WO2009135334A1 - Procédé et appareil de mesure de la concentration d’une composition durant un processus de fermentation - Google Patents

Procédé et appareil de mesure de la concentration d’une composition durant un processus de fermentation Download PDF

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Publication number
WO2009135334A1
WO2009135334A1 PCT/CN2008/000900 CN2008000900W WO2009135334A1 WO 2009135334 A1 WO2009135334 A1 WO 2009135334A1 CN 2008000900 W CN2008000900 W CN 2008000900W WO 2009135334 A1 WO2009135334 A1 WO 2009135334A1
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Prior art keywords
flow path
reagent
sample
measuring
concentration
Prior art date
Application number
PCT/CN2008/000900
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English (en)
Chinese (zh)
Inventor
蔡浩原
杨宏伟
郭旻
贺伯特·格里布
卓越
库特·贝腾豪森
Original Assignee
西门子公司
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Application filed by 西门子公司 filed Critical 西门子公司
Priority to PCT/CN2008/000900 priority Critical patent/WO2009135334A1/fr
Publication of WO2009135334A1 publication Critical patent/WO2009135334A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/02—Food
    • G01N33/14—Beverages
    • G01N33/146—Beverages containing alcohol
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/02—Devices for withdrawing samples
    • G01N1/10—Devices for withdrawing samples in the liquid or fluent state
    • G01N1/20—Devices for withdrawing samples in the liquid or fluent state for flowing or falling materials
    • G01N1/2035—Devices for withdrawing samples in the liquid or fluent state for flowing or falling materials by deviating part of a fluid stream, e.g. by drawing-off or tapping
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/40—Concentrating samples
    • G01N1/4005—Concentrating samples by transferring a selected component through a membrane
    • G01N2001/4016—Concentrating samples by transferring a selected component through a membrane being a selective membrane, e.g. dialysis or osmosis
    • 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
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N2021/775—Indicator and selective membrane
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00178—Special arrangements of analysers
    • G01N2035/00237—Handling microquantities of analyte, e.g. microvalves, capillary networks
    • 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
    • G01N21/05—Flow-through cuvettes

Definitions

  • the present invention relates to the field of monitoring of fermentation processes, and more particularly to a device for measuring the concentration of components in a fermentation process and a method for measuring the concentration of components in a fermentation process. Background technique
  • Fermentation is a very important process in the field of biochemistry, especially in the pharmaceutical analysis, food, beverage, energy and environmental industries.
  • FCC fermentation process component concentration
  • European Patent Application EP0445675 discloses a flow splitting device based on flow injection analysis (FIA) technology.
  • FIA flow injection analysis
  • this patent application requires multiple peristaltic pumps and multiple valves when implemented in an FIA system, resulting in a very complicated structure of the flow analysis device, increasing the operational complexity of the entire analysis process, and also resulting in the flow analysis device.
  • the working condition is unstable.
  • FIA systems are not flexible enough to be used in a variety of chemical reactions.
  • the apparatus includes a pump, a multi-channel valve, a storage member, a beaker for use as a reaction vessel, a mass sensor, and a conduit connecting them.
  • the pump is first sucked into the storage member through the multi-channel valve, then pushed into the beaker through the multi-channel valve, then the reagent is taken through the multi-channel valve and filled with the multi-channel valve, and then the reagent is passed through the multi-channel valve.
  • Another object of the present invention is to provide a method of measuring the concentration of components in a fermentation process.
  • the present invention provides an apparatus for measuring the concentration of a component of a fermentation process, the apparatus comprising:
  • a sample flow path for flowing a sample of the driven fermentation broth therein; a reagent flow path for flowing the driven reagent therein; the shape of the reagent flow path being designed such that Forming a cavity along the sample flow path at least partially overlapping the sample flow path and the reagent flow path;
  • a dialysis membrane positioned between the sample flow path and the reagent flow path to allow analytes in the fermentation broth sample to diffuse from the sample flow path into the reagent flow path for the analyte to The reagent reacts;
  • a monitoring chamber is disposed on the reagent flow path for measuring the light absorbance of the reagent after the reaction.
