CN106823475B - a blood diverter - Google Patents
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- CN106823475B CN106823475B CN201710066327.2A CN201710066327A CN106823475B CN 106823475 B CN106823475 B CN 106823475B CN 201710066327 A CN201710066327 A CN 201710066327A CN 106823475 B CN106823475 B CN 106823475B
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- 210000004369 blood Anatomy 0.000 title claims abstract description 18
- 239000008280 blood Substances 0.000 title claims abstract description 18
- 239000012530 fluid Substances 0.000 claims abstract description 62
- 230000001788 irregular Effects 0.000 claims description 13
- 230000004888 barrier function Effects 0.000 claims description 9
- 230000007423 decrease Effects 0.000 claims description 8
- 230000007704 transition Effects 0.000 claims description 8
- 238000000926 separation method Methods 0.000 abstract description 29
- 230000005779 cell damage Effects 0.000 abstract description 2
- 208000037887 cell injury Diseases 0.000 abstract description 2
- 239000007788 liquid Substances 0.000 abstract description 2
- 238000000034 method Methods 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 11
- 239000000243 solution Substances 0.000 description 8
- 239000012528 membrane Substances 0.000 description 7
- 239000012503 blood component Substances 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 210000000601 blood cell Anatomy 0.000 description 3
- 238000009295 crossflow filtration Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000006727 cell loss Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D17/00—Separation of liquids, not provided for elsewhere, e.g. by thermal diffusion
- B01D17/02—Separation of non-miscible liquids
- B01D17/0217—Separation of non-miscible liquids by centrifugal force
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Abstract
Description
技术领域technical field
本发明涉及一种血液分离装置,从使用上讲,是一种适合普通医疗机构进行血液细胞分离的一种血液分流器。The invention relates to a blood separation device, which is a blood shunt suitable for common medical institutions to separate blood cells in terms of use.
技术背景technical background
目前,血液细胞分离大致有两种技术方法来实现,即膜分离技术和离心分离分离技术。膜分离技术是利用具有选择透过能力的薄膜做分离介质,原液在一定压力下通过膜的一侧,溶剂及小分子溶质透过膜壁为透过液,而较大分子溶质被膜截留,从而达到物质分离及浓缩的目的。膜分离技术存在采用非错流过滤,膜易被堵塞,采用错流过滤,膜虽不易被堵塞,但对膜的性能要求高,成本增加。离心分离技术是通过离心机分离设备将血液组份按比重差异彼此分开,以得到所需要的血液成份,但容易造成细胞机械性损伤且易污染,细胞有相态变化,从而影响细胞质量;同时,对实验室的环境要求非常严格,增加了细胞分离的成本。At present, there are roughly two technical methods for blood cell separation, namely membrane separation technology and centrifugal separation technology. Membrane separation technology uses a thin film with selective permeability as the separation medium. The raw liquid passes through one side of the membrane under a certain pressure. To achieve the purpose of material separation and concentration. Membrane separation technology adopts non-cross-flow filtration, and the membrane is easy to be blocked. Using cross-flow filtration, although the membrane is not easy to be blocked, the performance requirements of the membrane are high and the cost increases. Centrifugal separation technology is to separate the blood components from each other according to the difference in specific gravity through centrifuge separation equipment to obtain the required blood components, but it is easy to cause mechanical damage to the cells and easy to pollute, and the cells have phase changes, which affects the quality of the cells; at the same time , the environmental requirements of the laboratory are very strict, which increases the cost of cell separation.
为此,本发明解决这一问题,提供一种细胞损失最小,无细胞相态变化的、便于后续分析的简单、高效的血液分流器的技术方案。Therefore, the present invention solves this problem, and provides a simple and efficient blood shunt technical solution with minimum cell loss, no cell phase change, and convenience for subsequent analysis.
