WO2000008203A1 - Procede de controle de la contamination bacterienne d'une plaie - Google Patents

Procede de controle de la contamination bacterienne d'une plaie Download PDF

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Publication number
WO2000008203A1
WO2000008203A1 PCT/GB1999/002585 GB9902585W WO0008203A1 WO 2000008203 A1 WO2000008203 A1 WO 2000008203A1 GB 9902585 W GB9902585 W GB 9902585W WO 0008203 A1 WO0008203 A1 WO 0008203A1
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Prior art keywords
atp
wound
luciferase
enzyme
concentration
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PCT/GB1999/002585
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English (en)
Inventor
Donald Francis Walker
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Johnson & Johnson Medical Limited
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Priority to AU52945/99A priority Critical patent/AU5294599A/en
Publication of WO2000008203A1 publication Critical patent/WO2000008203A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/38—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing enzymes
    • 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
    • C12Q1/04—Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
    • 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
    • C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
    • C12Q1/42—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase involving phosphatase
    • 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
    • C12Q1/66—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving luciferase

Definitions

  • the present invention relates to a method of monitoring the bacterial contamination of a wound by monitoring the ATP concentration of wound fluid or exudate.
  • the present invention also relates to devices and kits for use in such methods.
  • Wound healing is a complex dynamic process that results in the restoration of anatomic continuity and function; an ideally healed wound is one that has returned to normal anatomic structure, function and appearance.
  • TNF- ⁇ interleukin-1 and tumour necrosis factor alpha
  • Such a diagnostic would enable small-scale bacterial infection to be treated before wound chronicity sets in and would also allow the monitoring of an infected wound to assess the success of an anti-bacterial treatment.
  • adenosine triphosphate (ATP) concentration of a wound correlates closely with the level of bacterial contamination.
  • a method of monitoring the bacterial contamination of a wound comprising monitoring the ATP concentration of wound fluid.
  • the measurement of the ATP concentration of the wound fluid allows the level of bacterial contamination to be accurately assessed.
  • the step of monitoring is preferably carried out on wound fluid that has been removed from the body of the patient, but can also be performed on wound fluid in situ.
  • the wound may be an acute wound such as an acute traumatic laceration, perhaps resulting from an intentional operative incision, or the wound may be a chronic wound.
  • the method of the invention is envisaged as being most useful in the diagnosis of bacterial contamination of a chronic wound.
  • the chronic wound is selected from the group consisting of venous ulcers, pressure sores, decubitis ulcers, diabetic ulcers and chronic ulcers of unknown aetiology.
  • the diagnostic assay is designed so as to provide a correlation between a measurable signal and the size of the bacterial population that is associated with clinical infection.
  • bacterial infection of wounds is generally taken to be 10 cfu/cm .
  • the system should be set up so that a detectable response is tripped at around 10 cfu/cm bacteria so as to give a warning of bacterial contamination.
  • the ATP concentration correlated with such a level of bacteria is far in excess of the normal ATP turnover in the wound; accordingly, background ATP concentrations do not distort the signal to a significant extent.
  • wound fluid is meant to refer to the exudate that is secreted or discharged by cells in the environment of the wound. This fluid contains cells, both living and dead, and a variety of inflammatory cytokines.
  • ATP concentration is meant the free concentration of ATP in the wound fluid.
  • the ATP concentration may be assessed in situ, or alternatively a sample of wound fluid may be taken as a clinical swab or as a fluid sample.
  • the ATP concentration of the wound fluid may be monitored by any method known to those of skill in the art. Suitable methods include those utilising chemical or enzyme- linked reactions, or by conjugating the reaction of ATP to immunological, fluorogenic, chemiluminescent, chromogenic or radioactive detection mechanisms.
  • ATP ATP
  • hydrolysis a chemical reaction in which ATP participates as a substrate
