EP2198284A1 - Détecteur à stabilité à long terme pour bioprocédés - Google Patents

Détecteur à stabilité à long terme pour bioprocédés

Info

Publication number
EP2198284A1
EP2198284A1 EP08839608A EP08839608A EP2198284A1 EP 2198284 A1 EP2198284 A1 EP 2198284A1 EP 08839608 A EP08839608 A EP 08839608A EP 08839608 A EP08839608 A EP 08839608A EP 2198284 A1 EP2198284 A1 EP 2198284A1
Authority
EP
European Patent Office
Prior art keywords
sensor
substance
surface portion
medium
sensor according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP08839608A
Other languages
German (de)
English (en)
Inventor
Thilo Trapp
Michael Hanko
Annett Planitzer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Endress and Hauser Conducta GmbH and Co KG
Original Assignee
Endress and Hauser Conducta Gesellschaft fuer Mess und Regeltechnik mbH and Co KG
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 Endress and Hauser Conducta Gesellschaft fuer Mess und Regeltechnik mbH and Co KG filed Critical Endress and Hauser Conducta Gesellschaft fuer Mess und Regeltechnik mbH and Co KG
Publication of EP2198284A1 publication Critical patent/EP2198284A1/fr
Withdrawn legal-status Critical Current

Links

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
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G01N33/54373—Apparatus specially adapted for solid-phase testing involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
    • 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
    • G01N21/82—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 producing a precipitate or turbidity

