技术领域technical field
本发明涉及一种微液加热技术，尤其是涉及一种声表面波实现阵列式芯片的检测区内微液加热的装置及方法。The invention relates to a micro-liquid heating technology, in particular to a device and method for realizing micro-liquid heating in a detection area of an array chip by a surface acoustic wave.
背景技术Background technique
生物芯片是一门新兴的技术，其能够在单芯片上实现生物量和化学量的批量、快速、精确分析，其突出的优点是器件体积小、试剂消耗量少、能够避免分析中人为引入的误差等，其为众多专家、学者所重视，并已成为分析领域的一个重要研究热点，在生物工程、环境监测、毒品检测和食品安全等领域获得了广泛应用。阵列式芯片是生物芯片的一种重要结构形式，其在基片上构建阵列结构的检测区，以实现批量检测。在生化反应条件的探索性研究中，往往在阵列式的检测区中分别调整不同生化反应条件，以研究外界生化反应条件对检测性能的影响。温度是生化反应的一个重要影响因素，因此，对检测区中的微反应液的温度控制是生物芯片的一个重点研究课题。为此，需要研究阵列式芯片的特定检测区的加热方法及其温度特性。Biochip is an emerging technology, which can realize batch, fast and accurate analysis of biomass and chemical quantity on a single chip. It has been valued by many experts and scholars, and has become an important research hotspot in the field of analysis, and has been widely used in the fields of bioengineering, environmental monitoring, drug detection and food safety. Array chip is an important structural form of biochip, which builds the detection area of array structure on the substrate to realize batch detection. In the exploratory study of biochemical reaction conditions, different biochemical reaction conditions are often adjusted in the array detection area to study the influence of external biochemical reaction conditions on the detection performance. Temperature is an important factor affecting biochemical reactions. Therefore, the temperature control of the micro-reaction solution in the detection area is a key research topic of biochips. Therefore, it is necessary to study the heating method and temperature characteristics of the specific detection area of the array chip.
生物芯片的检测区中的微反应液的加热方法有多种。席文柱等专家采用微电子工艺制作PCR生物芯片，并在PCR生物芯片的微反应腔上制作NiCr金属薄膜微型加热器，以满足PCR生物芯片温度特性的要求。戴敬提出了以透明氧化铟锡薄膜玻璃作为加热元件，实现了透明氧化铟锡薄膜玻璃上的微反应液的加热，使微反应液的温度上升50℃。也有专家采用铂电阻和钛电极作为微加热单元，并集成于微流基片上，实现微反应液的加热，并成功地应用于逆转录聚合酶链反应定量检测肿瘤病毒。在此基础上，有学者提出了以铂为材料、应用微电子工艺在玻璃基片上制作了阵列型微加热器，使得检测区中热稳定性和均匀性得到了极大改善。这些在微流分析芯片上集成微加热器可以很好地实现片上微反应液对反应温度的要求，因而，在不同场合得到了应用，但它们无法适用于具有重要地位的压电微流分析芯片上。There are many ways to heat the micro-reaction liquid in the detection area of the biochip. Experts such as Xi Wenzhu used microelectronic technology to make PCR biochips, and made NiCr metal thin film micro-heaters on the micro-reaction chambers of PCR biochips to meet the temperature characteristics of PCR biochips. Dai Jing proposed to use transparent indium tin oxide thin film glass as a heating element to realize the heating of the micro-reaction liquid on the transparent indium tin oxide thin film glass, so that the temperature of the micro-reaction liquid increased by 50 °C. Some experts also use platinum resistors and titanium electrodes as micro-heating units, and integrate them on microfluidic substrates to realize heating of micro-reaction liquids, and have successfully applied them to the quantitative detection of tumor viruses by reverse transcription polymerase chain reaction. On this basis, some scholars proposed to use platinum as a material and apply microelectronics technology to fabricate array micro heaters on glass substrates, which greatly improved the thermal stability and uniformity in the detection area. These integrated micro-heaters on the micro-flow analysis chip can well meet the requirements of the on-chip micro-reaction liquid on the reaction temperature, so they have been applied in different occasions, but they cannot be applied to the important piezoelectric micro-flow analysis chip superior.
压电器件由于具有工艺简单、成熟，成本低等优点，已广泛应用于通信领域。近年来，声表面波所具有强大的微流操控能力已逐渐为微流控学专家所充分认识并逐渐得到重视，并在压电基片上实现了微流体输运、混合、萃取、生物分子快速富集等一系列微流操作及微流生化分析。但上述提及的微流分析芯片上微反应液的加热方法都很难在压电微流分析芯片上实现，也无法采用上述方法实现声表面波加热阵列式芯片的任意检测区中的微反应液，因此需要解决目前微流分析芯片中的加热单元与压电基片的相容性问题，以同时提高受热区域受热精准性和灵活性。Piezoelectric devices have been widely used in the field of communication due to their advantages of simple process, mature technology and low cost. In recent years, the powerful microfluidic manipulation ability of surface acoustic wave has gradually been fully understood by microfluidics experts and has been gradually paid attention to, and the microfluidic transport, mixing, extraction, and biomolecular rapid flow have been realized on piezoelectric substrates. A series of microfluidic operations such as enrichment and microfluidic biochemical analysis. However, the above-mentioned heating methods for the micro-reaction liquid on the micro-flow analysis chip are difficult to realize on the piezoelectric micro-flow analysis chip, and the above-mentioned method cannot be used to realize the micro-reaction in any detection area of the surface acoustic wave heating array chip. Therefore, it is necessary to solve the compatibility problem between the heating unit and the piezoelectric substrate in the current microfluidic analysis chip, so as to improve the heating accuracy and flexibility of the heated area at the same time.