  • the chemical energy released from hydrolysis is then utilised under physiological conditions in active transport, or may be converted to mechanical, light or electrical energy, or may be released as heat. Accordingly, any chemical reaction to which ATP concentration can be stoichiometrically coupled may be used in the method of the present invention.
  • ATP detection will involve the use of enzymes whose reaction with substrate is driven by ATP and which either themselves, or through coupled reactions give a detectable signal that is proportionate to ATP levels.
  • ATP concentration is coupled to the generation of a detectable signal through the action of enzymes that dissipate the energy of ATP hydrolysis as light or electrochemical energy.
  • Suitable enzymatic reactions include, but are not limited to the luciferase-luciferin reaction, the hydrolysis of ATP by alkaline phosphatase.
  • Alkaline phosphatase is an enzyme that catalyses the hydrolysis of orthophosphoric monoester to an alcohol and orthophosphate. ATP is a substrate of this enzyme.
  • ALP assays that couple the activity of this enzyme to ATP concentration by electrochemical modulation.
  • ECL electrochemical luminescence
  • Amersham may be used to couple the ALP-catalysed hydrolysis of ATP to give a measurable signal that is proportionate to the levels of ATP in wound fluid.
  • the "Alkphos direct" labelling and detection systems are of particular usefulness in this regard.
  • the method of the present invention may also utilise the luciferase-luciferin reaction.
  • This assay is particularly applicable to the method of the present invention due to its simplicity and sensitivity.
  • the luciferase enzyme catalyses reactions in which a singlet intermediate is formed in high quantum yield. This intermediate decays, simultaneously omitting visible light.
  • luciferin D-LH 2
  • ATP-Mg 2+ ATP-Mg 2+
  • molecular oxygen luciferase catalyses the production of light according to the following reactions determined by DeLuca et al. Method EnzvmoL vol. LVII, pages 3-15 (1978);
  • the first reaction involves the activation of luciferin and hydrolysis of ATP resulting in the formation of an enzyme-bound luciferyl adenylate (E.LH 2 AMP).
  • E.LH 2 AMP enzyme-bound luciferyl adenylate
  • the second reaction requires molecular oxygen and leads to the formation of enzyme-bound excited product, which subsequently decomposes to give off light and enzyme-bound product. Quantitative liberation of CO from the luciferin during the reaction is also observed.
  • Coenzyme A may be used as a co-factor in this reaction; in the presence of coenzyme A, oxidation occurs from luciferyl-CoA with more favourable total kinetics, resulting in the generation of constant light intensity that is proportionate to the ATP concentration.
  • a luminometer In order to measure the generation of light, a luminometer may be used. However, it will be apparent to the skilled artisan that this assay is easily adaptable to measurement of light generation in scintillation counters or using photographic film.
  • a sample of wound fluid must be added to the ATP assay system. Measurement may either be made in situ, or fluid may be removed from the wound for subsequent ATP measurement. The decision as to which method is used will depend upon the type of wound in question.
  • a clinical swab, dressing, "dipstick” or other biosensor device may be applied directly to the surface of the wound.
  • This device should contain all of the required components of the ATP-linked reaction so that the reaction itself may proceed in situ. The device can then be removed from the wound and the signal measured by the appropriate means.
  • a physician may not actually require an accurate assessment of the precise degree of bacterial infection, but may just wish to know whether there is a sufficient degree of infection to warrant prophylactic action. In these cases, visible assessment of the dressing may be sufficient to allow identification of the specific areas of infection. Unnecessary treatment of healthy granulating tissue can then be avoided.
  • a dressing that allows mapping of the infected areas of a wound will be preferable in certain instances. Diagnostic wound mapping sheets that could be adapted to the methods of the present invention are described in co-pending application GB 9705081.9 filed on 12th March 1997, the entire content of which is hereby incorporated by reference.
  • Immobilisation of reaction components onto a dipstick, wound mapping sheet or other solid or gel substrate offers the opportunity of performing a more quantitative measurement.
  • the device may be transferred to a spectrometer, a luminometer or a scintillation counter. Suitable methods of analysis will be apparent to those of skill in the art.
  • Immobilisation of the reaction components to a small biosensor device will also have the advantage that less of the components (such as enzyme and substrate) are needed.
