1. Field of the Invention
The present invention relates to a chemical analysis device equipped with a pipetting function of a liquid sample or a reagent to analyze chemical substances in the sample solution.
2. Description of the Related Art
In a system in which different liquid samples or reagents are pipetted to perform an analysis or a test, a channel or a liquid storage unit used for pipetting is frequently used in common for different samples or reagents, which causes a problem that the channel or liquid storage unit mutually becomes a source of contamination due to residual samples or reagents.
Thus, replacement of a tip part of a pipetting means is assumed in the conventional technology. However, among portions used repeatedly, there has a portion that comes into contact with liquids and there is a problem that it is difficult to avoid contamination of the portion by residual samples or reagents.
To prevent contamination, as described in Japanese Patent Application Laid-Open Publication No. 2000-121650, a pipetting channel of liquid or a portion containing a reagent cell is washed.
Moreover, in a genetic test accompanied by nucleic acid amplification, as described in Japanese Unexamined Patent Application Publication (Translation of PCT Application) No. 9-504690, a cell in which an amplification reaction occurs is sealed because nucleic acid may be leaked in an amplification process to become a source of contamination.
However, according to a technology described in Japanese Patent Application Laid-Open Publication No. 2000-121650, there is a problem that a means for washing a portion including a reagent cell is needed, complicating the configuration of an analysis device.
A technology described in Japanese Unexamined Patent Application Publication (Translation of PCT Application) No. 9-504690 also needs a means for sealing a cell in which an amplification reaction occurs and thus, there is also a problem that the configuration of an analysis device becomes complicated. In addition, stirring of a solution needed in the course of a reaction and also pipetting and dropping could also lead to contamination when analyzed repeatedly.
An object of the present invention is to construct a chemical analysis device for performing a chemical analysis or genetic test that can suppress deterioration of analysis accuracy and test accuracy while avoiding contamination by residual samples or reagents remaining in the device and having no complicated configuration.
To solve the above problems, the present invention is constituted as described below.
A chemical analysis device includes a pipetting means for sucking in and dispensing a liquid sample or a liquid reagent and a pipetting means movement drive means having a support unit for detachably supporting the pipetting means, a drive unit for driving the pipetting means to cause a suction or dispensing operation of the liquid sample or liquid reagent, and a movement unit for moving the pipetting means.
A pipetting unit which is used in a chemical analysis device or a genetic testing device for analyzing a liquid sample and which sucks in and dispenses the liquid sample or a liquid reagent, includes a needle unit having a nucleic acid capturing carrier therein for a genetic test and being used for sucking in and dispensing the liquid sample or liquid reagent, a plunger unit for sucking in and dispensing the liquid sample or liquid reagent via the needle unit, a syringe unit for movably supporting the plunger unit, a flange unit detachably supported by the chemical analysis device or genetic testing device, a drive end detachably supported by the chemical analysis device or genetic testing device so that the plunger unit is driven by a drive means of the chemical analysis device or genetic testing device, and a detection cell detachably supported by the needle unit, which cell serves as a protective cover of the needle unit and houses an object to be analyzed.
A genetic testing device having a testing unit for testing a gene in a liquid sample, includes a pipetting means having a nucleic acid capturing carrier therein and being used for sucking in and dispensing the liquid sample or a liquid reagent, and a pipetting means movement drive means having a support unit for detachably supporting the pipetting means, a drive unit for driving the pipetting means to cause a suction or dispensing operation of the liquid sample or liquid reagent, and a movement unit for moving the pipetting means.
A chemical analysis device for performing a chemical analysis or genetic test that can suppress deterioration of analysis accuracy and test accuracy while avoiding contamination by residual samples or reagents remaining in the device and having no complicated configuration can be constructed.
Embodiments of the present invention will be described below with reference to attached drawings. Embodiments below are examples where the present invention is applied to genetic testing devices among chemical analysis devices.
In
Amounts of suction and dispensing of a solution such as a reagent and a sample by the pipetting unit 2 and working speeds thereof are controlled by the push-pull distance and speed of the plunger 2b relative to the syringe 2a. Insertion of the needle unit 2c of the pipetting unit 2 into each reagent cell or the like and withdrawal of the needle unit 2c therefrom are controlled by a pipetting unit vertical drive unit 3a including a pulse motor and a ball screw. Push-pull of the plunger 2b, that is, suction and dispensing of a solution is controlled by a plunger drive unit 3b.
On the other hand, movement of the pipetting unit 2 in a horizontal direction, that is, movement between cells, is controlled by a pipetting unit horizontal drive unit 3c driven by the pulse motor and belt. The carrier 2d is formed from glass fibers, glass particles, silica particles, silica wool, or materials of crushed particles thereof containing silicon oxide.
