CN101799467A - Particle analyzer, constant-temperature reaction system and constant-temperature reaction method - Google Patents

Particle analyzer, constant-temperature reaction system and constant-temperature reaction method Download PDF

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Publication number
CN101799467A
CN101799467A CN 200910105403 CN200910105403A CN101799467A CN 101799467 A CN101799467 A CN 101799467A CN 200910105403 CN200910105403 CN 200910105403 CN 200910105403 A CN200910105403 A CN 200910105403A CN 101799467 A CN101799467 A CN 101799467A
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Prior art keywords
temperature
reaction tank
thermostatically
dyestuff
reaction
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CN 200910105403
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CN101799467B (en
Inventor
闫宝华
楚建军
郭文恒
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Shenzhen Mindray Scientific Co Ltd
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Shenzhen Mindray Bio Medical Electronics Co Ltd
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Abstract

The invention discloses a constant-temperature reaction system. The constant-temperature reaction system comprises a reaction tank, a dye pipe and a constant-temperature control device, wherein the reaction tank is used for providing a reaction place for a reactant; the dye pipe is used for delivering a fluorescent dye; one end of the dye pipe is communicated with the reaction tank; and the constant-temperature control device, the reaction tank and the dye pipe are arranged in such a manner that the constant-temperature control device controls the temperatures of the reaction tank and the dye pipe at a set temperature. Constant-temperature control is performed on the fluorescent dye according to the set temperature before the fluorescent dye enters the reaction tank, so heating or cooling time of the dye is prolonged, the temperature of the dye is closer to the set temperature, the effect of ambient temperature on the dye is reduced, and the correctness and the stability of a measuring result are finally enhanced.

Description

Particle analyzer, isothermal reaction system and method
[technical field]
The present invention relates to a kind of particle analyzer, relate in particular to the isothermal reaction system and method for the reagent of particle analyzer.
[background technology]
At present common particle analyzer (for example cytoanalyze) is based on the fluidic cell detection technique and comes particle is carried out statistic of classification, with the blood cell analyzer is example, in this blood cell analyzer, need and reagent carry out the reaction under the constant temperature before blood enters flow chamber and detects by Flow Cytometry, it is fluorescent dye that a kind of reagent is wherein arranged, be used for haemocyte is dyeed, in detection, detect fluorescence signal so that determine the nucleus amount by optical detection system.But this fluorescent dye is relatively more responsive for temperature, and fluorescence efficiency strengthens the solution of general fluorescent material along with the reduction of temperature, and fluorescence intensity increases.Fluorescence intensity descends when temperature rises, and main cause is that the transformation of intramolecule energy is accelerated with the rising of temperature, and some reversible photochemical reaction takes place between excited molecule and the solvent molecule simultaneously.Therefore to make fluorescence signal stable, when fluorescent dye and haemocyte reaction, must carry out thermostatic control.Though carry out thermostatic control when having in reaction tank fluorescent dye and haemocyte reaction in the prior art, final test result still remains to be improved aspect accuracy.
[summary of the invention]
The main technical problem to be solved in the present invention is, a kind of particle analyzer, isothermal reaction system and method are provided, by the fluorescent dye that enters before the reaction tank is taked innovative approach, reduce the influence of environment temperature to measurement result, improve the accuracy and the stability of measurement result.
According to an aspect of the present invention, provide a kind of isothermal reaction system, comprising: be used to reactant that the reaction tank of reacting environment is provided; Be used for fluorescent dye is transported to the dyestuff pipe of reaction tank, an end of described dyestuff pipe is communicated with reaction tank, sends dyestuff to reaction tank inside; It is design temperature that thermostatically-controlled equipment, described thermostatically-controlled equipment, reaction tank and dyestuff pipe are configured the temperature that makes described thermostatically-controlled equipment control described reaction tank and dyestuff pipe.
According to a further aspect in the invention, provide a kind of isothermal reaction method, comprise and carry out thermostatically controlled step entering reaction tank fluorescent dye before.