发明内容Contents of the invention
为解决上述问题,本发明的技术方案为:一种血液分流器,主要由主体和流体分流通道组成。其特征在于:主体呈圆盘状,在圆盘的边缘到圆心,加工有呈螺旋状、上下封闭、宽度不相等的流体分流通道。主体的流体分流通道≥3层。第一层分流通道从圆盘的边缘加工的总进样口开始,到第一层外流道出口结束。每层的分流通道开始处的通道中心线上,都加工有一段引流堤;引流堤下游加工有数量≥3个的分流岛墙,分流岛墙将分流通道从分流口处分为内流道和外流道;每个内流道处都加工有一个凸出的回旋撞墙,回旋撞墙下游紧挨着一个分选口;分选口在两个分流岛墙之间,将内流道与外流道连通。以上1个回旋撞墙和2个分流岛墙组成一个分选单元。分选口旁的内流道的入口又成为下一个分选单元的分流口。设计实际是以分选单元为单位,重复分层分选。第二层分流通道从第二层的引流堤开始,到第二层外流道出口结束。第三层分流通道从第三层的引流堤开始,到第三层外流道出口结束。以下各层流体分流通道依次类推,最后,内流道在主体圆心的总出样口结束。In order to solve the above problems, the technical solution of the present invention is: a blood diverter, mainly composed of a main body and a fluid diversion channel. It is characterized in that: the main body is in the shape of a disc, and there are helical, up and down closed fluid distribution channels with unequal width processed from the edge of the disc to the center of the circle. The fluid distribution channel of the main body is more than or equal to 3 layers. The first layer of distribution channel starts from the total inlet processed on the edge of the disc and ends at the outlet of the first layer of outer flow channel. A section of diversion dike is processed on the center line of the channel at the beginning of each layer of diversion channel; downstream of the diversion dike is processed with a number of ≥ 3 diversion island walls, and the diversion island wall divides the diversion channel from the diversion port into an inner flow channel and an outer flow Road; each inner runner is processed with a protruding swirl impact wall, and the downstream of the swirl impact wall is next to a sorting port; the sorting port is between the two diversion island walls, connecting the inner flow channel with the outer flow channel. Above 1 roundabout collision wall and 2 diversion island walls form a sorting unit. The inlet of the inner flow channel next to the sorting port becomes the splitting port of the next sorting unit again. The actual design is based on the unit of sorting unit, repeated layered sorting. The second layer of shunt channel starts from the drainage dike of the second layer and ends at the outlet of the second layer of the outer flow channel. The third layer of shunt channel starts from the drainage dike of the third layer and ends at the outlet of the third layer of the outer flow channel. The fluid distribution channels of the following layers are analogized in turn, and finally, the inner flow channel ends at the total sample outlet at the center of the main body.
上述技术方案中,所述引流堤是宽0.5mm~1mm,高度尺寸低于流体分流通道顶部2mm~5mm的条带。所述每层流体分流通道的宽度一致,宽度尺寸≥5mm,或各层的流体分流通道的宽度逐层增加或逐层减小。所述分流岛墙沿流体分流通道走向呈鱼形、波浪形、菱形,此设计使一个分选单元的内流道的弧形方向在通道的前段和后段相反不一致;或呈扇形、牛角形,此设计使一个分选单元的内流道的弧形方向在通道前段和后段一致。述分流岛墙的高度同流体分流通道的顶部平齐,即上下封闭流体分流通道。In the above technical solution, the drainage embankment is a strip with a width of 0.5 mm to 1 mm and a height of 2 mm to 5 mm lower than the top of the fluid distribution channel. The width of the fluid distribution channels in each layer is consistent, and the width dimension is ≥ 5 mm, or the width of the fluid distribution channels in each layer increases or decreases layer by layer. The said diversion island wall is fish-shaped, wavy, or rhombus-shaped along the direction of the fluid diversion channel. This design makes the arc direction of the inner flow channel of a sorting unit inconsistent in the front and rear sections of the channel; or it is fan-shaped or horn-shaped. , this design makes the arc direction of the inner channel of a sorting unit consistent in the front and rear sections of the channel. The height of the diversion island wall is flush with the top of the fluid diversion channel, that is, the fluid diversion channel is closed up and down.