  • the device will thus be less expensive to manufacture than a dressing that needs to have a large surface area in order to allow the mapping of a large wound area.
  • ATP concentration of a wound may alternatively be measured in an aqueous assay system.
  • Wound fluid may be extracted directly from the environment of the wound or can be washed off the wound using a saline buffer. The resulting solution can then be assayed for ATP concentration in a test tube or in a microassay plate. Clearly, this will allow a more accurate assessment of the exact levels of bacteria in a wound.
  • Such a method will be preferable for use in cases in which the wound is too small or too inaccessible to allow access of a diagnostic device such as a dipstick.
  • This method has the additional advantage that the wound exudate sample may be diluted. Under most diagnosis methods, dilution will still allow accurate assessment of ATP amount, yet will enable an operative to assess the concentration of a wound from which it is not possible to extract more than a few microlitres of exudate.
  • Such wounds will include small or internal ulcers and pressure sores.
  • an aqueous assay system is more applicable to use in a laboratory environment, whereas a wound dressing containing the necessary reaction components will be more suitable for use in a hospital or domestic environment.
  • Figure 1 shows a luciferase calibration curve at high concentrations of ATP.
  • Figure 2 shows a luciferase calibration curve at low concentrations of ATP.
  • Figure 3 shows the stability of luciferase at different temperatures.
  • Figure 4 shows the elucidation of ATP concentration for different amounts of E. coli using a luciferase assay.
  • Figure 5 shows the measurement of ATP concentration for different amounts of S. aureus using the Hy-Lite system (Merck & Co.).
  • Figure 6 shows the measurement of ATP concentration for different amounts of E. coli using the Hy-Lite system (Merck & Co.).
  • Figure 7 shows an ATP standard curve obtained using the Sigma ATP detection kit.
  • Figure 8 shows an ATP curve obtained using E. coli diluted in wound fluid analogue.
  • Figure 9 shows an ATP curve obtained using S. aureus diluted in wound fluid analogue.
  • Figure 10 shows an ATP standard curve measured in porcine wound fluid.
  • HEPES 4-(2-hydroxyethyl)-l- piperazine ethanesulfonic acid
  • Luciferin stock 5 mg of solid Luciferin (Sigma L6152) 1 ml of pH 7.8 Spectroscopy buffer • 1ml of 0.9 mM Luciferin containing:- 50 ⁇ l of 18 mM Luciferin stock
  • E. coli ranged between: 0-20 ⁇ l (0 - 2.6x10 cells of E.c ⁇ / /ml)
  • Example 1 Establishing the optimal conditions for the luciferase assay
  • spectrophotometer provided a maximum absorbance of a 40 ⁇ M ATP in 1ml of pH 7.8 spectroscopy buffer, in a spectrum scanned between 220 and 300 nm.
  • a typical assay mixture contained 1 ml pH 7.8 luciferase reaction buffer, 0.32nM luciferase (lO ⁇ l of 32nM) made in pH 7.8 luciferase storage buffer, and 9 ⁇ M luciferin (lO ⁇ l of 0.9mM).
  • Appropriate amounts of ATP ranging between 10 "2 nM - 10 4 nM were added to initiate the reaction and record the maximum chemiluminescence.
  • Figure 1 shows a calibration curve with high ATP concentrations, and confirms a maximum activity at 50 ⁇ M ATP.
  • Figure 2 shows lower ATP concentrations, however, this curve also confirms a detection limit of InM. The rate of ATP detected is clearly proportional to quantity of ATP.
  • the stability of the luciferase assay was investigated at different temperatures over a one week period in order to investigate the ideal temperature and length of storage for the assay.
  • a concentration of 32nM luciferase was found to be most stable at -20°C confirming a 37% luciferase degradation, over a one week period. Whereas, a 100% luciferase degradation at 20°C, and a 68% luciferase degradation was observed over a one week period [Figure 3].
  • Example 2 Testing luciferase assays on biological samples
  • ATP concentrations were investigated in saliva and in an E. coli culture, using the formulated assay.
  • a luciferase assay kit was developed in the addition of 0.32nM luciferase and 9 ⁇ M luciferin in 1ml pH 7.8 luciferase reaction buffer. Maximum chemiluminiscence was measured by the addition of 10 ⁇ l of saliva or tooth plaque dissolved in saliva from healthy individuals.
  • a luciferase assay kit was produced from the addition of 0.32 nM luciferase and 9 ⁇ M luciferin in 1 ml pH 7.8 luciferase reaction buffer. ATP detection was initiated in the addition of 10 ⁇ l of saliva and 10 ⁇ l of extractant (left for approximately 5 minutes), into the luciferase assay. The amount of extractant was varied between 10-30 ⁇ l.
  • a 5 0 was measured for 1/100 dilution of 10 ⁇ l Escherichia coli to calculate the concentration of the stock solution.