In accordance with a further aspect of the present invention, provide a kind of particle analyzer, comprise flow chamber and above-mentioned isothermal reaction system, the delivery outlet of described isothermal reaction system is communicated with the inlet of flow chamber, is used for detected material is transported to flow chamber.
The invention has the beneficial effects as follows: the present invention not only carries out thermostatic control to reaction tank according to design temperature, reactant in the reaction tank is reacted under design temperature, also the fluorescent dye that enters before the reaction tank is carried out thermostatic control according to design temperature, thereby the heating or the temperature fall time of dyestuff have been prolonged, make the temperature of dyestuff more level off to the temperature of setting, reduced the influence of environment temperature, the accuracy of measurement result and stability are improved dyestuff.
[description of drawings]
The scatter diagram of Fig. 1 for the dyestuff that enters before the reaction tank is not carried out temperature control;
Fig. 2 is for to entering the scatter diagram after dyestuff before the reaction tank carries out temperature control;
Fig. 3 is the structural representation of isothermal reaction system in an embodiment of the present invention;
Fig. 4 is a thermostatically-controlled equipment circuit diagram among a kind of embodiment;
Fig. 5 is thermostatically-controlled equipment control principle figure among a kind of embodiment;
Fig. 6 is one of structural representation of the isothermal reaction system among the another kind of embodiment of the present invention;
Fig. 7 is two of the structural representation of the isothermal reaction system among the another kind of embodiment of the present invention;
Fig. 8 is the fit structure synoptic diagram of dyestuff pipe and dyestuff pressure ring among the another kind of embodiment of the present invention.
[embodiment]
In conjunction with the accompanying drawings the present invention is described in further detail below by embodiment.
In one embodiment, the isothermal reaction system comprises reaction tank, dyestuff pipe and thermostatically-controlled equipment, reaction tank is that reactant (for example reagent and haemocyte) provides the isothermal reaction place, generally comprise mainboard and hatch the pond, hatching the pond is to be positioned at mainboard inside, for example will independently hatch the pond be installed in the cavity of mainboard or the mainboard cavity directly as hatching the pond, hatching the pond can have one or morely, hatches the pond and can be column, spherical or ellipsoid shape.The reaction that mainboard is mainly used in to reactant provides isoperibol, hatches the pond and provides reacting environment for reactant; The dyestuff pipe is used to carry fluorescent dye, the one end is communicated with reaction tank, be used for dyestuff is transported in the reaction tank, specifically can make dyestuff flow at least one by the pipeline that passes mainboard and hatch in the pond and mix, react with other reactant (for example other reagent or blood); Thermostatically-controlled equipment is used to control temperature, by thermostatically-controlled equipment, reaction tank and dyestuff pipe are configured, so that the temperature of thermostatically-controlled equipment control reaction tank and dyestuff pipe is a design temperature.
In the present embodiment, not only reaction tank is carried out thermostatic control according to design temperature, reactant in the reaction tank is reacted under design temperature, also the fluorescent dye (being the dyestuff in the dyestuff pipe) that enters before the reaction tank is carried out thermostatic control according to design temperature, thereby obtained following effect: the heating or the temperature fall time that have prolonged dyestuff, make the temperature of dyestuff more level off to the temperature of setting, thereby reduced the influence of environment temperature, the accuracy of measurement result and stability are improved dyestuff.Temperature control effect can be referring to Fig. 1 and Fig. 2, and wherein horizontal ordinate is the diffusing direction of side, and ordinate is the fluorescence direction, and side is loose and reflected the complexity of cell, fluorescence reflection nucleus amount.Fig. 1 enters the scatter diagram of measured same the blood of no temperature control measures before the reaction tank for dyestuff, about the environment temperature difference of two figure, the environment temperature of right figure is higher than the environment temperature of left figure, because of dyestuff does not have temperature control measures before entering reaction tank, so its temperature can be subjected to the influence of environment temperature, know that by Fig. 1 the rising of dye temperature descends before the fluorescence direction is with reaction tank.Fig. 2 enters the scatter diagram that measured same the blood of temperature control measures is arranged before the reaction tank for dyestuff, about the environment temperature difference of two figure, the environment temperature of right figure is higher than the environment temperature of left figure, because of dyestuff has temperature control measures before entering reaction tank, so its temperature is reduced by the influence of environment temperature, thus reduce the fluorescence direction because of reaction tank before the variable quantity that produces of the variation of dye temperature.
