Micro-fluidic chip

文档序号:248868 发布日期:2021-11-16 浏览:8次 中文

阅读说明:本技术 一种微流控芯片 (Micro-fluidic chip ) 是由 毛政 梁烽 罗浩月 彭娟 汪丽 石剑 陈勇 于 2021-07-16 设计创作,主要内容包括:本发明提供一种微流控芯片,包括:芯片本体,所述芯片本体表面开设至少一个第一开口及至少一个第二开口;设置在所述芯片本体内部的一个空腔或多个分离的空腔;一个或多条分离的微流通道,每条所述微流通道可连通一个或多个第一开口、一个或多个空腔及一个或多个第二开口;设置在芯片本体内部且与所述微通道隔离设置的工作电极、参比电极及对电极。本发明的有益效果在于:芯片设计成可逆封装,参比电极和工作电极及对电极可分别的制作上盖板和底板上,可对不同空腔的工作电极进行不同修饰即可实现多指标检测;芯片上盖板、底板体及附加层可以重复使用,而底板上的电极及隔离膜可以随时更换;芯片可用于流体动态检测或操作,可实现复杂流程自动化。(The present invention provides a microfluidic chip comprising: the chip comprises a chip body, wherein the surface of the chip body is provided with at least one first opening and at least one second opening; a cavity or a plurality of separate cavities disposed within the chip body; one or more separate microfluidic channels, each of which may communicate with one or more first openings, one or more cavities, and one or more second openings; and the working electrode, the reference electrode and the counter electrode are arranged in the chip body and are isolated from the micro channel. The invention has the beneficial effects that: the chip is designed to be packaged reversibly, the reference electrode, the working electrode and the counter electrode can be manufactured on the upper cover plate and the bottom plate respectively, and the working electrodes of different cavities can be modified differently to realize multi-index detection; the upper cover plate, the bottom plate body and the additional layer of the chip can be repeatedly used, and the electrode and the isolating film on the bottom plate can be replaced at any time; the chip can be used for fluid dynamic detection or operation, and can realize complex process automation.)

1. A microfluidic chip, comprising:

the chip comprises a chip body, wherein the surface of the chip body is provided with at least one first opening and at least one second opening;

a cavity or a plurality of separate cavities disposed within the chip body;

one or more separate microfluidic channels, each of which may communicate with one or more first openings, one or more cavities, and one or more second openings;

the working electrode, the reference electrode and the counter electrode are arranged in the chip body and are isolated from the micro-channel;

the working electrode comprises a working electrode testing part and a working electrode external connection part, and the working electrode testing part is in contact with the inner space of the cavity and corresponds to the cavity one by one;

the reference electrode comprises a reference electrode testing part and a reference electrode external connection part, the counter electrode comprises a counter electrode testing part and a counter electrode external connection part, and the counter electrode testing part and the reference electrode testing part penetrate through all the cavities;

the working electrode external connection part, the reference electrode external connection part and the counter electrode external connection part are arranged in an isolated mode with the cavity.

2. The microfluidic chip according to claim 1, further comprising a reference electrode transition slot, a working electrode transition slot, and a counter electrode transition slot; the reference electrode external connection part is connected with the reference electrode adapter groove; the working electrode switching grooves correspond to the working electrodes one by one, and the working electrode external connection part is connected with the working electrode switching grooves; the counter electrode external connection part is connected with the counter electrode switching groove.

3. The microfluidic chip according to claim 1, wherein if the microfluidic chip comprises a plurality of separated cavities, different cavities are distributed at the same height or different heights of the chip body or at the same height of a part of the chip body, and at different heights of another part of the chip body; different heights the cavity adopts different miniflow passageways, same height the cavity passes through same microchannel and connects, not co-altitude connect through the barrier film between the cavity, the barrier film is the pellicle or contains the material or the porous material of pellicle.

4. The microfluidic chip according to claim 1, wherein the chip body comprises an upper cover plate and a bottom plate which are detachably connected, and an isolation layer is arranged between the upper cover plate and the bottom plate; the upper cover plate comprises an upper cover plate lower surface opposite to the isolation layer, and the bottom plate comprises a bottom plate upper surface opposite to the isolation layer; the isolation layer comprises an isolation layer body; the cavity comprises the first cavity hole and the cavity groove, the first cavity hole is formed in the isolation layer body, the cavity groove is formed in the upper cover plate and corresponds to the first cavity hole in a one-to-one mode, two cavity openings are formed in two ends of the cavity groove respectively, and the cavity openings are connected with the micro-flow channel.