  • a luciferase assay kit was produced in the addition of 0.36 ⁇ M luciferase and 9 nM luciferin into 1 ml pH 7.8 luciferase reaction buffer. Maximum chemiluminescence was measured in the presence of 30 ⁇ l of extractant to varying amounts of 1.3 x 10 9 E.coli, ranging between 0 - 20 ⁇ l, which was inserted in the luciferase assay. The corrected chemiluminescence was read off the calibration curve to determine the amount of ATP in different amounts of E.coli under investigation.
  • DH 5 ⁇ E.coli (10 ⁇ l) has an absorbance of 0.267 at a wavelength of 560nm detected by a UN. spectrometer.
  • Absorbance 1 5x10 cells of bacteria/ml
  • Absorbance 0.267 1.3xl0 8 cells of E.coli/ml ATP detection was found to be proportional to the quantity of E. coli added to the luciferase assay. 45nM ATP was detected in extractant in the absence of E. coli [ Figure 4].
  • the designed luciferase assay was found to detect levels of ATP that correlated with the levels of bacteria in wound exudate. It is evident that there is some degree of product inhibition, and that the enzyme can turn over slowly in the present of ATP and excess luciferin (DeLuca, 1976).
  • the enzyme in principle can be used to measure total ATP in a sample or it can be coupled to ATP -producing or consuming reactions. One can confirm that higher ATP results in faster decay and therefore greater inhibition.
  • the sensitivity quoted by DeLuca et al, (1978) is such that as little as 10 *14 mol of ATP can be accurately measured. In this study, the minimum ATP detection was found to be InM. Luciferase is ideally stable at -20°C, however, it must not be stored for longer than a couple of days, due to the rapid degradation of luciferase confirmed.
  • the contents, cost, storage temperature and length of storage is summarised in Table 2.
  • Example 3 Use of the Hy-Lite system to determine levels of ATP in 2 bacterial strains
  • a commercial kit was used, based on an ATP-dependent reaction between Luciferin- Luciferase.
  • This kit is called the Hy-Lite system (Merck Diagnostics, Inc).
  • the kit consist of specific pens to take a sample and a luminometer with a digital readout for displaying relative light units (rlu) emitted from the sample.
  • This kit was used to measure ATP concentrations in different dilutions of various bacterial suspensions.
  • CS/DMEM is used as a Wound fluid analogue because it has similar protein profile as serum and protein concentration as wound fluid
  • DMEM Dulbecco's Modified Eagles Medium
  • TP Bacter Peptone Water
  • the Hy-Lite system (Merck Diagnostics, Inc) containing pens for taking a sample and a luminometer for measuring the relative light units emitted from each sample.
  • the cultures were transferred from glass bottles into plastic universals. The samples were centrifuged for 15 minutes at 3000rpm. The supernatant was decanted and the pellet was resuspended in 10ml TP; this was repeated three times.
  • each of the bacterial suspension was added to 9ml of TP and this gave the stock solution which was estimated to be a suspension of 10 10 bacteria using the Macfarlands Indicator kit.
  • the stock solution was then diluted 1 in 10 to obtain 10 7 , 10 6 , 10 5 , 10 4 and 10 3 suspensions.
  • the Hy-Lite kit was then used to measure ATP levels in each suspension, as follows;
  • Example 3 To confirm the results obtained in Example 3, another kit, which also uses enzymatic determination of ATP concentration, was obtained from Sigma. The reaction utilised in this kit is coupled with a dephosphorylation reaction that involves oxidation of NADH to NAD, hence the decrease in absorbance at 340nm can be used to calculate the ATP concentration.
  • CS Calf Serum
  • DMEM Dulbecco's Modified Eagles Medium
  • PBS Phosphate buffered Saline
  • Porcine Wound Fluid taken from J&J Medical, Biopolymer Group study. The wound fluid was obtained as follows:
  • the right wound had lmls of LPS solution at either 0.1 or 1.0 microgram/ml strength injected into the wound edge, 0.25mls in each edge. 5. Each wound was then covered with a 2.0 cm x 2.0 cm ReleaseTM J&J dressing and covered in BioclusiveTM before being wrapped in zinc oxide tape.
  • Rats of both LPS doses were culled at each time point by asphyxiation with carbon dioxide. A 5ml blood sample was retained in lithium heparin tubes for MMP analysis of plasma.
  • the wound fluid used was pooled from week 1,4,7,10,13,16 and 19 at 72h time point, injected with 1.0 microgram/ml LPS solution.
  • LPS stimulated wounds can be claimed to "imitate" an infected wound as LPS is found on the coat of bacteria and hence should cause a similar response to that of infection.
  • cap vial and invert several times to dissolve NADH.
  • the factor 195 is derived as follows:
  • ATP was also measurable in true wound fluid, indicating that there was no interference due to other wound proteins, for example from LPS.