Definitions

  • the present invention relates to a sensor for monitoring a physical or chemical parameter, in particular a pH sensor or other potentiometric sensor, or an optical sensor such as a photometric sensor, a turbidity sensor, or a spectrometric sensor.
  • a sensor for monitoring a physical or chemical parameter in particular a pH sensor or other potentiometric sensor, or an optical sensor such as a photometric sensor, a turbidity sensor, or a spectrometric sensor.
  • Such sensors are u. a. for monitoring so-called
  • Bio-processes are used, which are often particularly large demands for stable process conditions and purity.
  • the sensor according to the invention for detecting a measured variable of a
  • Medium in particular in a bio-process comprises a sensor body with at least surface, wherein at least a surface portion of the sensor body is acted upon by the medium, wherein the state of this surface portion has an effect on the measured value
  • Characterized in that the surface portion is a substance having biocidal properties.
  • a bioprocess according to the invention is, for example, a manufacturing processing or purification process in which microorganisms cause the reaction of media components.
  • a surface portion then has a substance with biocidal
  • Characteristics according to the invention if it is suitable, by chemical, physical or biological means, to destroy harmful organisms, to deter, to render harmless, to prevent damage by them or to combat them in another way.
  • the surface portion has a non-toxic substance.
  • the substance is hydrophilic and optionally water-soluble, wherein the substance is more preferably such anchored in the region of the surface portion of the surface that it is not released under bio-process conditions in the medium.
  • Bio-process conditions mean, on the one hand, such conditions with regard to temperature, pressure, pH and composition of the medium, including the microorganisms, in which usually a bio-process takes place.
  • the sensors are such that the substance in the surface portion, at least one cleaning or sterilization (CIP after English Cleaning in Process or SIP after English Sterilizing in Process) in the installed state substantially unscathed, ie in particular, without being detached and without losing their biocidal properties. More preferably, the substance withstands several cleanings or sterilizations. For example, a first sterilization of a sensor may be required after it has been installed in a process plant before it is charged with a medium to be processed. On the other hand, the system can be cleaned or sterilized even after the passage of a batch.
  • the substance comprises polyethylene glycol, which is immobilized in a suitable manner on the surface of the body in the region of the surface portion.
  • Surface section comprising glass or a ceramic material can be used according to an embodiment of the invention, for example silanes.
  • the polyethylene glycol for example, an average molecular weight of not less than 3000 Da, preferably not less than 4000 Da and more preferably not less than 4500 Da on.
  • the polyethylene glycol according to the invention for example, an average molecular weight of not more than 7500 Da, preferably not more than 6000 Da and more preferably not more than 5500 Da on.
  • the average molecular weight of the polyethylene glycol is about 5000 Da.
  • PEG polyethylene glycol
  • PEG is a hydrophilic, water-soluble and non-toxic polymer, which shows very little interaction with proteins and allows effective shielding of the surface.
  • the increased resistance of PEG-coated surfaces to protein adsorption can be attributed to various mechanisms. Most significant are the steric repulsion and hydration of the coated surface.
  • the steric repulsive forces are of the Magnitude much stronger and have a much greater range than any attractive acting electrostatic or van der Waals interactions.
  • a SiO 2 surface of the glasses to be coated is strongly influenced by the history of the material.
  • siloxane bonds are present instead of silanol groups.
  • a pretreatment of the glass surfaces is advantageous in order to free the surface from impurities and to improve the wettability.
  • the surface can be chemically activated to give rise to new silanol groups, which are available as additional binding sites for higher silane occupancy.
  • Freshly activated glass can have a silanol group density of up to 8 ⁇ mol / m 2 .
  • the silanization can be carried out, for example, with an aminosilane.
  • an aminosilane for example, commercially available 3-aminopropyltriethoxysilane (APTES) can be used, for example, the organic solvent toluene can be used for the silanization reaction.
  • APTES 3-aminopropyltriethoxysilane
  • the immobilization of PEG to the aminosilanes can be carried out according to the invention, for example, by reductive amination of methoxylated aldehyde-terminated PEG (aldehyde PEG) or by nucleophilic substitution of PEG monomethyl ether mesylate with mesylate as a reactive leaving group (mesylate PEG).
  • the senor comprises a pH sensor, in the form of a combination electrode or in the form of two separate half-cells, wherein the at least one surface portion comprising the substance having the biocidal properties, a pH glass membrane and / or may comprise a reference half-cell diaphragm.
  • an optical sensor such as a photometric sensor, a turbidity sensor, or a spectrometric sensor, wherein the at least one surface portion comprising the biocidal substance comprises windows or other optical elements through which the radiation of the sensor interacts with a measuring medium or through which the radiation of the sensor enters or exits into the measuring medium.
  • Fig. 1 is a diagram showing the aging behavior of pH sensors in a fermenter
  • FIG. 2 shows a side view of a pH sensor according to the invention in the form of a combination electrode
  • Fig. 3a the principle of silanization of the surface portion of the sensor
  • Fig. 3b the principle of immobilization of the polyethylene glycol on the silanized surface portion
  • Fig. 4 Detailed views of pH sensor surfaces with the reference half-cell diaphragm for visualizing the effect of the invention.
  • FIG. 1 show the measurement signal from various pH sensors undergoing continuous yeast fermentation under aerobic Conditions are exposed as a function of time.
  • Applicant's CPS 71 combination electrodes in a media-contacting surface portion comprising a pH glass membrane and a reference half-cell diaphragm were coated with PEG in accordance with the invention.
  • Fig. 2 such a combination electrode is shown, wherein the coating was carried out in section a, while section b remained uncoated.
  • the four combination electrodes according to the invention and four identical combination electrodes without coating were continuously exposed to the yeast fermentation for seven days.
  • the family of output signals of the sensors according to the invention after seven days is encircled by the circle marked "a", while the signals of the uncoated sensors are enclosed at the same time by the ellipse with the designation "b".
  • the combination electrodes according to the invention emit a substantially more stable measurement signal in a fermentation process than the sensors according to the prior art.
  • the pH combination electrodes (hereinafter referred to as sensor) were cleaned for 30 minutes in piranha solution in an ultrasonic bath.
  • the Piranha solution is a 30% solution of 30% hydrogen peroxide solution in concentrated sulfuric acid.
  • the sensors were rinsed in deionised water and dried with compressed air.
  • the silanization shown in Fig. 3a was carried out in anhydrous toluene. Under these conditions, ideally a uniform monomolecular polysiloxane layer is formed.
  • the silanization reagent used was 3-aminopropyltriethoxysilane (APTES) as a 5% (v / v) solution in absolute toluene.
  • APTES 3-aminopropyltriethoxysilane
  • the purified sensors were silanized for half an hour.
  • 10 ml APTES solution was filled into 15 ml containers and one sensor was placed in each vial.
  • Several containers were placed in a beaker and this was agitated by a shaker. This ensured a convective mixing of the medium.
  • the sensors were rinsed with toluene and dried with compressed air.
  • the post-crosslinking of the silane layer turned out to be a decisive step in amino silanization. Samples that were further coated with PEG immediately after silanization did not show any coating success.
  • the silanized sensors were allowed to air for at least 24 hours
  • FIG. 3b A variant of the PEG coupling to the silanized glass surfaces is shown in FIG. 3b. It shows the immobilization of methoxylated aldehyde-terminated PEG (aldehyde-PEG) M-PEG-Ald by (1) reductive amination of the amino groups of the APTES silanized glass surface.
  • the coupling of the reactive aldehyde group to the amino group of the silanized glass surface is carried out under cloud point conditions via the formation of a ship see base, which is reduced by the reducing agent sodium cyanoborohydride to a secondary amine.
  • the reaction is carried out in K 2 SO 4 buffer solution (pH 6.3). This pH ensures that the reducing agent does not interfere with the Carbonyl group of M-PEG-Ald reacts.
  • the salt buffer solution is said to reduce the repulsive monomer-monomer interactions due to its poor solvent properties for PEG.
  • FIG. 4 shows views of the ceramic diaphragm of the reference half cell.
  • the images a and b are from an uncoated sensor and the images c and d from a sensor according to the invention. Pictures a and c were taken before use in the bio-process, while the pictures in b and d were taken after one week in the bio-process.
  • Diaphragm while such changes on the diaphragm of the sensor according to the invention are not visible. This correlates with the finding from FIG. 1, according to which the measurement signals of the sensors according to the invention showed hardly any changes by the use of a yeast fermentation, whereas the measurement signals of the untreated sensors after one week in the medium show an age-dependent drift showed.