5. The microfluidic chip according to claim 4, wherein the reference electrode is connected to the upper cover plate or the bottom plate, and the reference electrode testing part passes through the cavity after the upper cover plate or the bottom plate is spliced with the isolation layer; the counter electrode is connected with the upper cover plate or the bottom plate, and the counter electrode testing part penetrates through all the cavities after the upper cover plate or the bottom plate is spliced with the isolation layer; the working electrode is connected with the upper cover plate or the bottom plate, after the upper cover plate or the bottom plate is spliced with the isolation layer, the working electrode testing part is contacted with the inner part of the corresponding cavity, and the working electrode testing part comprises a chemical modification layer; the reference electrode and the counter electrode are not connected with the upper cover plate or the bottom plate at the same time.

6. The microfluidic chip according to claim 4, wherein one end of the upper cover plate and one end of the bottom plate are both aligned with one end of the isolation layer, and a surface extending from the other end of the bottom plate or the other end of the upper cover plate at an extension position of the other end of the isolation layer is an extension surface compared with the isolation layer; the extension surface is provided with a counter electrode switching groove, a reference electrode switching groove and working electrode switching grooves corresponding to the working electrodes one by one.

7. The microfluidic chip according to claim 4, wherein the upper cover plate comprises a detachable upper cover plate body layer and an additional layer stacked in sequence, the additional layer comprises an additional layer body, the upper cover plate body layer comprises an upper cover plate body lower surface corresponding to the additional layer, and the counter electrode or the reference electrode is connected with the upper cover plate body lower surface; the additional layer comprises second cavity holes corresponding to the first cavity holes one to one, the two ends of each second cavity hole are respectively provided with the cavity openings, and the cavity grooves are formed by splicing the second cavity holes and the lower surface of the upper cover plate body.

8. The microfluidic chip according to claim 4, wherein one or more detachably connected composite layers are further disposed between the isolation layer and the bottom plate, each of the composite layers including one or more of the cavities; the isolation film is arranged between the first cavity hole of the isolation layer and the cavity of the composite layer and is detachably connected with the isolation layer and the composite layer; if a plurality of composite layers are arranged, the isolating film is arranged between the composite layers and the cavity of the composite layers.

9. The microfluidic chip according to claim 8, wherein the composite layer comprises a first microchannel isolation layer, an intermediate composite layer, and a second microchannel isolation layer, the first microchannel isolation layer comprises a first composite layer cavity hole, the intermediate composite layer comprises a second composite layer cavity hole, the second microchannel isolation layer comprises a third composite layer cavity hole, the cavity opening is opened at two ends of the second composite layer cavity hole, and the cavity opening is communicated with the microfluidic channel.

10. The electrochemical measurement chip according to claim 5, wherein if the counter electrode and the working electrode are connected to the upper cover plate or the bottom plate at the same time, the reference electrode external connection portion is connected to the reference electrode switching groove through a conductive sheet; if the reference electrode and the working electrode are simultaneously connected with the upper cover plate or the bottom plate, the counter electrode external connection part is connected with the counter electrode switching groove through a conducting strip.

Technical Field

The invention belongs to the field of electrochemical signal testing, and particularly relates to a micro-fluidic chip.

Background

Electrochemistry plays an important guiding role in drug screening, pathological research, disease detection or research and development of bionic materials.

The traditional electrochemical test equipment is large in size, limited in small signal measurement capability and prone to being interfered by external environment, so that the measurement method is large in limitation. The electrochemical test based on the microfluidic chip has small volume and high integration level, so that the detection sensitivity can be greatly improved, and the application range is also expanded.

At present, the testing principle of the microfluidic chip is still a three-electrode testing system consisting of a working electrode, a counter electrode and a reference electrode. However, with the intensive research, the electrochemical detection needs are diversified, for example, the real-time dynamic detection of fluid, the detection of multiple indexes of the same product, the high-throughput detection of different samples, and the like, and the existing devices are difficult to meet the diversified needs, and not only many microfluidic chips cannot be reused for many times, which results in higher detection cost.