A sample to be tested such as blood is pipetted into a sample cell 4 and, after pretreatment, the sample cell 4 is fitted to a sample cell holding unit 5. Similarly, a detection cell 6 doubling as a protective cover is fitted to the needle unit 2c of the pipetting unit 2, the pipetting unit 2 is fitted to a pipetting unit drive system 3 with the detection cell 6 being fitted to the needle unit 2c, and the reagent cell 1 is fitted to a reagent cell holding unit 7.
The pipetting unit 2 is configured to be easily mountable to and removable from the pipetting unit drive system 3 by an operator.
Then, to fix a flange unit 2f, a syringe fixing holder 3e is set to a syringe fixing position, a syringe fixing lock pin 3d is pushed in, and the syringe fixing holder 3e is locked to produce a state shown in
When the pipetting unit 2 is to be removed from the syringe holder 3k, the syringe fixing lock pin 3d is lifted to release the syringe fixing holder 3e. Then, the pipetting unit 2 is removed from the syringe holder 3k.
The plunger 2b of the pipetting unit 2 is configured to be push-pull driven by the pipetting unit drive system 3.
The whole pipetting unit 2 is configured to be moved vertically by the pipetting unit drive system 3.
Sample pretreatment is performed (step 100 in
While the sample solution is heated, as shown in
Next, the pipetting unit 2 is moved and, as shown in
In addition to nucleic acid, impurities contained in the sample adhere to the carrier 2d in the needle unit 2c, and impurities are removed by a cleaning reagent having ethanol as a main ingredient in the washing process to be performed next.
The first embodiment of the present invention has an integral structure in which cleaning reagent cells 1c to 1f at four locations are provided in the reagent cell 1. Impurities adhering to the carrier are washed away by replacing the cleaning reagent by sucking cleaning reagents from these cleaning reagent cells 1c to 1f into the syringe 2a and then dispensing the cleaning reagents to the cell (step 105).
Since the cleaning reagents could be a factor to inhibit a reaction in the subsequent nucleic acid amplification process, residual cleaning reagents inside the syringe 2a and on the carrier 2d are purged (step 106). To purge cleaning reagents, the needle unit 2c is inserted into a reagent waste cell 1g and an adsorbent contained in the reagent waste cell 1g is caused to absorb cleaning reagents inside the pipetting unit 2 by sucking air into the syringe 2a and dispensing it. A mist that is generated at this point and contains cleaning reagents is prevented from being leaked out of the cell by a filter provided to the reagent waste cell 1g.
Then, a nucleic acid elution reagent is sucked from a nucleic acid elution reagent cell 1h into the syringe 2a to elute nucleic acid captured by the carrier 2d (step 107). The nucleic acid elution reagent sucked into the syringe 2a contains a nucleic acid amplification enzyme and a specific nucleic acid can be caused to amplify by controlling the nucleic acid elution reagent containing eluted nucleic acid at optimum temperature.
To perform this amplification reaction of nucleic acid and a detection process, as shown in
The nucleic acid eluting solution in the detection cell 6 is put in an environment of a constant temperature by a heater 8a contained in the nucleic acid amplification detection unit 8 to allow an amplification reaction at a constant temperature to proceed. The first embodiment of the present invention assumes nucleic acid amplification at a constant temperature by the Nucleic Acid Sequence-Based Amplification (NASBA) method or the like, but nucleic acid amplification by the PCR method can also be performed by adopting cycle control of high temperature-low temperature as the temperature control in a nucleic acid detection amplification unit. Nucleic acid is fluorescence-tagged and, through a photo detection window 8b provided in the nucleic acid amplification detection unit, an excitation light is made incident on a nucleic acid solution in the cell and resulting fluorescence from there is detected to measure fluorescence in the solution (step 108).
If tubercle bacilli in concentration higher than the lower limit of detection are present in the sample solution, the presence thereof is detected as an increase in the amount of light of fluorescence and judged to be positive. If, on the other hand, tubercle bacilli in concentration lower than the lower limit of detection are present, the presence thereof is confirmed to be negative because the amount of light of fluorescence does not increase within a predetermined measuring time. The detection process terminates after the presence thereof is judged to be positive or negative, and the pipetting unit 2 having the sample cell 4 and the detection cell 6 fitted thereto, and the reagent cell 1 are removed from the device before being disposed of (step 109).
Thus, units brought into contact with a reagent or a sample solution are disposed of after each test so that mutual contamination by reagents or samples between tests can be prevented. Particularly the detection cell 6 is disposed of while being capped by the pipetting unit 2, and thus, amplified nucleic acid does not remain in the device and contamination by leakage of amplified nucleic acid can be prevented.
