CN2389384Y - Temp. control intrument for biologial probe diagnostic chip - Google Patents
Temp. control intrument for biologial probe diagnostic chip Download PDFInfo
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- CN2389384Y CN2389384Y CN 99230498 CN99230498U CN2389384Y CN 2389384 Y CN2389384 Y CN 2389384Y CN 99230498 CN99230498 CN 99230498 CN 99230498 U CN99230498 U CN 99230498U CN 2389384 Y CN2389384 Y CN 2389384Y
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Abstract
The temperature control unit for biological probe diagnosis chip of the utility model relates to a novel scheme of the temperature control technology of a micro array probe circulation detection type biochip. The utility model is composed of a casing of the temperature control unit, a front panel, a rear panel and a sensing driving device, and an electronic control circuit of the temperature control unit is provided with a hardware PID control circuit and a positive control electronic circuit. The utility model is characterized in that the sensing driving device is provided with a ceramic thermal insulating plate which is provided with a heating refrigerating device, and the outer part of the heating refrigerating device is provided with thermal insulating pieces or thermal insulating pieces of coating layers; a thermal insulating plate is arranged between the heating refrigerating device and the thermal insulating plate, the front end of the heating refrigerating device is provided with a micro heat transferring piece, and the front end of the micro heat transferring piece is provided with a thermal resistor temperature sensor.
Description
What a kind of temperature controller that is used for the bioprobe diagnosing chip of the utility model related to is a kind of temperature controller of microarray probe circulating detection type biological chip temperature control technology.The temperature control of particularly suitable PCR bioprobe diagnosis is a kind of semiconductor heating, novel reaction type temperature controller of refrigeration bidirectional temperature control of adopting.
Biochip mainly is meant by plane Micrometer-Nanometer Processing Technology and supermolecule self-assembling technique, in microanalysis unit and the system that the solid chip surface makes up.Biochip can integrate many difference in functionality devices, for example, the pre-service of biological sample, the extraction of inhereditary material, the amplification of specific gene fragment, biological probe array and Capillary Electrophoresis form whole microfluid system, with realize to compound, protein, nucleic acid, cell and other biological components accurately, fast, the screening or the detection of large information capacity.Genetic chip is a most important class biochip, and it the is integrated gene probe of dense arrangement in a large number can be analyzed a large amount of genes at short notice, makes people can promptly read and analyze the program of life.
Biochip has extremely important meaning on biological detection, medical test, drug screening and gene sequencing.For example in biology, along with molecular biological continuous development, since the Human Genome Project particularly highly visible was implemented, the data of related nucleic acid, protein sequence and structure were exponential increase.And the most challenging work of next century is exactly after the Human Genome Project is finished, and promptly at the back era gene, how we use a large amount of biomolecule information services in human society, and makes medical science, treatment produce basic revolution.In medical science, " the subordinate phase medical science on system, organ, tissue, the cell level " transforms to " on the gene level; DNA → RNA → protein → protein and nucleic acid interaction, and the phase III medical science on they and the environmental interaction level ".This gene diagnosis of carrying out on molecular level and gene therapy will be familiar with the root that disease produces at all, and will be hopeful basic understanding and treat the major disease that comprises cancer.The fundamental change of these biology, medical science, a mensuration and the analysis that basic prerequisite is a gene order.Can carry out gene sequencing and analysis effectively apace, will have influence on the enforcement of the Human Genome Project, thereby influence further developing of biology, medical science.The method that adopted of tradition gene sequencing comprises a series of numerous and diverse steps such as chemical reaction, gel electrophoresis, and these method spended times are longer, and operates complicated, especially time-consuming and be not suitable for portability and check order fast aspect large scale sequencing.Traditional gene order surveying method is being carried out in the improved process, is that the biochip technology of representative arises at the historic moment with the genetic chip.Biochip technology is with many discontinuous analytic process related in the life science, and as specimen preparation, chemical reaction and analyzing and testing etc. are by adopting microelectronics, technologies such as micromechanics are integrated in the chip, make it serialization, integrated, microminiaturization and robotization.The strong means that provide are obtained and analyzed to the maturation of this technology and use and will bring a revolution in medical diagnosis on disease and the life science association areas such as treatment, new drug development, judicial expertise, food and environment of next century for biological information.