Disclosure of Invention

In order to solve the technical problems, the invention provides a microfluidic chip.

The specific technical scheme is as follows:

a microfluidic chip, characterized by comprising:

the chip comprises a chip body, wherein the surface of the chip body is provided with at least one first opening and at least one second opening;

a cavity or a plurality of separate cavities disposed within the chip body;

one or more separate microfluidic channels, each of which may communicate with one or more first openings, one or more cavities, and one or more second openings;

the working electrode, the reference electrode and the counter electrode are arranged in the chip body and are isolated from the micro-channel;

the working electrodes correspond to the cavities one by one and comprise working electrode testing parts and working electrode external connection parts, and the working electrode testing parts are in contact with the inner space of the cavities;

the reference electrode comprises a reference electrode testing part and a reference electrode external connection part, the counter electrode comprises a counter electrode testing part and a counter electrode external connection part, and the counter electrode testing part and the reference electrode testing part penetrate through all the cavities;

the working electrode external connection part, the reference electrode external connection part and the counter electrode external connection part are arranged in an isolated mode with the cavity.

Furthermore, the micro-fluidic chip also comprises a reference electrode switching groove, a working electrode switching groove and a counter electrode switching groove; the reference electrode external connection part is connected with the reference electrode adapter groove; the working electrode switching grooves correspond to the working electrodes one by one, and the working electrode external connection part is connected with the working electrode switching grooves; the counter electrode external connection part is connected with the counter electrode switching groove.

Furthermore, two ends of the cavity are respectively provided with a cavity opening, and the microfluidic channel is connected with the cavity opening; the chip body comprises a chip body upper surface, and one or more first openings are formed in the chip body upper surface; and one or more second openings, wherein the first opening and the second opening are respectively connected with the microfluidic channel.

Further, if the microfluidic chip comprises a plurality of separated cavities, different cavities are distributed at the same height or different heights of the chip body or at the same height of a part of the chip body, and the other part of the chip body is at different heights; different heights the cavity adopts different miniflow passageways, same height the cavity passes through same microchannel and connects, not co-altitude connect through the barrier film between the cavity, the barrier film is the pellicle or contains the material or the porous material connection of pellicle.

Further, the chip body comprises an upper cover plate and a bottom plate which are detachably connected, and an isolation layer is arranged between the upper cover plate and the bottom plate; the upper cover plate comprises an upper cover plate lower surface opposite to the isolation layer, and the bottom plate comprises a bottom plate upper surface opposite to the isolation layer; the isolation layer comprises an isolation layer body; the cavity comprises the first cavity hole and the cavity groove, the first cavity hole is formed in the isolation layer body, the cavity groove is formed in the upper cover plate and corresponds to the first cavity hole in a one-to-one mode, two cavity openings are formed in two ends of the cavity groove respectively, and the cavity openings are connected with the micro-flow channel.

Further, the isolation layer body is further connected with a sealing ring, and the sealing ring is arranged on the periphery of the first cavity hole and opposite to the upper surface of the bottom plate.

Further, the reference electrode is connected with the upper cover plate or the bottom plate, and the reference electrode testing part penetrates through the cavity after the upper cover plate or the bottom plate is spliced with the isolation layer; the counter electrode is connected with the upper cover plate or the bottom plate, and the counter electrode testing part penetrates through all the cavities after the upper cover plate or the bottom plate is spliced with the isolation layer; the working electrode is connected with the upper cover plate or the bottom plate, after the upper cover plate or the bottom plate is spliced with the isolation layer, the working electrode testing part is contacted with the inner part of the corresponding cavity, and the working electrode testing part comprises a chemical modification layer; the reference electrode and the counter electrode are not connected with the upper cover plate or the bottom plate at the same time.

Furthermore, one end of the upper cover plate and one end of the bottom plate are both aligned with one end of the isolation layer, and the other end of the bottom plate or the other end of the upper cover plate is at the extension position of the other end of the isolation layer, and the extension surface is a surface extending out of the isolation layer; the extension surface is provided with a counter electrode switching groove, a reference electrode switching groove and working electrode switching grooves corresponding to the working electrodes one by one.

