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CN101881779B - Ultrasonic standing wave type micro-fluidic chip and preparation method thereof - Google Patents

Ultrasonic standing wave type micro-fluidic chip and preparation method thereof Download PDF

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CN101881779B
CN101881779B CN2010101921513A CN201010192151A CN101881779B CN 101881779 B CN101881779 B CN 101881779B CN 2010101921513 A CN2010101921513 A CN 2010101921513A CN 201010192151 A CN201010192151 A CN 201010192151A CN 101881779 B CN101881779 B CN 101881779B
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CN101881779A (en
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国世上
赵兴中
郭峰
李思晢
曾谦
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Wuhan University WHU
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Abstract

本发明公开了一种超声驻波式微流控芯片及其制备方法。其产品由载玻片、微流控芯片、印刷电路板(PCB板)、压电陶瓷和控制电路所构成。微流控芯片结构中包含有驻波反应腔,由聚二甲基硅氧烷(PDMS)液态预聚物通过阳模模板固化成型,并在其固化前将载玻片放置其上,待其固化连为一体后脱模;PCB板的正面镀有一层导电层,其通过该导电层和微流控芯片的非载玻片面与微流控芯片连成一体,且在PCB板的正面设置有与微流控芯片结构相对应的孔位,其对应驻波反应腔的孔位安装有压电陶瓷;控制电路布设在PCB板的背面。本发明制作过程简单,成本低廉,具有很高的可控性和可操作性,集成化程度高,很容易实现对细胞等生物活体样品的分离、捕获和操纵。

The invention discloses an ultrasonic standing wave microfluidic chip and a preparation method thereof. Its products are composed of glass slides, microfluidic chips, printed circuit boards (PCB boards), piezoelectric ceramics and control circuits. The microfluidic chip structure contains a standing wave reaction chamber, which is formed by solidifying a liquid polydimethylsiloxane (PDMS) prepolymer through a positive mold template, and placing a glass slide on it before it solidifies, and waits for it to After being solidified and connected as a whole, the mold is demoulded; the front of the PCB board is coated with a conductive layer, which is integrated with the microfluidic chip through the conductive layer and the non-glass slide surface of the microfluidic chip, and the front of the PCB board is provided with The holes corresponding to the structure of the microfluidic chip are equipped with piezoelectric ceramics corresponding to the holes of the standing wave reaction chamber; the control circuit is arranged on the back of the PCB board. The invention has simple manufacturing process, low cost, high controllability and operability, high degree of integration, and easy separation, capture and manipulation of biological living samples such as cells.

Description

一种超声驻波式微流控芯片及其制备方法An ultrasonic standing wave microfluidic chip and its preparation method

技术领域 technical field

本发明属于微全分析系统领域。特别涉及一种超声驻波式微流控芯片及其制备方法。The invention belongs to the field of micro total analysis system. In particular, it relates to an ultrasonic standing wave microfluidic chip and a preparation method thereof.

背景技术 Background technique

微流控芯片技术是20世纪90年代在分析化学领域发展起来的,它以微网络为结构特征,以生命科学为主要研究对象,将整个实验室的功能包括样片预处理、反应、分离、检测等集成在微芯片上,使分析速度得到极大提高,具有极为广泛的适用性和应用前景,是当前微全分析系统研究的重点。Microfluidic chip technology was developed in the field of analytical chemistry in the 1990s. It is characterized by micro-networks and life sciences as the main research object. The functions of the entire laboratory include sample pretreatment, reaction, separation, and detection. etc. are integrated on the microchip, which greatly improves the analysis speed, has extremely wide applicability and application prospects, and is the focus of current micro-analysis system research.

与此同时,由于声学检测和操作方法对活体生物样本检测的无损性,使得其成为研究的另一个热点。目前,在微流控系统中,一般通过湿法刻蚀方法,在硅片等硬质材料上刻蚀出微网络结构,再通过阳极键和的方式,将玻璃片键和到刻蚀有微结构的硅片上,以此来制作声波芯片。这种声波芯片加工效果较好,但是,它需要用到价值数百万的阳极键和设备,从而使得制备的芯片成本很高,不利于市场化。此外,目前的声波芯片还只是停留在实验室阶段,还缺乏对芯片可操作性和可控性方面的研究。At the same time, due to the nondestructiveness of acoustic detection and operation methods for the detection of living biological samples, it has become another research hotspot. At present, in the microfluidic system, the micro-network structure is generally etched on hard materials such as silicon wafers by wet etching, and then the glass wafer is bonded and etched to have a micro-network structure by means of anodic bonding. Structured silicon wafers are used to make acoustic chips. The processing effect of this kind of acoustic wave chip is better, but it needs to use anode bonds and equipment worth millions, so that the cost of the prepared chip is very high, which is not conducive to marketization. In addition, the current acoustic wave chip is still in the laboratory stage, and there is still a lack of research on the operability and controllability of the chip.