PCR (polymerase chain reaction, polymerase chain reaction) is as the method for a kind of selectivity outer-gene amplification, owing to just making 106 times of DNA cloning after taking turns circulation through 25~35, be used widely in scientific research and medical test for many years.But, forbidden being used for clinical diagnosis by health ministry from June, 98 because there are defectives such as false positive in PCR.Trace it to its cause, the labile factor that many experiment conditions in the first PCR process (primer design and selection, material mixture ratio, reaction time, temperature, cycle period etc.) cause causes producing the mistake amplification of PCR.It two is that the follow-up electrophoretic detection of PCR process only can be judged the fragment that whether obtains length-specific, and can't determine its concrete sequence.Its three, PCR reaction is two discrete processes with detecting, complex operation and increased the chance of polluting.Therefore, for testing conditions and equipment limited in, infirmary, the accuracy of the detection of PCR has been subjected to very big influence.In addition, current pcr amplification process has very high requirement for technical level of operators and quality.
Biological (gene) chip is an international research focus in recent years always, and advances just with surprising rapidity.Existing in the world many companies such as the U.S. enter the biochip field, work out PCR and the mutually integrated biochip of DNA array.These systems are PCR micro reaction pool of preparation on chip usually, by controlling the temperature cycles of little reaction, carries out the amplification of gene.In the gene introduced cross pond after then will increasing,, detect with the hybridization of solid phase micro probe array.Affymetrix company then further is prepared into the microfluid pipeline to the PCR micro reaction pool.But the chip that is used for scientific research and medical test at present is one or several individual devices mostly.Although the existing report that round pcr and chip detection are integrated, but be characterized in that whole PCR process carries out in a micro reaction pool, thereby, need be to the cooling that heats up repeatedly of the same position of device, this can't carry out dynamic tracking and real-time quantitative analysis to PCR result.And, prolonged the working time because the cooling that heats up needs the regular hour.
The present utility model people once existed weak point that a kind of reciprocating type PCR microarray probe circulating detection type biological chip is provided at present round pcr and chip detection, this is a kind of PCR of control reaction solution carries out reciprocating type mobile amplification in the different temperatures zone new departure, and round pcr and gene microarray probe technique be integrated, constitute an integrated-type biochip, both simplified operation steps, shorten the PCR time, raise the efficiency, the reaction system and the external world can be carried out tight effectively isolation again, and make pcr amplification one probe hybridization testing process integrated, with the sex change in the PCR circulation, annealing, extension process and micro probe array chip constitute an integral body, can be with sex change, annealing, the temperature of extending and hybridizing four steps is controlled at steady temperature respectively, thereby can avoid repeatedly intensification temperature-fall period and because the influence that the error of temperature control is brought.
The purpose of this utility model is the weak point that exists at present bioprobe diagnosing chip temperature control, a kind of temperature controller that is used for the bioprobe diagnosing chip is provided, cooperate the PCR microarray probe circulating detection type biological chip, initiatively new departure of temperature control of a kind of single-point or multiple spot reaction type has been proposed, by temperature control effectively, make sex change, annealing, the extension of PCR detection chip, the temperature of four steps of hybridization be controlled at constant different warm areas respectively, avoid repeatedly intensification temperature-fall period and because the influence that the error of temperature control is brought.This temperature controller accuracy of temperature control height can shorten detection time greatly, raises the efficiency.
A kind of temperature controller that is used for the bioprobe diagnosing chip is to adopt following scheme to realize.The temperature controller primary structure has temperature controller shell, front panel, rear panel, sensing drive unit, power switch, starting switch, digital display screen, passage turnover switch or socket are housed on the front panel, output wiring board is arranged on the rear panel, in the temperature controller shell control circuit board is housed, the electronic control circuit components and parts are housed on the wiring board.Electronic control circuit has hardware PID operation circuit, ACTIVE CONTROL electronic circuit.Hardware PID operation circuit is made of collection electric bridge, comparer, proportion differential circuit, proportional integral circuit.Hardware PID operation circuit adopts hardware PID control, thereby the signal of thermal resistance temperature sensor reaches the purpose of temperature control through the input voltage of PID operation circuit monitoring silicon controlled dutycycle control heating, cooling piece.The ACTIVE CONTROL electronic circuit keeps module, A/D modular converter, main control module (single-chip microcomputer), D/A modular converter, output driving amplification module, digital display module to form by sensor acquisition load module, sampling.The input signal of thermal resistance temperature sensor enters to gather and keeps module, sampling outputs to the data channel of main control module through the A/D modular converter, utilize the temperature control algorithm of main control module, output to D/A conversion modular converter from the control mouth of main control module, pass through the channel selecting module gating again, each control signal is by the temperature control voltage of comparer output heating and cooling device or the electric current after amplifier is put the people, to reach the initiatively purpose of temperature control.The sensing drive unit has ceramic heat-insulation board, device has the heating and cooling device on the ceramic heat-insulation board, the heating and cooling device is equipped with heat shield or coating heat shield outward, between heating and cooling device and ceramic responsibility hot plate, heat insulation is housed, be provided with little heat transfer sheet in heating and cooling device front portion, be provided with thermal resistance sensor, little heat transfer sheet during use at little heat transfer sheet front end, thermal resistance sensor inserts little reaction zone back side of bioprobe diagnosing chip, so that detect and control temperature.