虽然有文献报道采用声表面波加热压电基片上的微反应液。如期刊《超声、铁电和频率控制IEEE会刊》2005年第52卷第10期1881-1883页(IEEE,Transactions onultrasonics,Ferroelectrics and Frequency control,Vol.52(10),2005:1881-1883)公开了《压电基片上声表面波声流引起的液体热效应》(《Liquid heating effects by SAWstreaming on the piezoelectric substrate》)，它在压电基片上采用微电子工艺制作一对叉指换能器，电信号经功率放大器放大后加到叉指换能器上，激发声表面波，在声传播路径上贴合一滤纸条，滤纸条上进样微液，声表面波在压电基片上传播时，遇到滤纸条上的微液，能量辐射入微液，加热微液，提高微液温度，滤纸条上的微液温度随所加电信号功率增大而增大，并在一定时间内达到动态平衡，即当微液的温度上升到一定温度后，声表面波辐射入微液的能量与微液向外界释放的能量达到平衡，微液的温度不再继续上升。该方法可以有效实现压电基片上的微液加热，可以充分利用压电基片对微液操控能力的优点，但局限于微液紧贴于压电基片上，且声表面波持续直接辐射入微液，将降低微液中生物分子(如酶、蛋白质等)的活性；且无法采用单液滴输运方式来灵活加热微液，灵活性有限，有待改进。Although there are reports in the literature that surface acoustic waves are used to heat micro-reaction liquids on piezoelectric substrates. For example, the journal "IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control", 2005, Vol. 52, No. 10, pp. 1881-1883 (IEEE, Transactions on ultrasonics, Ferroelectrics and Frequency control, Vol.52(10), 2005:1881-1883) published "Liquid heating effects by SAWstreaming on the piezoelectric substrate" ("Liquid heating effects by SAWstreaming on the piezoelectric substrate"), which uses microelectronics technology to fabricate a pair of interdigital transducers on a piezoelectric substrate, After the electric signal is amplified by the power amplifier, it is added to the interdigital transducer to excite the surface acoustic wave, and a filter paper strip is pasted on the sound propagation path. When propagating, when encountering the micro liquid on the filter paper strip, the energy radiates into the micro liquid, heats the micro liquid, increases the temperature of the micro liquid, and the temperature of the micro liquid on the filter paper increases with the power of the applied electric signal, and within a certain period of time A dynamic equilibrium is reached inside, that is, when the temperature of the micro-liquid rises to a certain temperature, the energy radiated by the surface acoustic wave into the micro-liquid and the energy released by the micro-liquid to the outside reach a balance, and the temperature of the micro-liquid does not continue to rise. This method can effectively realize the heating of micro-liquid on the piezoelectric substrate, and can make full use of the advantages of the piezoelectric substrate's ability to control the micro-liquid, but it is limited to the fact that the micro-liquid is close to the piezoelectric substrate, and the surface acoustic wave continues to directly radiate into the micro-liquid. The liquid will reduce the activity of biomolecules (such as enzymes, proteins, etc.) in the micro-liquid; and the single-droplet transport method cannot be used to flexibly heat the micro-liquid, and the flexibility is limited and needs to be improved.
发明内容Contents of the invention
本发明所要解决的技术问题是提供一种声表面波实现阵列式芯片的检测区内微液加热的装置及方法，该装置结构简单、使用方便、体积小、易于集成，且声表面波间接、精准地加热检测区内的微液，避免了声表面波直接辐射微液对微液中生物分子的活性的影响。The technical problem to be solved by the present invention is to provide a device and method for surface acoustic wave to realize micro-liquid heating in the detection area of an array chip. The device has a simple structure, is convenient to use, is small in size, and is easy to integrate. Precise heating of the micro-liquid in the detection area avoids the influence of surface acoustic waves directly radiating the micro-liquid on the activity of biomolecules in the micro-liquid.
