GB2177801A - Apparatus for detecting growth of microorganisms - Google Patents
Apparatus for detecting growth of microorganisms Download PDFInfo
- Publication number
- GB2177801A GB2177801A GB8616341A GB8616341A GB2177801A GB 2177801 A GB2177801 A GB 2177801A GB 8616341 A GB8616341 A GB 8616341A GB 8616341 A GB8616341 A GB 8616341A GB 2177801 A GB2177801 A GB 2177801A
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- GB
- United Kingdom
- Prior art keywords
- electrodes
- organisms
- culture system
- growth
- titanium
- 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.)
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
- C12M41/36—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of biomass, e.g. colony counters or by turbidity measurements
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Wood Science & Technology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Analytical Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Sustainable Development (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
Growth of micro-organisms in a culture system (2) comprising sterile nutrient medium is sensed as a change in one or more electrical properties of the medium between titanium electrodes (6a and 6b) of specified dimensions. The electrical property may be conductance, preferably at a frequency between 5 and 100 KHz, or capacitance. <IMAGE>
Description
SPECIFICATION
Apparatus and method for detecting growth of micro-organisms
This invention relates to an apparatus and to a method for detecting growth of micro-organisms (for example bacteria, fungi or yeasts) in a culture system comprising sterile nutrient medium by using means comprising opposed electrodes to sense one or more electrical properties of the culture which properties are affected by the growth of the organisms whereby detection of changes in a sensed property can be used to detect growth of the organisms.
Detection of the growth of bacteria in sterile nutrient media by detecting changes in the electrical conductance of the culture system was described by G.N. Stewart as long ago as 1898 and is reported in his article in Volume 4 of the "Journal of Experimental Medicine" published in 1899 (see pages 235 to 243 the contents of which are herein incorporated by reference). Stewart explained that growing bacteria create ionic metabolic products which can flow between opposed electrodes when a difference in electrical potential is established between them and hence the metabolic products increase the conductivity of the culture system. Growth of the bacteria can therefore be detected by detecting the increase in the conductance of the culture system.
Modern apparatus suitable for use in the performance of Stewart's method are described in
United States patent specification 3743581 and in British patent specification 1585047, the contents of both of which are herein incorporated by reference. The electrodes used in such apparatus must meet stringent electrical and chemical criteria. One important electrical criterion is that the resistance of an opposed electrode pair should be low relative to that of the culture system which usually means in practice that the resistance of the electrode pair should be less than 50 ohms and preferably less than 40 ohms. An equally important electrical criterion is that the ability of the electrodes to sense an electrical property of the culture system should remain very steady with respect to time.For example, if the electrode pair is used to measure the conductance of the pure nutrient medium in the absence of organisms, then a second identical measurement made one hour later should not differ by more than 2,us. An important chemical criterion is that the electrode must resist corrosion by the culture system and especially corrosion by the ionic metabolic products of the Organisms. Also the electrode pairs must withstand sterilisation by steam for 20 minutes at 121"C and at a pressure of 1 bar above atmospheric.
Electrodes made from aluminium and stainless steel have only poor resistance to corrosion by culture systems and stainless steel electrodes are relatively insensitive to small changes in conductance when the frequency of an alternating current is above 5kHz. For these reasons many of the most modern apparatus use electrodes made from platinum or substrates coated with platinum. However platinum is too expensive for use in making disposable electrodes.It is an object of the present invention to provide an apparatus which comprises and a method which uses electrodes which are suitable for use in detecting of micro-organisms but which are cheap enough to be disposable after one or two uses and which are sufficiently corrosion resistant to enable disposable units comprising a sealed internally sterilised container containing sterile nutrient medium with the electrodes dipping into the medium to have a shelf like of at least one and preferably two years.