Measurement by to the temperature of different nodes utilizes the ACTIVE CONTROL master unit, and heating, cooling module are given corresponding temperature control instruction.Utilize the digital collection system, and the correlation technique of single-chip microcomputer, in the integrated intelligence instrument unit of master unit.The principle of temperature control adopts the principle of ACTIVE CONTROL, and its cardinal principle is as follows: establishing the temperature that needs in the reaction is T
0, then sensor temperature is T
f, the efficient of heat transfer is q
1, radioreaction is q
2, making close efficient is q
3, the efficiency of heating surface is q
4
W(T
0)=W(T
f)-q
1t-q
2t+q
4t,(T
f≤T
0)
W(T
0)=W(T
f)-q
1t-q
2t-q
3t,(T
f≥T
0)
Thereby set instrument A.T.C constant according to different warm area situation.And can set the parameters such as reaction time of constant temperature.In the actual temperature control process, utilize PID control, the dutycycle of restriction semiconductor heating and cooling element is controlled its heating and cooling efficient, thus the control micro-area temperature.
The present utility model is less at PCR reaction chip reaction microcell yardstick, and temperature differs big and the interactional characteristics of temperature, the measure of the minimizing temperature disturbance below proposing.
1. utilize the new technology of semiconductor refrigerating, between temperature controlled region, realize heating or refrigeration automatically.
2. directly embed little sheet metal at little reaction zone, to improve the efficient of conduction.
3. in the both sides of semiconductor heating plate, embed the metal of light or the organism sheet of coated heat insulating coat, adjacent to reduce
The radiation of warm area.
4. between different warm areas, add heat-barrier material, to reduce heat radiation.
5. in the bottom of heating plate, utilize the ceramic powders liner of perforate to improve necessary heat conduction and heat radiation.A kind of temperature controller that is used for the bioprobe diagnosing chip is to cooperate microarray probe circulating detection type biological chip, carry out single-point or multiple spot reaction type active temperature control or PID and control warm new departure, adopt hardware PID control or ACTIVE CONTROL mode to carry out the sex change that temperature control makes detection chip, annealing, extend, hybridize four step temperature and be controlled at constant different temperatures district respectively, avoid intensification repeatedly, temperature-fall period and because the influence that brings of temperature control error, simultaneously because the principle of the microcell of PCR reaction, optimal design by closed loop temperature control mode and machinery, make control accuracy of temperature at ± 0.2 ℃, and shorten the PCR time greatly, increase work efficiency.
The utility model is described in further detail below with reference to accompanying drawing.Fig. 1 is a kind of temperature controller front view that is used for the bioprobe diagnosing chip.Fig. 2 is a kind of temperature controller rear view that is used for the bioprobe diagnosing chip.Fig. 3 is a kind of temperature controller sensing driving device structure synoptic diagram that is used for the bioprobe diagnosing chip.Fig. 4 is a kind of temperature controller hardware PID control electronic circuit schematic diagram that is used for the bioprobe diagnosing chip.Fig. 5 is a kind of temperature controller ACTIVE CONTROL electronic circuit schematic diagram that is used for the bioprobe diagnosing chip.
The temperature controller primary structure that is used for the bioprobe diagnosing chip with reference to 1 one kinds in accompanying drawing has temperature controller shell 1, sensor drive device, front panel, rear panel, device has power switch 2, starting switch 3, digital display screen 4, channel selector switch or socket 5 on the front panel, output wiring board 6 is arranged on the rear panel, handle 7 is housed on the shell 1.In the temperature controller shell control circuit board is housed, the operation circuit components and parts are housed on the wiring board.Electronic control circuit has hardware PID operation circuit, ACTIVE CONTROL electronic circuit.Referring to accompanying drawing 4, hardware PID control circuit is made of collection electric bridge, comparer, proportion differential circuit, proportional integral circuit.Gather electric bridge in the hardware PID control circuit by resistance R 1--R4, adjustable resistance RW1, RW2 constitute, comparer is by comparer integrated package A4, the proportion differential circuit is made of comparer A1, resistance R 5, R6, capacitor C 1, adjustable resistance RW3, RW4 operational amplifier A 2, and the proportional integral circuit is made of operational amplifier A 3, capacitor C 2, C3, adjustable resistance RW5.