本发明解决上述技术问题所采用的技术方案为：一种阵列式芯片的检测区内微液加热的装置，其特征在于包括压电基片，所述的压电基片的上表面为工作表面，所述的压电基片的工作表面的四侧区域上各制作有一排用于激发声表面波的叉指换能器，所述的压电基片的工作表面的中央区域上架设有一个阵列式芯片，所述的阵列式芯片包括PDMS聚合体，所述的PDMS聚合体上开设有以阵列方式排布的多个竖直通孔，所述的竖直通孔的下端口上封接有金属传热片形成上端开口而下端封闭的用于放置微反应液的检测区，所述的金属传热片的底部连接有金属传热柱，所述的PDMS聚合体的底部的四角上各安装有一个PDMS垫块，所述的PDMS聚合体通过四个所述的PDMS垫块垫高以架设于所述的压电基片的工作表面的中央区域上，且使所述的金属传热柱的底部与所述的压电基片的工作表面互不接触，所述的压电基片的工作表面的中央区域上放置有油相微流体，所述的叉指换能器激发的声表面波作用于所述的油相微流体上，所述的油相微流体产生的热量经所述的金属传热柱和所述的金属传热片导热加热所述的检测区内的微反应液。The technical scheme adopted by the present invention to solve the above-mentioned technical problems is: a device for micro-liquid heating in the detection area of an array chip, which is characterized in that it includes a piezoelectric substrate, and the upper surface of the piezoelectric substrate is a working surface , a row of interdigital transducers for exciting surface acoustic waves is made on the four side regions of the working surface of the piezoelectric substrate, and a central region of the working surface of the piezoelectric substrate is erected An array chip, the array chip includes a PDMS polymer, and the PDMS polymer is provided with a plurality of vertical through holes arranged in an array, and the lower port of the vertical through hole is sealed There is a metal heat transfer sheet forming a detection area with an open upper end and a closed lower end for placing a micro-reaction liquid. The bottom of the metal heat transfer sheet is connected with a metal heat transfer column, and each of the four corners of the bottom of the PDMS polymer A PDMS pad is installed, and the PDMS polymer is raised by four of the PDMS pads so as to be erected on the central area of the working surface of the piezoelectric substrate, and the metal conducts heat The bottom of the column is not in contact with the working surface of the piezoelectric substrate, the oil phase microfluid is placed on the central area of the working surface of the piezoelectric substrate, and the acoustic wave excited by the interdigital transducer The surface wave acts on the oil-phase microfluid, and the heat generated by the oil-phase microfluid heats the micro-reaction in the detection area via the metal heat transfer column and the metal heat transfer sheet. liquid.
所述的压电基片的工作表面的每侧区域上制作的一排所述的叉指换能器中，相邻两个所述的叉指换能器之间的间隔距离为0.4～0.6毫米。在此，限定相邻两个叉指换能器之间的间隔距离，是为了确保叉指换能器激发的声表面波能作用于位于压电基片的工作表面的中央区域上的油相微流体上，使油相微流体能够运动到阵列式芯片的任一个检测区的正下方，从而能够利用声表面波和油相微流体实现对该检测区内的微反应液的加热；如果相邻两个叉指换能器之间的间隔距离太大，则极有可能达不到上述目的；如果相邻两个叉指换能器之间的间隔距离太小，则叉指换能器的数量会增大，工艺难度也会增加，从而将导致成本增大。In a row of the interdigital transducers fabricated on each side of the working surface of the piezoelectric substrate, the distance between two adjacent interdigital transducers is 0.4 to 0.6 mm. Here, the distance between two adjacent IDTs is limited to ensure that the surface acoustic waves excited by the IDTs can act on the oil phase located in the central area of the working surface of the piezoelectric substrate. On the micro-fluid, the oil-phase micro-fluid can be moved to directly below any detection area of the array chip, so that the micro-reaction liquid in the detection area can be heated by using the surface acoustic wave and the oil-phase micro-fluid; If the distance between adjacent two interdigital transducers is too large, the above purpose may not be achieved; if the distance between adjacent two interdigital transducers is too small, the interdigital transducer The number will increase, and the difficulty of the process will also increase, which will lead to an increase in cost.
所述的PDMS聚合体的厚度即所述的竖直通孔的高度为2～3毫米。由于竖直通孔的高度与微反应液的量有关，因此PDMS聚合体太厚没必要，而太薄的话若要达到检测区内一定的容量，则要求竖直通孔的直径较大，而这样在阵列式芯片内相同检测数情况下必会增加阵列式芯片的面积，也增加了压电基片的面积，大大提高了该装置的器件成本。The thickness of the PDMS aggregate, that is, the height of the vertical through holes is 2-3 mm. Since the height of the vertical through hole is related to the amount of the micro-reaction solution, it is not necessary for the PDMS polymer to be too thick, and if it is too thin to reach a certain capacity in the detection area, the diameter of the vertical through hole is required to be larger, while In this way, under the condition of the same detection number in the array chip, the area of the array chip will be increased, and the area of the piezoelectric substrate will also be increased, which greatly increases the device cost of the device.
所述的金属传热片的尺寸大于所述的竖直通孔的孔径，以完全覆盖住所述的竖直通孔的下端口。在实际设计时可将金属传热片的尺寸设计为大于竖直通孔的孔径1～3毫米，以确保金属传热片能够完全覆盖住竖直通孔的下端口；金属传热片封接竖直通孔的下端口的方式为：在金属传热片的顶部涂覆未固化的PDMS，然后将金属传热片贴于竖直通孔的下端口上，再在100℃的恒温炉中固化，形成了上端开口而下端封闭的检测区。The size of the metal heat transfer sheet is larger than the diameter of the vertical through hole, so as to completely cover the lower port of the vertical through hole. In actual design, the size of the metal heat transfer sheet can be designed to be 1 to 3 mm larger than the diameter of the vertical through hole to ensure that the metal heat transfer sheet can completely cover the lower port of the vertical through hole; the metal heat transfer sheet is sealed The method of the lower port of the vertical through hole is: coating uncured PDMS on the top of the metal heat transfer sheet, and then attaching the metal heat transfer sheet to the lower port of the vertical through hole, and then in a constant temperature furnace at 100°C After solidification, a detection zone with an open upper end and a closed lower end is formed.