Further, the upper cover plate comprises a detachable upper cover plate body layer and an additional layer which are sequentially overlapped, the additional layer comprises an additional layer body, the upper cover plate body layer comprises an upper cover plate body lower surface corresponding to the additional layer, and the counter electrode or the reference electrode is connected with the upper cover plate body lower surface; the additional layer comprises second cavity holes corresponding to the first cavity holes one to one, the two ends of each second cavity hole are respectively provided with the cavity openings, and the cavity grooves are formed by splicing the second cavity holes and the lower surface of the upper cover plate body.

Furthermore, one or more composite layers which are detachably connected are arranged between the isolation layer and the bottom plate, and each composite layer comprises one or more cavities; the isolation film is arranged between the first cavity hole of the isolation layer and the cavity of the composite layer and is detachably connected with the isolation layer and the composite layer; if a plurality of composite layers are arranged, the isolating film is arranged between the composite layers and the cavity of the composite layers.

Further, the composite layer includes first microchannel isolation layer, middle composite layering and second microchannel isolation layer that can dismantle the connection, first microchannel isolation layer includes first composite layer cavity hole, middle composite layering includes second composite layer cavity hole, second microchannel isolation layer includes third composite layer cavity hole, the cavity opening has been seted up at the both ends of second composite layer cavity hole, the cavity opening with the miniflow channel intercommunication.

Further, if the counter electrode and the working electrode are connected with the upper cover plate or the bottom plate at the same time, the reference electrode external connection part is connected with the reference electrode switching groove through a conducting strip; if the reference electrode and the working electrode are simultaneously connected with the upper cover plate or the bottom plate, the counter electrode external connection part is connected with the counter electrode switching groove through a conducting strip.

Compared with the prior art, the invention has the beneficial effects that:

(1) according to the invention, the cavity is respectively connected with the first opening and the second opening, so that dynamic detection and operation of fluid can be realized, automation of complex processes such as electrode cleaning and electrode re-modification can be realized, and meanwhile, fluid cleaning can be adopted before and after detection, so that the operation is convenient and the device can be repeatedly used; meanwhile, each microfluidic channel can form a fluid line, and multi-channel multi-index measurement can be carried out by matching with a plurality of working electrodes, a common reference electrode and a common counter electrode through microfluidic channel design and different modifications of the working electrodes in different chambers.

(2) According to the invention, the cavities with the same height can be used for testing one sample by dividing the cavities with different heights, and the cavities with different heights are communicated by isolation, so that the interaction among different samples can be researched by electrochemical testing; meanwhile, the isolation membrane can be customized into a product to be researched, and the property of the isolation membrane can be researched through an electrochemical test.

(3) The chip is designed into a detachable split structure, and the cavity structure is spliced in a layer-by-layer splicing mode, so that the difficulty of the integrated manufacturing process of the microporous chip is reduced, and mass production can be realized; and element replacement or different modifications can be carried out on the working electrode according to the test requirements, so that later maintenance and test are facilitated, and the maintenance cost is reduced.

(4) The split type structure is adopted to integrate the counter electrode and the reference electrode on different planes, so that the difficulty of simultaneously integrating the counter electrode and the reference electrode on the same plane is reduced.

(5) The counter electrode transfer groove, the reference electrode transfer groove and the working electrode transfer groove are integrated on the extension surface, and can be simultaneously connected, so that the follow-up operation is facilitated.

Drawings

FIG. 1 is a schematic view of a microfluidic channel circuit according to the present invention;

FIG. 2 is a sectional view of an electrochemical test chip according to example 1;

FIG. 3 is a bottom view of the upper lid plate of embodiment 1;

FIG. 4 is a bottom view of the barrier layer of example 1;

FIG. 5 is a top view of the base plate of embodiment 1;

FIG. 6 is a cross-sectional view of a split electrochemical test chip according to example 2;

FIG. 7 is a bottom view of the upper cover plate body layer of example 2;

FIG. 8 is a top view of an additional layer of example 2;

FIG. 9 is a top view of an isolation layer of embodiment 2;

FIG. 10 is a top view of a first microchannel spacer layer of example 2;

FIG. 11 is a top view of an intermediate composite layer of example 2;

FIG. 12 is a top view of a second microchannel spacer layer of example 2;

FIG. 13 is a top view of the bottom plate of embodiment 2;

FIG. 14 is a detection chart of example 3.

