The present invention relates to a reaction container kit suitable for carrying out various analyses such as biological analyses, biochemical analyses, and general chemical analyses in the fields of medical care, chemistry, and the like.
In biochemical analyses, general chemical analyses, and the like, micro multi-chamber devices are used as small-size reaction devices. As such a device, for example, a microwell reaction plate such as a microtiter plate, which has a flat plate substrate with a plurality of wells on the surface of the substrate, are used.
Further, a reaction container having a reaction portion for carrying out a reaction of a sample and a reagent container containing a reagent for use in the reaction of a sample has been proposed as a reagent kit.
In such a reaction container, a reagent which has been previously selected for an inspection item to be performed on a sample is contained in the reagent container.
In a case where a sample is inspected using a reaction container having a reagent previously prepared, it is necessary to use a reaction container suitable for a requested inspection item. However, it is likely that the mistake of injecting a sample into an incorrect reaction container will be caused by human error.
Further, depending on the kind of reaction container, there is a case where it is difficult to determine whether a sample has already been injected or has not yet been injected thereinto.
It is therefore an object of the present invention to prevent a sample from being injected into an incorrect reaction container as well as to make it possible to easily determine whether a sample has already been injected or has not yet been injected.
A reaction container kit according to the present invention includes a reaction portion for carrying out a reaction of a sample, a reagent container containing a reagent for use in the reaction of a sample, a first bar code label to be read before sample dispensation into a reaction container, and a second bar code label to be read after sample dispensation into the reaction container. The first bar code label is previously stuck to the reaction container, and the second bar code label is provided so as to be able to be stuck to the reaction container. Data contained in the first bar code label and data contained in the second bar code label are different from each other, and the first bar code label contains at least data indicating information unique to the reaction container.
The first bar code label is read by a bar code reader before sample injection to automatically determine whether or not the reaction container is a correct one suitable for an inspection item requested to be performed on a sample to be injected thereinto.
The first bar code label may further contain data indicating that a sample has not yet been injected into the reaction container, and the second bar code label may contain data indicating that a sample has already been injected into the reaction container. When the reaction container has the first bar code label stuck thereto, it is possible, by reading the bar code label using a bar code reader, to confirm that a sample has not yet been injected into the reaction container. When the reaction container has the second bar code label stuck thereto, it is possible, by reading the bar code label using a bar code reader, to confirm that a sample has already been injected into the reaction container.
In order to prevent the first bar code label from being kept stuck to the reaction container even after sample injection, the first bar code label is preferably designed to be able to be entirely or partially removed from the reaction container after data reading.
In a case where the first bar code label is designed to be able to be partially removed, a portion of the first bar code label to be kept stuck to the reaction container without being removed therefrom may contain data indicating information unique to the reaction container, such as an inspection item to be performed using the reaction container, and a portion of the first bar code label that should be removed may contain data indicating that a sample has not yet been injected into the reaction container, and the second bar code label may contain data indicating that a sample has already been injected into the reaction container.
In a case where the first bar code label is designed to be able to be entirely or partially removed after data reading, it is preferred that the reaction container has an opening constituting a sample introduction unit and the first bar code label is previously stuck to the sample introduction unit so that the opening can be opened only after removing a portion of the first bar code label that should be removed. In this case, it is preferred that the second bar code label also serves as a sealing member for hermetically sealing the opening after sample injection.
In the case of a conventional microwell reaction plate, the top surface of the reaction plate is exposed to the atmosphere during use. Therefore, it is likely that a foreign matter will enter a sample from outside, and on the other hand, there is also a case where a reaction product will pollute an environment outside the reaction plate. For this reason, the reaction container kit according to the present invention is preferably designed to prevent the entry of a foreign matter from outside and the pollution of a surrounding environment.
One example of such a reaction container kit is one including a reaction plate having, on the top surface side thereof, a reaction portion and a reagent container, a dispensation tip arranged above the top surface of the reaction plate, and a cover for covering the space above the top surface of the reaction plate and movably supporting the dispensation tip so that a distal end portion of the dispensation tip is inside the space and a proximal end portion of the dispensation tip is outside the space. In this case, the opening described above is provided on the cover, and the sample introduction unit is designed so that a sample can be introduced into the space from outside through the opening.
The reagent container provided on the top surface side of the reaction plate is preferably sealed with a film. The film sealing the reagent container to prevent a reagent from spilling out of the reagent container is a film through which the dispensation tip can penetrate.