上述技术方案中,所述外流道是两侧壁面光滑平顺的沿主体圆弧同向平稳过渡的弧形通道;各层的外流道宽度一致,宽度尺寸≤1/4流体分流通道宽度尺寸,或各层的外流道的宽度尺寸逐渐减小或逐渐增加。In the above technical solution, the outer flow channel is an arc-shaped channel with smooth and smooth wall surfaces on both sides and a smooth transition along the arc of the main body in the same direction; the outer flow channels of each layer have the same width, and the width dimension is ≤ 1/4 of the fluid diversion channel width dimension, or The width dimensions of the outer runners of each layer gradually decrease or gradually increase.
上述技术方案中,所述内流道在一个分选单元的前、中、后各段通道的宽度尺寸不一致,各层的内流道宽度尺寸不一致。所述内流道的形状:由于分流岛墙在内流道一侧前半段呈反向主体圆弧弧度的弧形,在对应回旋撞墙凸面的后半段,又呈同向主体圆弧弧度的弧形;再由于所述回旋撞墙的凸出部位是反向主体的圆弧弧度方向。即分流岛墙与回旋撞墙对应配合,将内流道的前半段呈反向主体圆弧弧度的弧形回旋弯道,在通过回旋撞墙后又呈同向主体圆弧弧度的通道。或者内流道的形状:由于分流岛墙在内流道的一侧与回旋撞墙都是反向主体的圆弧弧度方向,将内流道呈反向主体圆弧弧度的通道。In the above technical solution, the widths of the inner runners in the front, middle and rear sections of a sorting unit are inconsistent, and the widths of the inner runners in each layer are inconsistent. The shape of the inner flow channel: because the first half of the side of the inner flow channel of the diversion island wall is in the arc shape of the arc of the main body in the opposite direction, and in the second half of the convex surface corresponding to the swinging wall, it is in the same direction as the arc of the main body arc; and because the protruding part of the wall hits the wall is the opposite direction of the arc of the main body. That is to say, the diversion island wall is matched with the whirling and bumping wall, so that the first half of the inner flow channel forms an arc-shaped roundabout that is opposite to the arc of the main body. Or the shape of the inner runner: because the side of the diversion island wall and the whirling wall are both opposite to the arc direction of the main body, the inner runner is formed as a passage against the arc of the main body.
上述技术方案中,所述总进样口与总出样口的直径一致,且都大于各层外流道的出口直径。设计保证内流道有足够的流速。各层外流道的出口直径需要按总体设计的形状及尺寸,运用流体模拟软件测算。所述外流道的外流道底部的高度尺寸高于内流道的内流道底部的高度0.5mm~2mm。所述外流道底部与内流道底部在分选口处,是通过圆弧凸起的分选口底部连接过渡;外流道底部连接过渡后呈水平底面,或连接过渡后呈过渡处高、外侧低的倾斜底面。In the above technical solution, the diameters of the total sample inlet and the total sample outlet are consistent, and both are larger than the diameters of the outlets of the outer channels of each layer. The design ensures sufficient flow velocity in the inner runner. The outlet diameter of the outer channel of each layer needs to be measured and calculated by fluid simulation software according to the shape and size of the overall design. The height of the bottom of the outer runner of the outer runner is 0.5 mm to 2 mm higher than the bottom of the inner runner of the inner runner. The bottom of the outer runner and the bottom of the inner runner are at the sorting port, and are connected and transitioned by the bottom of the sorting port raised by a circular arc; Low sloped bottom.