发明内容 Contents of the invention

本发明的目的就是针对上述现有技术的状况提供一种制作过程简单、制作成本低且集成度高的超声驻波式微流控芯片及其制备方法。The object of the present invention is to provide an ultrasonic standing wave microfluidic chip with simple manufacturing process, low manufacturing cost and high integration and its preparation method in view of the above-mentioned prior art.

实现本发明目的采用的技术方案是:The technical scheme that realizes the object of the present invention adopts is:

超声驻波式微流控芯片,由载玻片、微流控芯片、印刷电路板(PCB板)、压电陶瓷和控制电路所构成。微流控芯片结构中包含有驻波反应腔,由聚二甲基硅氧烷(PDMS)液态预聚物通过阳模模板成型,并在其液态预聚物固化前将所述的载玻片放置其上,待其固化连为一体后脱模;PCB板的正面上具有一层导电层,其通过该导电层和微流控芯片的非载玻片面与微流控芯片连成一体,且在PCB板的正面设置有与微流控芯片结构相对应的孔位,其对应驻波反应腔的孔位安装有压电陶瓷;控制电路布设在PCB板的背面。The ultrasonic standing wave microfluidic chip is composed of a glass slide, a microfluidic chip, a printed circuit board (PCB board), piezoelectric ceramics and a control circuit. The microfluidic chip structure includes a standing wave reaction chamber, which is formed by a polydimethylsiloxane (PDMS) liquid prepolymer through a positive mold template, and the glass slide is placed before the liquid prepolymer is solidified. Place it on it, and demould after it is solidified and connected as a whole; there is a conductive layer on the front of the PCB board, which is integrated with the microfluidic chip through the conductive layer and the non-glass slide surface of the microfluidic chip, and Holes corresponding to the structure of the microfluidic chip are provided on the front of the PCB, and piezoelectric ceramics are installed in the holes corresponding to the standing wave reaction chamber; the control circuit is arranged on the back of the PCB.

实际应用中,上述微流控芯片上的驻波反应腔的数目可≥1,且上述PCB析上的孔位和压电陶瓷与之相对应;与之相对应的控制电路为一组开关电路,开关的输入端连在一起,其输出端与各压电陶瓷分别相连。In practical applications, the number of standing wave reaction chambers on the above-mentioned microfluidic chip can be ≥1, and the hole positions and piezoelectric ceramics on the above-mentioned PCB analysis correspond to it; the corresponding control circuit is a set of switch circuits , the input ends of the switches are connected together, and the output ends of the switches are respectively connected with the piezoelectric ceramics.

超声驻波式微流控芯片的制备方法由下述步骤所构成:The preparation method of the ultrasonic standing wave microfluidic chip consists of the following steps:

1、用软光刻的方法制备所需的含有驻玻反应腔的微流控芯片用的阳模模板;1. Prepare the required positive mold template for the microfluidic chip containing the standing glass reaction chamber by soft lithography;

2、在表面具有一层导电层的印刷电路板(PCB板)上的导电层面上加工出与微流控芯片中结构相对应的孔位,并在与超声驻波反应腔相对应的孔位里安装压电陶瓷片,接着在PCB板的非导电层面上布设相应的控制电路;2. On the conductive layer of the printed circuit board (PCB board) with a conductive layer on the surface, the holes corresponding to the structure in the microfluidic chip are processed, and the holes corresponding to the ultrasonic standing wave reaction chamber are processed. Install the piezoelectric ceramic sheet inside, and then lay out the corresponding control circuit on the non-conductive layer of the PCB board;

3、将聚二甲基硅氧烷(PDMS)液态预聚物置入制备的微流控芯片的阳模模板上,并将载玻片放置在阳模模板上的PDMS液态预聚物上,待PDMS液态预聚物反应固化后,一起脱模,形成与载玻片一体的微流控芯片,用打孔器打孔;3. Put the polydimethylsiloxane (PDMS) liquid prepolymer on the positive mold template of the prepared microfluidic chip, and place the glass slide on the PDMS liquid prepolymer on the positive mold template. After the PDMS liquid prepolymer reacts and solidifies, it is released from the mold together to form a microfluidic chip integrated with the glass slide, and punch holes with a puncher;

4、将与载玻片一体的微流控芯片通过其上的非载玻片层面和PCB板上的导电层面与制4. Connect the microfluidic chip integrated with the glass slide through the non-slide layer on it and the conductive layer on the PCB

备的PCB板对应地连接在一起。The prepared PCB boards are connected together correspondingly.

