measuring System
WO2012062829A1 (fr) * 2010-11-12 2012-05-18 Endress+Hauser Conducta Gesellschaft Für Mess- Und Regeltechnik Mbh+Co. Kg Capteur uv miniature utilisant une cellule d'écoulement jetable
JP2014209063A (ja) * 2013-04-16 2014-11-06 横河電機株式会社 分光分析装置

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