上述技术方案中,所述分流岛墙面对流体、与流体方向相反的一端是呈锥形的分流岛墙尖。分流岛墙尖的锥形尖被削尖处理成一个宽度尺寸≥1mm的端面,端面从内流道一侧开始加工有凸起的不规则凸面;不规则凸面的面积向外流道一侧逐渐上下分叉减小,高度也逐渐降低,最后与不规则凸面上下分叉的叉中间的不规则凹面融为一体。所述回旋撞墙面对流体、与流体方向相反的侧壁面上,加工有大小不一,分布不均匀的不规则凸面和不规则凹面。此设计在于增加流体回旋,增加流体混流和涡流,减少微通道中的层流现象。以利于分离血液成分及细胞。In the above technical solution, the end of the diversion island wall facing the fluid and opposite to the direction of the fluid is a tapered diversion island wall tip. The tapered tip of the diversion island wall tip is sharpened into an end face with a width ≥ 1mm, and the end face is processed with a raised irregular convex surface from the side of the inner flow channel; the area of the irregular convex surface gradually goes up and down toward the side of the outer flow channel The bifurcation decreases, and the height gradually decreases, and finally merges with the irregular concave surface in the middle of the bifurcated fork on the irregular convex surface. On the side wall facing the fluid and opposite to the direction of the fluid, the whirling collision wall is processed with irregular convex surfaces and irregular concave surfaces of different sizes and uneven distribution. This design is to increase fluid swirl, increase fluid mixed flow and eddy flow, and reduce laminar flow phenomenon in the microchannel. To facilitate the separation of blood components and cells.
上述技术方案中,所述主体在分选单元的分流口处能够加工有暗阻挡堤;暗阻挡堤是呈横向贯通拦截在内流道中,高度尺寸低于内流道顶部2mm~5mm的堤墙。此设计在于增加流体进入内流道的初速度。所述主体的分流岛墙在分选口处能够加工有分选口暗堤;分选口暗堤是在分流岛墙背对流体、与流体方向相同的一端,加工凸出的一段、呈横向拦截在分选口处,但不全部贯通分选口的高度尺寸低于分选口顶部2mm~5mm的堤墙。此设计在于增加分选口的分离效率,进一步控制分离尺寸。In the above technical solution, the main body can be processed with a dark barrier dike at the diversion port of the sorting unit; the dark barrier dike is a dike wall that is transversely penetrated and intercepted in the inner flow channel, and the height dimension is 2 mm to 5 mm lower than the top of the inner flow channel . This design is to increase the initial velocity of the fluid entering the inner channel. The diversion island wall of the main body can be processed with a sorting port dark dike at the sorting port; the sorting port dark dike is at the end of the diversion island wall facing away from the fluid and in the same direction as the fluid. It is intercepted at the sorting port, but does not completely pass through the embankment wall whose height dimension is 2mm~5mm lower than the top of the sorting port. This design is to increase the separation efficiency of the sorting port and further control the separation size.
本发明运用了都江堰水利的“飞沙”分离原理,即运用了回旋流的理论和离心力作用,将此运用到血液分离的设计中。目前,国内外,均有大量研究微通道芯片的血液分离,但是,微通道大多是层流,常规流体理论多不适用。本发明将常规水利流体与血液流体相结合,运用在非微米级通道的血液成分和细胞的分离上。大质量的蛋白和细胞,在分选口分离出。通过循环多次分选,达到血液细胞的分离目的。The present invention uses the "flying sand" separation principle of Dujiangyan Water Conservancy, that is, uses the theory of swirling flow and centrifugal force, and applies this to the design of blood separation. At present, there are a lot of studies on the blood separation of microchannel chips at home and abroad. However, most of the microchannels are laminar flow, and the conventional fluid theory is not applicable. The present invention combines conventional water conservancy fluid with blood fluid, and applies it to the separation of blood components and cells in non-micron channels. Large-mass proteins and cells are separated at the sorting port. The separation of blood cells is achieved through multiple cycles of sorting.
本发明的目的在于能够提供一种可以快速分离细胞,操作简便、不易造成细胞损伤的细胞分离装置,该细胞装置可以一边进液,边进行分离,并且可以多次、循环分离,提高了分离的效率。该分液器使得细胞分离和收集的操作,变得简单易行。The purpose of the present invention is to provide a cell separation device that can quickly separate cells, is easy to operate, and is not easy to cause cell damage. efficiency. The dispenser makes the operation of cell separation and collection simple and easy.
附图说明Description of drawings
图1为本发明的俯视示意图。Fig. 1 is a schematic top view of the present invention.
图2为本发明的一个分选单元示意图。Fig. 2 is a schematic diagram of a sorting unit of the present invention.
图3为本发明的分流岛墙尖的A端面示意图。Fig. 3 is a schematic view of the A-end surface of the wall tip of the diversion island of the present invention.
