USRE43389E1 - Vessel for blood sampling - Google Patents
Vessel for blood sampling Download PDFInfo
- Publication number
- USRE43389E1 USRE43389E1 US11/506,164 US50616499A USRE43389E US RE43389 E1 USRE43389 E1 US RE43389E1 US 50616499 A US50616499 A US 50616499A US RE43389 E USRE43389 E US RE43389E
- Authority
- US
- United States
- Prior art keywords
- vessel
- blood
- buffer
- solution
- guanidinium
- 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.)
- Expired - Lifetime
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/14—Devices for taking samples of blood ; Measuring characteristics of blood in vivo, e.g. gas concentration within the blood, pH-value of blood
- A61B5/1405—Devices for taking blood samples
- A61B5/1438—Devices for taking blood samples using pre-evacuated means
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/15—Devices for taking samples of blood
- A61B5/150007—Details
- A61B5/150015—Source of blood
- A61B5/15003—Source of blood for venous or arterial blood
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/15—Devices for taking samples of blood
- A61B5/150007—Details
- A61B5/150351—Caps, stoppers or lids for sealing or closing a blood collection vessel or container, e.g. a test-tube or syringe barrel
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/15—Devices for taking samples of blood
- A61B5/150007—Details
- A61B5/150755—Blood sample preparation for further analysis, e.g. by separating blood components or by mixing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/15—Devices for taking samples of blood
- A61B5/153—Devices specially adapted for taking samples of venous or arterial blood, e.g. with syringes
- A61B5/154—Devices using pre-evacuated means
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1003—Extracting or separating nucleic acids from biological samples, e.g. pure separation or isolation methods; Conditions, buffers or apparatuses 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
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6806—Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
- Y10T436/2525—Stabilizing or preserving
Definitions
- the present invention relates to a vessel for withdrawing blood, and the blood withdrawn should especially be used for stabilizing and analyzing nucleic acids.
- nucleic acids such as (m)RNA or DNA are to be analyzed.
- nucleic acids contained in the sample should optimally be stabilized already at the moment of withdrawal, i.e. a degradation of the existing nucleic acids should be prevented, but also the new synthesis of mRNA.
- Cells contain nucleases, enzymes, which destroy nucleic acids as soon as they come into contact with the substrates thereof (RNA, DNA).
- RNA substrates thereof
- the effect of cellular and extracellular nucleases is normally under physiological control as long as the cells are in their normal environment.
- the withdrawal of blood effects more or less strong changes in the nucleic acids contained in the cells.
- Nucleases are then released within the cells and/or by the lysis of cells to the outside.
- nucleic acids are synthetized more or less strongly. In particular the long-term storage of blood leads to aging and destruction of the cells.
- nucleic acids the whole method ranging from sampling to the measurement of nucleic acids can be controlled under standardized conditions.
- a quantitatively and qualitatively defined standard nucleic acid should already be added to the sample material during withdrawal and should be subjected to the whole process of sampling and determination. This can also not be accomplished with the conventional withdrawal systems.
- a further drawback of conventional blood withdrawal is the risk of transferring infectious material because manual process steps have so far been needed for the isolation of nucleic acids. Contact with potentially infectious germs cannot be ruled out.
- nucleases are extremely active enzymes which can only be inhibited under extremely denaturing conditions. Denaturation depends on the concentration of the guanidinium salt in solution. An inhibiting concentration of guanidinium salt in solution does not exist in the cited method right from the beginning. Thus, there is an uncontrolled degradation of nucleic acids during the dissolution process. Moreover, in this method the addition of reducing agents is omitted, without which an efficient inhibition, in particular of RNases, is not ensured (see Example no. 5).
- the sample prepared in this way cannot directly be used for the further nucleic acid isolation on glass surfaces.
- the use of guanidinium salt powder does not permit the addition of internal nucleic acid standards. Such standards are mandatory for process control and exact quantification.
- the present invention has been based on the technical problem of providing a vessel for withdrawing blood which does not have the drawbacks of the prior art.
- a vessel for withdrawing blood the vessel containing an aqueous solution comprising the following components:
- the vessel of the invention has the following advantages: 1. Blood is already lysed at the moment of withdrawal in that the withdrawal vessel already contains a nucleic acid-stabilizing substance in solution. 2.