Wherein, the chip comprises a chip body-1, a chip body upper surface-1 a, a first opening-2, a second opening-3, a cavity-4, a micro-flow channel-5, a working electrode-6, a reference electrode-7, a counter electrode-8, a reference electrode transfer groove-9, a working electrode transfer groove-10, a counter electrode transfer groove-11, an isolating membrane-12, a composite layer-13, a conducting strip-14, a Runner opening-15, a conducting strip cavity-16, an upper cover plate-101, a bottom plate-102, an isolating layer-103, a micro-channel hole-201 corresponding to the first opening, a micro-channel hole-301 corresponding to the second opening, a first cavity hole-401, a cavity groove-402, a cavity opening-403, a first composite layer cavity hole-404, a second composite layer cavity hole-405, a third composite layer cavity hole-406, a working electrode test part-601, a chemical modification layer-6011, a working electrode external connection part-602, a reference electrode test part-701, a reference electrode external connection part-702, a counter electrode test part-801, a counter electrode external connection part-802, a lower surface-101 a of an upper cover plate, an upper surface-102 a of a bottom plate, a body layer-1011 of an upper cover plate, an additional layer-1012, an isolation layer body-1031, a sealing ring-1032, an extension surface-102 a1, a lower surface-1011 a of the upper cover plate body, a second cavity hole-4021, a first microchannel isolation layer-1301, a middle composite layer-1302, a second microchannel isolation layer-1303, a conductive slice-1401 and an alignment mark-102 a 2.

Detailed Description

The principles and features of this invention are described below in conjunction with the following drawings, which are set forth by way of illustration only and are not intended to limit the scope of the invention.

The invention provides a microfluidic chip, which is characterized by comprising the following components:

the chip comprises a chip body 1, wherein the surface of the chip body is provided with at least one first opening 2 and at least one second opening 3;

a cavity or a plurality of separate cavities 4 arranged inside the chip body 1;

one or more separate microfluidic channels 5, each microfluidic channel 5 being in communication with one or more first openings 2, one or more cavities 4 and one or more second openings 3;

the working electrode 6, the reference electrode 7 and the counter electrode 8 are arranged in the chip body 1 and are separated from the micro channel 5;

the working electrodes 6 correspond to the cavities 4 one by one and comprise working electrode testing parts 601 and working electrode external connection parts 602, and the working electrode testing parts 601 are in contact with the inner space of the cavities 4;

the reference electrode 7 comprises a reference electrode testing part 701 and a reference electrode external connection part 702, the counter electrode 8 comprises a counter electrode testing part 801 and a counter electrode external connection part 802, and the counter electrode testing part 801 and the reference electrode testing part 701 penetrate through all the cavities 4;

the working electrode external connection portion 602, the reference electrode external connection portion 702 and the counter electrode external connection portion 802 are isolated from the cavity 4.

In the present invention, separate microfluidic channels refer to microfluidic channels that circulate different flow lines.

In the present invention, the working electrode external connection portion 602, the reference electrode external connection portion 702 and the counter electrode external connection portion 802 may be connected to an external electrical signal providing apparatus (e.g., an electrochemical station).

In the invention, the working electrode 6, the counter electrode 8 and the reference electrode 7 are arranged to bypass the microfluidic channel 5, so that the working electrode, the counter electrode and the reference electrode can be isolated from the microfluidic channel 5.

In the invention, the micro-fluidic chip also comprises a reference electrode transfer groove 9, a working electrode transfer groove 10 and a counter electrode transfer groove 11; the reference electrode external connection part 702 is connected with the reference electrode transfer groove 9; the working electrode switching grooves 10 correspond to the working electrodes 6 one by one, and the working electrode external connection part 602 is connected with the working electrode switching grooves 10; the counter electrode external connection part 802 is connected with the counter electrode transfer groove 9; through the arrangement of the reference electrode transfer groove 9, the working electrode transfer groove 10 and the counter electrode transfer groove 11, the reference electrode external connection part 702, the working electrode external connection part 602 and the counter electrode external connection part 802 are isolated from the cavity 4, and then the connecting wires of external electric signal providing instruments are connected with the electrodes in the transfer grooves.