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Abstract

L'invention concerne un procédé de contrôle de la contamination bactérienne d'une plaie. Ce procédé consiste à contrôler la concentration d'adénosine triphosphate (ATP) du liquide prélevé au niveau de la plaie. Le contrôle est effectué de préférence au moyen d'une réaction à couplage enzymatique telle que la réaction luciferine-luciferase. Cette invention se rapporte également à des trousses de diagnostic et des pansements convenant au procédé utilisé.
PCT/GB1999/002585 1998-08-05 1999-08-05 Procede de controle de la contamination bacterienne d'une plaie WO2000008203A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU52945/99A AU5294599A (en) 1998-08-05 1999-08-05 Method of monitoring bacterial contamination of a wound

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9817059A GB2340235A (en) 1998-08-05 1998-08-05 Monitoring bacterial contamination of a wound involving assay of adenosine triphosphate
GB9817059.0 1998-08-05

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WO2000008203A1 true WO2000008203A1 (fr) 2000-02-17

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Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003040406A2 (fr) * 2001-11-05 2003-05-15 Johnson & Johnson Medical Limited Surveillance d'une plaie
WO2004030711A1 (fr) * 2002-10-01 2004-04-15 Johnson & Johnson Medical Limited Pansements therapeutiques sensibles aux enzymes
WO2004086043A1 (fr) * 2003-03-26 2004-10-07 Johnson & Johnson Medical Limited Prediction et detection d'une infection de plaie
GB2426335A (en) * 2005-05-20 2006-11-22 Ethicon Inc Marker of wound infection
GB2399881B (en) * 2003-03-26 2007-04-25 Johnson & Johnson Medical Ltd Prediction and detection of wound infection
US8124370B2 (en) 2003-01-31 2012-02-28 Systagenix Wound Management (Us), Inc. Cationic anti-microbial peptides and methods of use thereof
US9017963B2 (en) 2002-01-31 2015-04-28 Woundchek Laboratories (Us), Inc. Method for detecting microorganisms
US9024751B2 (en) 2012-04-12 2015-05-05 Elwha Llc Dormant to active appurtenances for reporting information regarding wound dressings
US9084530B2 (en) 2012-04-12 2015-07-21 Elwha Llc Computational methods and systems for reporting information regarding appurtenances to wound dressings
AU2009256172B2 (en) * 2008-06-04 2015-11-26 Kci Licensing, Inc. Detecting infection in reduced pressure wound treatment
US9562253B1 (en) 2012-11-09 2017-02-07 Point Of Care Diagnostics, Llc Distinguishing between a bacterial and non-bacterial infection at the point of care
US10130518B2 (en) 2012-04-12 2018-11-20 Elwha Llc Appurtenances including sensors for reporting information regarding wound dressings
US10158928B2 (en) 2012-04-12 2018-12-18 Elwha Llc Appurtenances for reporting information regarding wound dressings
US10226212B2 (en) 2012-04-12 2019-03-12 Elwha Llc Appurtenances to cavity wound dressings
US10265219B2 (en) 2012-04-12 2019-04-23 Elwha Llc Wound dressing monitoring systems including appurtenances for wound dressings
CN111089859A (zh) * 2018-10-23 2020-05-01 北京中医药大学 新型三磷酸腺苷生物发光测定方法及其用途
US10739352B2 (en) 2007-11-20 2020-08-11 Convatec Technologies Inc. Diagnosis and treatment of wound infection with procalcitonin as diagnostic marker
CN116803432A (zh) * 2022-03-17 2023-09-26 江苏迈健生物科技发展股份有限公司 一种判断伤口感染的敷料