Accordingly this invention provides apparatus for detecting growth of micro-organisms in a culture system comprising sterile nutrient medium by using means comprising opposed electrodes to sense one or more electrical properties of the system which properties are affected by the growth of the organisms whereby detection of changes in the sensed properties can be used to detect growth of the organisms wherein at least the effective surface area of the electrodes consists of titanium. Preferably the opposed electrodes are spaced from 2 to 7 (especially from 3 to 5)mm apart. It is also preferred that the surface area of the electrodes should be from 0.4 to 6mm2.It has been discovered that the electrical and chemical properties of titanium are sufficiently comparable to those of platinum to enable titanium electrodes to be used in the electrical detection of the growth of micro-organisms. The preferred electrode spacings and the preferred electrode surface areas help to achieve the optimum ability to detect changes caused by microbiological activity. More particularly this invention provides an apparatus for detecting growth of micro-organisms in a culture system comprising a sterile nutrient medium wherein the apparatus comprises a container for the culture system and means for sensing one or more electrical properties of the culture system and comprising opposed electrodes positioned so as to dip into the culture system when present in the container and wherein at least the effective surface area of the electrodes consists of titanium.
It is probable that the corrosion resistance of the electrodes is at least in part to the thin layer of oxide which forms spontaneously on the metal surface. More importantly if this oxide layer is accidentally removed, a fresh oxide layer forms almost instantaneously.
The electrodes are most conveniently used in the form of cylindrical wire. Preferably the wire should have a diameter of from 0.4 to 1.8 mm and the length which serves as an electrode should be from 1 to 2mm. It is convenient to sheath the wire in a plastics composition (for example a heat-shrinkable material such as crosslinked polyethylene or polypropylene) because this enables a pre-determined length of wire to be exposed for use as the electrode by simply cutting away an appropriate length of the sheath. Alternatively the sheath may be provided by injection moulding plastics compositions onto the wire.
Changes in various electrical properties such as conductance, capacitance or impedance are indicative of the growth of micro-organisms and accordingly the sensing means used in this invention may be used to sense any one or more of these properties. However conductance has been found to be the most reliable indicator of growth and accordingly the sensing means is preferably a conductivity meter used in combination with means for establishing an alternating potential difference between the electrodes. In order to suppress interference to the sensing of conductance caused by variations in the resistance of any solid-state switches that may be used in the circuit, it is preferred to use a large resistance (for example 100 to 1000 ohms) in series with the electrodes.It has also been found that the sensitivity of titanium in measuring conductance is dependant on frequency of the alternating potential difference between the electrodes.
Sensitivity increases greatly with increasing frequency and accordingly it is preferred to use frequencies of at least 5 kHz. However background noise also increases with frequency and so it is preferred not to use frequencies beyond 100kHz.
This invention also provides a method for detecting the growth of micro-organisms which comprises inoculating the micro-organism into a culture system comprising sterile nutrient medium in which is positioned opposed electrodes wherein at least the effective surface area of the electrodes consists of titanium then establishing an alternating potential difference between the electrodes (preferably alternating with a frequency of from 5 to 200 kHz and especially 8 to 20 kHz) and using the potential difference to sense one or more electrical properties of the culture system at a plurality of time intervals whereby changes in the sensed properties with respect to time can be detected and used to detect growth of the organisms. Preferably the properties are sensed at intervals of from 6 to 200 minutes and usually repeated sensings are performed for 5 to 200 hours.
This invention also provides for use in the performance of the invention a cell system ready for inoculation with micro-organisms which comprises a sterilised sealed container containing sterile nutrient medium and a pair of opposed titanium electrodes wherein at least the effective area of the electrodes consists of titanium.
This invention is also suitable for use in the detection of enzyme activity.
Opposed electrodes suitable for use in the performance of this invention will now be described with reference to the drawing which is a part perspective, part sectional view of opposed electrodes located in a culture system. The drawing shows a sterilised container 1 containing a culture system 2 consisting of sterile nutrient medium containing micro-organisms and closed by a puncturable rubber cover 3. Pushed through cover 3 are a pair of parallel polypropylene sleeves 4a and 4b which have each been shrunk around a length 5a or 5b of cylindrical titanium wire 1 mum in diameter. The lower end of sleeves 4a and 4b are cut away to expose 1.5mm lengths of wire which provide the effective surface areas of a pair of opposed electrodes 6a and 6b spaced 3mm apart and which dip into culture system 2.Upper ends of lengths of wire 5a and 5b are connected electrically to conventional means (not shown) for sensing the conductance of the culture system between opposed electrode 6a and 6b. When sensing conductance, the means establishes an electrical potential difference between opposed electrodes 6a and 6b whereupon ions produced by the metabolism of the micro-organisms flow in between the opposed electrodes 6a and 6b essentially in the directions indicated by arrows 7.