实际应用中,上述制备微流控芯片用的阳模模板可选用单晶硅阳模模板;上述PCB板上安装有压电陶瓷的孔位里可填充封装压电陶瓷的环氧树脂。In practical application, the male mold template for preparing the microfluidic chip can be a single crystal silicon male mold template; the holes on the above PCB board where piezoelectric ceramics are installed can be filled with epoxy resin for packaging piezoelectric ceramics.

本发明超声驻波的声源来自安装在PCB孔洞里面的压电陶瓷,其工作频率由其自身性质决定。根据各个压电陶瓷的谐振频率的不同,通过调节输入信号的强度和频率,可以实现对细胞之类的生物活体样品的分离和捕获。The sound source of the ultrasonic standing wave in the present invention comes from the piezoelectric ceramic installed in the hole of the PCB, and its operating frequency is determined by its own properties. Depending on the resonance frequency of each piezoelectric ceramic, by adjusting the intensity and frequency of the input signal, the separation and capture of biological samples such as cells can be realized.

本发明通过包埋的方法实现了超声驻波在微流控芯片中的集成。与现有方法相比,具有如下的优点:此装置加工过程简单,无需湿法刻蚀等复杂步骤;成本低,制作过程中不需要价格昂贵的阳极键和设备;超声驻波场的产生和调节可控;通过使用尺寸更加小的压电陶瓷片可以使得装置具有更高的集成度。利用本发明能够很容易地实现对细胞等生物活体样品的分离、捕获和操纵。据此,本发明可广泛应用于生命科学、药物科学和医学等领域。The invention realizes the integration of the ultrasonic standing wave in the microfluidic chip by embedding. Compared with the existing method, it has the following advantages: the device has a simple processing process and does not need complicated steps such as wet etching; the cost is low, and expensive anode bonds and equipment are not required in the manufacturing process; the generation of ultrasonic standing wave field and The adjustment is controllable; the device can have a higher degree of integration by using smaller piezoelectric ceramic chips. The invention can easily realize the separation, capture and manipulation of biological living samples such as cells. Accordingly, the present invention can be widely used in the fields of life science, pharmaceutical science, medicine and the like.

附图说明: Description of drawings:

图1是本发明超声驻波式微流控芯片的横剖面结构示意图。Fig. 1 is a cross-sectional schematic diagram of the ultrasonic standing wave microfluidic chip of the present invention.

图2是本发明实施例1产品的俯视图。Fig. 2 is a top view of the product of Example 1 of the present invention.

图3是本发明实施例2产品的俯视图。Fig. 3 is a top view of the product of Embodiment 2 of the present invention.

图4是本发明实施例3产品的俯视图。Fig. 4 is a top view of the product of Embodiment 3 of the present invention.

附图中:1——PCB板,2——PDMS,3——载玻片,4——超声驻波反应腔,5——PZT压电陶瓷片,6——封装PZT的环氧树脂,7——芯片的进/出液孔。In the drawings: 1—PCB board, 2—PDMS, 3—glass slide, 4—ultrasonic standing wave reaction chamber, 5—PZT piezoelectric ceramic sheet, 6—epoxy resin for encapsulating PZT, 7——The inlet/outlet hole of the chip.

具体实施方式: Detailed ways:

实施例1Example 1

1、用软光刻的方法制取超声驻波微流控芯片用的单晶硅阳模模板,此模板中只设计有一个驻波反应腔(4),形成1×1的驻波反应腔阵列;1. Use the method of soft lithography to prepare the single crystal silicon positive mold template for the ultrasonic standing wave microfluidic chip. Only one standing wave reaction chamber (4) is designed in this template, forming a 1×1 standing wave reaction chamber array;