  • the sample flow path is a groove formed on an upper part
  • the reagent flow path is a groove formed on a lower part
  • the upper part and/or the lower part is made of poly Made of decyl acrylate (PMMA), glass or silicon.
  • sample flow path and the reagent flow path may each be a half tube which is cut in the longitudinal direction.
  • the sample flow path and the reagent flow path are twisted and twisted to extend the flow path in a limited space.
  • a downstream end of the sample flow path is provided with a fermentation liquid outlet, and a downstream end of the reagent flow path is provided with a reagent outlet.
  • the upper member and the lower member are respectively provided with positioning mechanisms that cooperate with each other, and when the upper member and the lower member are closed, the sample flow path and the reagent flow path are aligned with each other to form a cavity. .
  • a temperature measuring element and a temperature control element are disposed in the sample flow path, and the temperature control element is used to adjust the temperature of the fermentation liquid sample in the sample flow path.
  • the dialysis membrane may fill the area where the sample flow path is located.
  • the monitoring chamber is located downstream of the reagent flow path and outside the portion where the reagent flow path overlaps the sample flow path.
  • one side of the monitoring room is connected to one input fiber, and the other side is connected with an output fiber, the input fiber and the output fiber are aligned with each other; the input fiber is connected to a light source, and the output fiber is Connected to a detector.
  • the optical path length between the input fiber and the output fiber of the monitoring chamber is adjustable.
  • two slots are disposed in the lower member for respectively fixing the input fiber and the output fiber.
  • the device is coupled to a sequential injection analysis flow system comprising: a pump, a multi-channel valve, and a reservoir, wherein the pump is coupled to one end of the reservoir
  • the multi-channel valve has a plurality of ports respectively connected to the other end of the liquid storage tube, the inlet of the sample flow path, the inlet of the reagent flow path, the outlet of the reagent container, and an outlet of the container of the fermentation liquid to be measured.
  • the multi-channel valve further includes: a port connected to the container of the calibration solution and/or a port for discharging the waste liquid.
  • the invention also proposes a method for measuring the concentration of components in a fermentation process, comprising: inputting a sample of the fermentation broth into a sample flow path, inputting the reagent into a reagent flow path; utilizing between the sample flow path and the reagent flow path Dialyzing the membrane, passing the analyte in the fermentation broth sample through the dialysis membrane into the reagent flow path, and reacting with the reagent; passing light through the post-reaction reagent in the reagent flow path, and measuring the The light absorbance of the reagent after the reaction;
  • the analyte concentration in the fermentation broth sample is calculated based on the light absorbance.
  • the method further comprises: adjusting before the measuring the light absorbance of the reagent after the reaction The length of the optical path in the reagent after the reaction.
  • the method further comprises: replacing the fermentation broth sample with a calibration solution, and measuring an analyte concentration in the calibration solution; analyzing the standard value and the measured concentration of the analyte concentration in the calibration solution The concentration of the analyte, the concentration of the analyte in the sample of the fermentation broth is calibrated.
  • the method further includes: introducing a cleaning fluid into the sample flow path and/or the reagent flow path to clean the sample flow path and/or the reagent flow path.
  • the device of the present invention adopts a unique structure, it is not necessary to use a large-capacity container for the reaction, and only a small amount of the fermentation broth sample and the reagent can be used for the measurement. , reducing the adverse effects on the fermentation process.
  • the device of the present invention can be directly rinsed with a cleaning solution, and the cleaning process is simple, and the fermentation liquid sample and reagent are not easily left, thereby avoiding the problem that the residual fermentation liquid sample or reagent affects the next measurement.
  • the sensitivity of the measurement can be varied by adjusting the length of the light path in the reagent after the reaction. With the technical solution of the present invention, it is not necessary to perform a pretreatment step of separating the fermentation broth sample and the reagent, thereby simplifying the measurement step.