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GB2390157B (en) * 2002-06-25 2005-09-28 Johnson & Johnson Medical Ltd Wound fluid collecting and indicating device
GB201502350D0 (en) * 2015-02-12 2015-04-01 Microarray Ltd Determining the condition of a wound

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DE9304954U1 (de) * 1992-04-13 1993-08-12 Biolac GmbH Gesellschaft für industrielle Nutzung von Milchinhaltsstoffen, 31097 Harbarnsen Analyse-Kit zur Bestimmung der bakteriellen Keimzahl in Molke und Molkeninhaltsstoffen

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Publication number Priority date Publication date Assignee Title
EP0309429A2 (fr) * 1987-09-23 1989-03-29 Life Science International Ab Détermination d'ATP cellulaire par luminescence

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003040406A3 (fr) * 2001-11-05 2003-10-16 Johnson & Johnson Medical Ltd Surveillance d'une plaie
US7794925B2 (en) 2001-11-05 2010-09-14 Systagenix Wound Management (Us), Inc. Diagnosis of clinical infection of a wound
WO2003040406A2 (fr) * 2001-11-05 2003-05-15 Johnson & Johnson Medical Limited Surveillance d'une plaie
US9017963B2 (en) 2002-01-31 2015-04-28 Woundchek Laboratories (Us), Inc. Method for detecting microorganisms
WO2004030711A1 (fr) * 2002-10-01 2004-04-15 Johnson & Johnson Medical Limited Pansements therapeutiques sensibles aux enzymes
US8124370B2 (en) 2003-01-31 2012-02-28 Systagenix Wound Management (Us), Inc. Cationic anti-microbial peptides and methods of use thereof
WO2004086043A1 (fr) * 2003-03-26 2004-10-07 Johnson & Johnson Medical Limited Prediction et detection d'une infection de plaie
GB2399881B (en) * 2003-03-26 2007-04-25 Johnson & Johnson Medical Ltd Prediction and detection of wound infection
GB2426335A (en) * 2005-05-20 2006-11-22 Ethicon Inc Marker of wound infection
US8491852B2 (en) 2005-05-20 2013-07-23 Systagenix Wound Management (Us), Inc. Marker of wound infection
US10739352B2 (en) 2007-11-20 2020-08-11 Convatec Technologies Inc. Diagnosis and treatment of wound infection with procalcitonin as diagnostic marker
AU2009256172B2 (en) * 2008-06-04 2015-11-26 Kci Licensing, Inc. Detecting infection in reduced pressure wound treatment
US9024751B2 (en) 2012-04-12 2015-05-05 Elwha Llc Dormant to active appurtenances for reporting information regarding wound dressings
US9451340B2 (en) 2012-04-12 2016-09-20 Elwha Llc Computational methods and systems for reporting information regarding appurtenances to wound dressings
US9510781B2 (en) 2012-04-12 2016-12-06 Elwha Llc Dormant to active appurtenances for reporting information regarding wound dressings
US10130518B2 (en) 2012-04-12 2018-11-20 Elwha Llc Appurtenances including sensors for reporting information regarding wound dressings
US10158928B2 (en) 2012-04-12 2018-12-18 Elwha Llc Appurtenances for reporting information regarding wound dressings
US10226212B2 (en) 2012-04-12 2019-03-12 Elwha Llc Appurtenances to cavity wound dressings
US10265219B2 (en) 2012-04-12 2019-04-23 Elwha Llc Wound dressing monitoring systems including appurtenances for wound dressings
US9084530B2 (en) 2012-04-12 2015-07-21 Elwha Llc Computational methods and systems for reporting information regarding appurtenances to wound dressings
US9562253B1 (en) 2012-11-09 2017-02-07 Point Of Care Diagnostics, Llc Distinguishing between a bacterial and non-bacterial infection at the point of care
CN111089859A (zh) * 2018-10-23 2020-05-01 北京中医药大学 新型三磷酸腺苷生物发光测定方法及其用途
CN116803432A (zh) * 2022-03-17 2023-09-26 江苏迈健生物科技发展股份有限公司 一种判断伤口感染的敷料

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