Landscapes

  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

L'invention concerne un détecteur pour la détection d'une variable mesurée d'un milieu, en particulier dans un bioprocédé, comprenant un corps de détecteur, au moins une zone superficielle du corps du détecteur étant soumise à l'action du milieu, un état de cette zone superficielle affectant la valeur de mesure, caractérisé en ce que ladite zone superficielle présente une substance ayant des propriétés biocides.
EP08839608A 2007-10-11 2008-10-09 Détecteur à stabilité à long terme pour bioprocédés Withdrawn EP2198284A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102007049013A DE102007049013A1 (de) 2007-10-11 2007-10-11 Sensor mit Langzeitstabilität für Bio-Prozesse
PCT/EP2008/063543 WO2009050105A1 (fr) 2007-10-11 2008-10-09 Détecteur à stabilité à long terme pour bioprocédés

Publications (1)

Publication Number Publication Date
EP2198284A1 true EP2198284A1 (fr) 2010-06-23

Family

ID=40254383

Family Applications (1)

Application Number Title Priority Date Filing Date
EP08839608A Withdrawn EP2198284A1 (fr) 2007-10-11 2008-10-09 Détecteur à stabilité à long terme pour bioprocédés

Country Status (4)

Country Link
US (1) US20110033917A1 (fr)
EP (1) EP2198284A1 (fr)
DE (1) DE102007049013A1 (fr)
WO (1) WO2009050105A1 (fr)

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* Cited by examiner, † Cited by third party
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DE102011082983A1 (de) * 2011-09-19 2013-03-21 Endress + Hauser Conducta Gesellschaft für Mess- und Regeltechnik mbH + Co. KG Membran und Sensor mit Membran
DE102012110871A1 (de) 2011-11-17 2013-06-20 Endress + Hauser Conducta Gesellschaft für Mess- und Regeltechnik mbH + Co. KG Sensor zum Erfassen einer Messgröße eines Mediums
DE102011089671A1 (de) * 2011-12-22 2013-06-27 Endress + Hauser Conducta Gesellschaft für Mess- und Regeltechnik mbH + Co. KG Referenzhalbzelle und elektrochemischer Sensor mit der Referenzhalbzelle
DE102013101735A1 (de) * 2012-04-17 2013-10-17 Endress + Hauser Conducta Gesellschaft für Mess- und Regeltechnik mbH + Co. KG Potentiometrische Sensorvorrichtung
JP6510284B2 (ja) * 2015-03-24 2019-05-08 本田技研工業株式会社 異種材接合品及びその製造方法
FR3049644B1 (fr) 2016-04-01 2018-04-13 Safran Aircraft Engines Aube directrice de sortie pour turbomachine d'aeronef, presentant une fonction amelioree de refroidissement de lubrifiant a l'aide d'une matrice de conduction thermique logee dans un passage interieur de l'aube

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EP0010802B1 (fr) * 1978-10-31 1982-12-29 EASTMAN KODAK COMPANY (a New Jersey corporation) Dispositifs potentiométriques pour la détection d'une seule espece d'ions halogènes
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JPH11110133A (ja) * 1997-10-01 1999-04-23 Daicel Chem Ind Ltd タッチセンサ用ガラス基板およびタッチパネル
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Also Published As

Publication number Publication date
DE102007049013A1 (de) 2009-04-16
WO2009050105A1 (fr) 2009-04-23
US20110033917A1 (en) 2011-02-10

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