Therefore, according to the first embodiment of the present invention, a genetic testing device capable of suppressing deterioration of analysis accuracy and test accuracy while avoiding contamination by residual samples or reagents remaining in the device and having no complicated configuration, can be constructed.
If a plurality of pipetting unit holding units is provided in the pipetting unit drive system 3 and accordingly holding units for reagent cells or sample cell are equipped, that is, a plurality of units of the pipetting unit drive system 3 shown in
In the second embodiment, as is clear from
According to the second embodiment of the present invention, in addition to being able to achieve an effect similar to that of the first embodiment, the treatment time can be reduced compared with mixing and stirring by suction and dispensing using the pipetting unit 2, by mixing and stirring being performed by the sample cell rotating unit 9.
In the case of a mechanical mixing method by a stirring spatula or the like, the treatment time can be reduced more than that of mixing and stirring through suction/dispensing, there is a possibility of contamination because a stirring means and a solution are brought into contact.
In contrast, the possibility of contamination can be reduced, like the second embodiment of the present invention, by rotating the sample cell for mixing and stirring.
In the third embodiment, the pipetting unit 2 uses two types of tips, a nucleic acid purification tip 10 and a solution pipetting tip 11, by attaching and detaching these tips. The pipetting unit 2 is initially configured by the syringe 2a and the plunger 2b, and the nucleic acid purification tip 10 and the solution pipetting tip 11 are each fitted to the reagent cell 1.
The nucleic acid purification tip 10 contains a carrier for capturing nucleic acid and the reagent cell 1 is covered with a protective film like in the first embodiment and further, a septum 12 is fitted inside the cell. The septum 12 is made from a material such as chloroprene rubber that has resistance to reagents encapsulated in a cell and is rich in elasticity. The protective film is manually removed from the reagent cell 1 by an operator immediately before the reagent cell being fitted to the genetic testing device or immediately thereafter and before an automatic operation being started.
The pipetting unit 2 moves to the nucleic acid amplification detection unit 8 (not shown in
Then, the pipetting unit 2 with the nucleic acid purification tip 10 mounted thereon moves to the nucleic acid amplification detection unit 8 before being inserted into the detection cell 6. Subsequent operations are the same as those in the first embodiment.
In the third embodiment, suction and dispensing of a solution is performed by the nucleic acid purification tip 10 or the solution pipetting tip 11 being inserted into the cell through the septum 12. When either of tips 10 and 11 is not inserted, the mouth of the septum 12 is closed so that leakage and scattering of a reagent or a sample solution therein can be prevented.
The nucleic acid purification tip 10 is fitted to the pipetting unit 2 and used for the nucleic acid binding and washing processes and also for the nucleic acid elution process. The solution pipetting tip 11, on the other hand, is used for addition of a nucleic acid binding reagent to a sample solution and also for mixing of a sample solution and a nucleic acid binding reagent by repeated suction and dispensing.
The first embodiment exemplifies a case in which a nucleic acid amplification enzyme and a nucleic acid elution reagent are mixed in advance. However, in order to improve keeping quality, if both should have been separated with the nucleic acid amplification enzyme separated in a dry state to be mixed after starting the testing process, the nucleic acid elution reagent is required to be pipetted with high accuracy of about ±5 μL in a working range of 20 μL to 100 μL.
By using the solution pipetting tip 11 made to match high-accuracy pipetting, the third embodiment achieves an effect of being able to improve pipetting accuracy compared with a case in which the tip is made to match both of nucleic acid purification and solution pipetting.
According to the present invention, as described above, contamination caused by residual samples or reagents remaining in a device can be prevented by making portions that come into contact with such samples or reagents in the device during analysis or testing disposable.
To perform a pipetting operation to a reagent cell covered with a protective film, scattering of a solution can be prevented by piercing the protective film with a needle fitted to the pipetting unit and sucking or dispensing the solution through resultant pore of the film. Contamination inside or outside the device by leakage of amplified nucleic acid can be prevented by using a protective cover at a tip of the pipetting unit as a detection cell for a nucleic acid amplification reaction and making amplified nucleic acid and pipetting means disposable as a package.
Operations such as pipetting and nucleic acid purification can be performed with a single device by incorporating a carrier for nucleic acid purification into the pipetting unit and also solution scattering accompanying tip replacement can be prevented.
Further, contamination by mist scattering of a solution can be prevented by providing a reagent waste cell equipped with a filter and an adsorbent inside a reagent cell for a purge process of a cleaning liquid needed for processes.
Further, both effects of reduced treatment time for mixing and contamination prevention can be achieved by providing a transmission unit for mixing a reagent and a sample.
The above examples are examples where the present invention is applied to a genetic testing device, but the present invention is not limited to the genetic testing device and can also be applied to other chemical analysis devices.
Number | Date | Country | Kind |
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2007-181314 | Jul 2007 | JP | national |