Further, since the space above the top surface of the reaction plate is covered with the cover so as to be cut off from the outside, the reaction of a sample is carried out in the space. The detection of a reaction product obtained by the reaction is also carried out in the space covered with the cover without taking the reaction product out of the space covered with the cover. After the detection, the reaction container is disposed of with the reaction product remaining in the space covered with the cover. That is, the reaction container is disposable.
The dispensation tip may be one to be attached to a tip of a dispensation nozzle. In this case, it is necessary to additionally prepare a nozzle mechanism in order to carry out dispensation. In order to eliminate the necessity to prepare a nozzle mechanism, the dispensation tip to be used in the present invention preferably has a syringe to be operated from the outside of the cover. In this case, operation of dispensation can be carried out by operating the syringe. Further, in a case where the dispensation tip has a syringe, the channel of the dispensation tip is sealed with the syringe, thereby preventing the space covered with the cover from communicating with the space outside the cover through the channel of the dispensation tip.
In a case where the dispensation tip does not have a syringe, the space covered with the cover is hermetically sealed with a nozzle mechanism during operation of dispensation, but is brought into communication with the space outside the cover through the dispensation tip when the dispensation tip is not used, such as during reaction or detection. In order to prevent the entry of a foreign matter from outside and the leakage of a sample or a reaction product into the outside even in such a case, the dispensation tip preferably has a filter inside the tip portion thereof.
In a case where the reaction container is intended for use in gene analysis, the reaction plate preferably has, on the top surface side thereof, a gene amplification portion for carrying out gene amplification reaction. The gene amplification portion preferably has a shape suitable for temperature control to be performed according to a predetermined temperature cycle. In this case, the reaction portion formed to have such a shape may be used as a gene amplification portion, or a gene amplification container may be provided separately from the reaction portion. Examples of the gene amplification reaction include PCR and LAMP.
The analysis of a reaction product may be carried out in the reaction portion of the reaction container. Alternatively, a reaction product may be transferred from the reaction portion to another site on the reaction plate in order to analyze the reaction product.
In a case where the reaction container is designed to carry out the analysis of a reaction product in the reaction portion, the reaction portion is preferably made of an optically-transparent material so that an optical measurement can be carried out from the bottom side of the reaction portion.
In a case where the reaction container is designed so that a reaction product can be transferred from the reaction portion to another site in order to analyze the reaction product, the reaction plate further has, on the top surface side thereof, an analysis section for analyzing a reaction product produced in the reaction portion.
One example of such an analysis section is an electrophoresis portion for carrying out electrophoretic separation of a reaction product.
In a case where a reaction product to be analyzed contains a gene, the analysis section is, for example, a region where probes which react with the gene are arranged. Examples of such a region where probes are arranged include DNA chips and hybridization regions.
One example of a structure for holding and movably supporting the dispensation tip is one in which the dispensation tip is held and movably supported by an airtight and flexible material such as a diaphragm or a film. In this case, the cover includes a cover main body having stiffness and integrated with the reaction plate and an upper cover which is attached to the cover main body so as to be arranged above the top surface of the reaction plate and which is made of an airtight and flexible material, such as a diaphragm or a film, and holds and movably supports the dispensation tip. Further, the opening constituting a sample introduction unit is provided on the cover main body, and the sealing member for hermetically sealing the opening is to be stuck to the cover main body.
Another example of the structure for holding and movably supporting the dispensation tip is one in which the cover includes a cover main body integrated with the reaction plate and a cover plate arranged above the top surface of the reaction plate and held by the cover main body by means of a sealing material so as to be able to slide in a horizontal plane while the air tightness of the reaction container is kept, and the dispensation tip is held by the cover plate by means of another sealing material so as to be able to slide in a vertical direction while the air tightness of the reaction container is kept. Also in this case, the opening constituting a sample introduction unit is provided on the cover main body, and the sealing member for hermetically sealing the opening is to be stuck to the cover main body.
The reaction container kit according to the present invention can be used for measurements of various reactions such as chemical reactions and biochemical reactions.
Examples of a sample to be measured using the reaction container kit according to the present invention include, but are not particularly limited to, various samples such as chemical substances, biological samples, and living body-derived samples.
In the reaction container kit according to the present invention, since the first bar code label to be read before sample dispensation is previously stuck to the reaction container and contains data indicating information unique to the reaction container, it is possible, by reading the first bar code label using a bar code reader before sample injection, to automatically determine whether or not the reaction container is a correct one suitable for an inspection item requested to be performed on a sample to be injected thereinto, thereby preventing an incorrect reaction container from being selected by human error.