When carrying out thermostatic control to entering dyestuff before the reaction tank, can adopt one independently the temperature of thermostatically-controlled equipment control dyestuff pipe be design temperature, adopt again another independently the temperature of thermostatically-controlled equipment control reaction tank be design temperature, be that thermostatically-controlled equipment comprises first thermostatically-controlled equipment and second thermostatically-controlled equipment, first thermostatically-controlled equipment is used to control the temperature of reaction tank, and second thermostatically-controlled equipment is used to control the temperature of dyestuff pipe.
When carrying out thermostatic control, also can adopt same set of thermostatically-controlled equipment control to enter fluorescent dye (being the dyestuff pipe) before the reaction tank and the temperature of reaction tank is a design temperature to entering dyestuff before the reaction tank.
Be that example describes to adopt same set of thermostatically-controlled equipment that dyestuff pipe and reaction tank are carried out temperature control below.
Please refer to Fig. 3, in a kind of specific embodiment, the temperature of thermostatically-controlled equipment control reaction tank is a design temperature; And be used in and carry fluorescent dye between the dyestuff pipe of reaction tank and reaction tank, to carry out heat interchange.Reaction tank comprise mainboard 1 and be positioned at mainboard 1 at least one hatch pond 3, reagent enters by the pipeline 13 that passes mainboard 1 and hatches the pond and export by the pipeline 14 that passes mainboard 1.For blood cell analyzer, reaction tank provides the isothermal reaction environment for the reaction of reagent and haemocyte, therefore must carry out thermostatic control to reaction tank.In the present embodiment; thermostatically-controlled equipment comprises temperature-control circuit; temperature sensor and thermode; as shown in Figure 4; temperature sensor 8 and thermode 5; 6 link to each other with temperature-control circuit 10 respectively; temperature sensor 8 is installed on the mainboard 1; for example can be attached to the outer wall of mainboard 1 or the inside of inserting mainboard 1; be used to respond to the temperature of reaction tank; the output of temperature-control circuit 10 response temperature sensors 8, control thermode 5; 6 electric power makes thermode 5; 6 change temperature; temperature switch 9 is used for overheat protector; when temperature is higher or lower than certain temperature threshold, control thermode 5; 6 energisings or outage, thus make it reach design temperature.In the embodiment shown in fig. 3, thermode 5,6 contact with the mainboard 1 of reaction tank and and mainboard 1 between carry out heat interchange, the dyestuff pipe is contacted with reaction tank and make dyestuff in the dyestuff pipe and reaction tank between carry out heat interchange, thereby reach dyestuff pipe and the shared same set of thermostatically-controlled equipment of reaction tank.For example offer through hole in mainboard 1, the dyestuff pipe inserts in the through hole, and then enters and hatch the pond by entering the pipeline of hatching the pond, carries out heat interchange between dyestuff and the reaction tank thereby make, and realizes entering the thermostatic control of the dyestuff before the reaction tank.For prolonging the temperature control time of dyestuff, can make through hole is curve-like, increases the distance of dye stream warp.
Be illustrated in figure 5 as the temperature control principle of first thermostatically-controlled equipment, adopt the PID close-loop control mode, with 11 actual temperature value that obtain are as the input of increment type PID controller 12 from temperature sensor from controlled device, process controller 12 resolves acquisition with respect to present actual temperature control increment with target temperature.Temperature control is converted into control heat time heating time, the final temperature closed loop control that realizes controlled device 11.