  • FIG. 1 is an exploded perspective view of an apparatus for online measurement of a component concentration in a fermentation process according to an embodiment of the present invention
  • Figure 2 is a schematic view of the device shown in Figure 1 as a whole;
  • Figure 3 is a schematic view of the upper part when the apparatus of Figure 1 further includes a temperature control element and a temperature measuring element;
  • Figure 4 is a schematic view showing the structure of an SIA system connected to the apparatus shown in Figure 1. detailed description
  • the technical solution proposed by the present invention can be used to measure the concentration of components in the fermentation process during fermentation, such as the concentration of the substrate or the concentration of the product. Since glucose is an important carbon source in many fermentation processes, glucose is used as the analyte in the following description.
  • the solution of the present invention is exemplified, but the present invention is not limited to measuring the glucose concentration, and other analytes such as glutamic acid, lactic acid, ethanol and the like can also be measured by selecting the corresponding reagent.
  • the detection methods of analytes such as glucose can be roughly classified into two types, one is an enzyme-based electrochemical (EC) method, and the other is a photometric method.
  • the present invention mainly relates to photometric methods.
  • the photometric method obtains the concentration of glucose by measuring the light absorbance of the solution after the reaction of the glucose and the reagent.
  • the photometric method can be very accurate where the temperature and pH of the solution remain stable. Also, at room temperature, a typical measurement can be done quickly in less than a minute, allowing measurements to be used to control the fermentation process in real time.
  • glucose is oxidized by glucose oxidase to form gluconic acid and hydrogen peroxide, while hydrogen peroxide is reacted with peroxylase and 4-amino-anthracene.
  • Bilin (4-APP) and N-ethyl-N-sulfopropyl-m-mercaptoaniline (TOPS) react to form quinone.
  • the quinone imine has a color and has an absorption peak for light having a wavelength of 545 nm.
  • A sLC ( 3 )
  • A the light absorbance
  • the coefficient represents the light absorbance of the solution per unit mole (mol)
  • L the optical path length in the solution
  • C the concentration of the analyte, in this embodiment C
  • A sLC ( 3 )
  • an embodiment of the present invention provides a device for measuring the concentration of components in a fermentation process on-line, the device measuring the light absorbance of the reagent solution after the reaction, The concentration of glucose in the fermentation broth is obtained, so that the state of fermentation can be known.
  • the apparatus 100 for measuring the concentration of components in a fermentation process includes an upper member 101, a lower member 102, a dialysis membrane 103, an input fiber 106, an output fiber 107, a light source 108, and a detector 109. .
  • the upper member 101 includes a sample flow path 104 through which the fermentation broth sample flows.
  • the lower member 102 includes a reagent flow path 105 through which the reagent flows.
  • the upper member 101 and the lower member 102 are joined together such that the sample flow path 104 and the reagent flow path 105 at least partially overlap each other, thereby forming a cavity along the sample flow path 105.
  • the sample flow path may be a groove formed in the upper member 101
  • the reagent flow path 105 may be a groove formed in the lower member 102.
  • the upper member 101 and the lower member 102 may be respectively provided with positioning mechanisms that cooperate with each other such that when the upper member 101 and the lower member 102 are closed, the sample flow path 104 and the reagent flow path 105 are overlapped with each other. Form a cavity.
  • the upper member 101 and/or the lower member 102 may be made of a material such as polymethyl methacrylate (PMMA), glass or silicon.
  • the device 100 can be constructed in a more compact configuration.
  • the sample flow path 104 and the reagent flow path 105 are respectively a half pipe which is longitudinally cut, thereby eliminating the upper member 101 and the lower member 102.
  • sample flow path 105 and the reagent flow path 105 may be arranged in a meandering manner, for example, arranged in a "Z" shape, an "S" shape, a sinusoidal function shape, or a shape as shown in FIG. 1, thereby extending the flow path in a limited space.
  • a meandering manner for example, arranged in a "Z" shape, an "S" shape, a sinusoidal function shape, or a shape as shown in FIG. 1, thereby extending the flow path in a limited space.