图4为本发明的分流岛墙尖A端面的D-D截面示意图。Fig. 4 is a D-D cross-sectional schematic view of the end face of the tip A of the diversion island wall of the present invention.
图5为本发明的回旋撞墙的B端面示意图。Fig. 5 is a schematic diagram of the end face B of the swinging wall of the present invention.
图6为本发明的引流堤的横截面示意图。Fig. 6 is a schematic cross-sectional view of the drainage embankment of the present invention.
图7为本发明的一种扇形分流岛墙的三个分选单元示意图。Fig. 7 is a schematic diagram of three sorting units of a fan-shaped diversion island wall of the present invention.
图8为本发明的外流道底部水平底面的分选口A-A截面示意图。Fig. 8 is a schematic cross-sectional view of the sorting port A-A on the horizontal bottom surface of the outer channel bottom of the present invention.
图9为本发明的外流道底部倾斜底面的分选口A-A截面示意图。Fig. 9 is a schematic cross-sectional view of the sorting port A-A on the inclined bottom surface of the outer channel bottom of the present invention.
图10为本发明的一种具有暗阻挡堤的三个分选单元示意图。Fig. 10 is a schematic diagram of three sorting units with dark barrier banks according to the present invention.
图11为本发明的暗阻挡堤的B-B截面示意图。Fig. 11 is a B-B cross-sectional schematic view of the dark barrier bank of the present invention.
图12为本发明的分选口暗堤的C-C截面示意图。Fig. 12 is a schematic cross-sectional view of C-C of the submerged dike of the sorting port of the present invention.
图中:1.总进样口;2.第一层分流通道;3.引流堤;4.分流口;5.分流岛墙;6.内流道;7.外流道;8.分选口;9.回旋撞墙;10.总出样口;11.主体;12.第三层分流通道;13.第三层外流道出口;14.第二层外流道出口;15.第二层分流通道;16.第一层外流道出口;17.回旋弯道;18.暗阻挡堤;19.分选口暗堤;20.分流岛墙尖;21.不规则凸面;22.不规则凹面;23.内流道底;24.分选口底部;25.外流道底部。In the figure: 1. The total injection port; 2. The first layer of split channel; 3. Drain bank; 4. Split port; 5. Split island wall; 6. Inner channel; 7. Outer channel; 8. Sorting port ;9. Whirling and hitting the wall; 10. Total sample outlet; 11. Main body; 12. Third-layer shunt channel; ; 16. Outlet of the first layer of outer flow channel; 17. Roundabout; 18. Concealed barrier embankment; 19. Concealed embankment of sorting port; 20. Distributor island wall tip; 21. Irregular convex surface; .The bottom of the inner runner; 24. The bottom of the sorting port; 25. The bottom of the outer runner.
具体实施方式Detailed ways
下面结合附图和实施例进一步对本发明加以说明。The present invention will be further described below in conjunction with the accompanying drawings and embodiments.