为使金属传热柱的底部与压电基片的工作表面不接触，即需确保金属传热柱的底部略高于压电基片的工作表面，这样需保证金属传热柱的高度与金属传热片的厚度之和略小于PDMS垫块的高度，在实际设计时可使所述的金属传热柱的底部距离所述的压电基片的工作表面0.2～0.5毫米。In order to keep the bottom of the metal heat transfer column out of contact with the working surface of the piezoelectric substrate, it is necessary to ensure that the bottom of the metal heat transfer column is slightly higher than the working surface of the piezoelectric substrate, so that the height of the metal heat transfer column and the metal The sum of the thicknesses of the heat transfer sheets is slightly smaller than the height of the PDMS spacer, and in actual design, the bottom of the metal heat transfer column can be 0.2-0.5 mm away from the working surface of the piezoelectric substrate.
该装置还包括用于产生RF电信号的信号发生装置、多路拨码开关、PCB板，所述的信号发生装置由用于产生RF电信号的信号发生器及与所述的信号发生器的输出端连接的功率放大器组成，所述的PCB板连接于所述的压电基片的下表面上，所述的PCB板上设置有与每个所述的叉指换能器对应的引线脚，所述的引线脚与其对应的所述的叉指换能器的汇流条连接，所述的引线脚通过所述的多路拨码开关与所述的功率放大器的输出端连接，所述的多路拨码开关有选择地将所述的功率放大器的输出端输出的放大后的RF电信号加载于一个所述的叉指换能器上或两个对称的所述的叉指换能器上。在此，在功率放大器与引线脚之间设置一个多路拨码开关，利用多路拨码开关选择地将功率放大器输出的放大后的RF电信号加载到任一个叉指换能器上以将油相微流体输送到任一检测区的下方，或加载到任一对对称的叉指换能器上以对位于该对称的两个叉指换能器之间的油相微流体辐射声表面波使油相微流体产生热量。The device also includes a signal generating device for generating RF electrical signals, a multi-way dial switch, and a PCB board. The signal generating device is composed of a signal generator for generating RF electrical signals and the signal generator and the signal generator The power amplifier connected to the output end is composed of, the PCB board is connected to the lower surface of the piezoelectric substrate, and the lead pins corresponding to each of the interdigital transducers are arranged on the PCB board , the lead pin is connected to the bus bar of the corresponding IDT, the lead pin is connected to the output end of the power amplifier through the multi-way dial switch, and the The multi-channel DIP switch selectively loads the amplified RF electrical signal output from the output terminal of the power amplifier on one of the IDTs or two symmetrical IDTs superior. Here, a multi-way DIP switch is set between the power amplifier and the lead pin, and the amplified RF electrical signal output by the power amplifier is selectively loaded on any IDT by using the multi-way DIP switch. The oil-phase microfluid is transported below any detection area, or loaded onto any pair of symmetrical interdigital transducers to radiate the acoustic surface to the oil-phase microfluidic located between the two symmetrical interdigital transducers The waves generate heat in the oil-phase microfluidics.
一种阵列式芯片的检测区内微液加热的方法，其特征在于在上述的一种阵列式芯片的检测区内微液加热的装置上实现，其包括以下步骤：A method for heating micro-fluids in the detection area of an array chip, characterized in that it is implemented on the device for heating micro-liquids in the detection area of an array chip, which includes the following steps:
①连接信号发生器与功率放大器，连接功率放大器与多路拨码开关，连接多路拨码开关与引线脚，连接引线脚与其对应的叉指换能器的汇流条；①Connect the signal generator and the power amplifier, connect the power amplifier and the multi-channel DIP switch, connect the multi-channel DIP switch and the lead pin, connect the lead pin and the bus bar of the corresponding IDT;
②将油相微流体放置于压电基片的工作表面的中央区域上；将微反应液进样到其中一个或多个检测区内；② Place the oil-phase microfluid on the central area of the working surface of the piezoelectric substrate; inject the micro-reaction liquid into one or more of the detection areas;
③启动信号发生器和功率放大器，信号发生器输出RF电信号，并传输RF电信号给功率放大器；③Start the signal generator and the power amplifier, the signal generator outputs the RF electrical signal, and transmits the RF electrical signal to the power amplifier;
④通过多路拨码开关将功率放大器输出的放大后的RF电信号先后加载到不同的叉指换能器上，不同的叉指换能器先后激发的声表面波作用于油相微流体上使油相微流体运动至放置有微反应液的检测区下方的金属传热柱处；然后通过多路拨码开关将功率放大器输出的放大后的RF电信号加载到位于油相微流体的对称两侧的叉指换能器上，这两个对称的叉指换能器激发的声表面波同时作用于油相微流体上使油相微流体产生热量，油相微流体产生的热量经油相微流体接触的金属传热柱导热后到达放置有微反应液的检测区，实现该检测区内微反应液的加热；④ Load the amplified RF electrical signal output by the power amplifier to different IDTs successively through a multi-channel DIP switch, and the surface acoustic waves excited by different IDTs act on the oil-phase microfluidic Make the oil-phase microfluid move to the metal heat transfer column under the detection area where the micro-reaction liquid is placed; then load the amplified RF electrical signal output by the power amplifier to the symmetrical On the interdigital transducers on both sides, the surface acoustic waves excited by the two symmetrical interdigital transducers act on the oil-phase microfluid at the same time to make the oil-phase microfluid generate heat, and the heat generated by the oil-phase microfluid passes through the oil The metal heat transfer column in contact with the microfluid reaches the detection area where the micro-reaction liquid is placed after conducting heat, and realizes the heating of the micro-reaction liquid in the detection area;
⑤若有多个检测区内进样有微反应液，则重复步骤④的过程，以完成每个检测区内微反应液的加热；⑤ If there are micro-reaction liquids injected into multiple detection areas, repeat the process of step ④ to complete the heating of the micro-reaction liquids in each detection area;
⑥关闭信号发生器和功率放大器。⑥ Turn off the signal generator and power amplifier.