  • the dialysis membrane 103 is located at least between the sample flow path 104 and the reagent flow path 105, and the area of the dialysis membrane 103 may be larger than a portion where the fermentation sample flow path 104 and the reagent flow path 105 overlap, for example, the area where the sample flow path 104 is filled. It is even possible to cover the entire portion where the upper part 101 and the lower part 102 are in contact, which facilitates assembly.
  • the dialysis membrane 103 separates the sample flow path 104 from the reagent flow path 105 to form two independent flow paths. The width of the two flow paths can be tens of microns to several centimeters.
  • the sample flow path 104 has a sample inlet 110 and a sample outlet 11 1, the sample inlet 1 10 for the fermentation liquid sample to flow in, and the sample outlet 1 11 for the fermentation liquid sample to flow out.
  • the reagent flow path 105 has a reagent inlet 1 12 and a reagent outlet 1 13, and a reagent inlet 112 for The reagent flows in, and the reagent outlet 113 supplies the reagent out.
  • the dialysis membrane 103 located between the sample flow path 104 and the reagent flow path 105 can allow analytes such as glucose in the sample of the fermentation liquid in the sample flow path 104, and small molecules such as salt ions to pass, that is, glucose is allowed to be
  • the analyte diffuses from the fermentation broth sample into the reagent of the reagent flow path 105, and those large or large particles having a diameter larger than the pore diameter of the dialysis membrane 103 are blocked by the dialysis membrane 103.
  • the dialysis membrane 103 may be a cellulose membrane, a polycarbonate membrane or the like.
  • the pore diameter of the dialysis membrane 103 needs to be larger than the diameter of the analyte such as glucose.
  • the diameter of the pores of the dialysis membrane 103 can be less than 0.22 ⁇ m, so that it is possible to block bacteria and the like while transmitting an analyte such as glucose. Since the dialysis membrane 103 separates the fermentation broth sample and the reagents and allows the glucose to permeate and blocks the large particles, the centrifugation of the fermentation broth sample and the reagent pretreatment are not required before the measurement, thereby shortening the measurement time.
  • the apparatus 100 of the embodiment of the present invention can inject a calibration solution into the sample flow path and obtain a calibration solution measurement result, and use the measurement result and calibration.
  • the standard value of the solution can be used to calibrate the measurement of the actual fermentation broth sample.
  • a monitoring chamber 114 is disposed in the reagent flow path 105.
  • the monitoring chamber 1 14 can be located anywhere in the reagent flow path 105, preferably downstream of the reagent flow path 105, to ensure that there is a fully reacted post-reaction reagent in the monitoring chamber 114.
  • the monitoring chamber 114 may be located within the portion of the reagent flow path 105 that is aligned with the sample flow path 104, or may be located outside of the portion of the reagent flow path 105 that is aligned with the sample flow path 104. In the example shown in the drawings, the monitoring chamber 114 is located outside the portion of the reagent flow path 105 that is aligned with the sample flow path 104.
  • the monitoring chamber 114 is connected to an input fiber 106 and an output fiber 107.
  • the length L of the optical path in the monitoring chamber 114 i.e., the distance between the input fiber 106 and the output fiber 107, can be designed to be adjustable. It can be seen from the formula (3) that by adjusting the optical path length of the monitoring chamber 144, the sensitivity of the measurement can be adjusted very easily, and thus applied to different fermentation broth samples.
  • the input fiber 106 and the output fiber 107 may be misaligned or aligned. In the case of misalignment, the output optical fiber 107 receives less light intensity than that received under alignment, so the present invention preferably employs two The structure of the alignment.
  • Two aligned or misaligned guiding grooves can be formed at both ends of the monitoring chamber 114 in the lower member 102, and the input optical fiber 106 and the output optical fiber 107 can be respectively fixed in the guiding groove, so that it can be both accurate and convenient.
  • the input fiber 106 and the output fiber 107 are fixed.
  • the incident light input from the input fiber 106 passes through the post-reaction reagent solution in the monitoring chamber 114 and is received by the output fiber 107.