Further, since the first bar code label is previously stuck to the reaction container and the second bar code label to be read after sample dispensation is provided so as to be able to be stuck to the reaction container, it is possible, by reading the bar code label stuck to the reaction container using a bar code reader, to determine whether or not a sample has already been injected into the reaction container, thereby preventing a sample from being injected again into the reaction container, into which the sample has already been injected, due to human error before the reaction container is attached to an inspection apparatus.
By allowing the first bar code label to be entirely or partially removed after data reading, it is possible to prevent the first bar code label from being kept stuck to the reaction container even after sample injection. In this case, whether or not sample injection has been carried out can be more reliably determined by the bar code label.
By allowing the reaction container to have an opening constituting a sample introduction unit and by previously sticking the first bar code label to the sample introduction unit so that the opening can be opened only after removing a portion of the first bar code label that should be removed, it is possible to reliably prevent the first bar code label from being kept stuck to the reaction container even after sample injection.
By allowing the second bar code label to also serve as a sealing member for hermetically sealing the opening after sample injection, it is possible to hermetically seal the inside of the reaction container with the second bar code label. This eliminates the necessity to prepare another sealing member for hermetically sealing the opening, which contributes to cost reduction.
In one embodiment of the reaction container kit according to the present invention, in which the space above the top surface of the reaction plate has, on the top surface side thereof, a reaction portion and a reagent container may be covered with a cover, and an opening constituting a sample introduction unit may be provided on the cover so that a sample can be introduced into the space covered with the cover from outside through the opening, by hermetically sealing the opening after the sample is introduced into the space covered with the cover, it is possible to prevent the entry of a foreign matter into the sample from outside and the pollution of a surrounding environment by a reaction product.
Further, in a case that a dispensation tip movably supported by the cover covering the space above the top surface of the reaction plate may be provided, by allowing the dispensation tip to have a syringe to be operated from the outside of the cover, it is possible to eliminate the necessity to additionally provide a nozzle mechanism.
By allowing the reaction plate to further have a gene amplification portion, it is possible to amplify a gene to be detected by gene amplification reaction such as PCR or LAMP even when the amount of the gene contained in a sample is very small and thereby to improve analytical accuracy.
By allowing the dispensation tip to have a filter inside the tip portion thereof, it is possible to prevent the entry of a foreign matter from outside through the dispensation tip even when the dispensation tip does not have a syringe. In addition, it is also possible to prevent the leakage of a reaction product into the outside through the dispensation tip and thereby to prevent the pollution of a surrounding environment.
In a case where gene amplification reaction is carried out, there is a problem that another DNA or the like will enter a sample from outside. Further, there is also a problem that another sample will be contaminated with an amplified gene. However, in the case of using the reaction container kit according to the present invention, it is possible to carry out gene amplification reaction in a closed space and to dispose of the reaction container kit with an amplified gene being trapped in the space after the completion of analysis, thereby preventing the contamination of a sample with a foreign matter entering from outside and eliminating the fear of contamination of another sample.
By allowing a reaction product to be analyzed in the reaction portion or in another site provided separately from the reaction portion in the reaction container, such as an electrophoresis portion or a region where probes which react with a gene are arranged, it is possible to increase the types of samples which can be treated using the reaction container kit according to the present invention.
The structure for holding and movably supporting the dispensation tip can be easily achieved by, for example, using an airtight and flexible material or a cover constituted from a cover main body and a cover plate. In the latter case, the dispensation tip is supported so as to be able to be moved by sliding the cover plate supported by the cover main body and by sliding the dispensation tip itself supported by the cover plate.
As shown in
The reaction portion 4 is provided as a recess in the top surface of the substrate 3. In a case where the reaction portion 4 is intended for reaction carried out under externally-controlled temperature conditions, a part of the reaction portion 4 subjected to temperature control preferably has a small thickness to enhance heat conductivity.
Each of the reagent containers 12 is also provided as a recess on the top surface of the substrate 3, and contains a reagent to be used for reaction, and is covered with the film 14 through which the dispensation tip 20 (which will be described later) can pass. Examples of such a film 14 include an aluminum foil and a laminated film having an aluminum film and a resin film such as a PET (polyethylene terephthalate) film. The film 14 is attached by welding or adhesion so as not to be easily detached.
If necessary, a mixing chamber for mixing a sample with a reagent may be provided as a recess in the top surface of the substrate 3. Further, such a mixing chamber may be covered with the film 14 with its recess being empty.