Make the dyestuff pipe contact and make another kind of embodiment such as the Fig. 6 that carries out heat interchange between dyestuff and the reaction tank with reaction tank, shown in 7, the outer wall of mainboard 1 inwardly is provided with groove 15, one end of groove 15 extends to the edge of described mainboard 1 outer wall, the other end extends to dyestuff pipe 4 and the place that is communicated with of hatching the pond, dyestuff pipe 4 enters from the groove 15 at the edge of mainboard 1 outer wall, be contained in the described groove 15, the other end passes in the groove 15 and is connected with pipeline that the pond is hatched in connection, the one section dyestuff pipe 4 that is positioned at groove 15 is contacted with mainboard 1, and carry out exchange heat between the mainboard, carry out heat interchange between dyestuff and the reaction tank thereby make, realize entering the thermostatic control of the dyestuff before the reaction tank.For prolonging the temperature control time of dyestuff, can make groove is curve-like, for example groove is made into letter " U " or " R " shape, to increase the distance of dye stream warp.In further improved embodiment, comprise also being used for dyestuff pipe 4 is fixed on pressure ring 2 in the groove that shown in Fig. 6,7, dyestuff pipe 4 is fixed on the reaction tank mainboard 1 through pressure ring 2, dyestuff pipe 4 and hatch pond 3 and be communicated with, the dyestuff pipes in the pressure ring 2 are in the control of reaction tank temperature.The diagram that Fig. 8 passes pressure ring 2 for dyestuff pipe 4.Because pressure ring 2 is except the fixed dye pipe, also played the effect (for example, with reaction tank mainboard heat transferred to the dyestuff pipe to add hot dye) of hot transmission.Therefore can adopt metal material, for example aluminium, aluminium alloy, copper or silver with high thermal conductivity.Smear Heat Conduction Material between dyestuff pipe and pressure ring, the groove, for example heat-conducting silicone grease strengthens the exchange capability of heat between them.
Heated dye volume V is by the sectional area S of dyestuff pipe and be fixed on dyestuff length of tube L decision on the reaction tank mainboard.Relational expression is V=SL.
In the isothermal reaction system, volume is that thermode was by carrying out heat interchange after the dyestuff of V entered dyestuff pipe on the reaction tank mainboard between reaction tank mainboard and the dyestuff.
Temperature control to dyestuff pipe and reaction tank can be to make it reach design temperature by adding hot dye pipe and reaction tank, also can be by making it reach design temperature to dyestuff pipe and reaction tank cooling.Therefore in the foregoing description, thermode 5,6 can be a heating arrangement, also can be refrigerating plant.Heating arrangement can be attached to heating plate, the heating film on mainboard surface, or heating rod etc.
In the foregoing description, the reaction tank mainboard is the main heat that transmits in structure of controlling temperature, therefore can adopt the metal material with high thermal conductivity, for example aluminium, copper or silver.The dyestuff pipe also adopts the material with high thermal conductivity, to improve rate of heat exchange.Reagent and haemocyte are hatched the pond internal reaction constant temperature, and therefore hatching the pond should have better chemical stability, can select metal, plastics, pottery etc. to have higher chemical stability material, and for example connection metal can be used titanium, stainless steel etc.
In the foregoing description, reaction tank can also adopt integral structure, one or more cavitys promptly are set as hatching the pond in mainboard, on the mainboard wall, offer different through holes for the reactant input and output, for example an end and the dyestuff charging through hole with the dyestuff pipe is communicated with, dyestuff is delivered into hatches the pond, as shown in Figure 3.
In certain embodiments, in order further to keep the temperature of reaction tank, in the outside of mainboard or heating plate, the heating film outside also be coated with thermofin 7, shown in Fig. 3,7, thermofin 7 is used to hinder reaction tank and extraneous heat interchange.For example thermofin 7 is bonded in reaction tank mainboard 1 around, be wrapped in heating film, reduced the heat dissipation capacity of heating film to external environment, improved the efficiency of heating surface, also reduced simultaneously the heat dissipation capacity of mainboard 1 to external environment.