与现有技术相比，本发明的优点在于：Compared with the prior art, the present invention has the advantages of:
1)该装置先利用不同的叉指换能器先后激发的声表面波作用于油相微流体上，使油相微流体在压电基片的工作表面上运动，直至到达进样有微反应液的检测区下方的金属传热柱处；再利用位于油相微流体的对称两侧的叉指换能器激发的声表面波同时作用于油相微流体上，使油相微流体产生热量，热量经金属传热柱和金属传热片导热给检测区内的微反应液加热；即利用声表面波可实现阵列式芯片中的任一个检测区内微反应液的加热，提高了阵列式芯片的特定检测区内微反应液加热的灵活性和精准性，且无需声表面波直接辐射入所加热的微反应液，避免了声表面波直接辐射对微反应液中生物分子的活性的影响。1) The device first uses the surface acoustic waves excited by different interdigital transducers to act on the oil-phase microfluid, so that the oil-phase microfluid moves on the working surface of the piezoelectric substrate until it reaches the sample injection and has a micro-reaction The metal heat transfer column under the detection area of the liquid; the surface acoustic waves excited by the interdigital transducers located on both symmetrical sides of the oil-phase microfluid act on the oil-phase microfluid at the same time, so that the oil-phase microfluid generates heat , the heat conducts heat through the metal heat transfer column and the metal heat transfer sheet to heat the micro-reaction liquid in the detection area; that is, the surface acoustic wave can be used to heat the micro-reaction liquid in any detection area in the array chip, which improves the array type. The flexibility and precision of heating the micro-reaction liquid in the specific detection area of the chip does not require surface acoustic waves to directly radiate into the heated micro-reaction liquid, avoiding the influence of direct surface acoustic wave radiation on the activity of biomolecules in the micro-reaction liquid.
2)该装置在压电基片的工作表面的四周区域上各制作一排叉指换能器，在中央区域上架设一个阵列式芯片，且油相微流体也放置于中央区域上，不仅结构简单，而且体积小，易于集成，可用于压电微流分析芯片进行微流生化分析。2) The device makes a row of interdigital transducers on the surrounding area of the working surface of the piezoelectric substrate, and erects an array chip on the central area, and the oil phase microfluid is also placed on the central area, not only the structure Simple, small in size and easy to integrate, it can be used in piezoelectric microfluidic analysis chips for microfluidic biochemical analysis.
附图说明Description of drawings
图1为本发明的阵列式芯片的检测区内微液加热的装置的结构示意图。FIG. 1 is a schematic structural diagram of a microfluidic heating device in the detection area of the array chip of the present invention.
具体实施方式detailed description
以下结合附图实施例对本发明作进一步详细描述。The present invention will be further described in detail below in conjunction with the accompanying drawings and embodiments.