- the nucleic acid-stabilizing substance is composed such that the sample material, in particular the nucleic acids contained therein, are directly stabilized upon contact with the solution. 3. In contrast to all of the former standard withdrawal systems, such as EDTA or heparin-containing withdrawal vessels, the stabilized sample need no longer be handled as infectious material. 4.
- the nucleic acid-stabilizing substance is composed such that the sample material can directly be used in subsequent isolating methods. 5.
- the nucleic acid-stabilizing substance can be separated during subsequent isolation so efficiently that an inhibition of PCR is not observed. 6.
- the nucleic acid-stabilizing substance may have added thereto an internal standard. This permits the control of the whole method from the moment of sampling up to the detection of nucleic acids.
- the withdrawal vessel mentioned under item 1 is a conventional blood withdrawing vessel (small tube) which has introduced thereinto a defined volume of a nucleic acid-stabilizing substance.
- the small tube is then preferably subjected to a defined vacuum which guarantees that only a specific volume of blood can flow thereinto during withdrawal.
- the small tube can be handled by conventional blood-taking methods.
- the solution contained in the tube contains the following reagents in a specially preferred embodiment: Guanidinium thiocyanate, Triton-X-100, dithiothreitol and a suitable buffer system, such as citrate, Tris or HEPES.
- the solution is compatible with the vacuum tube.
- This solution can be stored in the vacuum tube without any problems and without any impairment of the desired stabilizing function.
- the whole system presents no problems, in particular to blood donors, and is safe during sampling.
- the solution containing the guanidinium salt, the buffer substance, the reducing agent and/or the detergent is stable in storage and converts the supplied and freshly taken blood into a material which is also stable in storage and can directly be subjected to the standard nucleic-acid analysis kits (e.g. those of Roche or Qiagen).
- the standard nucleic-acid analysis kits e.g. those of Roche or Qiagen.
- Guanidinium thiocyanate and/or guanidinium chloride are preferred as guanidinium salt.
- the guanidinium salt is present in a concentration of 2.0 to 8.0 M.
- Tris or citrate is preferred as the buffer substance, the exact pH being preferably adjusted with HCl.
- Further possible buffers are however HEPES, MOPS, citrate and phosphate buffer, such as PBS.
- the buffer concentration is preferably between 10 and 300 mM, particularly preferably between 10 and 100 mM.
- Triton-X-100 is preferred as the detergent. Further possible detergents are NP40, Tween 20, polydocanol or other detergents.
- the detergent concentration is preferably at 5 to 30% (w/v), particularly preferably at 10 to 20% (w/v).
- DTT is preferred as the reducing agent, but ⁇ -mercaptoethanol, TCEP (Tris(2-carboxyethyl)phosphine) or other reducing agents can also be used.
- TCEP Tris(2-carboxyethyl)phosphine
- the preferred concentration of the reducing agent is at 0.1 to 10% (w/v), particularly preferred are 0.5 to 2% (w/v).
- the pH of the solution is preferably at 3.0 to 9.0, particularly preferably at 4.0 to 7.5, particularly preferably at 5 to 6.
- the pH of the solution is in particular chosen such that a pH ranging from 5.0 to 7.6 is set after addition of the sample material. Particularly preferred is a pH between 6.3 and 6.9 (see Example no. 8).
- a particularly preferred solution preferably contains 4 M guanidinium thiocyanate, 45 mM Tris/HCl, 18%, preferably 15% (w/v) Triton-X-100, 0.8% (w/v) DTT and has a pH of 6.0.
- the volume for receiving the blood sample has a negative pressure which can be adjusted such that a previously determined blood volume is sucked into the vessel after a blood vessel has been pierced.
- a negative pressure which can be adjusted such that a previously determined blood volume is sucked into the vessel after a blood vessel has been pierced.
- Correspondingly evacuated vessels are available on the market.
- the vessel which contains the blood taken can then immediately be subjected to further analyses or, however, may be stored for a long period of time (up to several days) without any disadvantages for the quality of the sample.
- the freshly taken blood is directly contacted in the blood withdrawing vessel with the above-described solution so that all processes which might change the nucleic acid pattern of the sample are immediately stopped. Therefore, the data determined at a later time with respect to the detected nucleic acids very accurately represent the actual state at the time of blood withdrawal, i.e. both with respect to the quantities and the types of nucleic acids.