2、在表面镀有一层铜的PCB板(1)上加工出一个与微流控芯片中结构相对应的孔位,在超声驻波反应腔的孔位里安装固定上PZ26压电陶瓷片(5),作为超声驻波的声源,同时在PCB板(1)的背面进行布线,将压电陶瓷片(5)输入信号连接到控制电路的输出端;2. Process a hole corresponding to the structure in the microfluidic chip on the PCB board (1) plated with a layer of copper on the surface, and install and fix the PZ26 piezoelectric ceramic sheet in the hole of the ultrasonic standing wave reaction chamber ( 5), as the sound source of the ultrasonic standing wave, wiring is carried out on the back of the PCB board (1) at the same time, and the input signal of the piezoelectric ceramic sheet (5) is connected to the output end of the control circuit;

3、将PDMS液态预聚物(2)倒在阳模模板上,再将一块载玻片(3)放入阳模模板上的PDMS液态预聚物(2)上,待反应固化后,一起脱模成型,制成与载玻片一体的微流控芯片,用打孔器打孔;3. Pour the PDMS liquid prepolymer (2) on the positive mold template, and then put a glass slide (3) on the PDMS liquid prepolymer (2) on the male mold template. Demoulding, making a microfluidic chip integrated with the glass slide, and punching holes with a puncher;

4、将以上制得的与载玻片一体的微流控芯片和以上制备的PCB板(1)用螺丝固定在一起,即得到集成有一个超声驻波反应腔(4)的微流控芯片。4. Fix the above-prepared microfluidic chip integrated with the glass slide and the above-prepared PCB board (1) together with screws to obtain a microfluidic chip integrated with an ultrasonic standing wave reaction chamber (4) .

实施例2Example 2

1、用软光刻的方法制取超声驻波微流控芯片用的玻璃阳模模板,此模板中设计有三个驻波反应腔(4),形成1×3的驻波反应腔阵列;1. The glass positive mold template for the ultrasonic standing wave microfluidic chip is prepared by soft lithography. Three standing wave reaction chambers (4) are designed in the template to form a 1×3 standing wave reaction chamber array;

2、在表面镀有一层铂的PCB板(1)上加工出与微流控芯片中结构相对应的孔位,在与超声驻波反应腔相对应的孔位里安装固定上三个PZ26压电陶瓷片(5),作为超声驻波的声源,同时在PCB板(1)的背面进行布线,将所有的压电陶瓷片(5)输入信号连接到三路开关电路的输出端,并将焊接有三路开关的电路板固定在PCB板(1)的两侧,作为支架;2. Process holes corresponding to the structure in the microfluidic chip on the PCB (1) coated with a layer of platinum on the surface, and install and fix three PZ26 pressure gauges in the holes corresponding to the ultrasonic standing wave reaction chamber. The electric ceramic sheet (5), as the sound source of the ultrasonic standing wave, is wired on the back of the PCB board (1) at the same time, and all the input signals of the piezoelectric ceramic sheet (5) are connected to the output ends of the three-way switch circuit, and Fix the circuit board welded with the three-way switch on both sides of the PCB board (1) as a bracket;

3、将PDMS液态预聚物(2)倒在阳模模板上,再将一块载玻片(3)放入阳模模板上的PDMS液态预聚物(2)上,待反应固化后,一起脱模成型,制成与载玻片一体的微流控芯片,用打孔器打孔;3. Pour the PDMS liquid prepolymer (2) on the positive mold template, and then put a glass slide (3) on the PDMS liquid prepolymer (2) on the male mold template. Demoulding, making a microfluidic chip integrated with the glass slide, and punching holes with a puncher;

4、将以上制得的与载玻片一体的微流控芯片和已安装有支架的PCB板(1)用螺丝固定在一起,即得到集成有三个驻波反应腔(4)的微流控芯片。4. Fix the above-prepared microfluidic chip integrated with the glass slide and the PCB board (1) with the bracket installed together with screws to obtain a microfluidic chip integrated with three standing wave reaction chambers (4). chip.

实施例3Example 3

1、用软光刻的方法制取超声驻波微流控芯片用的单晶硅阳模模板,此模板中设计有9个驻波反应腔(4),形成3×3阵列式分布;1. The monocrystalline silicon positive mold template for the ultrasonic standing wave microfluidic chip is prepared by soft lithography, and 9 standing wave reaction chambers (4) are designed in the template to form a 3×3 array distribution;