The invention is further illustrated by the following Example and Comparative Examples.
EXAMPLE 1
A cell comprising a container, a puncturable rubber seal and opposed titanium electrodes protruding from a polypropylene sheath as shown in Fig. 1 was charged with lOmls of a sterile nutrient medium which was tryptone soya broth. The container had a capacity of just over lOmIs and the titanium wire had been cleaned by immersing in dilute (15wt%) sulphuric acid for
15 minutes at 40"C and then scrubbing with a nylon scouring pad and rinsing with distilled water. The cells were sterilised by heating in an air autoclave at 121"C for 1 5 minutes and then allowed to stand at room temperature for at least two days.
Next the cell was placed in the water bath of a Malthus Microbiological Growth Analyser sold by Matthey Printed Product Limited of Burslem, Stoke on Trent, England. The water bath maintained the cells at 37.2"C+0.002"C.
The Malthus Analyser is an apparatus which provides means for sensing the conductance of the media between the opposed titanium electrodes. Essentially the means comprises an oscillator which provides a 10 kHz alternating current of 240,uA at 24 volts through a 100 k ohm resistor to the electrodes so establishing between the opposed electrodes a potential difference which causes ions to move. The analyser senses the potential difference between the opposed electrodes and supplies the information to a conductance meter which converts the sensed potential difference to a measurement of conductance and hence indirectly senses the conductance of the medium between the opposed electrodes.The Malthus analyser also comprises means for making repeated sensings at regular time intervals and for recording the repeated conductance measurements so that a change in conductance and hence the growth of the microorganisms can be easily detected.
Before using the cell to detect the growth of micro-organisms, the steadyness of the titanium electrodes in sensing conductance was evaluated. This was done by measuring the conductance of the uninoculated nutrient medium at hourly intervals over a period of eight hours. The results are shown in Table 1.Table 1 shows
TABLE 1
Period of time in hours after which the Conductance measurement was made 1 2 3 4 5 6 7 8 Changes in Conductance in uS from previous 0.1 0.7 1.1 0.2 1.3 1.1 0.3 1.2 measurement that over the eight hour period the hourly shift in the conductance measurements was always less than 2,glS and that the average hourly shift is 0.7/S.
The cell was next used to detect the growth of the bacterium Escherichia coli also known as
E. coli. The E. coli was obtained by scraping it from an agar slide into lOmls of trytone soya broth and incubated overnight at 37.2"C. The incubated culture was then diluted by pouring it into one quarter strength Ringer's solution as defined on page 1482 of the second; edition of "Butterworths Medical Dictionary" edited by M. Critchley and published by Butterworths of
London, (the contents of that definition are herein incorporated by reference).
Enough of the diluted culture to fully cover the electrodes was injected into the cell which continued to be maintained at 37.2"C+0.002"C. The conductance of the culture system between the two opposed titanium electrodes was then measured at intervals of 100 minutes in order to detect any increase in conductance with respect to time. The increase in conductance which was detected is shown in Table 2. More particularly Table 2 shows the increase in conductance which had occurred since the previous measurement made 100 minutes earlier.From Table 2 it
TABLE 2
7 1 7 1 Time elapsed in minutes 100 200 300 400 500 600 700 800 900 Increase in Conductance of Culture System since 17 250 235 265 296 306 317 331 331 previous measurement in us can be seen that the rate of increase in conductance as detected by the titanium electrodes is quite large over the first 600 minutes and thereafter it is still large enough to be detected with confidence. Therefore the titanium electrodes are clearly capable of detecting the growth of bacteria by conductance measurements. The electrode pair had a resistance of less than 40 ohms.The electrodes were fully biocompatible and highly resistant to corrosion by the culture system. They withstood sterilisation by steam for 20 minutes at 121"C and at a pressure of 1 bar above atmospheric without losing their ability to detect the growth of bacteria.