- the blood amount taken is 0.1 to 4 times the solution fed into the vessel.
- the solution is preferably 0.5 to 5.0 ml.
- the final concentration of guanidinium salt after blood addition is at 1.0 to 5 M, preferably at 1 to 3 M, particularly preferred are 2-3 M (see Example 7).
- the vessel according to the invention is preferably used for blood withdrawal when the blood sample is to be used for analyzing nucleic acids.
- the use of the above-mentioned solution as a component of the described withdrawal system solely guarantees the immediate lysis of the cells and the simultaneous stabilization of the sample by immediate inactivation of the nucleases.
- the blood sample obtained thereby can be stored even at room temperature or higher for several days.
- the withdrawal system guarantees a contamination-free and non-infectious handling ranging from sampling via nucleic acid isolation to analysis. In the conventional methods of nucleic acid isolation, additional handling steps have so far been required (e.g. the transfer of the blood sample taken into the reagents for nucleic acid isolation, etc.), which entails an additional risk of infection.
- the sample obtained with the blood withdrawing system is compatible with all of the conventional standard methods of nucleic acid isolation. Particular attention should here be paid to methods which are based on the binding of nucleic acids to glass surfaces, but also sequence-specific binding to complementary nucleic acid and solvent-based extraction methods.
- the invention as described consists of a blood withdrawing system which is conceived such that the following conditions are satisfied. 1. Controlled sampling and simultaneous stabilization of the nucleic acids (DNA, RNA) contained in the sample material. 2. Sampling in which the use of anticoagulants can be completely omitted. 3. The sample obtained by way of the above-described blood withdrawing system can be used in a universal manner in all of the known systems for isolating nucleic acids. 4. The blood withdrawing system is stable in storage.
- the sample obtained by way of the described withdrawal system can be stored in the vessel for a long period of time without degradation of the nucleic acids (see Examples 2, 3, 7, 8).
- the blood withdrawing system may be composed in a preferred embodiment as follows (see FIG. 1 ): A small tube is filled with a defined volume of the nucleic acid-stabilizing substance and is provided with a defined vacuum and sealed with a septum.
- the septum is constructed such that it is compatible with the standard sampling accessories (cannula, etc.).
- 2.2 ml reagent was supplied and the vacuum was adjusted such that exactly 2.2 ml blood could flow in during sampling.
- the nucleic acids contained in the inflowing blood flow were immediately converted into a stable form.
- N-sS nucleic acid-stabilizing substance
- the nucleic acid-stabilizing substance was, unless indicated otherwise, mixed with the sample in the ratio of 1 to 1 (1 volume N-sS plus 1 volume sample material).
- a lower concentration of N-sS e.g. 1 volume N-sS plus 5 volumes sample, might effect a degradation of RNA.
- sample material for the DNA and RNA isolation was directly used after withdrawal, after storage at 4° C. for 6 days, and after storage at ⁇ 20° C. for 1 month.
- the High Pure RNA Isolation Kit (Boehringer Mannheim, cat. no. 1828 665) was used for isolating RNA ( FIG. 2 ).
- the instructions given in the package leaflet were modified as follows: A volume of 2.4 ml sample lysate was applied in 4 aliquots at 600 ⁇ l each to the column, so that a sample material of 2.4 ml lysate was applied on the whole. All of the other steps were carried out in accordance with the package leaflet. The RNA was finally eluted with 100 ⁇ l elution buffer.
- the QiaAmp Blood Kit (Qiagen cat. no. 29104) was used.
- the standard procedure described in the package leaflet was modified in various points: 400 ⁇ l sample volume was directly applied to the column; the binding reagent contained in the kit was not used. 25 ⁇ l proteinase-K batch solution was added and the sample was incubated at room temperature for 10 min. Subsequently, the column was put into a collection vessel and centrifuged as described in the package leaflet. All of the further steps were carried out in accordance with the description in the package leaflet, except for the use of ethanol. The elution volume was 200 ⁇ l.
- wash buffer 1 (10 mM Tris-HCl, 200 mM NaCl, 1% Triton-X-100, pH 7.5
- wash buffer 2 10 mM Tris-HCl, 200 mM NaCl, pH 7.5
- wash steps: resuspension, magnetic separation, removal of the supernatant After the last wash step the supernatant was completely removed and the particles were resuspended in 20 ⁇ l distilled water.