The reaction portion 4 may be used as a detection chamber for detecting a reaction product formed in the reaction portion 4. In this case, detection of a reaction product can be carried out by, for example, means for externally irradiating the reaction portion 4 with light. Alternatively, a detection chamber may be provided separately from the reaction portion 4. For example, in a case where a plurality of detection chambers are provided separately from the reaction portion 4, the detection chambers may previously contain different reagents for detecting the state of a reaction mixture obtained by the reaction of a sample with a reagent, and the reaction mixture is dispensed into the detection chambers by the dispensation tip 20. The opening of such a detection chamber may be covered with a film through which the dispensation tip 20 can pass. As in the case of the film 14, examples of the film for covering the detection chamber include an aluminum foil and a laminated film having an aluminum film and a resin film such as a PET film, and the film can be attached by welding or adhesion so as not to be easily detached.
The material of the substrate 3 having the reaction portion 4 is not particularly limited, but is preferably cheaply available because the reaction container is disposable. Preferred examples of such a material include resin materials such as polypropylene and polycarbonate. In a case where the reaction container is designed to allow a reaction product to be detected by absorbance, fluorescence, chemiluminescence, or bioluminescence in the reaction portion 4 or a detection chamber provided separately from the reaction portion 4, the substrate 3 is preferably made of an optically-transparent resin so that the reaction product can be optically detected from the bottom surface side of the substrate 3. Particularly, in a case where a reaction product is detected by fluorescence, the substrate 3 is preferably made of a low self-fluorescence (i.e., the amount of fluorescence emitted from a material itself is small) and an optically-transparent resin such as polycarbonate. The thickness of the substrate 2 is in the range of 0.3 to 4 mm, preferably in the range of 1 to 2 mm. From the viewpoint of low self-fluorescence, the thickness of the substrate 3 is preferably small.
The dispensation tip 20 is arranged above the top surface of the reaction plate 2. The dispensation tip 20 is used to dispense a sample and a reagent. Further, in a case where the reaction plate 2 has a detection chamber provided separately from the reaction portion 4, the dispensation tip 20 is used also to dispense a reaction mixture obtained by reacting a sample with a reagent into the detection chamber. The dispensation tip 20 has a syringe 22, and the syringe 22 is driven from the outside of a cover 24 to carry out dispensation operation.
As shown in
The cover 24 is provided so as to cover a space above the top surface of the reaction plate 2. The cover 24 includes a cover main body 26 for covering the periphery of the reaction plate 2 and a bellows film 28 for covering the top of the reaction plate 2 so that a space above the top surface of the reaction plate 2 is cut off from the outside. The cover main body 26 is provided integrally with the reaction plate 2 by fixing the lower end of the cover main body 26 to the reaction plate 2 or by using a sealant provided between the lower end of the cover main body 26 and the reaction plate 2, and has stiffness to maintain the shape of the cover 24. The bellows film 28 is formed from a flexible diaphragm or a flexible film, and movably holds the dispensation tip 20 so that a distal end thereof is located inside a space covered with the cover 24 and a proximal end thereof is located outside the space covered with the cover 24.
The material of the cover 24 is not particularly limited as long as it can cover a space above the top surface of the reaction plate 2 while keeping the reaction container kit hermetically sealed. However, the cover 24 is preferably made of a cheaply-available material because the reaction container is disposable. Preferred examples of a material for forming the cover main body 26 include resin materials such as polypropylene and polycarbonate, and preferred examples of a material for forming the bellows film 28 include Nylon®, polyvinyl chloride, and rubber materials such as silicone rubber and the like.
A holding member 30 for holding the dispensation tip 20 before and after its use is provided on the cover main body 26 or the substrate 3. When used for dispensation operation, the dispensation tip 20 is detached from the holding member 30 so as to be freely moved over the top surface of the reaction plate 2.
A cover main body 26 has an opening 31 for introducing a sample from the outside of a cover 24 into the reaction plate 2, and a sample container 32 is attached to the opening 31 so that the opening 31 can be opened and closed. The opening 31 and the sample container 32 constitute a sample introduction unit.
As shown in
Before sample injection, the bar code 132 of the first bar code label is read by a bar code reader to automatically determine whether or not the reaction container is a correct one suitable for an inspection item requested to be performed on a sample to be injected thereinto and to confirm that a sample has not yet been injected into the reaction container.
As described above, since the first bar code label 130 is stuck so as to cover the sample container 32, the opening 31 can be opened only by removing the first bar code label 130.