Adopt same set of thermostatically-controlled equipment to the additional embodiments that dyestuff pipe and reaction tank carry out temperature control can be: thermostatically-controlled equipment comprises temperature-control circuit, temperature sensor and constant temperature oven, temperature sensor links to each other with temperature-control circuit respectively with constant temperature oven, the output of temperature-control circuit response temperature sensor, the control constant temperature oven changes temperature, and reaction tank and dyestuff pipe are positioned in the constant temperature oven, constant temperature oven can be a gas tank, controls the temperature of reaction tank and dyestuff pipe with temperature air bath relatively uniformly; Also can be water tank, by the thermostatic control of water-bath realization to reaction tank and dyestuff pipe.
The present invention is flowed out the back at dyestuff and dyestuff is carried out thermostatic control to entering before hatching the pond from dye reservoir, the temperature that makes dyestuff reduces the influence of environment temperature to dyestuff as far as possible near design temperature.
Above-mentioned any embodiment can be applied to comprise cytoanalyze etc. in the various particle analyzers.Particle analyzer comprises flow chamber and isothermal reaction system, and the delivery outlet of isothermal reaction system is communicated with the inlet of flow chamber, is used for that detected material is transported to flow chamber and detects.Testing result outputs to processor and carries out analytic statistics.
Above content be in conjunction with concrete preferred implementation to further describing that the present invention did, can not assert that concrete enforcement of the present invention is confined to these explanations.For the general technical staff of the technical field of the invention, without departing from the inventive concept of the premise, can also make some simple deduction or replace, all should be considered as belonging to protection scope of the present invention.

Claims (12)

1. isothermal reaction system is characterized in that comprising:
Be used to reactant that the reaction tank of reacting environment is provided;
Be used for fluorescent dye is transported to the dyestuff pipe of reaction tank, an end of described dyestuff pipe is communicated with reaction tank;
It is design temperature that thermostatically-controlled equipment, described thermostatically-controlled equipment, reaction tank and dyestuff pipe are configured the temperature that makes described thermostatically-controlled equipment control described reaction tank and dyestuff pipe.
2. isothermal reaction as claimed in claim 1 system, it is characterized in that: described thermostatically-controlled equipment comprises temperature-control circuit, temperature sensor and thermode, described temperature sensor links to each other with temperature-control circuit respectively with thermode, described temperature sensor is used to respond to the temperature of described reaction tank, the output of described temperature-control circuit response temperature sensor, the control thermode changes temperature, described thermode contacts with described reaction tank also and between the reaction tank and carries out heat interchange, and described dyestuff pipe contacts and makes with reaction tank and carries out heat interchange between dyestuff and the reaction tank.
3. isothermal reaction as claimed in claim 2 system, it is characterized in that: described reaction tank comprise mainboard and be positioned at mainboard inside at least one hatch the pond, the outer wall of described mainboard inwardly is provided with groove, and described dyestuff pipe is contained in the described groove, an end of described dyestuff pipe with hatch the pond and be communicated with.
4. isothermal reaction as claimed in claim 3 system, it is characterized in that: described groove is a curve-like, and an end of described groove extends to the edge of the outer wall of described mainboard, the other end extends to described dyestuff pipe and the place that is communicated with of hatching the pond.
5. as claim 3 or 4 described isothermal reaction systems, it is characterized in that: also comprise being used for described dyestuff pipe is fixed on pressure ring in the described groove.
6. isothermal reaction as claimed in claim 2 system, it is characterized in that: described reaction tank comprise mainboard and be positioned at mainboard inside at least one hatch the pond, have passage in the wooden partition of described mainboard, described dyestuff pipe is contained in the described passage, an end of described dyestuff pipe with hatch the pond and be communicated with.
7. isothermal reaction as claimed in claim 1 system is characterized in that: described thermostatically-controlled equipment comprises second thermostatically-controlled equipment that is used to control first thermostatically-controlled equipment of described reaction tank temperature and is used to control described dyestuff pipe temperature.