- the sample was heated to 70° C. for 5 min.
- the magnetic particles were separated, and the supernatant which contained the mRNA was analyzed by means of gel electrophoresis.
- RNA was pelleted. The pellet was resuspended in 0.3 ml buffer (4 M guanidinium thiocyanate, 25 mM sodium citrate, pH 7.0, 0.5% sarcosyl, 0.1 M 2-mercaptoisopropanol), transferred into a new 1.5 ml Eppendorf vessel and mixed with 1 volume of isopropanol. After incubation at ⁇ 20° C. for 1 hour the solution was centrifuged in an Eppendorf centrifuge at 4° C. for 10 minutes. The RNA pellet was received in 75% ethanol and concentrated by centrifugation (Speed vac) and dried. For further processing the sample was dissolved in 100 ⁇ l 10 mM Tris-HCl, pH 6.5.
- Stabilizing solution used 4.0 M GTC; 13.5% Triton X100; 45 mM Tris//HCl; with or without 120 mM DTT.
- 700 ⁇ l serum was mixed with 700 ⁇ l stabilizing solution.
- MS2-RNA 0.8 ⁇ g/ ⁇ l of Roche
- the samples were incubated at 40° C. for 180 min and then processed in aliquots of 400 ⁇ l each with the High Pure total RNA Kit of Roche.
- the samples were applied in one step to the column without addition of the binding reagent of the kit and centrifuged in accordance with the instructions.
- the following wash steps and the elution of the RNA in 50 ⁇ l elution buffer were carried out in accordance with the instructions.
- RNA degradation in serum was stopped by adding 250 ⁇ l stabilizing solution. All batches were analyzed twice. As a standard, a sample was only mixed with MS2-RNA after addition of the stabilizing solution to the serum and was processed in parallel.
- pH of the solutions about 4.0
- pH of the solutions after addition of serum about 6.7.
- the PCR was carried out on the Lightcycler at an annealing temperature of 61° C. using SYBR-Green as detection system.
- Batch for PCR :
- the amplificate of the PCR was completely applied to a 2% agarose gel (see FIG. 9 ).
- the agarose gel in FIG. 8 shows 20 ⁇ l of the eluted MS2-RNA after incubation at 40° C. for 3 days. After this period distinct differences in the RNA integrity can be made out in dependence upon the GTC content. Thus a salt content of less than 2 M in the serum/stabilization solution is of advantage to the integrity of the RNA.
- the amplificate of the PCR was fully applied to a 2% agarose gel (see FIG. 9 ).
- the pH of the serum/stabilization solution and thus the pH and the buffer range of the stabilization solution are decisive for the long-term stabilization of RNA. While at a pH of 8.0 an intact RNA could no longer be detected already after 2 days, intact RNA is still detectable within a pH range between 6.6 and 7.0 after 13 days of incubation at room temperature.
- FIG. 1 is a diagrammatic representation of FIG. 1 :
- FIG. 2
- FIG. 3 is a diagrammatic representation of FIG. 3 :
- FIG. 4
- FIG. 5
- FIG. 6 is a diagrammatic representation of FIG. 6 :
- FIG. 7
- FIG. 8
- FIG. 9 is a diagrammatic representation of FIG. 9 .
- FIG. 10 is a diagrammatic representation of FIG. 10 :
Abstract
Description
-
- a guanidinium salt;
- a buffer substance;
- a reducing agent; and/or
- a detergent.
Batch for RT: | 4.0 | μl AMV-RT buffer |
(42° C. for 1 h) | 2.0 | μl dNTP's ( |
0.5 | μl RNase inhibitor (Roche, 20 units) | |
1.0 | μl Primer 2827 ( |
|
1.9 | μl DMPC water | |
0.6 | μl AMV-RT (Roche, 15 units) | |
10 | μl | |
Σ | ||
20 | μl | |
1.6 | μl MgCl2 (batch solution 25 mM) | |||
5.9 | μl DMPC water | |||
0.25 | μl Primer 2827 ( |
|||
0.25 | μl Primer 2335 ( |
|||
1.0 | μl SYBR-Green-Mastermix (Roche) | |||
1.0 | μl RT batch (1:50 diluted) | |||
|
10 | μ1 | ||
Solution used: | 4M (5M) | GTC | ||
14.4% | Triton X 100 | |||
50 mM | DTT | |||
45 mM | Tris/HCl | |||
pH after serum addition between 6.7 and 8.0
Claims (158)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/506,164 USRE43389E1 (en) | 1998-08-12 | 1999-08-12 | Vessel for blood sampling |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19836559 | 1998-08-12 | ||
DE19836559A DE19836559A1 (en) | 1998-08-12 | 1998-08-12 | Blood collection vessel |
US09/762,643 US6776959B1 (en) | 1998-08-12 | 1999-08-12 | Vessel for blood sampling |
US11/506,164 USRE43389E1 (en) | 1998-08-12 | 1999-08-12 | Vessel for blood sampling |
PCT/EP1999/005857 WO2000009746A1 (en) | 1998-08-12 | 1999-08-12 | Vessel for blood sampling |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/762,643 Reissue US6776959B1 (en) | 1998-08-12 | 1999-08-12 | Vessel for blood sampling |
Publications (1)
Publication Number | Publication Date |
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USRE43389E1 true USRE43389E1 (en) | 2012-05-15 |
Family
ID=7877311
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/506,164 Expired - Lifetime USRE43389E1 (en) | 1998-08-12 | 1999-08-12 | Vessel for blood sampling |
US09/762,643 Ceased US6776959B1 (en) | 1998-08-12 | 1999-08-12 | Vessel for blood sampling |
US13/446,444 Abandoned US20130066234A1 (en) | 1998-08-12 | 2012-04-13 | Vessel for blood sampling |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/762,643 Ceased US6776959B1 (en) | 1998-08-12 | 1999-08-12 | Vessel for blood sampling |
US13/446,444 Abandoned US20130066234A1 (en) | 1998-08-12 | 2012-04-13 | Vessel for blood sampling |
Country Status (12)
Country | Link |
---|---|
US (3) | USRE43389E1 (en) |
EP (3) | EP1105533B1 (en) |
JP (1) | JP4607323B2 (en) |
CN (1) | CN1196796C (en) |
AT (1) | ATE426677T1 (en) |
AU (1) | AU771212B2 (en) |
BR (1) | BR9912949A (en) |
CA (1) | CA2348152C (en) |
DE (2) | DE19836559A1 (en) |
ES (3) | ES2325009T3 (en) |
WO (1) | WO2000009746A1 (en) |
ZA (1) | ZA200102036B (en) |
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US20080307117A1 (en) * | 2004-04-08 | 2008-12-11 | Judy Muller-Cohn | Integration of sample storage and sample management for life science |
US20120064525A1 (en) * | 2009-05-20 | 2012-03-15 | Olympus Corporation | Method for collection of nucleic acid derived from mammalian cell, method for analysis of nucleic acid, and kit for collection of feces |
US9376709B2 (en) | 2010-07-26 | 2016-06-28 | Biomatrica, Inc. | Compositions for stabilizing DNA and RNA in blood and other biological samples during shipping and storage at ambient temperatures |
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DE19836559A1 (en) * | 1998-08-12 | 2000-03-23 | Antigen Gmbh | Blood collection vessel |
DE10006662A1 (en) | 2000-02-15 | 2001-08-23 | Antigen Produktions Gmbh | Sample vessel for stabilizing and isolating nucleic acid, contains a lytic solution that stabilizes nucleic acid and a solid phase that binds it, especially for sampling whole blood |
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WO2005064010A1 (en) * | 2003-12-19 | 2005-07-14 | Preanalytix Gmbh | Composition for binding a nucleic acid to a solid phase |
US20080146790A1 (en) * | 2004-08-18 | 2008-06-19 | Daniel Grolz | Additive, Method, and Article For Dna Collection, Stabilization, and Purification |
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EP1932913B1 (en) | 2006-12-11 | 2013-01-16 | Roche Diagnostics GmbH | Nucleic acid isolation using polidocanol and derivatives |
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US20090053704A1 (en) * | 2007-08-24 | 2009-02-26 | Natalia Novoradovskaya | Stabilization of nucleic acids on solid supports |
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US20130066234A1 (en) | 2013-03-14 |
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US6776959B1 (en) | 2004-08-17 |
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ZA200102036B (en) | 2002-06-07 |
AU5514099A (en) | 2000-03-06 |
AU771212B2 (en) | 2004-03-18 |
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WO2000009746A1 (en) | 2000-02-24 |
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