2、在表面镀有一层金的PCB板(1)上加工出与微流控芯片中结构相对应的孔位,在超声驻波反应腔(4)的孔位里安装固定上九个PZ26压电陶瓷片(5),作为超声驻波的声源,同时在PCB板(1)的背面进行布线,将所有的压电陶瓷片(5)输入信号连接到九路开关电路的输出端,并将焊接有九路开关的电路板固定在PCB板(1)的两侧,作为支架;2. Process holes corresponding to the structure in the microfluidic chip on the PCB plated with a layer of gold on the surface, and install and fix nine PZ26 pressure sensors in the holes of the ultrasonic standing wave reaction chamber (4). The electric ceramic sheet (5), as the sound source of the ultrasonic standing wave, is wired on the back side of the PCB board (1) at the same time, and all the input signals of the piezoelectric ceramic sheet (5) are connected to the output ends of the nine-way switch circuit, and Fix the circuit board welded with the nine-way switch on both sides of the PCB board (1) as a bracket;

3、将PDMS液态预聚物(2)倒在阳模模板上,再将一块载玻片(3)放入阳模模板上的PDMS液态预聚物(2)上,待反应固化后,一起脱模成型,制成与载玻片一体的微流控芯片,用打孔器打孔;3. Pour the PDMS liquid prepolymer (2) on the positive mold template, and then put a glass slide (3) on the PDMS liquid prepolymer (2) on the male mold template. Demoulding, making a microfluidic chip integrated with the glass slide, and punching holes with a puncher;

4、将以上制得的与载玻片一体的微流控芯片和已安装有支架的PCB板(1)用螺丝固定在一起,即得到集成有一个3×3共9个驻波反应腔(4)的微流控芯片。4. Fix the above-prepared microfluidic chip integrated with the glass slide and the PCB board (1) with the bracket installed together with screws, that is, a 3×3 total of 9 standing wave reaction chambers ( 4) The microfluidic chip.

Claims (5)

1. a ultrasonic standing wave type micro-fluidic chip is made up of microslide, micro-fluidic chip, printed circuit board (PCB), piezoelectric ceramics and control circuit, it is characterized in that:
1) includes the standing wave reaction chamber in the described microfluidic chip structure, pass through the moulding of formpiston template, and before its liquid prepolymer is solidified, described microslide is placed on it, treat its back demoulding that is cured as a single entity by the dimethyl silicone polymer liquid prepolymer;
2) has one deck conductive layer on the front of said printed circuit board (PCB); Its non-microslide aspect and micro-fluidic chip through this conductive layer and micro-fluidic chip fuses; And the front of printed circuit board (PCB) is provided with and position, the corresponding hole of microfluidic chip structure, and the position, hole of its corresponding standing wave reaction chamber is equipped with piezoelectric ceramics;
3) described control circuit is laid in the back side of printed circuit board (PCB).
2. a kind of ultrasonic standing wave type micro-fluidic chip according to claim 1 is characterized in that: described control circuit is one group of on-off circuit; The input end of its switch connects together, and the output terminal of its switch links to each other respectively with each piezoelectric ceramics.
3. the preparation method of a ultrasonic standing wave type micro-fluidic chip is characterized in that being made up of following step:
1) method with soft lithographic prepares the formpiston template that the required micro-fluidic chip that contains reaction chamber in the glass is used;
2) the surface have process on the conductor planes on the printed circuit board (PCB) of one deck conductive layer with micro-fluidic chip in position, the corresponding hole of structure; And, then on the non-conductive aspect of printed circuit board (PCB), lay correspondent control circuits piezoelectric ceramic piece being installed with the corresponding Kong Weili of ultrasonic standing wave reaction chamber;
3) the dimethyl silicone polymer liquid prepolymer is inserted on the formpiston template of micro-fluidic chip of preparation; And microslide is placed on the dimethyl silicone polymer liquid prepolymer on the formpiston template; After treating that the reaction of dimethyl silicone polymer liquid prepolymer is solidified; The demoulding together, the micro-fluidic chip of formation and microslide one punches with card punch;
4) will link together accordingly through the non-microslide aspect on it and the conductor planes on the printed circuit board (PCB) and the printed circuit board (PCB) of preparation with the micro-fluidic chip of microslide one.
4. the preparation method of a kind of ultrasonic standing wave type micro-fluidic chip according to claim 3, it is characterized in that: the formpiston template that described preparation micro-fluidic chip uses is the silicon mold template.
5. according to the preparation method of claim 3 or 4 described a kind of ultrasonic standing wave type micro-fluidic chips, it is characterized in that the Kong Weili that piezoelectric ceramics is installed on the described printed circuit board (PCB) is filled with the epoxy resin that encapsulates piezoelectric ceramics.
CN2010101921513A 2010-05-31 2010-05-31 Ultrasonic standing wave type micro-fluidic chip and preparation method thereof Active CN101881779B (en)

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