The reaction container further has a second bar code label 134 to be read after sample dispensation. The second bar code label 134 is partially attached to the reaction container with the adhesive-coated surface thereof being covered with a release sheet so as to be able to be stuck to the reaction container. The release sheet is removed when the second bar code label 134 is stuck to the reaction container, and the second bar code label 134 is stuck so as to cover the sample container 32. As a result, the opening 31 is hermetically sealed. The second bar code label 134 has a bar code 136 (see
The back surface of each of the bar code labels 130 and 134 (a surface having a bar code printed thereon is defined as a front surface) is an adhesive-coated surface. Specific examples of the bar code labels 130 and 134 include labels obtained by applying an adhesive onto a base material. Examples of the base material include polyethylene film, polypropylene film, polystyrene film, synthetic paper, polyimide film, and film for variable information labeling. Examples of the adhesive to be applied onto the base material include PVA-based emulsions, SBR-based emulsions, acrylic emulsions, synthetic rubber-based emulsions, pressure-sensitive adhesives, and heat-sensitive adhesives. As described above, since the bar code label 130 is removed at the time of sample injection, the adhesive to be applied onto the base material is preferably a pressure-sensitive adhesive which makes it possible to easily remove the bar code label.
The sample container 32 has a recess facing upward to receive an injected sample. After a sample is injected into the recess, the sample container 32 is placed inside the cover 24 so that the opening 31 is closed by a plate 34 holding the sample container 32. Then, the release sheet attached to the adhesive-coated surface of the bar code label 134 is removed, and the bar code label 134 is stuck to the cover main body 26 so as to cover the plate 34. As a result, the opening 31 is hermetically sealed with the bar code label 134.
The reaction container is disposable, and therefore the entire reaction container is disposed of with the reaction plate 2 being covered with the cover 24 after the completion of the analysis of one sample.
Hereinafter, a process for analyzing a sample using the reaction container kit according to the above-described embodiment of the present invention will be described.
The unused reaction container is supplied in such a state as shown in
Then, as shown in
As described above, since the second bar code label 134 has the bar code 136 containing data indicating that a sample has already been injected into the reaction container, it is possible, by reading the bar code 136 using a bar code reader, to automatically confirm that a sample has already been injected into the reaction container.
A bar code label 138 shown in
In the drawings of other embodiments according to the present invention which will be described below, the bar code labels are not shown. However, also in each of the following embodiments according to the present invention, as in the case of the embodiment shown in
After the sample is introduced into the reaction container kit, as shown in
First, as shown in
Then, as shown in
Next, as shown in
The dispensation tip 20 is moved to the sample container 32 to take a sample, and then the sample is dispensed into the reaction portion 4 by the dispensation tip 20.
Then, the dispensation tip 20 is moved to the reagent container 12, and the distal end of the dispensation tip 20 is passed through the film 14 to take a reagent from the reagent container 12, and the reagent is dispensed into the reaction portion 4 by the dispensation tip 20 to react the sample with the reagent. If necessary, the reaction portion 4 is brought into contact with an external heat source during the reaction to adjust the temperature of the reaction portion 4 to a predetermined temperature.
During or after the reaction, detection of a reaction product is carried out. In this case, it is assumed that a reaction product contained in the reaction portion 4 is optically detected from the outside of the reaction plate 2. Therefore, a detection unit is arranged below the reaction portion 4 to detect a reaction product by optical means or other means.
As described above, the reaction plate 2 of the embodiment has reagent containers 12, but the reagent containers 12 can be omitted from the reaction plate 2. In this case, both a sample and a reagent may be injected into the sample container 32 to introduce them into the reaction container, or another container not shown may be used to introduce a reagent into the reaction container.
A detection unit 38a includes an irradiation optical system. The irradiation optical system has, on its optical path, a light source 40a, a pair of lenses 42a for once condensing light emitted from the light source 40a to obtain parallel light and then condensing the parallel light to irradiate the reaction portion 4 with condensed light, a filter 44a arranged between the pair of lenses 42a at a position where the parallel light travels to select light having a predetermined wavelength from light emitted from the light source 40a to obtain measuring light, and mirrors 46 for guiding the measuring light to the light incident surface of the reaction portion 4. As the light source 40a, a lamp light source such as a tungsten lamp which emits light having wavelengths ranging from the ultraviolet light region to the visible light region, a light-emitting diode (LED), a laser diode (LD), or the like is used. Further, the detection unit 38a includes a light-receiving optical system. The light-receiving optical system has, on its optical path, a photodetector 48a, mirrors 50 for guiding light exiting from the reaction portion 4 through its light exiting surface to the photodetector 48a, a pair of lenses 52 for once converting the light into parallel light and then condensing the parallel light to introduce condensed light into the photodetector 48a, and a filter 54a arranged between the pair of lenses 52 at a portion where the parallel light travels to select light having a predetermined wavelength suitable for measurement.