  • the light absorbance of the reagent solution after the reaction can be calculated based on the input light intensity and the output light intensity, and then the glucose concentration in the fermentation liquid can be calculated according to the formula (3).
  • the light source 108 is used to generate incident light.
  • a laser diode, a light emitting diode or the like can be used.
  • the output spectral range of the light source 108 includes an absorption peak of an analyte such as glucose.
  • the incident light generated by the light source 108 is not necessarily a laser, but may be other types of light such as white light.
  • the detector 109 can be a photodiode, a photomultiplier tube or the like for measuring the intensity of light passing through the reagent solution after the reaction.
  • the light absorbance A in the formula (3) can be calculated by using the intensity of the light output from the light source 108 and the intensity of the light measured by the detector 109.
  • the combination of the structures shown in Fig. 1 can form a device 100 as shown in Fig. 2, which may be referred to as a small on-line photometer (MOP) integrated chip.
  • the apparatus 100 can be fabricated using a fine processing or microelectromechanical system (MEMS) processing process, and the material can be made of polymethyl methacrylate, glass or silicon or the like according to various needs.
  • MEMS microelectromechanical system
  • the process of measuring the concentration of components in the fermentation process using the apparatus shown in Figures 1 and 2 can include the following steps:
  • Step S1 1 a sample of the fermentation broth is extracted from a fermentation broth container such as a fermenter, and a sample of the fermentation broth is introduced into the sample flow path 104 through the sample inlet 110.
  • step S12 the reagent is introduced into the reagent flow path 105 through the reagent inlet 112.
  • steps S1 1 and S12 do not have a strict sequence, and may be performed simultaneously, or step S11 or S 12 may be performed first.
  • step S13 since the concentration of the analyte in the fermentation liquid sample in the sample flow path 104 and the reagent flow path 105 is different, the analyte in the fermentation liquid sample passes through the pore of the dialysis membrane 103 into the reagent. And chemically reacting with related substances in the reagent, for example, the reactions shown by the chemical formulas (1) and (2), forming a post-reaction reagent including the reaction product, and the reagent is colored after the reaction.
  • Step S14 it is possible to wait for a period of time so that the reaction proceeds sufficiently. Then, light is output by the light source 108, and the light enters the monitoring chamber 113 through the input fiber 106. After absorption in the monitoring chamber 113, the reagent is absorbed by the output fiber 107 and transmitted to the detector 109. In step S15, the detector 109 measures the intensity of the light absorbed by the reagent after the reaction. Step S16, the light absorbance A of the reagent after the reaction is calculated based on the intensity of the light output from the light source 108 and the intensity of the light measured by the detector 109.
  • Step S17 based on the calculated light absorbance and the optical path length L in the coefficient solution, the concentration C of the analyte is calculated according to the formula (1), so that the fermentation state can be known.
  • Step S18 the fermentation broth sample is output from the sample outlet 1 1 1 , and the reagent is output from the reagent outlet 1 13 .
  • the method may further include: step S19, inputting the cleaning liquid from the sample inlet 110 and outputting from the sample outlet 111, and inputting the cleaning liquid from the reagent inlet 112 and outputting from the reagent outlet 113, thereby cleaning the device 100 for the next Used for secondary measurements.
  • the method may also include a calibration process: performing the above steps S11 to S18 with the calibration solution instead of the fermentation liquid, thereby measuring the concentration of the analyte in the calibration solution; using the standard value of the analyte concentration in the calibration solution and The resulting analyte concentration is measured to calibrate the measured concentration in the measured fermentation broth sample.
  • the above method can also adjust the optical path length L in the detection chamber 114 to change the sensitivity of the measurement. For example, increasing the length L of the optical path reduces the sensitivity of the measurement; reduces the length L of the optical path to increase the sensitivity of the measurement.
  • Fig. 3 is another embodiment of the apparatus for online measurement of the concentration of components in a fermentation process in the present invention.