In the present invention, a microfluidic channel 5 is connected to a fluid circuit, and the fluid circuit of the present invention includes at least (fig. 1):

a first opening, a cavity and a second opening are connected (1 a);

a first opening, a cavity and a plurality of second openings are connected (1 b);

a first opening, a plurality of cavities and a second opening are connected (1 c);

a first opening, a plurality of cavities and a plurality of second openings are connected (1 d);

a plurality of first openings, a cavity and a second opening are connected (1 e);

a plurality of first openings, a cavity and a plurality of second openings are connected (1 f);

a plurality of first openings, a plurality of parallel cavities, cavities in series with the plurality of parallel cavities, and a second opening (1 g);

a plurality of first openings, a plurality of parallel cavities, a cavity in series with the plurality of parallel cavities, and a pair of second openings (1 h).

The realization of diversified circuits can be realized by parallel-serial design of microfluidic channels, and particularly, the realization method is shown in figure 1.

In the present invention, if the microfluidic chip includes a plurality of separated cavities 4, different cavities 4 are distributed at the same height or different heights or a part of the same height of the chip body 1, and another part of the same height.

In the invention, in order to research the interaction of different substances, the cavities 4 are divided into different heights, the cavities 4 with different heights adopt different micro-flow channels 5, the cavities 4 with the same height are connected through the same micro-channel 5, the cavities with different heights are connected through an isolating membrane 12, and the isolating membrane 12 is a semi-permeable membrane or a substance containing the semi-permeable membrane or a porous material; the fluid in the cavities with different heights can realize mutual permeation, and real-time monitoring is carried out; the isolation diaphragm 12 may be a custom-made material whose permeability or diffusivity can be studied by detecting electrical impedance signals in the cavity fluid.

In the invention, the microfluidic chip adopts a split structure, the chip body 1 comprises an upper cover plate 101 and a bottom plate 102 which are detachably connected, and an isolation layer 103 is arranged between the upper cover plate 101 and the bottom plate 102; the upper cover plate 101 comprises an upper cover plate lower face 101a opposite to said spacer layer 103, and the base plate 102 comprises a base plate upper face 102a opposite to said spacer layer 103; the isolation layer 103 comprises an isolation layer body 1031, the isolation layer body 1031 is provided with first cavity holes 401, the lower surface 101a of the upper cover plate is provided with cavity grooves 401 corresponding to the first cavity holes 401, and two ends of each cavity groove 402 are respectively provided with a cavity opening 403.

In the present invention, the lower surface 101a of the upper cover plate is further provided with a microchannel hole and a microchannel track cavity 501, which are communicated with the cavity opening 403, and the microchannel track cavity can be communicated with one or more microchannel holes 201 corresponding to the first opening, one or more cavity grooves 401, and one or more microchannel holes 301 corresponding to the second opening.

In the present invention, the reference electrode 7 is connected to the upper cover plate 101 or the bottom plate 102, and the position where the reference electrode testing part 701 is connected corresponds to the position where the first cavity hole 401 is formed in the isolation layer 103; the counter electrode 8 is connected with the upper cover plate 101 or the bottom plate 102, and the connection position of the counter electrode testing part 801 corresponds to the position of the first cavity hole 401; the working electrode 6 is connected with the upper cover plate 101 or the bottom plate 102, and the connection position of the working electrode testing part 601 corresponds to the position of the isolation layer 103 where the first cavity hole 401 is arranged; the reference electrode 7 and the counter electrode 8 are not connected to the upper cover plate 1 or to the bottom plate 2 at the same time. In conventional designs, three electrodes are typically integrated on the same substrate. The materials of the three electrodes are different materials, wherein the working electrode is usually chemically modified according to different test objects, so that the manufacturing process of the chip substrate for electrochemistry is complex, the integration is difficult, and the application is greatly limited.

In the present invention, the isolating layer body 1031 is further connected with a sealing ring 1032, and the sealing ring 1032 is disposed around the first cavity hole 401 and opposite to the upper surface 102a of the base plate. Seal ring 1032 may further isolate the seal of the layer from the underlying connecting layer.

In the present invention, one end of the upper cover plate 101 and one end of the bottom plate 102 are both aligned with one end of the isolation layer 103, and the extended position of the other end of the bottom plate 102 or the other end of the upper cover plate 101 at the other end of the isolation layer 103 is an extended surface 102a1 compared with the extended surface of the isolation layer 103; the extending surface 102a1 is provided with a counter electrode transfer groove 11, a reference electrode transfer groove 9, and working electrode transfer grooves 10 corresponding to the working electrodes one by one. The counter electrode transfer groove 11, the reference electrode transfer groove 9 and the working electrode transfer groove 10 are integrated on the extension surface, and can be simultaneously connected, so that the subsequent operation is convenient.