COMPARATIVE EXAMPLE A
Example 1 was repeated except that the wire electrodes used were made from nickel instead of titanium. The nickel electrodes gave a very steady measurement of conductance but were too easily corroded. It was found that the sterile nutrient medium absorbed nickel from the electrodes at the rate of about 100 parts per million (based on the weight of the nutrient) per week.
This is too great an absorption rate for disposable electrodes bearing in mind that disposable electrodes are intended to be sold in piace in nutrient medium as part of a cell system ready for inoculation and that the cell system is expected to have a shelf life of about 2 years.
COMPARATIVE EXAMPLE B
Example 1 was repeated except that the titanium wire electrodes were replaced by electrodes made by coating nylon filament lmm in diameter with a layer of platinum 100nm thick. The platinum was deposited by vapour deposition. The electrical resistance of the coated filament was about 150 k ohm/cm which increased even further after sterilisation in the autoclave.
Accordingly the coated filaments were unsuitable for use in the performance of this invention.
Attempts to decrease the resistance of the coated filaments by increasing the thickness of the platinum layer would make them too expensive for use as disposable electrodes.
COMPARATIVE EXAMPLE C
Example 1 was repeated except that the titanium wire electrodes were replaced by electrodes composed of commercially available lmm diameter filaments of carbon-filled nylon. The filaments had a resistance of 60 k ohms/cm which increased ten-fold during sterilisation in the autoclave.
Accordingly these filaments too were unsuitable.
Claims (10)
1. Apparatus for detecting growth of micro-organisms in a culture system comprising sterile nutrient medium by using means comprising opposed electrodes to sense one or more electrical properties of the system which properties are effected by the growth of the organisms whereby detection of changes in the sensed properties can be used to detect growth of the organisms wherein at least the effective surface area of the electrodes consists of titanium.
2. Apparatus for detecting growth of micro-organisms in a culture system comprising a sterile nutrient medium wherein the apparatus comprises a container for the culture system and means for sensing one or more electrical proprties of the culture system and comprising opposed electrodes positioned so as to dip into the culture system when present in the container and wherein at least the effective surface area of the electrodes consists of titanium.
3. Apparatus according to Claim 1 or Claim 2 wherein the electrodes comprise cylindrical wire having the maximum dimension of from 0.4 to 1.8mm.
4. Apparatus according to any one of the preceeding claims wherein the electrodes have a length of from 0.1 to 2mm.
5. Apparatus according to any one of Claims 2 to 4 wherein the means for sensing electrical properties comprises a conductance meter and a resistance of from 100 to 1000 ohms in series with the electrodes.
6. Apparatus according to any one of Claims 2 to 5 wherein the means for sensing electrical properties comprises an oscillator for establishing an alternating potential difference between the opposed electrodes which alternates with a frequency of from 5 to 100 kHz.
7. A method for detecting the growth of micro-organisms which comprises inoculating the micro-organism into a culture system comprising sterile nutrient medium in which is positioned opposed electrodes wherein at least the effective surface area of the electrodes consists of titanium, then establishing an alternating potential difference between the electrodes and using the potential difference to sense one or more electrical properties of the culture system at a plurality of time intervals whereby changes in the sensed properties with respect ta time can be detected and used to detect growth of the organisms.
8. A method according to Claim 7 wherein the alternating potential difference alternates with a frequency of from 50 to 100 kHz.
9. A method according to Claim 7 or Claim 8 wherein the properties are sensed at regular time intervals of from 6 to 200 minutes.