Referring to accompanying drawing 5, the ACTIVE CONTROL electronic circuit keeps module, A/D modular converter, main control module, D/A modular converter, output driving amplification module, digital display module to form by sensor acquisition load module, sampling.The sensor acquisition input keeps module to be made of collection electric bridge, channel selector switch IC1 in the ACTIVE CONTROL electronic circuit, gathers electric bridge and comprises resistance R 1, R2, adjustable resistance RW1, RW2.A/D modular converter IC2 can adopt the ICL7109 integrated package, be connected with crystal oscillator JZ1, capacitor C 1, C2, C3, resistance R 3, R4, link to each other with main control module IC3 (single-chip microcomputer) by data line, main control module can adopt 8051, main control module IC3 is connected with latch IC7, memory IC 6, the control output end of main control module IC3 links to each other with the D/A modular converter, the D/A modular converter can adopt 0832 ic chip, and the D/A modular converter is connected with driving amplifier A1, through channel selecting module IC5 gating, channel selecting module is connected to comparer exclusive disjunction amplifier A2, A3, A4, A5, main control module IC3 (single-chip microcomputer) also is connected with decoder driver IC8, digital display module LED.
Referring to accompanying drawing 3, the sensing drive unit has ceramic heat-insulation board 8, ceramic heat-insulation board has the hole, device has heating and cooling device 9 on the ceramic heat-insulation board, the heating and cooling device can adopt semiconductor heating and cooling device, heating and cooling device 9 outer heat shield or the coating heat shields 11 of being equipped with, heat insulation 10 is housed between heating and cooling device and ceramic heat-insulation board, is provided with little heat transfer sheet 12, be provided with thermal resistance sensor 14 at little heat transfer sheet front end in heating and cooling device front.During use, the sensing drive installation is at the back side of pcr chip 13, and the position corresponds respectively to four humidity provinces of sex change, annealing, extension, hybridization of pcr chip, heats automatically or refrigeration, to reach the temperature control purpose in different temperatures district.
Claims (4)
1. a temperature controller that is used for the bioprobe diagnosing chip has temperature controller shell, front panel, rear panel, sensing drive unit, in the temperature controller shell control circuit board is housed, and the electronic control circuit components and parts are housed on the wiring board.Electronic control circuit has hardware PID operation circuit, the ACTIVE CONTROL electronic circuit, hardware PID operation circuit is by gathering electric bridge, comparer, the proportional integral circuit, the proportion differential circuit constitutes, the ACTIVE CONTROL electronic circuit is by the sensor acquisition load module, sampling keeps module, the A/D modular converter, main control module, the D/A modular converter, output drives amplification module, the digital display module is formed, it is characterized in that the sensing drive unit has ceramic heat-insulation board, device has the heating and cooling device on the ceramic heat-insulation board, the heating and cooling device is equipped with heat shield or coating heat shield outward, between heating and cooling device and ceramic heat-insulation board, heat insulation is housed, be provided with little heat transfer sheet in heating and cooling device front, be provided with thermal resistance sensor at little heat transfer sheet front end.
2. a kind of temperature controller that is used for the bioprobe diagnosing chip according to claim 1, it is characterized in that gathering in the hardware PID control circuit electric bridge by resistance R 1--R4, adjustable resistance RW1, RW2 constitute, comparer is by comparer integrated package A4, the proportion differential circuit is made of comparer A1, resistance R 5, R6, capacitor C 1, adjustable resistance RW3, RW4 operational amplifier A 2, and the proportional integral circuit is made of operational amplifier A 3, capacitor C 2, C3, adjustable resistance RW5.