实施例一：Embodiment one:
本实施例提出的一种阵列式芯片的检测区内微液加热的装置，如图所示，其包括压电基片1，压电基片1的上表面为工作表面，压电基片1的工作表面的四侧区域上采用集成电路工艺各制作有一排用于激发声表面波的叉指换能器2，压电基片1的工作表面的中央区域上架设有一个阵列式芯片3，阵列式芯片3包括呈长方体结构的PDMS聚合体31，PDMS聚合体31上通过打孔机开设有以阵列方式排布的多个竖直通孔32，竖直通孔32的下端口上封接有金属传热片33形成上端开口而下端封闭的用于放置微反应液的检测区，由于检测区的下端封闭，因此微反应液不会流出检测区，金属传热片33的底部以焊接方式连接有金属传热柱34，PDMS聚合体31的底部的四角上各安装有一个PDMS垫块4，PDMS聚合体31通过四个PDMS垫块4垫高以架设于压电基片1的工作表面的中央区域上，且使金属传热柱34的底部与压电基片1的工作表面互不接触，压电基片1的工作表面的中央区域上放置有油相微流体9，叉指换能器2激发的声表面波作用于油相微流体9上，油相微流体9产生的热量经金属传热柱34和金属传热片33导热加热检测区内的微反应液。A device for micro-fluid heating in the detection area of an array chip proposed in this embodiment, as shown in the figure, includes a piezoelectric substrate 1, the upper surface of the piezoelectric substrate 1 is a working surface, and the piezoelectric substrate 1 A row of interdigital transducers 2 for exciting surface acoustic waves are respectively fabricated on the four side areas of the working surface of the piezoelectric substrate 1 by using integrated circuit technology, and an array chip 3 is erected on the central area of the working surface of the piezoelectric substrate 1, The array chip 3 includes a PDMS polymer 31 in a rectangular parallelepiped structure. A plurality of vertical through holes 32 arranged in an array are opened on the PDMS polymer 31 through a punching machine, and the lower ports of the vertical through holes 32 are sealed. A metal heat transfer sheet 33 forms a detection area for placing the micro-reaction solution with an open upper end and a closed lower end. Because the lower end of the detection area is closed, the micro-reaction liquid will not flow out of the detection area. The bottom of the metal heat transfer sheet 33 is welded. A metal heat transfer column 34 is connected, and a PDMS spacer 4 is installed on each of the four corners of the bottom of the PDMS polymer 31, and the PDMS polymer 31 is raised by four PDMS spacers 4 to be erected on the working surface of the piezoelectric substrate 1 On the central area of the metal heat transfer column 34, and the bottom of the metal heat transfer column 34 is not in contact with the working surface of the piezoelectric substrate 1, the oil phase microfluid 9 is placed on the central area of the working surface of the piezoelectric substrate 1, and the fingers are exchanged The surface acoustic wave excited by the energy device 2 acts on the oil-phase microfluid 9, and the heat generated by the oil-phase microfluid 9 passes through the metal heat transfer column 34 and the metal heat transfer sheet 33 to heat the micro-reaction liquid in the detection area.
在本实施例中，压电基片1的工作表面的每侧区域上制作的一排叉指换能器2中，相邻两个叉指换能器2之间的间隔距离为0.4～0.6毫米，如实际中将相邻两个叉指换能器2之间的间隔距离为0.5毫米，限定相邻两个叉指换能器2之间的间隔距离，是为了确保叉指换能器2激发的声表面波能作用于位于压电基片1的工作表面的中央区域上的油相微流体9上，使油相微流体9能够运动到阵列式芯片3的任一个检测区的正下方，从而能够利用声表面波和油相微流体9实现对该检测区内的微反应液的加热；如果相邻两个叉指换能器2之间的间隔距离太大，则极有可能达不到上述目的；如果相邻两个叉指换能器2之间的间隔距离太小，则叉指换能器2的数量会增大，工艺难度也会增加，从而将导致成本增大。In this embodiment, in a row of interdigital transducers 2 fabricated on each side area of the working surface of the piezoelectric substrate 1, the distance between two adjacent interdigital transducers 2 is 0.4 to 0.6 mm, as in practice, the distance between two adjacent interdigital transducers 2 is 0.5 mm, and the distance between adjacent two interdigital transducers 2 is limited to ensure that the interdigital transducers 2 The excited surface acoustic wave energy acts on the oil-phase microfluid 9 located in the central area of the working surface of the piezoelectric substrate 1, so that the oil-phase microfluid 9 can move to the front of any detection area of the array chip 3. Below, so that surface acoustic waves and oil-phase microfluidics 9 can be used to heat the micro-reaction liquid in the detection area; if the distance between two adjacent interdigital transducers 2 is too large, it is very likely The above purpose cannot be achieved; if the distance between two adjacent interdigital transducers 2 is too small, the number of interdigital transducers 2 will increase, and the difficulty of the process will also increase, which will lead to an increase in cost .
在本实施例中，PDMS聚合体31的厚度即竖直通孔32的高度为2～3毫米，如设计为2.5毫米。由于竖直通孔32的高度与微反应液的量有关，因此PDMS聚合体31太厚没必要，而太薄的话若要达到检测区内一定的容量，则要求竖直通孔32的直径较大，而这样在阵列式芯片内相同检测数情况下必会增加阵列式芯片的面积，也增加了压电基片的面积，大大提高了该装置的器件成本。In this embodiment, the thickness of the PDMS polymer 31 , that is, the height of the vertical through holes 32 is 2-3 mm, for example, it is designed to be 2.5 mm. Since the height of the vertical through hole 32 is related to the amount of the micro-reaction solution, it is not necessary for the PDMS polymer 31 to be too thick, and if it is too thin to reach a certain capacity in the detection area, the diameter of the vertical through hole 32 is required to be relatively small. Large, and in the case of the same detection number in the array chip, the area of the array chip will be increased, and the area of the piezoelectric substrate will also be increased, which greatly increases the device cost of the device.
在本实施例中，金属传热片33的尺寸大于竖直通孔32的孔径，以完全覆盖住竖直通孔32的下端口。在实际设计时可将金属传热片33的尺寸设计为大于竖直通孔32的孔径1～3毫米如2毫米，以确保金属传热片33能够完全覆盖住竖直通孔32的下端口；金属传热片33封接竖直通孔32的下端口的方式为：在金属传热片33的顶部涂覆未固化的PDMS，然后将金属传热片33贴于竖直通孔32的下端口上，再在100℃的恒温炉中固化，形成了上端开口而下端封闭的检测区。In this embodiment, the size of the metal heat transfer fin 33 is larger than the diameter of the vertical through hole 32 so as to completely cover the lower port of the vertical through hole 32 . In actual design, the size of the metal heat transfer sheet 33 can be designed to be larger than the diameter of the vertical through hole 32 by 1 to 3 mm, such as 2 mm, to ensure that the metal heat transfer sheet 33 can completely cover the lower port of the vertical through hole 32 ; the metal heat transfer sheet 33 seals the lower port of the vertical through hole 32 as follows: the top of the metal heat transfer sheet 33 is coated with uncured PDMS, and then the metal heat transfer sheet 33 is attached to the bottom of the vertical through hole 32 On the lower port, it is cured in a constant temperature furnace at 100°C to form a detection area with an open upper end and a closed lower end.