10. A cell system ready for inoculation for use in an apparatus according to any one of
Claims 1 to 6 or in a method according to any one of Claims 7 to 9 which comprises a sterilised sealed container containing sterile nutrient medium and a pair of opposed titanium electrodes.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8516912A GB8516912D0 (en) | 1985-07-04 | 1985-07-04 | Detecting growth of micro-organisms |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB8616341D0 GB8616341D0 (en) | 1986-08-13 |
| GB2177801A true GB2177801A (en) | 1987-01-28 |
Family
ID=10581768
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8516912A Pending GB8516912D0 (en) | 1985-07-04 | 1985-07-04 | Detecting growth of micro-organisms |
| GB8616341A Withdrawn GB2177801A (en) | 1985-07-04 | 1986-07-04 | Apparatus for detecting growth of microorganisms |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8516912A Pending GB8516912D0 (en) | 1985-07-04 | 1985-07-04 | Detecting growth of micro-organisms |
Country Status (1)
| Country | Link |
|---|---|
| GB (2) | GB8516912D0 (en) |
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0277789A2 (en) * | 1987-02-04 | 1988-08-10 | Kabushiki Kaisha Kobe Seiko Sho | Method for measuring biomass |
| GB2211615A (en) * | 1987-10-23 | 1989-07-05 | Mb Group Plc | Methods of detecting micro-organisms |
| EP0397362A1 (en) * | 1989-05-08 | 1990-11-14 | CarnaudMetalbox plc | Electrochemical detection of growth of micro-organisms |
| US5182193A (en) * | 1987-02-04 | 1993-01-26 | Kabushiki Kaisha Kobe Seiko Sho | Method for measuring biomass |
| US5300428A (en) * | 1989-05-08 | 1994-04-05 | Cmb Packaging (Uk) Limited | Electrochemical detection of growth of micro-organisms |
| WO1997033973A1 (en) * | 1996-03-13 | 1997-09-18 | Delta Biotechnology Limited | Fermentation control |
| US6649402B2 (en) * | 2001-06-22 | 2003-11-18 | Wisconsin Alumni Research Foundation | Microfabricated microbial growth assay method and apparatus |
| FR2867279A1 (en) * | 2004-03-05 | 2005-09-09 | Nanotec Solution | Determination of a biomass, useful in the process of fermentation, comprises combination of a technique of measuring capacitance and physico-chemical parameters and treating the data of measurement obtained to determine the variables |
| WO2010010313A2 (en) * | 2008-07-25 | 2010-01-28 | Nanotec Solution | Single-use biomass sensor device, method for producing same, and single-use bioreactor with said sensor built therein |
| US8708319B2 (en) | 2004-01-07 | 2014-04-29 | Pall Technology Uk Limited | Mixing bag with integral sparger and sensor receiver |
| US8986979B2 (en) | 2008-11-13 | 2015-03-24 | Pall Artelis Bvba | Cell culture device and method of culturing cells |
| GB2553895A (en) * | 2016-09-16 | 2018-03-21 | Aber Instruments Ltd | Process |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1529715A (en) * | 1974-10-15 | 1978-10-25 | Bactomatic Inc | Measurement of the impedance of impedance elements |
| GB1561431A (en) * | 1975-10-06 | 1980-02-20 | Kabi Ab | Method for effecting a quantitative determination of a substance in an enzymatic or other biochemical reaction |
| GB2049199A (en) * | 1979-04-26 | 1980-12-17 | Gr International Electronics L | Bacterial activity sensing probe |
| GB1585067A (en) * | 1976-10-19 | 1981-02-25 | Nat Res Dev | Detection of bacterial activity |
| EP0036274A2 (en) * | 1980-03-08 | 1981-09-23 | Japan Tectron Instruments Corporation | Methods of monitoring micro-organisms and media for culture |
| GB2142433A (en) * | 1983-06-29 | 1985-01-16 | Metal Box Plc | Apparatus for detecting micr-organisms |
-
1985
- 1985-07-04 GB GB8516912A patent/GB8516912D0/en active Pending
-
1986
- 1986-07-04 GB GB8616341A patent/GB2177801A/en not_active Withdrawn
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1529715A (en) * | 1974-10-15 | 1978-10-25 | Bactomatic Inc | Measurement of the impedance of impedance elements |
| GB1561431A (en) * | 1975-10-06 | 1980-02-20 | Kabi Ab | Method for effecting a quantitative determination of a substance in an enzymatic or other biochemical reaction |