3. a kind of temperature controller that is used for the bioprobe diagnosing chip according to claim 1, it is characterized in that the sensor acquisition input keeps module by gathering electric bridge in the ACTIVE CONTROL electronic circuit, channel selector switch IC1 constitutes, gather electric bridge and comprise resistance R 1, R2, adjustable resistance RW1, RW2, A/D modular converter IC2 is connected with crystal oscillator JZ1, capacitor C 1, C2, C3, resistance R 3, R4, link to each other with main control module IC3 by data line, main control module IC3 is connected with latch IC7, memory IC 6, the control output end of main control module IC3 links to each other with the D/A modular converter, the D/A modular converter is connected with driving amplifier A1, through channel selecting module IC5 gating, channel selecting module is connected to comparer exclusive disjunction amplifier A2, A3, A4, A5, main control module IC3 also is connected with decoder driver IC8, digital display module LED.
4. a kind of temperature controller that is used for the bioprobe diagnosing chip according to claim 1 is characterized in that device has power switch, starting switch, digital display screen, channel selector switch or socket on the front panel, and output wiring board is arranged on the rear panel.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN 99230498 CN2389384Y (en) | 1999-09-17 | 1999-09-17 | Temp. control intrument for biologial probe diagnostic chip |
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CN 99230498 CN2389384Y (en) | 1999-09-17 | 1999-09-17 | Temp. control intrument for biologial probe diagnostic chip |
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CN2389384Y true CN2389384Y (en) | 2000-07-26 |
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CN 99230498 Expired - Fee Related CN2389384Y (en) | 1999-09-17 | 1999-09-17 | Temp. control intrument for biologial probe diagnostic chip |
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Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101086009B (en) * | 2006-06-06 | 2010-05-12 | 北京大学 | Temperature-control matrix biochip and its processing method |
CN101972188A (en) * | 2010-11-10 | 2011-02-16 | 韩俊江 | Precise temperature-controlling tumor therapeutic apparatus and control method thereof |
CN101365996B (en) * | 2005-12-19 | 2011-06-15 | 皇家飞利浦电子股份有限公司 | Active matrix temperature controller array |
CN103135634A (en) * | 2013-01-18 | 2013-06-05 | 上海交通大学 | Temperature control method and device for polymerase chain reaction biochip |
CN103376805A (en) * | 2012-04-17 | 2013-10-30 | 深圳迈瑞生物医疗电子股份有限公司 | Temperature control method and reaction cup cleaning method for IVD (in vitro diagnostic) equipment |
CN106257371A (en) * | 2015-06-16 | 2016-12-28 | 鹦鹉无人机股份有限公司 | Including because becoming in temperature to compensate the unmanned plane of the higher-level device of inertance element deviation |
CN108949509A (en) * | 2018-09-29 | 2018-12-07 | 深圳市艺盛科五金电子有限公司 | A kind of accurate temperature regulating device and method for probe anneals processing |
CN111346685A (en) * | 2020-03-10 | 2020-06-30 | 中国科学院苏州生物医学工程技术研究所 | Device and method capable of realizing rapid temperature control |
-
1999
- 1999-09-17 CN CN 99230498 patent/CN2389384Y/en not_active Expired - Fee Related
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101365996B (en) * | 2005-12-19 | 2011-06-15 | 皇家飞利浦电子股份有限公司 | Active matrix temperature controller array |
CN101086009B (en) * | 2006-06-06 | 2010-05-12 | 北京大学 | Temperature-control matrix biochip and its processing method |
CN101972188A (en) * | 2010-11-10 | 2011-02-16 | 韩俊江 | Precise temperature-controlling tumor therapeutic apparatus and control method thereof |
CN103376805A (en) * | 2012-04-17 | 2013-10-30 | 深圳迈瑞生物医疗电子股份有限公司 | Temperature control method and reaction cup cleaning method for IVD (in vitro diagnostic) equipment |
CN103376805B (en) * | 2012-04-17 | 2015-07-29 | 深圳迈瑞生物医疗电子股份有限公司 | For temperature-controlled process and the reaction cup cleaning method of in-vitro diagnosis equipment |
CN103135634A (en) * | 2013-01-18 | 2013-06-05 | 上海交通大学 | Temperature control method and device for polymerase chain reaction biochip |
CN106257371A (en) * | 2015-06-16 | 2016-12-28 | 鹦鹉无人机股份有限公司 | Including because becoming in temperature to compensate the unmanned plane of the higher-level device of inertance element deviation |
CN108949509A (en) * | 2018-09-29 | 2018-12-07 | 深圳市艺盛科五金电子有限公司 | A kind of accurate temperature regulating device and method for probe anneals processing |
CN111346685A (en) * | 2020-03-10 | 2020-06-30 | 中国科学院苏州生物医学工程技术研究所 | Device and method capable of realizing rapid temperature control |
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