The reason for once converting light into parallel light by the lenses 42a and 52a is to improve the precision of wavelength selection by the filters 44a and 54a.
In the case of using such a detection unit 38a, light having a wavelength suitable for detecting a reaction product is selected from light emitted from the light source 40a by the filters 44a and 54a, and absorbance is measured at the selected wavelength to detect the reaction product.
A detection unit 38b includes an excitation optical system. The excitation optical system has a light source 40b, a pair of lenses 42b for once condensing light emitted from the light source 40b to obtain parallel light and then condensing the parallel light to irradiate the reaction portion 4 with condensed light, and a filter 44b arranged on the optical path of parallel light beams obtained by the lens 42b to select light having a predetermined excitation wavelength from light emitted from the light source 40b. Further, the detection unit 38b includes a light-receiving optical system. The light-receiving optical system has a photodetector 48b, a pair of lenses 52b for receiving fluorescence emitted from the reaction portion 4, once converting the fluorescence into parallel light, and condensing the parallel light to introduce condensed light into the photodetector 48b, and a filter 54b arranged on the optical path of the parallel fluorescence beams obtained by the lens 52b to select light having a predetermined fluorescence wavelength. Similarly, the reason for once converting light into parallel light by the lenses 42b and 52b is to improve the precision of wavelength selection by the filters 44b and 54b.
In the case of using such a detection unit 38b, light having an excitation wavelength for exciting a reaction product is selected from light emitted from the light source 40b by the filter 44b to irradiate the reaction product contained in the reaction portion 4 with the selected light, and fluorescence emitted from the reaction product is received by the light-receiving optical system, and light having a predetermined fluorescence wavelength is selected by the filter 54b, and the selected fluorescence is detected by the photodetector 48b.
A detection unit 38c has a photodetector 48c for detecting light emitted from the reaction portion 4, a lens 52c for receiving light emitted from the reaction portion 4 and guiding condensed light to the photodetector 48c, and a filter 54c for selecting light having a predetermined emission wavelength from the condensed light.
In the case of using such a detection unit 38c, chemiluminescence or bioluminescence emitted from a reaction product contained in the reaction portion 4 is condensed by the lens 52c, and light having a predetermined emission wavelength is selected by the filter 54c, and the selected light is detected by the photodetector 48c.
A reaction plate 2a of the embodiment shown in
The reaction plate 2a further has a separation buffer container 15 provided in the top surface thereof to receive a separation buffer to be injected into the channels 102 and 104. The separation buffer container 15 is sealed with a film through which the tip of the dispensation tip 20 can pass.
The electrodes 106a to 106d for applying an electrophoresis voltage are connected to both ends of the channel 102 and 104, respectively. These electrodes 106a to 106d are extended to the outside of the cover 24 so as to be connected to a power supply provided outside the reaction container.
Each of the channels 102 and 104 has a reservoir at its end, and a separation buffer contained in the separation buffer container 15 is injected into the reservoirs.
In a case where the embodiment is used for gene analysis, the reagent container 12 is allowed to previously contain a PCR reaction reagent. In this case, the reaction portion 4 serves as a PCR reaction container.
In a case where a gene sample is measured using the reaction container kit of the embodiment, a sample is introduced into the sample container 32, and then the reaction container is attached to the reaction container kit treatment equipment. In the reaction container kit treatment equipment, the sample contained in the sample container 32 is dispensed into the reaction portion 4 by the dispensation tip 20, and then a PCR reaction reagent contained in the reagent container 12 is also dispensed into the reaction portion 4 by the dispensation tip 20. Further, mineral oil (not shown) is layered over a mixture of the sample and the reagent contained in the reaction portion 4, and then PCR reaction is carried out by controlling the temperature of the reaction mixture contained in the reaction portion 4 according to a predetermined temperature cycle.
A separation buffer is supplied by the dispensation tip 20 from the separation buffer container 15 to the channels 102 and 104 through the reservoirs in the electrophoresis chip 100.
After the completion of the PCR reaction, an obtained reaction mixture is supplied as a sample by the dispensation tip 20 from the reaction portion 4 to the injection section 103 of the electrophoresis chip 100 having the separation buffer previously supplied. Then, a voltage is applied from a power supply 101 (see
In order to detect sample components separated by electrophoresis, the reaction container kit treatment equipment has a detection unit 38d.
It is to be noted that in this case, the reaction portion 4 is used as a PCR reaction container, but a PCR reaction container may be provided separately from the reaction portion 4.