在本实施例中，为使金属传热柱34的底部与压电基片1的工作表面不接触，即需确保金属传热柱34的底部略高于压电基片1的工作表面，这样需保证金属传热柱34的高度与金属传热片33的厚度之和略小于PDMS垫块4的高度，在实际设计时可使金属传热柱34的底部距离压电基片1的工作表面0.2～0.5毫米，如设计为0.3毫米。In this embodiment, in order to make the bottom of the metal heat transfer column 34 not in contact with the working surface of the piezoelectric substrate 1, it is necessary to ensure that the bottom of the metal heat transfer column 34 is slightly higher than the working surface of the piezoelectric substrate 1, so that It is necessary to ensure that the sum of the height of the metal heat transfer column 34 and the thickness of the metal heat transfer sheet 33 is slightly smaller than the height of the PDMS spacer 4, and the bottom of the metal heat transfer column 34 can be distanced from the working surface of the piezoelectric substrate 1 in actual design. 0.2 ~ 0.5 mm, such as the design is 0.3 mm.
在本实施例中，该装置还包括用于产生RF电信号的信号发生装置8、多路拨码开关7、PCB板6，信号发生装置8由用于产生RF电信号的信号发生器81及与信号发生器81的输出端连接的功率放大器82组成，PCB板6连接于压电基片1的下表面上，PCB板6上设置有与每个叉指换能器2对应的引线脚61，引线脚61通过导电银胶和银丝与其对应的叉指换能器2的汇流条21连接，引线脚61通过多路拨码开关7与功率放大器82的输出端连接，多路拨码开关7有选择地将功率放大器82的输出端输出的放大后的RF电信号加载于一个叉指换能器2上或两个对称的叉指换能器2上。在此，在功率放大器82与引线脚61之间设置一个多路拨码开关7，利用多路拨码开关7选择地将功率放大器82输出的放大后的RF电信号加载到任一个叉指换能器2上以将油相微流体9输送到任一检测区的下方，或加载到任一对对称的叉指换能器2上以对位于该对称的两个叉指换能器2之间的油相微流体9辐射声表面波使油相微流体9产生热量。In this embodiment, the device also includes a signal generating device 8 for generating RF electrical signals, a multi-way dial switch 7, and a PCB board 6, and the signal generating device 8 is composed of a signal generator 81 for generating RF electrical signals and Composed of a power amplifier 82 connected to the output end of the signal generator 81, the PCB board 6 is connected to the lower surface of the piezoelectric substrate 1, and the PCB board 6 is provided with a lead pin 61 corresponding to each IDT 2 , the lead pin 61 is connected with the bus bar 21 of the corresponding IDT 2 through conductive silver glue and silver wire, the lead pin 61 is connected with the output end of the power amplifier 82 through the multi-way dial switch 7, and the multi-way dial switch 7. Selectively load the amplified RF electrical signal output from the output terminal of the power amplifier 82 on one IDT 2 or two symmetrical IDTs 2. Here, a multi-way dial switch 7 is set between the power amplifier 82 and the lead pin 61, and the multi-way dial switch 7 is used to selectively load the amplified RF electrical signal output by the power amplifier 82 to any interdigital switch. Transducer 2 to transport the oil-phase microfluid 9 to the bottom of any detection area, or load it on any pair of symmetrical interdigital transducers 2 so as to detect the difference between the two symmetrical interdigital transducers 2 The oil-phase microfluid 9 radiates surface acoustic waves to make the oil-phase microfluid 9 generate heat.
在本实施例中，压电基片1可采用机电耦合系数稍大的压电基片，基本可取机电耦合系数大于5.5％的压电基片，如1280-YX LiNbO3压电基片；叉指换能器2采用现有技术；PDMS聚合体31和PDMS垫块4均采用聚二甲基硅氧烷(PDMS)制作而成；油相微流体9可为石蜡油等；信号发生器81、功率放大器82、多路拨码开关7、PCB板6均采用现有技术，PCB板6也可由其它现有的可以固定导线的基板替代；PDMS垫块4的底部可通过未固化的PDMS贴于压电基片1的工作表面上，并固化形成一体。In this embodiment, the piezoelectric substrate 1 can adopt a piezoelectric substrate with a slightly larger electromechanical coupling coefficient, basically a piezoelectric substrate with an electromechanical coupling coefficient greater than 5.5%, such as a 1280 -YX LiNbO3 piezoelectric substrate; The interdigital transducer 2 adopts the prior art; the PDMS polymer 31 and the PDMS block 4 are all made of polydimethylsiloxane (PDMS); the oil phase microfluid 9 can be paraffin oil, etc.; the signal generator 81. The power amplifier 82, the multi-way dial switch 7, and the PCB board 6 all adopt the existing technology, and the PCB board 6 can also be replaced by other existing substrates that can fix wires; the bottom of the PDMS spacer 4 can pass through the uncured PDMS Paste on the working surface of the piezoelectric substrate 1 and solidify to form a whole.