  • the apparatus shown in FIG. 3 adds a temperature control for controlling the temperature of the fermentation broth sample in the sample flow path 104 in the sample flow path 104 of the upper member 101 on the basis of the apparatus 100 shown in FIGS. 1 and 2.
  • a component such as a Peltier line 201. By applying a current in a different direction to the Peltier line 201, the temperature of the fermentation broth sample in the sample flow path 104 can be controlled.
  • the Peltier line 201 absorbs heat, thereby lowering the temperature of the fermentation liquid sample, and when the current is applied in the other direction, that is, in the opposite direction, the Peltier line 201 emits heat, thereby increasing the fermentation liquid. The temperature of the sample.
  • the apparatus shown in Fig. 3 can further provide a temperature measuring element for measuring the temperature of the fermentation liquid sample in the medium sample flow path 104 in the sample flow path 104 of the upper member 101, such as a temperature sensor 202, a thermometer, or the like.
  • a temperature measuring element for measuring the temperature of the fermentation liquid sample in the medium sample flow path 104 in the sample flow path 104 of the upper member 101
  • closed loop control of the temperature of the fermentation liquid in the sample flow path 104 can be achieved.
  • the temperature of the fermentation broth sample is measured by the temperature sensor 202.
  • the temperature of the fermentation broth sample is lowered by applying a current to the Peltier line 201.
  • the temperature of the fermentation broth sample is increased by applying a current to the Peltier line 201. In this way, the temperature of the fermentation broth sample can be controlled within a suitable range.
  • Figure 4 shows an embodiment in which a device for measuring the concentration of components in a fermentation process is combined with an SIA flow system 300.
  • the apparatus for measuring the concentration of components in the fermentation process on-line in Fig. 4 may employ the apparatus 100 shown in Fig. 1, Fig. 2 or Fig. 3, and will not be described again.
  • the SIA flow system 300 shown in Figure 4 includes a pump 301, "- a multi-channel valve 302, a reservoir 303, and a line connecting them.
  • the pump 301 is coupled to one end of the reservoir 303.
  • the reservoir 303 The other end, the inlet 110 of the sample flow path 104, the inlet 112 of the reagent flow path 105, the fermentation liquid container (e.g., fermentor, not shown), and the reagent container 304 are respectively connected to one port of the multi-channel valve 302.
  • the end to which the pump 301 and the liquid storage tube 303 are connected is also connected to a cleaning liquid container 305.
  • the multi-channel valve 302 has a discharge port for discharging waste liquid.
  • the above measurement fermentation can be completed by the SIA flow system 300.
  • the pump 301 is connected to the fermentation liquid container through the liquid storage tube 303, the multi-channel valve 302, and the sample of the fermentation liquid in the fermentation liquid container is pumped into the liquid storage tube 303 by the pump 301, and then the pump 301 is passed through the storage.
  • the liquid tube 303, the multi-channel valve 302 is connected to the sample inlet 110 of the sample flow path 104, and the fermentation liquid sample in the liquid storage tube 303 is pushed to the sample inlet 110 by the pump 301, thereby inputting the fermentation liquid sample into the sample flow path 104.
  • the reservoir 303 is purged by the pump 301 to purge the reservoir 303, and the purge is discharged from the discharge port of the multi-channel valve 302.
  • the pump 301 is connected to the reagent container 304 through the reservoir 303, the multi-channel valve 302, the reagent in the reagent container 304 is pumped into the reservoir 303 by the pump 301, and then the pump 301 is passed through the reservoir 303, the multi-channel valve 302 is connected to the reagent inlet 112 of the reagent flow path 104, and the reagent in the liquid storage tube 303 is pushed by the pump 301 to the reagent inlet 112 of the reagent flow path 105, thereby inputting the reagent into the reagent flow path 105.
  • the fermentation broth sample and the reagent can be separately input into the sample flow path 104 and the reagent flow path 105 of the apparatus 100.
  • the analyte such as glucose in the fermentation liquid sample is diffused into the reagent of the reagent flow path 105 through the dialysis membrane 103, and reacts with the reagent. If you need to, you can wait a while for the reaction to be more adequate.