8. isothermal reaction as claimed in claim 1 system, it is characterized in that: described thermostatically-controlled equipment comprises temperature-control circuit, temperature sensor and constant temperature oven, described temperature sensor links to each other with temperature-control circuit respectively with constant temperature oven, the output of described temperature-control circuit response temperature sensor, the control constant temperature oven changes temperature, and described reaction tank and dyestuff pipe are positioned at constant temperature oven.
9. an isothermal reaction method is characterized in that comprising: carry out thermostatically controlled step to entering reaction tank fluorescent dye before.
10. isothermal reaction method as claimed in claim 9 is characterized in that: carry out the thermostatic control step and comprise entering fluorescent dye before the reaction tank:
The temperature that adopts thermostatically-controlled equipment independently to control described fluorescent dye is a design temperature; Or
Adopt the control of same thermostatically-controlled equipment to enter fluorescent dye before the reaction tank and the temperature of reaction tank is a design temperature.
11. isothermal reaction method as claimed in claim 10 is characterized in that: adopt the control of same thermostatically-controlled equipment to enter fluorescent dye before the reaction tank and the temperature of reaction tank comprises for the design temperature step:
The temperature that thermostatically-controlled equipment is controlled described reaction tank is a design temperature;
Be used in fluorescent dye is transported between the dyestuff pipe of reaction tank and the reaction tank and carry out heat interchange.
12. a particle analyzer comprises flow chamber, it is characterized in that also comprising as each described isothermal reaction system in the claim 1 to 8, the delivery outlet of described isothermal reaction system is communicated with the inlet of flow chamber, is used for detected material is transported to flow chamber.
CN 200910105403 2009-02-05 2009-02-05 Particle analyzer, constant-temperature reaction system and constant-temperature reaction method Active CN101799467B (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102590487A (en) * 2011-07-29 2012-07-18 深圳雷杜生命科学股份有限公司 Blood reagent constant temperature reaction system and method
CN103091231A (en) * 2011-10-31 2013-05-08 深圳迈瑞生物医疗电子股份有限公司 Method for reducing measure errors of erythrocyte parameters, and temperature control device
CN108181210A (en) * 2016-12-08 2018-06-19 深圳市帝迈生物技术有限公司 A kind of blood cell analyzer and its reaction tank temperature control equipment
CN112881383A (en) * 2019-11-30 2021-06-01 深圳市帝迈生物技术有限公司 Blood analyzer and detection device

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4002720B2 (en) * 2000-11-22 2007-11-07 独立行政法人科学技術振興機構 Single cell long-term culture microscope
EP1784505B1 (en) * 2004-09-02 2016-06-22 Bioneer Corporation Miniaturized apparatus for real-time monitoring
CN101008649B (en) * 2007-01-26 2011-04-06 中国科学院上海光学精密机械研究所 Multiprobe fiber optical evanescent wave biotester based on correlation detection

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102590487A (en) * 2011-07-29 2012-07-18 深圳雷杜生命科学股份有限公司 Blood reagent constant temperature reaction system and method
CN102590487B (en) * 2011-07-29 2013-09-18 深圳雷杜生命科学股份有限公司 Blood reagent constant temperature reaction system and method
CN103091231A (en) * 2011-10-31 2013-05-08 深圳迈瑞生物医疗电子股份有限公司 Method for reducing measure errors of erythrocyte parameters, and temperature control device
CN103091231B (en) * 2011-10-31 2015-06-17 深圳迈瑞生物医疗电子股份有限公司 Method for reducing measure errors of erythrocyte parameters, and temperature control device
CN108181210A (en) * 2016-12-08 2018-06-19 深圳市帝迈生物技术有限公司 A kind of blood cell analyzer and its reaction tank temperature control equipment
CN112881383A (en) * 2019-11-30 2021-06-01 深圳市帝迈生物技术有限公司 Blood analyzer and detection device

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