实施例二：Embodiment two:
本实施例提出的一种阵列式芯片的检测区内微液加热的方法，其在实施例一给出的一种阵列式芯片的检测区内微液加热的装置上实现，其包括以下步骤：The method for heating the microfluid in the detection area of the array chip proposed in this embodiment is implemented on the device for heating the microfluid in the detection area of the array chip given in Example 1, which includes the following steps:
①连接信号发生器81与功率放大器82，连接功率放大器82与多路拨码开关7，连接多路拨码开关7与引线脚61，连接引线脚61与其对应的叉指换能器2的汇流条21。①Connect the signal generator 81 and the power amplifier 82, connect the power amplifier 82 and the multi-channel DIP switch 7, connect the multi-channel DIP switch 7 and the lead pin 61, and connect the lead pin 61 and the confluence of the corresponding IDT 2 Article 21.
②将油相微流体9放置于压电基片1的工作表面的中央区域上；将微反应液进样到其中一个或多个检测区内。② Place the oil-phase microfluid 9 on the central area of the working surface of the piezoelectric substrate 1; inject the micro-reaction liquid into one or more detection areas.
③启动信号发生器81和功率放大器82，信号发生器81输出RF电信号，并传输RF电信号给功率放大器82。③ Start the signal generator 81 and the power amplifier 82 , the signal generator 81 outputs the RF electrical signal, and transmits the RF electrical signal to the power amplifier 82 .
④通过多路拨码开关7将功率放大器82输出的放大后的RF电信号(功率为31～33dBm)先后加载到不同的叉指换能器2上，不同的叉指换能器2先后激发的声表面波作用于油相微流体9上使油相微流体9运动至放置有微反应液的检测区下方的金属传热柱34处；然后通过多路拨码开关7将功率放大器82输出的放大后的RF电信号加载到位于油相微流体9的对称两侧的叉指换能器2上，这两个对称的叉指换能器2激发的声表面波同时作用于油相微流体9上使油相微流体9产生热量，油相微流体9产生的热量经油相微流体9接触的金属传热柱34导热后到达放置有微反应液的检测区，实现该检测区内微反应液的加热。④ Load the amplified RF electrical signal (with a power of 31-33dBm) output by the power amplifier 82 to different IDTs 2 successively through the multi-channel DIP switch 7, and the different IDTs 2 successively excite The surface acoustic wave acts on the oil-phase microfluid 9 to move the oil-phase microfluid 9 to the metal heat transfer column 34 below the detection area where the micro-reaction liquid is placed; then the power amplifier 82 is output through the multi-way dial switch 7 The amplified RF electrical signal is loaded on the IDTs 2 located on both symmetrical sides of the oil-phase microfluid 9, and the surface acoustic waves excited by the two symmetrical IDTs 2 act on the oil-phase microfluidics simultaneously. The fluid 9 makes the oil-phase micro-fluid 9 generate heat, and the heat generated by the oil-phase micro-fluid 9 reaches the detection area where the micro-reaction liquid is placed after being conducted through the metal heat transfer column 34 in contact with the oil-phase micro-fluid 9, so as to realize the detection area within the detection area. Heating of the microreaction solution.
位于油相微流体9的对称两侧的叉指换能器2激发的声表面波需同时作用于油相微流体9上，这样在使油相微流体9产生热量的同时，很好的避免了油相微流体9运动；当然若加载到叉指换能器2上的放大后的RF电信号较小时，即使一个叉指换能器2激发的声表面波作用于油相微流体9上也不会使油相微流体9运动，但这也会导致微反应液的温度上升量不大。The surface acoustic waves excited by the interdigital transducers 2 located on both symmetrical sides of the oil-phase microfluid 9 need to act on the oil-phase microfluid 9 at the same time, so that while the oil-phase microfluid 9 generates heat, it is well avoided oil phase microfluid 9 movement; of course, if the amplified RF electrical signal loaded on the interdigital transducer 2 is small, even if the surface acoustic wave excited by an interdigital transducer 2 acts on the oil phase microfluid 9 It also does not make the oil phase microfluid 9 move, but this also leads to a small increase in the temperature of the microreaction liquid.
⑤若有多个检测区内进样有微反应液，则重复步骤④的过程，以完成每个检测区内微反应液的加热。⑤ If there are micro-reaction liquids injected into multiple detection areas, repeat the process of step ④ to complete the heating of the micro-reaction liquids in each detection area.
⑥关闭信号发生器81和功率放大器82。⑥ Turn off the signal generator 81 and the power amplifier 82 .
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| CN201710101719.8ACN106824315B (en) | 2017-02-24 | 2017-02-24 | The device and method of micro- liquid heating in a kind of detection zone of array chip |
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| CN201710101719.8ACN106824315B (en) | 2017-02-24 | 2017-02-24 | The device and method of micro- liquid heating in a kind of detection zone of array chip |
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