The detection unit 38d is shown in
The excitation optical system has a light source 40c, a lens 42c for condensing light emitted from the light source 40c to obtain parallel light, and a filter 44c provided on the optical path of parallel light beams obtained by the lens 42c to select light having a predetermined excitation wavelength from light emitted from the light source 40c.
The detection unit 38d further includes a dichroic mirror 53 and an objective lens 55 to irradiate a predetermined position in the electrophoretic separation channel 102 with excitation light obtained by the excitation optical system from the back surface side of the electrophoresis chip 100 and to receive fluorescence emitted from the position and convert it into parallel light. It is to be noted that the dichroic mirror 53 is designed so as to reflect light having an excitation wavelength to be used for the embodiment and transmit light having a fluorescence wavelength.
The fluorescence-receiving optical system of the detection unit 38d is arranged at a position where it can receive fluorescence converted into parallel light by the objective lens 55 and passed through the dichroic mirror 53. The fluorescence-receiving optical system has a filter 54c for selecting light having a predetermined fluorescence wavelength from fluorescence passed through the dichroic mirror 53 and a lens 52c for condensing the fluorescence having a wavelength selected by the filter 54c to introduce condensed light into a detector 48c. As described above, the reason for once converting light into parallel light by the lenses 42c and 55 is to improve the precision of wavelength selection by the filters 44c and 54c.
In the case of using such a detection unit 38d, light having an excitation wavelength for exciting a reaction product is selected by the filter 44c from light emitted from the light source 40c to irradiate the reaction product passing through a predetermined position in the electrophoretic separation channel 102 with the light, and fluorescence emitted from the reaction product is received by the light-receiving optical system, and light having a predetermined fluorescence wavelength is selected by the filter 54c and detected by the photodetector 48c.
A reaction plate 2b of the embodiment shown in
The reaction plate 2a further has cleaning solution containers 17 formed in the top surface thereof. The cleaning solution containers 17 contain a cleaning solution for separating and removing the reaction product not having been bound to the probes from the reaction product having been bound to the probes in the DNA chip 110. Further, the cleaning solution containers 17 are sealed with a film through which the tip of the dispensation tip 20 can pass.
In a case where the embodiment is used for gene analysis, the reagent container 12 is allowed to previously contain a PCR reaction reagent. In this case, the reaction portion 4 serves as a PCR reaction container.
In a case where a gene sample is measured using the reaction container kit of the embodiment, the sample is introduced into the sample container 32, and then the reaction container is attached to the reaction container kit treatment equipment. In the reaction container kit treatment equipment, the sample contained in the sample container 32 is dispensed into the reaction portion 4 by the dispensation tip 20, and then a PCR reaction reagent contained in the reagent container 12 is also dispensed into the reaction portion 4 by the dispensation tip 20. Further, mineral oil (not shown) is layered onto a mixture of the sample and the reagent contained in the reaction portion 4, and then PCR reaction is carried out by controlling the temperature of the mixture contained in the reaction portion 4 according to a predetermined temperature cycle.
After the completion of the PCR reaction, an obtained reaction mixture is supplied as a sample from the reaction portion 4 to the DNA chip 110 by the dispensation tip 20. After the completion of incubation, a cleaning solution is supplied from the cleaning solution container 17 to the DNA chip 110 by the dispensation tip 20, and then a reaction product not having been bound to the probes is removed by sucking the cleaning solution into the dispensation tip 20.
The reaction product having been bound to the probes can be detected by fluorescence by previously labeling the reaction product with a fluorescent material. The detection of the presence of fluorescence in the DNA chip 110 indicates that a gene corresponding to the probe immobilized at a position where fluorescence has been detected is contained in the sample.
In order to detect the reaction product having been bound to the probes in the dispensation tip 20, the reaction container kit treatment equipment includes a detection unit 38e.
The detection unit 38e is shown in
A reaction plate 2c of the embodiment shown in
When a reaction product contains a gene, probes, which react with the gene, are immobilized to the DNA chip 120. Each of the probes is connected to an electrode provided on the back surface of the reaction plate so that the current value thereof can be measured. In the case of using the embodiment, it is not necessary to previously label a sample with a fluorescent material.
The electrodes provided on the back surface of the reaction plate and connected to the probes are connected also to a detector 122 provided in the reaction container kit treatment equipment to measure the current value of each of the probes to detect the reaction product in the DNA chip 120.