In the invention, the upper cover plate 101 comprises an upper cover plate body layer 1011 and an additional layer 1012 which are detachably connected and sequentially overlapped, the upper cover plate body layer 1011 comprises an upper cover plate body lower surface 101a corresponding to the additional layer 1012, the additional layer 1012 comprises second cavity holes 4021 corresponding to the first cavity holes 401 one by one, two ends of each second cavity hole 4021 are respectively provided with the cavity openings 403, and the second cavity holes 4021 and the upper cover plate body lower surface 101a are spliced to form the cavity grooves 402. If the structure is adopted to splice the cavity groove 402, the difficulty of the manufacturing process is further reduced, the situation that grooves are dug on one plane at the same time is avoided, a micro-flow channel is constructed due to the connection of the cavity opening, a counter electrode 8 or a reference electrode 7 is required to be installed subsequently, and the electrodes can be installed separately after splicing.

In the invention, one or more composite layers which are detachably connected are also arranged between the isolation layer and the bottom plate, and each composite layer comprises one or more cavities; the isolation film is arranged between the first cavity hole of the isolation layer and the cavity of the composite layer and is detachably connected with the isolation layer and the composite layer; if a plurality of composite layers are arranged, the isolating film is arranged between the composite layers and the cavity of the composite layers.

In the present invention, the composite layer 13 also adopts a split structure, the composite layer 13 includes a first microchannel isolation layer 1301, a middle composite layer 1302, and a second microchannel isolation layer 1303 that are detachably connected, the first microchannel isolation layer 1301 includes a first composite layer cavity hole 404, the middle composite layer 1302 includes a second composite layer cavity hole 405, the second microchannel isolation layer 1303 includes a third composite layer cavity hole 406, the cavity openings 403 are formed at two ends of the second composite layer cavity hole 1303, and the cavity openings 403 are connected to the microchannels 5. The first microchannel isolation layer 1301 can prevent a sample introduced into the composite layer microchannel 5 from entering the upper cavity through the isolation film 12, the second microchannel isolation layer 1302 can prevent the fluid of the composite layer microchannel 5 from entering the lower cavity 4, and the middle composite layer can guide the fluid into the composite layer 13 through the cavity opening 403 and the microfluidic channel 5. Therefore, the fluid of the microfluidic channel 5 with the rest height is isolated from the cavity 4 of the composite layer, and simultaneously the fluid required by the test of the composite layer is introduced.

In the invention, if a composite layer 13 is arranged between an isolation layer 103 and a bottom plate 102 and the composite layer adopts a split structure, the isolation layer 103 only needs to be provided with micro-hole openings 201 corresponding to part of first openings 2 one by one and micro-hole openings 301 corresponding to part of second openings 3 one by one, the part of first openings 2 are connected with a cavity 4 of a subsequent composite layer, and the part of second openings 3 are connected with the cavity 4 of the subsequent composite layer 13; the first microchannel isolation layer 1301 is provided with microchannel openings corresponding to the upper adjacent layers one by one; the middle composite layer 1302 is provided with microchannel openings and a microchannel track cavity 501 which are in one-to-one correspondence with the first microchannel isolation layer, and the microchannel track cavity 501 can be communicated with one or more microchannel holes corresponding to the first openings, one or more cavity holes and one or more microchannel holes corresponding to the second openings; the second microchannel isolation layer 1303 is provided with microchannel holes 201 corresponding to a part of the first openings 2 one to one, and microchannel holes 301 corresponding to a part of the second openings 3 one to one, wherein the part of the first openings 2 are connected with the cavities 4 of the subsequent composite layers 13, and the part of the second openings 3 are connected with the cavities 4 of the subsequent composite layers 13.

In the present invention, if the counter electrode 8 and the working electrode 6 are connected to the upper cover plate 1 or the bottom plate 2 at the same time, the reference electrode external connection portion 702 is connected to the conductive sheet 14, the conductive sheet 14 is disposed in the reference electrode transfer groove 9 or the conductive sheet 14 is embedded in the isolation layer 103, and the conductive sheet can be inserted into the reference electrode transfer groove 9; or the conducting strip is designed into a structure formed by conducting slices which are overlapped layer by layer, and then the conducting strip extends to the reference electrode switching groove 9 in a layer-by-layer overlapping mode.