| GB1585067A (en) * | 1976-10-19 | 1981-02-25 | Nat Res Dev | Detection of bacterial activity |
| GB2049199A (en) * | 1979-04-26 | 1980-12-17 | Gr International Electronics L | Bacterial activity sensing probe |
| EP0036274A2 (en) * | 1980-03-08 | 1981-09-23 | Japan Tectron Instruments Corporation | Methods of monitoring micro-organisms and media for culture |
| GB2142433A (en) * | 1983-06-29 | 1985-01-16 | Metal Box Plc | Apparatus for detecting micr-organisms |
Non-Patent Citations (1)
| Title |
|---|
| WO A1 80/02849 * |
Cited By (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0277789A2 (en) * | 1987-02-04 | 1988-08-10 | Kabushiki Kaisha Kobe Seiko Sho | Method for measuring biomass |
| EP0277789A3 (en) * | 1987-02-04 | 1988-10-05 | Kabushiki Kaisha Kobe Seiko Sho | Method for measuring biomass |
| US5182193A (en) * | 1987-02-04 | 1993-01-26 | Kabushiki Kaisha Kobe Seiko Sho | Method for measuring biomass |
| GB2211615A (en) * | 1987-10-23 | 1989-07-05 | Mb Group Plc | Methods of detecting micro-organisms |
| EP0397362A1 (en) * | 1989-05-08 | 1990-11-14 | CarnaudMetalbox plc | Electrochemical detection of growth of micro-organisms |
| US5300428A (en) * | 1989-05-08 | 1994-04-05 | Cmb Packaging (Uk) Limited | Electrochemical detection of growth of micro-organisms |
| WO1997033973A1 (en) * | 1996-03-13 | 1997-09-18 | Delta Biotechnology Limited | Fermentation control |
| US6150133A (en) * | 1996-03-13 | 2000-11-21 | Delta Biotechnology Limited | Fermentation control |
| US6649402B2 (en) * | 2001-06-22 | 2003-11-18 | Wisconsin Alumni Research Foundation | Microfabricated microbial growth assay method and apparatus |
| US8708319B2 (en) | 2004-01-07 | 2014-04-29 | Pall Technology Uk Limited | Mixing bag with integral sparger and sensor receiver |
| WO2005085412A2 (en) * | 2004-03-05 | 2005-09-15 | Nanotec Solution | Method and device for the measurement and characterisation of a biomass, application thereof in relation to on-line biomass data measuring in a fermentation process and associated control method |
| WO2005085412A3 (en) * | 2004-03-05 | 2006-01-19 | Nanotec Solution | Method and device for the measurement and characterisation of a biomass, application thereof in relation to on-line biomass data measuring in a fermentation process and associated control method |
| FR2867279A1 (en) * | 2004-03-05 | 2005-09-09 | Nanotec Solution | Determination of a biomass, useful in the process of fermentation, comprises combination of a technique of measuring capacitance and physico-chemical parameters and treating the data of measurement obtained to determine the variables |
| WO2010010313A2 (en) * | 2008-07-25 | 2010-01-28 | Nanotec Solution | Single-use biomass sensor device, method for producing same, and single-use bioreactor with said sensor built therein |
| WO2010010313A3 (en) * | 2008-07-25 | 2010-03-25 | Nanotec Solution | Single-use biomass sensor device, method for producing same, and single-use bioreactor with said sensor built therein |
| US9567561B2 (en) | 2008-07-25 | 2017-02-14 | Hamilton Bonaduz Ag | Single-use biomass sensing device, method for producing this device and single-use bioreactor incorporating this sensor |
| US8986979B2 (en) | 2008-11-13 | 2015-03-24 | Pall Artelis Bvba | Cell culture device and method of culturing cells |
| GB2553895A (en) * | 2016-09-16 | 2018-03-21 | Aber Instruments Ltd | Process |
| GB2553895B (en) * | 2016-09-16 | 2019-08-14 | Aber Instruments Ltd | Obtaining multiple biomass measurements from one or more biological media using a probe which can be sterilised and re-used |
| US20190256815A1 (en) * | 2016-09-16 | 2019-08-22 | Aber Instruments Limited | Biomass monitoring process and biomass monitoring probe suitable to perform the process |
Also Published As
| Publication number | Publication date |
|---|---|
| GB8516912D0 (en) | 1985-08-07 |
| GB8616341D0 (en) | 1986-08-13 |
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| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |