US20070048877A1 - Method and device for preparing a biological sample for biological analyses - Google Patents
Method and device for preparing a biological sample for biological analyses Download PDFInfo
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- US20070048877A1 US20070048877A1 US11/212,454 US21245405A US2007048877A1 US 20070048877 A1 US20070048877 A1 US 20070048877A1 US 21245405 A US21245405 A US 21245405A US 2007048877 A1 US2007048877 A1 US 2007048877A1
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- biological sample
- secondary structure
- volume
- chamber
- amino acid
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/44—Sample treatment involving radiation, e.g. heat
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/113—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure
- C07K1/1136—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure by reversible modification of the secondary, tertiary or quarternary structure, e.g. using denaturating or stabilising agents
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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
Definitions
- the present invention relates to a method for preparing a biological sample for biological analyses.
- the present invention relates to a device for preparing a biological sample for biological analyses.
- the primary structure deals with the sequence of amino acids and the secondary structure is defined by the phi and psi angles of the backbone atoms of the amino acid residues, and the hydrogen bonds between main chain atoms. In some cases, these dihedral angles and patterns of hydrogen bonds are repeated throughout subsequences of several consecutive residues, giving rise to secondary structures, e.g. alpha helices and beta sheets.
- a tertiary structure concerns how the secondary structure units associate within a polypeptide chain providing a three dimensional structure.
- a quaternary structure describes how at least two polypeptide chains associate to form a native protein structure, even though there are proteins that consist of a single polypeptide chain.
- Proteins and peptides have been widely investigated by methods such as two dimensional gels and mass spectrometry. Post-mortem activity of proteases and oxidative stress has been shown to play an important role on peptide and protein concentration in the brain, as well as for detecting post-translational modifications. Previous studies have shown that the peptide and protein content in brain tissue is affected by the time-interval from death to the inactivation of proteases.
- a method for preparing a biological sample for biological analyses comprises at least one amino acid sequence from an organism, and it is a subject of degradation.
- the method comprises physically preparing the biological sample to enable altering a secondary structure of the at least one amino acid sequence to a deactivated secondary structure, and altering the secondary structure of the at least one amino acid sequence to a deactivated secondary structure by heating the biological sample.
- Physically preparing implies, in an embodiment, that the biological sample is given a shape that is preferred for facilitating an effective heating in terms of the heating being uniform and fast. This helps to shorten the time needed to reach a deactivated secondary structure. By blocking biological processes driven by proteins degradation of a sample is avoided.
- the method preserves the primary structure of proteins and peptides by altering their original secondary, and their tertiary structure.
- the heating of the tissue therefore has several advantages; it enables the relatively low-abundant neuropeptides and proteins to remain intact. In addition it minimizes degradation of neuropeptides and proteins in a reproducible manner.
- This method also makes it possible to compare the content and levels of proteins and peptides from different samples. Also, the method may be non fatal, i.e. the organism does not have to perish as a consequence of using the method.
- Non-limiting examples of biological samples constitute biopsies from tissue such as muscles, skin, brain, liver, kidney, or others or body fluids such as blood, urine, CSF, or others, or cell extracts such as cell cultures.
- heating the biological sample to a temperature of the following ones is done: 50, 60, 70, 80, or 90 degrees Centigrade. In an embodiment, the heating reaches or exceeds a temperature similar to the temperature at which the secondary structure of an amino acid sequence is altered to the deactivated secondary structure.
- the step of physically preparing comprises shaping the biological sample to enable altering a secondary structure of the at least one amino acid sequence to a deactivated secondary structure, leading to effective heat transfer.
- shaping the biological sample comprises creating a volume comprising the biological sample. Another advantage is that when shaping the biological sample, the biological sample is given a shape that is preferred for the heating, which should be quick and uniform in order to stop the degradation in the whole sample as soon as possible after taking the biological sample. It should be pointed out that the volume may comprise only the biological sample.
- creating the volume comprises filling the volume with filler presenting similar electric and/or thermal properties, such as heat capacity, as the biological sample.
- the filler is inert. This offers a basis for a uniform heating process after which the whole biological sample is heated.
- creating the volume comprises filling the volume with filler presenting similar light characteristics in terms of refractive indices and absorption coefficients as the biological sample. This allows shaping, i.e.
- the filler and the biological sample is constituted by materials presenting similar light properties. This offers a basis for a uniform heating process after which the whole biological sample is heated.
- the heating is microwave heating.
- creating the volume comprises designing the shape to present a large heat transfer surface in relation to its volume. This leads to an advantageous shape since a large surface allows more heating effect to be received by the biological sample. Also, this leads to that the longest distance in an unheated point in the biological sample is short. This leads to an opportunity of stopping, or at least delaying the degradation of the biological sample even faster.
- creating the volume comprises shaping the biological sample to a slice. In an embodiment, creating the volume comprises providing a thin and oblong shape to the biological sample. In an embodiment, heating is contact heat conduction. In an embodiment, the contact heat conduction is done by at least of one gas, condensing gas, a fluid and at least one warm plate transferring heat into the biological sample. In an embodiment, the heating is heating caused by radiation. In an embodiment, creating the volume includes cutting the biological sample. In an embodiment, creating the volume includes pressing the biological sample. In an embodiment, prior to creating the volume, freezing the biological sample is done for instance in order to make it easier to cut a slice of the biological sample.
- creating the volume comprises, in case the biological sample presents a coagulating or a fluid characteristic, placing the biological sample in a container, vacuuming the container, and sealing the container. This offers the advantage of being able to handle coagulating biological samples.
- creating the volume comprises, in case the biological sample presents a fluid characteristic, leading the biological sample into, or alternatively through, a tube, presenting heating means for heat transfer into the biological sample.
- the tube may be replaced by a flat passage, or a whirl canal.
- a device for preparing a biological sample for biological analyses comprises at least one amino acid sequence from an organism.
- the at least one amino acid sequence is a subject of degradation.
- the device comprises a power transfer location for receiving the biological sample and heating means for altering the secondary structure of the at least one amino acid sequence to a deactivated secondary structure.
- the heating means is responsive for heating the power transfer location.
- the power transfer location receives power from the heating means and transfers power to the biological sample and as a consequence the biological sample is heated. Due to similarities with the first aspect, reference is hereby made to the first aspect.
- the power transfer location is constituted by a chamber.
- the chamber presents one of a circular cross section (e.g. a tube), a rectangular cross section (e.g. a flat passage), and a triangular cross section.
- the device further comprises an opening for allowing the biological sample to enter the chamber. This embodiment is applicable to both fluid and solid biological samples.
- the device further comprises a second opening allowing the biological sample to exit the chamber.
- a second opening allowing the biological sample to exit the chamber.
- the biological sample is comprised by a container. This embodiment is applicable to both fluid and solid biological samples.
- an inner wall of the chamber is essentially in contact with the container, when the container is inserted into the chamber. This leads to an advantageous heating situation since effectiveness of contact heating increases in case there is contact between the heating means and the container comprising the biological sample.
- the container is one of a needle and a tube. This embodiment is applicable to both fluid and solid biological samples.
- the opening presents a seal, such as an O ring, allowing insertion of the container comprising the biological sample into the container.
- the chamber comprises a plurality of openable matching parts and a locking means for maintaining the plurality of openable matching parts in a locked state.
- the device further comprises a steam generator with an inlet, wherein the chamber further comprises a steam inlet.
- a steam generator with an inlet
- the chamber further comprises a steam inlet.
- the steam may be replaced by a fluid.
- the power transfer location is constituted by at least one plate.
- the heating means is one of a radiation generator and a micro wave generator.
- the power transfer location presents a large power transfer surface.
- the power transfer location is constituted by a warm plate receiving a biological sample or a container comprising the biological sample.
- the biological sample, or the container comprising the biological sample is maintained in a position in which there is a contact between the power transfer location and the biological sample, or the container comprising the biological sample by a negative pressure, or even vacuum, for instance acting via a hole through the warm plate, and thus maintaining the biological sample, or the container, in contact with the warm plate.
- a negative pressure, or even vacuum for instance acting via a hole through the warm plate, and thus maintaining the biological sample, or the container, in contact with the warm plate.
- FIG. 1 steps of an embodiment of the method are shown.
- FIG. 2 four schematic illustrations of preferred shapes of biological samples are shown.
- FIG. 3 an embodiment of a device for preparing a biological sample for biological analyses is shown.
- FIG. 4 an embodiment of a device for preparing a biological sample for biological analyses is shown.
- FIG. 5 an embodiment of a device for preparing a biological sample for biological analyses is shown.
- FIG. 6 an embodiment of a device for preparing a biological sample for biological analyses is shown.
- FIG. 7 an embodiment of a device for preparing a biological sample for biological analyses is shown.
- Steps of a method for preparing a biological sample for biological analyses are shown in FIG. 1 in combination with its application when in use.
- the biological sample comprises at least one amino acid sequence from an organism.
- the at least one amino acid sequence is a subject of degradation.
- First the biological sample is physically prepared to enable altering a secondary structure of the at least one amino acid sequence to a deactivated secondary structure.
- this step comprises shaping the biological sample to enable altering a secondary structure of the at least one amino acid sequence to a deactivated secondary structure.
- This is followed by altering the secondary structure of the at least one amino acid sequence to a deactivated secondary structure by heating the biological sample.
- FIG. 2 four embodiments of shapes of biological samples are shown. Two parallelipeds 1 , 3 are shown. To the right a cylinder shaped biological sample 5 and a biological sample 7 covered in filler 9 and provided in a paralleliped are shown.
- the first three samples 1 , 3 , 5 are a thin and oblong in relation to their thickness, facilitating fast heat transfer in case of contact heat conduction by at least of one gas, condensing gas, and at least one warm plate contacting the biological sample 1 , 3 , 5 , or at least contacting a container comprising the biological sample 1 , 3 , 5 .
- the filler 9 it presents similar electric properties as the biological sample 7 .
- An embodiment of a device 11 shown in FIG. 3 , comprises a chamber 13 for receiving the biological sample 1 , 3 , 5 , and heating means 15 for altering the secondary structure of the at least one amino acid sequence to a deactivated secondary structure.
- the embodiment also comprises an opening 17 for allowing the biological sample 1 , 3 , 5 to enter the chamber 13 .
- the biological sample 1 , 3 , 5 comprised by a container (not shown), such as a tube or a needle, is entered into the chamber 13 via the opening 17 and an inner wall 19 of the chamber 13 is essentially in contact with the container, when the container is inserted into the chamber 13 .
- a thermally insulating layer 21 is provided around the chamber 13 .
- a heat sensor 23 and heat control means 25 are provided for controlling the heating means 15 .
- the heat control means 25 may incorporate a timing function controlling the heating means 15 so that the biological sample 1 , 3 , 5 is exposed to an effective amount of heating.
- the device 11 is powered by a battery or means via a cord (not shown in FIG. 3 ).
- the biological sample 1 , 3 , 5 may be either fluid or solid.
- An embodiment of a device 31 shown in FIG. 4 , comprises a chamber 13 for receiving a fluid biological sample and heating means 15 for altering the secondary structure of the at least one amino acid sequence to a deactivated secondary structure.
- a thermally insulating layer 21 is provided around the chamber 13 .
- a heat sensor 23 and heat control means 25 are provided for controlling the heating means 15 .
- the embodiment also comprises an opening 17 for allowing the fluid biological sample to enter the chamber 13 .
- the fluid biological sample flows via the opening 17 into the chamber 13 .
- This embodiment further comprises a second opening 33 allowing the fluid biological sample to flow out of the chamber 13 .
- a heat sensor 23 and heat control means 25 are provided for controlling the heating means 15 .
- the heat control means 25 may incorporate a timing function controlling the heating means 15 .
- the device 31 is powered by a battery or means via a cord (not shown in FIG. 4 ).
- the biological sample is non-coagulating.
- the biological sample is physically shaped during the flow in the chamber 13 .
- the chamber 13 presents a large heat transfer surface in relation to its volume.
- the cross section of the chamber 13 is designed so that it presents a wide base and a low height, with the intention of a fast and uniform heat transfer through the whole biological sample.
- the device 41 comprises a chamber 13 for receiving a biological sample 1 , 3 , 5 , and heating means 25 for altering the secondary structure of the at least one amino acid sequence to a deactivated secondary structure.
- the embodiment also comprises an opening 17 for allowing the biological sample 1 , 3 , 5 to enter the chamber 13 .
- the biological sample 1 , 3 , 5 comprised by a container 43 , such as a tube or a needle, is entered into the chamber 13 via the opening 17 .
- the opening 17 presents an O ring 45 , allowing sealed insertion of the container 43 into the chamber 13 .
- the heating means 15 is constituted by a steam generator with a steam inlet 47 , wherein the chamber 13 further comprises a steam pressure control (not shown). As the steam enters the chamber 13 the container 43 and the biological sample 1 , 3 , 5 is heated. A thermally insulating layer 21 is provided around the chamber 13 . A heat sensor 23 and heat control means 25 are provided for controlling the heating means 15 . The heat control means 25 may incorporate a timing function controlling the heating means 15 . Also, the device 41 is powered by a battery or means via a cord (not shown in FIG. 5 ). In this embodiment, the biological sample 1 , 3 , 5 is fluid or solid. In this embodiment there is space between the container 43 and an inner wall of the chamber 13 . This allows fast and uniform heat transfer through the whole biological sample 1 , 3 , 5 .
- the device 51 comprises a chamber 13 for receiving the biological sample 1 , 3 , 5 , and heating means 25 for altering the secondary structure of the at least one amino acid sequence to a deactivated secondary structure.
- the chamber 13 comprises two openable matching parts 53 , 55 and a locking means 57 for maintaining the two openable matching parts 53 , 55 in a locked state.
- the biological sample 1 , 3 , 5 comprised by a container 43 , such as a tube or a needle, is put into the chamber 13 when the openable matching parts 53 , 55 are in an opened state.
- the heating means 25 is activated.
- the heating 25 is already activated.
- a hinge 57 is provided along sides of the openable matching parts 53 , 55 .
- the device 51 according to this embodiment is opened and closed as indicated by the arrows.
- a thermally insulating layer 21 is provided around the chamber 13 .
- a heat sensor 23 and heat control means 25 are provided for controlling the heating means 25 .
- the heat control means 25 may incorporate a timing function controlling the heating means 15 .
- the device 51 is powered by a battery or means via a cord (not shown in FIG. 6 ).
- the biological sample 1 , 3 , 5 is fluid or solid.
- an inner wall 19 of the chamber 13 is essentially in contact with the container 43 . This allows fast and uniform heat transfer through the whole biological sample 1 , 3 , 5 .
- the number of openable matching parts 53 , 55 is three.
- the power transfer location is a single plate heated by the heating means and the biological sample, regardless whether placed in a container, receives heat from one side, i.e. there is a single contact surface allowing power to transfer into the biological sample.
- the device 61 comprises a chamber 13 for receiving the biological sample 7 covered in a filler 9 , and heating means 15 for altering the secondary structure of the at least one amino acid sequence to a deactivated secondary structure.
- the heating means 15 is constituted by a micro wave generator.
- the embodiment also comprises an opening 17 , such as a door, for allowing the biological sample 7 to enter the chamber 13 .
- the biological sample 7 comprised by the filler 9 presenting a similar dielectric constant as the biological sample, is entered into the chamber 13 via the opening 17 .
- a heat sensor 23 and heat control means 25 are provided for controlling the heating means 15 .
- the heat control means 25 may incorporate a timing function controlling the heating means 15 .
- the device 61 is powered by means via a cord (not shown in FIG. 7 ).
- the biological sample is fluid or solid.
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Abstract
The method and devices are for preparing a biological sample for biological analyses. The biological sample has at least one amino acid sequence from an organism. The amino acid sequence is a subject of degradation. The biological sample is physically prepared to enable altering a secondary structure of the amino acid sequence to a deactivated secondary structure, and altering the secondary structure of the amino acid sequence to a deactivated secondary structure by heating the biological sample.
Description
- According to a first aspect, the present invention relates to a method for preparing a biological sample for biological analyses. According to a second aspect, the present invention relates to a device for preparing a biological sample for biological analyses.
- The primary structure deals with the sequence of amino acids and the secondary structure is defined by the phi and psi angles of the backbone atoms of the amino acid residues, and the hydrogen bonds between main chain atoms. In some cases, these dihedral angles and patterns of hydrogen bonds are repeated throughout subsequences of several consecutive residues, giving rise to secondary structures, e.g. alpha helices and beta sheets.
- A tertiary structure concerns how the secondary structure units associate within a polypeptide chain providing a three dimensional structure. A quaternary structure describes how at least two polypeptide chains associate to form a native protein structure, even though there are proteins that consist of a single polypeptide chain.
- Proteins and peptides have been widely investigated by methods such as two dimensional gels and mass spectrometry. Post-mortem activity of proteases and oxidative stress has been shown to play an important role on peptide and protein concentration in the brain, as well as for detecting post-translational modifications. Previous studies have shown that the peptide and protein content in brain tissue is affected by the time-interval from death to the inactivation of proteases.
- According to the first aspect, a method for preparing a biological sample for biological analyses is disclosed. The biological sample comprises at least one amino acid sequence from an organism, and it is a subject of degradation. The method comprises physically preparing the biological sample to enable altering a secondary structure of the at least one amino acid sequence to a deactivated secondary structure, and altering the secondary structure of the at least one amino acid sequence to a deactivated secondary structure by heating the biological sample. Physically preparing implies, in an embodiment, that the biological sample is given a shape that is preferred for facilitating an effective heating in terms of the heating being uniform and fast. This helps to shorten the time needed to reach a deactivated secondary structure. By blocking biological processes driven by proteins degradation of a sample is avoided. Since the time between taking the biological sample and the performing a biological analysis has a large impact on the level of degradation, even after a short time, e.g. already after 1-3 min, it is important that heating takes place immediately after taking the sample. By heating the tissue protein functioning as proteases, their secondary and tertiary structure and thereby their function is lost.
- The method preserves the primary structure of proteins and peptides by altering their original secondary, and their tertiary structure. The heating of the tissue therefore has several advantages; it enables the relatively low-abundant neuropeptides and proteins to remain intact. In addition it minimizes degradation of neuropeptides and proteins in a reproducible manner. This method also makes it possible to compare the content and levels of proteins and peptides from different samples. Also, the method may be non fatal, i.e. the organism does not have to perish as a consequence of using the method.
- Non-limiting examples of biological samples constitute biopsies from tissue such as muscles, skin, brain, liver, kidney, or others or body fluids such as blood, urine, CSF, or others, or cell extracts such as cell cultures.
- In embodiments, heating the biological sample to a temperature of the following ones is done: 50, 60, 70, 80, or 90 degrees Centigrade. In an embodiment, the heating reaches or exceeds a temperature similar to the temperature at which the secondary structure of an amino acid sequence is altered to the deactivated secondary structure.
- In an embodiment, the step of physically preparing comprises shaping the biological sample to enable altering a secondary structure of the at least one amino acid sequence to a deactivated secondary structure, leading to effective heat transfer. In an embodiment, shaping the biological sample comprises creating a volume comprising the biological sample. Another advantage is that when shaping the biological sample, the biological sample is given a shape that is preferred for the heating, which should be quick and uniform in order to stop the degradation in the whole sample as soon as possible after taking the biological sample. It should be pointed out that the volume may comprise only the biological sample.
- In an embodiment, creating the volume comprises filling the volume with filler presenting similar electric and/or thermal properties, such as heat capacity, as the biological sample. This allows shaping, i.e. creating the volume, so that the heat is transferred into the biological sample without discontinuities in the contact between the filler and the biological sample, i.e. it appears that the filler and the biological sample is constituted by materials presenting similar electric properties. In an embodiment, the filler is inert. This offers a basis for a uniform heating process after which the whole biological sample is heated. In an embodiment, creating the volume comprises filling the volume with filler presenting similar light characteristics in terms of refractive indices and absorption coefficients as the biological sample. This allows shaping, i.e. creating the volume, so that the heat is transferred into the biological sample without discontinuities in the contact between the filler and the biological sample, i.e. it appears that the filler and the biological sample is constituted by materials presenting similar light properties. This offers a basis for a uniform heating process after which the whole biological sample is heated.
- In an embodiment, the heating is microwave heating. In an embodiment, creating the volume comprises designing the shape to present a large heat transfer surface in relation to its volume. This leads to an advantageous shape since a large surface allows more heating effect to be received by the biological sample. Also, this leads to that the longest distance in an unheated point in the biological sample is short. This leads to an opportunity of stopping, or at least delaying the degradation of the biological sample even faster.
- In an embodiment, creating the volume comprises shaping the biological sample to a slice. In an embodiment, creating the volume comprises providing a thin and oblong shape to the biological sample. In an embodiment, heating is contact heat conduction. In an embodiment, the contact heat conduction is done by at least of one gas, condensing gas, a fluid and at least one warm plate transferring heat into the biological sample. In an embodiment, the heating is heating caused by radiation. In an embodiment, creating the volume includes cutting the biological sample. In an embodiment, creating the volume includes pressing the biological sample. In an embodiment, prior to creating the volume, freezing the biological sample is done for instance in order to make it easier to cut a slice of the biological sample.
- In an embodiment, after freezing the biological sample, warming the biological sample to a sub zero temperature allowing cutting the sample. In an embodiment, after warming the biological sample, cutting the biological sample.
- Having so far dealt with biological samples that present a more solid characteristic, a few embodiments dealing with less solid characteristics will now be presented.
- In an embodiment, creating the volume comprises, in case the biological sample presents a coagulating or a fluid characteristic, placing the biological sample in a container, vacuuming the container, and sealing the container. This offers the advantage of being able to handle coagulating biological samples. In an embodiment, creating the volume comprises, in case the biological sample presents a fluid characteristic, leading the biological sample into, or alternatively through, a tube, presenting heating means for heat transfer into the biological sample. In embodiments, the tube may be replaced by a flat passage, or a whirl canal.
- According to a second aspect, a device for preparing a biological sample for biological analyses is disclosed. The biological sample comprises at least one amino acid sequence from an organism. The at least one amino acid sequence is a subject of degradation. The device comprises a power transfer location for receiving the biological sample and heating means for altering the secondary structure of the at least one amino acid sequence to a deactivated secondary structure. The heating means is responsive for heating the power transfer location. The power transfer location receives power from the heating means and transfers power to the biological sample and as a consequence the biological sample is heated. Due to similarities with the first aspect, reference is hereby made to the first aspect.
- In an embodiment, the power transfer location is constituted by a chamber. In an embodiment, the chamber presents one of a circular cross section (e.g. a tube), a rectangular cross section (e.g. a flat passage), and a triangular cross section. In an embodiment, the device further comprises an opening for allowing the biological sample to enter the chamber. This embodiment is applicable to both fluid and solid biological samples.
- In an embodiment, the device further comprises a second opening allowing the biological sample to exit the chamber. This embodiment is applicable to both fluid and solid biological samples. In an embodiment, the biological sample is comprised by a container. This embodiment is applicable to both fluid and solid biological samples.
- In an embodiment, an inner wall of the chamber is essentially in contact with the container, when the container is inserted into the chamber. This leads to an advantageous heating situation since effectiveness of contact heating increases in case there is contact between the heating means and the container comprising the biological sample. In an embodiment, the container is one of a needle and a tube. This embodiment is applicable to both fluid and solid biological samples.
- In an embodiment, the opening presents a seal, such as an O ring, allowing insertion of the container comprising the biological sample into the container. In an embodiment, the chamber comprises a plurality of openable matching parts and a locking means for maintaining the plurality of openable matching parts in a locked state. By opening the matching parts and thereby allowing placing the container, or the biological sample directly, between the matching parts and closing, leads to an effective way of heating the biological sample.
- In an embodiment, the device further comprises a steam generator with an inlet, wherein the chamber further comprises a steam inlet. This allows the biological sample to be heated using steam, which offers an effective way of heating the biological sample. To control condensation temperature by changing pressure is an alternative to accommodate effective heat transfer to the biological sample.
- In embodiments, the steam may be replaced by a fluid. In an embodiment, the power transfer location is constituted by at least one plate. In an embodiment, the heating means is one of a radiation generator and a micro wave generator. In an embodiment, the power transfer location presents a large power transfer surface. In an embodiment, the power transfer location is constituted by a warm plate receiving a biological sample or a container comprising the biological sample. In this embodiment, the biological sample, or the container comprising the biological sample, is maintained in a position in which there is a contact between the power transfer location and the biological sample, or the container comprising the biological sample by a negative pressure, or even vacuum, for instance acting via a hole through the warm plate, and thus maintaining the biological sample, or the container, in contact with the warm plate. By increasing the pressure, the biological sample, or container, may be removed.
- In
FIG. 1 , steps of an embodiment of the method are shown. - In
FIG. 2 , four schematic illustrations of preferred shapes of biological samples are shown. - In
FIG. 3 , an embodiment of a device for preparing a biological sample for biological analyses is shown. - In
FIG. 4 , an embodiment of a device for preparing a biological sample for biological analyses is shown. - In
FIG. 5 , an embodiment of a device for preparing a biological sample for biological analyses is shown. - In
FIG. 6 , an embodiment of a device for preparing a biological sample for biological analyses is shown. - In
FIG. 7 , an embodiment of a device for preparing a biological sample for biological analyses is shown. - Steps of a method for preparing a biological sample for biological analyses are shown in
FIG. 1 in combination with its application when in use. The biological sample comprises at least one amino acid sequence from an organism. The at least one amino acid sequence is a subject of degradation. First the biological sample is physically prepared to enable altering a secondary structure of the at least one amino acid sequence to a deactivated secondary structure. In an embodiment, this step comprises shaping the biological sample to enable altering a secondary structure of the at least one amino acid sequence to a deactivated secondary structure. This is followed by altering the secondary structure of the at least one amino acid sequence to a deactivated secondary structure by heating the biological sample. - In
FIG. 2 , four embodiments of shapes of biological samples are shown. Twoparallelipeds biological sample 5 and abiological sample 7 covered infiller 9 and provided in a paralleliped are shown. The first threesamples biological sample biological sample filler 9, it presents similar electric properties as thebiological sample 7. - Embodiments of a device for preparing a biological sample for biological analyses will now be discussed. An embodiment of a device 11, shown in
FIG. 3 , comprises achamber 13 for receiving thebiological sample opening 17 for allowing thebiological sample chamber 13. Thebiological sample chamber 13 via theopening 17 and aninner wall 19 of thechamber 13 is essentially in contact with the container, when the container is inserted into thechamber 13. A thermally insulatinglayer 21 is provided around thechamber 13. Aheat sensor 23 and heat control means 25 are provided for controlling the heating means 15. When thebiological sample chamber 13, the biological sample comes in contact with theinner wall 19 of thechamber 13, thus transferring heat to thebiological sample biological sample FIG. 3 ). In this embodiment, thebiological sample - An embodiment of a
device 31, shown inFIG. 4 , comprises achamber 13 for receiving a fluid biological sample and heating means 15 for altering the secondary structure of the at least one amino acid sequence to a deactivated secondary structure. A thermally insulatinglayer 21 is provided around thechamber 13. Aheat sensor 23 and heat control means 25 are provided for controlling the heating means 15. The embodiment also comprises anopening 17 for allowing the fluid biological sample to enter thechamber 13. The fluid biological sample flows via theopening 17 into thechamber 13. This embodiment further comprises asecond opening 33 allowing the fluid biological sample to flow out of thechamber 13. Aheat sensor 23 and heat control means 25 are provided for controlling the heating means 15. As the fluid biological sample flows through thechamber 13, the fluid biological sample comes in contact with aninner wall 19 of thechamber 13, thus transferring heat to the fluid biological sample. The heat control means 25 may incorporate a timing function controlling the heating means 15. Also, thedevice 31 is powered by a battery or means via a cord (not shown inFIG. 4 ). In this embodiment, the biological sample is non-coagulating. The biological sample is physically shaped during the flow in thechamber 13. Thechamber 13 presents a large heat transfer surface in relation to its volume. In this embodiment, the cross section of thechamber 13 is designed so that it presents a wide base and a low height, with the intention of a fast and uniform heat transfer through the whole biological sample. - In an embodiment of the device, shown in
FIG. 5 , thedevice 41 comprises achamber 13 for receiving abiological sample opening 17 for allowing thebiological sample chamber 13. Thebiological sample container 43, such as a tube or a needle, is entered into thechamber 13 via theopening 17. Theopening 17 presents anO ring 45, allowing sealed insertion of thecontainer 43 into thechamber 13. In this embodiment the heating means 15 is constituted by a steam generator with asteam inlet 47, wherein thechamber 13 further comprises a steam pressure control (not shown). As the steam enters thechamber 13 thecontainer 43 and thebiological sample layer 21 is provided around thechamber 13. Aheat sensor 23 and heat control means 25 are provided for controlling the heating means 15. The heat control means 25 may incorporate a timing function controlling the heating means 15. Also, thedevice 41 is powered by a battery or means via a cord (not shown inFIG. 5 ). In this embodiment, thebiological sample container 43 and an inner wall of thechamber 13. This allows fast and uniform heat transfer through the wholebiological sample - In an embodiment of the device shown in
FIG. 6 , thedevice 51 comprises achamber 13 for receiving thebiological sample chamber 13 comprises twoopenable matching parts openable matching parts biological sample container 43, such as a tube or a needle, is put into thechamber 13 when theopenable matching parts openable matching parts heating 25 is already activated. Ahinge 57 is provided along sides of theopenable matching parts device 51 according to this embodiment is opened and closed as indicated by the arrows. A thermally insulatinglayer 21 is provided around thechamber 13. Aheat sensor 23 and heat control means 25 are provided for controlling the heating means 25. The heat control means 25 may incorporate a timing function controlling the heating means 15. Also, thedevice 51 is powered by a battery or means via a cord (not shown inFIG. 6 ). In this embodiment, thebiological sample inner wall 19 of thechamber 13 is essentially in contact with thecontainer 43. This allows fast and uniform heat transfer through the wholebiological sample openable matching parts - In an embodiment, the power transfer location is a single plate heated by the heating means and the biological sample, regardless whether placed in a container, receives heat from one side, i.e. there is a single contact surface allowing power to transfer into the biological sample. In an embodiment of the device shown in
FIG. 7 , thedevice 61 comprises achamber 13 for receiving thebiological sample 7 covered in afiller 9, and heating means 15 for altering the secondary structure of the at least one amino acid sequence to a deactivated secondary structure. The heating means 15 is constituted by a micro wave generator. - The embodiment also comprises an
opening 17, such as a door, for allowing thebiological sample 7 to enter thechamber 13. Thebiological sample 7, comprised by thefiller 9 presenting a similar dielectric constant as the biological sample, is entered into thechamber 13 via theopening 17. Aheat sensor 23 and heat control means 25 are provided for controlling the heating means 15. The heat control means 25 may incorporate a timing function controlling the heating means 15. Also, thedevice 61 is powered by means via a cord (not shown inFIG. 7 ). In this embodiment, the biological sample is fluid or solid. - While the present invention has been described in accordance with preferred compositions and embodiments, it is to be understood that certain substitutions and alterations may be made thereto without departing from the spirit and scope of the following claims.
Claims (33)
1. A method for preparing a biological sample for biological analyses, the biological sample having an one amino acid sequence from an organism, the amino acid sequence being a subject of degradation, the method comprising:
physically preparing the biological sample to enable altering a secondary structure of the amino acid sequence to a deactivated secondary structure, and
altering the secondary structure of the amino acid sequence to a deactivated secondary structure by heating the biological sample.
2. The method according to claim 1 , wherein the method further comprises step of physically preparing comprises shaping the biological sample to enable altering a secondary structure of the amino acid sequence to a deactivated secondary structure.
3. The method according to claim 2 , wherein the method further comprises step of shaping the biological sample comprises creating a volume comprising the biological sample.
4. The method according to claim 3 , wherein the method further comprises step of creating the volume by filling the volume with a filler presenting a similar dielectric constant as the biological sample.
5. The method according to claim 4 , wherein the method further comprises step of the heating is microwave heating.
6. The method according to claim 3 , wherein the method further comprises step of creating the volume by designing the shape to present a large heat transfer surface in relation to the volume of the shape.
7. The method according to claim 6 , wherein the method further comprises step of creating the volume by shaping the biological sample to a slice.
8. The method according to claim 6 , wherein the method further comprises step of the creating the volume by providing a thin and oblong shape to the biological sample.
9. The method according to claim 2 , wherein the method further comprises step of heating by contact heat conduction.
10. The method according to claim 9 , wherein the contact heat conduction is done by at least of one gas, condensing gas, a fluid and at least one warm plate transferring heat into the biological sample.
11. The method according to claim 2 , wherein the method further comprises step of heating by using radiation.
12. The method according to claim 7 , wherein the method further comprises step of creating the volume by cutting the biological sample.
13. The method according to claim 7 , wherein the method further comprises step of creating the volume by pressing the biological sample.
14. The method according to claim 2 , wherein prior to creating the volume, freezing the biological sample.
15. The method according to claim 14 , wherein after freezing the biological sample, warming the biological sample to a sub zero temperature allowing cutting the sample.
16. The method according to claim 15 , wherein after warming the biological sample, cutting the biological sample.
17. The method according to claim 6 , wherein the method further comprises step of creating the volume by placing the biological sample in a container, vacuuming the container, and sealing the container.
18. The method according to claim 6 , wherein the method further comprises step of creating the volume by leading the biological sample into a tube, presenting heating means for heat transfer into the biological sample.
19. The method according to claim 2 , wherein the heating exceeds a temperature similar to the temperature at which the secondary structure of the amino acid sequence is altered to the deactivated secondary structure.
20. A device for preparing a biological sample for biological analyses, the biological sample has at least one amino acid sequence from an organism, the one amino acid sequence is being a subject of degradation, comprising:
a power transfer location for receiving the biological sample, and
heating means for altering the secondary structure of the amino acid sequence to a deactivated secondary structure, the heating means being responsive for heating the power transfer location.
21. Device according to claim 20 , wherein the biological sample has a container.
22. The device according to claim 20 , wherein the power-transfer location is constituted by a chamber.
23. The device according to claim 22 , wherein the chamber presents one of a circular cross section, a rectangular cross section, and a triangular cross section.
24. The device according to claim 22 , wherein the device has an opening defined therein.
25. The device according to claim 24 , wherein the device has a second opening defined therein for allowing the biological sample to exit the chamber.
26. The device according to claim 21 , wherein an inner wall of the chamber is essentially in contact with the container, when the container is inserted into the chamber.
27. The device according to claim 21 , wherein the container is one of a needle and a tube.
28. The device according to claim 24 , wherein the opening presents a sealing, allowing insertion of the container into the chamber.
29. The device according to claim 22 , wherein the chamber has a plurality of openable matching parts and a locking means for maintaining the plurality of openable matching parts in a locked state.
30. The device according to claim 22 , wherein the device has a steam generator that has an inlet defined therein and the chamber has a steam inlet defined therein.
31. The device according to claim 20 , wherein the power-transfer location is constituted by at least one plate.
32. The device according to claim 20 , wherein the heating means is one of a radiation generator and a micro wave generator.
33. The device according to claim 20 , wherein the power-transfer location presents a large power transfer surface.
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/212,454 US20070048877A1 (en) | 2005-08-26 | 2005-08-26 | Method and device for preparing a biological sample for biological analyses |
CA2617968A CA2617968C (en) | 2005-08-26 | 2006-08-27 | Preparing biological samples for analysis |
PCT/SE2006/000979 WO2007024185A1 (en) | 2005-08-26 | 2006-08-27 | Preparing biological samples for analysis |
US11/996,545 US9017964B2 (en) | 2005-08-26 | 2006-08-27 | Preparing biological samples for analysis |
AU2006282124A AU2006282124B2 (en) | 2005-08-26 | 2006-08-27 | Preparing biological samples for analysis |
EP06784114.8A EP1917516B1 (en) | 2005-08-26 | 2006-08-27 | Preparing biological samples for analysis |
US11/467,820 US8663959B2 (en) | 2005-08-26 | 2006-08-28 | Preparing biological samples for analysis |
US14/668,204 US20150198510A1 (en) | 2005-08-26 | 2015-03-25 | Preparing biological samples for analysis |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/212,454 US20070048877A1 (en) | 2005-08-26 | 2005-08-26 | Method and device for preparing a biological sample for biological analyses |
Related Child Applications (3)
Application Number | Title | Priority Date | Filing Date |
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US11/996,545 Continuation-In-Part US9017964B2 (en) | 2005-08-26 | 2006-08-27 | Preparing biological samples for analysis |
PCT/SE2006/000979 Continuation-In-Part WO2007024185A1 (en) | 2005-08-26 | 2006-08-27 | Preparing biological samples for analysis |
US11/467,820 Continuation-In-Part US8663959B2 (en) | 2005-08-26 | 2006-08-28 | Preparing biological samples for analysis |
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US20070048877A1 true US20070048877A1 (en) | 2007-03-01 |
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US11/212,454 Abandoned US20070048877A1 (en) | 2005-08-26 | 2005-08-26 | Method and device for preparing a biological sample for biological analyses |
US11/467,820 Active 2029-11-15 US8663959B2 (en) | 2005-08-26 | 2006-08-28 | Preparing biological samples for analysis |
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EP (1) | EP1917516B1 (en) |
AU (1) | AU2006282124B2 (en) |
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WO (1) | WO2007024185A1 (en) |
Cited By (1)
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US20120122150A1 (en) * | 2009-07-30 | 2012-05-17 | Denator Aktiebolag | Stabilization method for biological samples by combination of heating and chemical fixation |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2009126099A1 (en) * | 2008-04-10 | 2009-10-15 | Denator Aktiebolag | Device for storing a biological sample and for preparing the biological sample |
CN103782151A (en) * | 2011-07-13 | 2014-05-07 | 德纳托股份公司 | Method for stabilization of fluid biological samples |
CN106455862B (en) * | 2014-05-16 | 2020-05-19 | 比奥利弗解决方案公司 | System, device and method for automatic sample thawing |
CN113295730B (en) * | 2021-05-25 | 2022-06-10 | 中国核动力研究设计院 | Fine surface single-phase and two-phase convective heat and mass transfer experimental device and preparation method thereof |
Family Cites Families (9)
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DE3433133A1 (en) | 1984-09-08 | 1986-03-20 | Werner Dr.med. 4330 Mülheim Schubert | Appliance for organ-tissue fixation |
US5782897A (en) * | 1987-06-26 | 1998-07-21 | Microwave Medical Systems, Inc. | Microwave heating apparatus for rapid tissue fixation |
US4891239A (en) * | 1988-07-05 | 1990-01-02 | Raytheon Company | Method and apparatus for ultrafast microwave tissue fixation |
US5281516A (en) * | 1988-08-02 | 1994-01-25 | Gene Tec Corporation | Temperature control apparatus and method |
DE4239232A1 (en) * | 1992-11-21 | 1994-05-26 | Schubert Werner | Thermal denaturing appts. for a histological laboratory - has containers for hot and cold water with temp. control |
US5588827A (en) * | 1993-12-17 | 1996-12-31 | Brooks Automation Inc. | Passive gas substrate thermal conditioning apparatus and method |
FR2728683A1 (en) | 1994-12-23 | 1996-06-28 | Kyung Chang Ind Co | Fixation of biological samples by microwave |
ATE390491T1 (en) * | 1996-06-04 | 2008-04-15 | Univ Utah Res Found | CONTAINER FOR CARRYING OUT AND OBSERVING BIOLOGICAL PROCESSES |
US20040209331A1 (en) * | 2001-07-16 | 2004-10-21 | Kirk Ririe | Thermal cycling system and method of use |
-
2005
- 2005-08-26 US US11/212,454 patent/US20070048877A1/en not_active Abandoned
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2006
- 2006-08-27 AU AU2006282124A patent/AU2006282124B2/en not_active Ceased
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- 2006-08-27 EP EP06784114.8A patent/EP1917516B1/en not_active Not-in-force
- 2006-08-28 US US11/467,820 patent/US8663959B2/en active Active
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20120122150A1 (en) * | 2009-07-30 | 2012-05-17 | Denator Aktiebolag | Stabilization method for biological samples by combination of heating and chemical fixation |
US8986947B2 (en) * | 2009-07-30 | 2015-03-24 | Denator Aktiebolag | Stabilization method for biological samples by combination of heating and chemical fixation |
Also Published As
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CA2617968A1 (en) | 2007-03-01 |
EP1917516B1 (en) | 2017-05-24 |
WO2007024185A1 (en) | 2007-03-01 |
US20070048792A1 (en) | 2007-03-01 |
US8663959B2 (en) | 2014-03-04 |
CA2617968C (en) | 2016-07-05 |
EP1917516A1 (en) | 2008-05-07 |
AU2006282124B2 (en) | 2012-08-02 |
AU2006282124A1 (en) | 2007-03-01 |
EP1917516A4 (en) | 2014-03-12 |
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