The reaction plate 2c also has a cleaning solution container 17 formed in the top surface thereof. The cleaning solution container 17 contains a cleaning solution for separating the reaction product not having been bound to the probes immobilized to the DNA chip 120 from the reaction product having been bound to the probes and removing the former from the DNA chip 120. Further, the cleaning solution container 17 is sealed with a film through which the tip of the dispensation tip 20 can pass. The reagent container 12 previously contains a PCR reaction reagent. The reaction portion 4 serves as a PCR reaction container.
In a case where a gene sample is measured by the reaction container kit of the embodiment, the sample is introduced into the sample container 32, and then the reaction container is attached to the reaction container kit treatment equipment. In the reaction container kit treatment equipment, the sample contained in the sample container 32 is dispensed into the reaction portion 4 by the dispensation tip 20, and then a PCR reaction reagent contained in the reagent container 12 is also dispensed into the reaction portion 4 by the dispensation tip 20. Further, mineral oil (not shown) is layered onto a mixture of the sample and the reagent contained in the reaction portion 4, and then PCR reaction is performed by controlling the temperature of the mixture contained in the reaction portion 4 according to a predetermined temperature cycle.
After the completion of the PCR reaction, an obtained reaction mixture is supplied as a sample from the reaction portion 4 to the DNA chip 120 by the dispensation tip 20. Then, a cleaning solution is supplied from the cleaning solution container 17 to the DNA chip 120 by the dispensation tip 20, and then a reaction product not having been bound to the probes is removed by sucking the cleaning solution into the dispensation tip 20.
In order to detect the reaction product having been bound to the probes in the dispensation tip 20, the reaction container kit treatment equipment includes a detector 122. After the reaction product not having been bound to the probes is removed, the current value of each probe is measured by the detector 122.
It is to be noted that a gene sample can be measured even when the DNA chip 110 or 120 of the embodiment shown in
In the embodiment shown in
The detection unit 38a, 38b, or 38c is arranged in the reaction container kit treatment equipment so as to be located under the reaction plate 2 of the reaction container kit attached to the treatment equipment.
The embodiment shown in
In the embodiment shown in
By rotating the cover plate 64a, it is possible to move the dispensation tip 20 on the circumference of a circle whose center is the rotational center of the cover plate 64a. Therefore, the reaction portion 4 and the reagent containers 12 provided in the reaction plate 2 and the sample container 32 are arranged so as to be located on the movement locus of the dispensation tip 20.
The dispensation tip 20 can be moved also in the in-plane direction by the sealant 72. Therefore, the dispensation tip 20 can be moved within a range defined by both the circumference of a circle obtained by rotating the cover plate 64a and a horizontal plane obtained by moving the smaller cover plate 71 movable by the sealant 72, that is, within a doughnut-shaped range whose center is the rotational center of the cover plate 64a. In the case of the embodiment shown in
The reference numeral 80 denotes the reaction container kit of the embodiment described above. The reaction container 80 is attached onto a table 82 provided as a reaction container attachment section. The table 82 has an opening on its surface facing the lower surface of the reaction container 80. Under the table 82, a detection unit 38 is arranged to optically detect a reaction product contained in the reaction portion 4 of the reaction container 82. On the table 82, a temperature control unit 83 is arranged to control the temperature of the reaction container 82. In a case where gene amplification reaction is carried out in the reaction portion 4 or a reaction container for gene amplification provided separately from the reaction portion 4 of the reaction container, the temperature control unit 83 is used to carry out temperature control for gene amplification reaction. Further, in a case where the reaction container has an analysis section requiring temperature control, the temperature control unit 83 is used to carry out temperature control of the analysis section. The temperature control unit 83 may have both the function of carrying out temperature control for gene amplification reaction and the function of carrying out temperature control of the analysis section. The detection unit 38 shown in
The drive unit 36 for driving the dispensation tip 20 is attached near the table 82 so as to be able to move in the Y and Z directions. As shown in
In some drawings of the embodiments according to the present invention, the bar code label 134 is not shown, but what all the embodiments have in common is that a sealing member to be stuck to the cover main body so as to cover the outside of the sample container is provided outside the cover main body in order to hermetically seal the opening, through which the sample container is inserted into the space covered with the cover, after a sample is introduced into the space by the sample container.
In order to use the control section 84 as an input section externally operated or a monitor for displaying detection results, an external computer such as a personal computer (PC) 86 may be connected to the control section 84.
The present invention can be applied to measurements of various reactions such as chemical reactions and biochemical reactions.
Number | Date | Country | Kind |
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2006-132055 | May 2006 | JP | national |
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/JP2007/059687 | 5/10/2007 | WO | 00 | 10/21/2008 |