  • the light absorption rate A is obtained, and then the glucose-glucose concentration can be calculated according to the formula (3), so that the glucose concentration in the fermentation liquid can be known. .
  • the cleaning liquid in the cleaning liquid container 305 is pumped by the pump 301, and the cleaning liquid is pushed to the sample flow path 104 and the reagent flow path 105 through the liquid storage tube 303 and the multi-channel valve 302, respectively, to clean the two flow paths.
  • the cleaned liquid can be directly discharged from the sample outlet 111 of the sample flow path 104 and the reagent outlet 113 4 of the reagent flow path 105.
  • the multi-channel valve 302 in the SIA flow system 300 can also have a port that is coupled to a calibration solution container 306 containing a calibration solution.
  • concentration of the analyte in the calibration solution is measured by the above process, and the analyte concentration of the measured fermentation broth sample can be calibrated using the measured analyte concentration and the actual analyte concentration of the calibration solution.

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Abstract

La présente invention concerne un appareil (100) de mesure de la concentration d’une composition durant un processus de fermentation qui comprend une ligne pour échantillons (104), une ligne pour réactifs (105), dont la configuration est destinée à ce que les deux lignes se chevauchent au moins partiellement l’une l’autre pour former une chambre, une membrane à dialyse (103) montée entre la ligne d’échantillons (104) et la ligne de réactifs (105), permettant que l’échantillon à analyser dans l’échantillon de liqueur de fermentation se diffuse de ladite ligne d’échantillons (104) dans ladite ligne de réactifs (105), pour faire analyser ledit échantillon et réagir ledit réactif, et un dispositif d’exploitation (114) monté dans ladite ligne de réactif pour mesurer le degré d’absorption optique du réactif après la réponse. Un procédé de mesure de la concentration d’une composition durant un processus de fermentation peut être réalisé avec uniquement une petite quantité d’échantillon de liqueur de fermentation et de réactif.
PCT/CN2008/000900 2008-05-05 2008-05-05 Procédé et appareil de mesure de la concentration d’une composition durant un processus de fermentation WO2009135334A1 (fr)

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PCT/CN2008/000900 WO2009135334A1 (fr) 2008-05-05 2008-05-05 Procédé et appareil de mesure de la concentration d’une composition durant un processus de fermentation

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PCT/CN2008/000900 WO2009135334A1 (fr) 2008-05-05 2008-05-05 Procédé et appareil de mesure de la concentration d’une composition durant un processus de fermentation

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WO2009135334A1 true WO2009135334A1 (fr) 2009-11-12

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4715237A (en) * 1984-07-06 1987-12-29 Metrohm Ag Process and apparatus for quantitative and/or qualitative analysis of liquids
EP0445675A2 (fr) * 1990-03-08 1991-09-11 Forschungszentrum Jülich Gmbh Méthode et appareil d'analyse à écoulement continu
CN1056122A (zh) * 1990-03-29 1991-11-13 中国科学院大连化学物理研究所 一种生产六氨基青霉烷酸的膜反应器
US6096274A (en) * 1997-06-03 2000-08-01 Applikon B.V. Analysis device
CN1511062A (zh) * 2002-03-29 2004-07-07 ����ŷ�������ʽ���� 化学反应装置以及动力供给系统

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4715237A (en) * 1984-07-06 1987-12-29 Metrohm Ag Process and apparatus for quantitative and/or qualitative analysis of liquids
EP0445675A2 (fr) * 1990-03-08 1991-09-11 Forschungszentrum Jülich Gmbh Méthode et appareil d'analyse à écoulement continu
CN1056122A (zh) * 1990-03-29 1991-11-13 中国科学院大连化学物理研究所 一种生产六氨基青霉烷酸的膜反应器
US6096274A (en) * 1997-06-03 2000-08-01 Applikon B.V. Analysis device
CN1511062A (zh) * 2002-03-29 2004-07-07 ����ŷ�������ʽ���� 化学反应装置以及动力供给系统

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