实施例一Embodiment one
参照图1至图9的形状结构,一种血液分流器,主体11的流体分流通道数量是3层,每层9个的分流岛墙5,组成8个分选单元,即有8个分选口8。Referring to the shape and structure of Fig. 1 to Fig. 9, a blood diverter, the number of fluid diversion channels of the
每层流体分流通道深度8mm,宽度10mm。引流堤3宽1mm,高6mm。分流岛墙5沿流体分流通道走向呈鱼形,高8mm同流体分流通道的顶部平齐;分流岛墙尖20的端面宽2mm。各层的外流道7宽2.5mm;各层的外流道底部25的高度尺寸高于内流道底部23的高度2mm;外流道底部25连接过渡后呈水平底面。各层的内流道6两头喇叭开口,前半段呈反向主体11圆弧弧度的弧形回旋弯道17,回旋弯道17结束处宽度最窄;内流道6在通过回旋撞墙9后又呈同向主体11圆弧弧度的通道。总进样口1与总出样口10的直径一致为ϕ2mm,第一层外流道出口16、第二层外流道出口14和第三层外流道出口13的直径为ϕ0.9mm。Each layer of fluid distribution channels has a depth of 8mm and a width of 10mm. The
实施例二Embodiment two
参照图1至图12的形状结构,一种血液分流器,主体11的流体分流通道数量是5层,每层6个的分流岛墙5,组成5个分选单元,即有5个分选口8。Referring to the shape and structure of Figures 1 to 12, a blood diverter, the number of fluid diversion channels in the
第一层流体分流通道深度10mm,宽度12mm;第二层流体分流通道深度10mm,宽度11mm;第三层流体分流通道深度10mm,宽度10mm;第四层流体分流通道深度10mm,宽度9mm;第五层流体分流通道深度10mm,宽度8mm。引流堤3宽0.5mm,高5mm。分流岛墙5沿流体分流通道走向呈扇形,高10mm同流体分流通道的顶部平齐;分流岛墙尖20的端面宽1mm。第一层外流道7宽3mm;第二层外流道7宽2.5mm;第三层外流道7宽2mm;第四层外流道7宽1.5mm;第五层外流道7宽1.5mm。各层的外流道底部25的高度尺寸高于内流道底部23的高度1mm;外流道底部25连接过渡后呈过渡处高、外侧低的倾斜底面。各层的内流道6两头喇叭开口,呈反向主体11圆弧弧度的弧形回旋弯道17,回旋弯道17结束处宽度最窄。总进样口1与总出样口10的直径一致为ϕ3mm,第一层到第五层外流道出口的直径均为ϕ1.2mm。The depth of the first layer of fluid distribution channel is 10mm, and the width is 12mm; the depth of the second layer of fluid distribution channel is 10mm, and the width is 11mm; the depth of the third layer of fluid distribution channel is 10mm, and the width is 10mm; The depth of the laminar fluid distribution channel is 10mm, and the width is 8mm. The
在第三层、第五层分选单元的各个分流口4加工有高度尺寸低于内流道6顶部5mm的暗阻挡堤18。在第三层、第五层分流岛墙5分选口8处加工有高度尺寸低于分选口8顶部2mm的分选口暗堤19。Each
实施例三Embodiment three
参照图1至图12的形状结构,一种血液分流器,主体11的流体分流通道=4层,每层7个的分流岛墙5,组成6个分选单元,即有6个分选口8。Referring to the shape and structure of Figures 1 to 12, a blood diverter, the fluid diversion channel of the
第一层流体分流通道深度10mm,宽度9mm;第二层流体分流通道深度10mm,宽度10mm;第三层流体分流通道深度10mm,宽度11mm;第四层流体分流通道深度10mm,宽度12mm。引流堤3宽0.5mm,高7mm。分流岛墙5沿流体分流通道走向呈鱼形,高10mm同流体分流通道的顶部平齐;分流岛墙尖20的端面宽1mm。第一层外流道7宽1.5mm;第二层外流道7宽2mm;第三层外流道7宽2.5mm;第四层外流道7宽3mm。各层的外流道底部25的高度尺寸高于内流道底部23的高度1.5mm;外流道底部25连接过渡后呈过渡处高、外侧低的倾斜底面。各层的内流道6两头喇叭开口,呈反向主体11圆弧弧度的弧形回旋弯道17,回旋弯道17结束处宽度最窄;内流道6在通过回旋撞墙9后又呈同向主体11圆弧弧度的通道。总进样口1与总出样口10的直径一致为ϕ2.5mm,第一层到第五层外流道出口的直径均为ϕ1mm。The depth of the first layer of fluid distribution channel is 10mm, and the width is 9mm; the depth of the second layer of fluid distribution channel is 10mm, and the width is 10mm; the depth of the third layer of fluid distribution channel is 10mm, and the width is 11mm; the depth of the fourth layer of fluid distribution channel is 10mm, and the width is 12mm. The
在各层的分选单元的分流口4加工有高度尺寸低于内流道6顶部3mm的暗阻挡堤18。在各层的分流岛墙5分选口8处加工有高度尺寸低于分选口8顶部3mm的分选口暗堤19。A
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