Similarly, in the present invention, if the reference electrode 7 and the working electrode 6 are connected to the upper cover plate 1 or the bottom plate 2 at the same time, the counter electrode external connection portion 802 is connected to the conductive sheet in the same manner as described above.

In the invention, the chip body 1 comprises a chip body upper surface 1a, and one or more first openings 2 are formed in the chip body upper surface 1 a; and one or more second openings 3.

In the invention, the reference electrode is Ag or AgCl, the counter electrode is Au, Pt, C or Pt black, the working electrode is Au, Pt, C or Pt black, and the chemical modification layer is processed according to the requirement.

Example 1

The embodiment provides a microfluidic chip, which has a specific structure as shown in fig. 2 to 5:

chip body 1, chip body 1 include chip body upper surface 1a, and a first opening 2 and two second openings 3 are seted up to chip body 1 upper surface, simultaneously at first opening and second opening part design robust port 15, the follow-up operation of being convenient for.

The chip body 1 adopts a split structure and comprises an upper cover plate 101 and a bottom plate 102 which are detachably connected, and an isolation layer 103 is arranged between the upper cover plate 101 and the bottom plate 102; the upper cover 101 includes an upper cover lower face 101a opposite the spacer 103, and the base plate 102 includes a base upper face 102a opposite the spacer 103; the isolation layer 103 comprises an isolation layer body 1031, wherein the isolation layer body 1031 is provided with four side-by-side first cavity holes 402 in a group of two; a sealing ring 1032 is disposed along the periphery of the four cavity holes 402 on the side of the isolation layer 103 opposite the bottom plate 102.

The lower surface 101a of the upper cover plate is provided with a cavity groove 402, a micro-channel hole and a micro-channel track cavity 501; the cavity grooves 402 correspond to the cavity holes 401 one by one, and two ends of each cavity groove 402 are respectively provided with a cavity opening 403; the micro-channel holes correspond to the first openings 2 and the second openings 3 one by one; the microchannel track cavity 501 is branched into four branches from the microchannel hole 201 corresponding to the first opening 2, the four branches are respectively connected with the cavity openings 403 of the four cavity grooves, and every two branches are combined into one branch from the other cavity opening 403 of the four cavity grooves 402 to form two new branch channels, and the two branch channels are respectively connected with the microchannel hole 301 corresponding to the second opening 3.

The reference electrode 7 is connected with the lower surface 101a of the upper cover plate, as shown in fig. 3, the reference electrode is L-shaped, the reference electrode testing part 701 and the reference electrode external connection part 702 are arranged perpendicular to each other, as shown in fig. 2, the reference electrode testing part 701 is arranged in the cavity groove 402, and the tail end of the reference electrode external connection part 702 is connected with the conductive slice 1401 embedded in the isolation layer 103; as shown in fig. 5, one counter electrode 8 is connected to the upper surface 102a of the bottom plate, the counter electrode is also provided in an "L" shape, the counter electrode testing portion 801 and the counter electrode external connection portion 802 are vertically arranged, and the connection position of the counter electrode testing portion 801 corresponds to the position of the first cavity hole 401; four working electrodes 6 are connected to the upper surface 102a of the base plate, and the connection positions of the working electrode test portions 601 correspond to the positions of the first cavity holes 401. After the upper cover plate, the isolation layer and the lower cover plate are spliced to form a cavity, the reference electrode testing part 701 transversely penetrates through all the cavities at the upper part, and the counter electrode testing part 802 transversely penetrates through all the cavities from the lower part.

One end of the upper cover plate 101, one end of the isolation layer 103 and one end of the bottom plate 102 are aligned, the other end of the upper cover plate 101 is aligned with the other end of the isolation layer 103, the other end 102 of the bottom plate is at the extending position of the other end of the isolation layer, the surface which is not in contact with the isolation layer 103 is an extending surface 102a1, a counter electrode transfer groove 11, a reference electrode transfer groove 9 and a working electrode transfer groove 10 which are in one-to-one correspondence with the working electrode 6 are formed in the extending surface 102a1, and an alignment mark 102a2 is formed between the extending surface and the non-extending surface, so that alignment during subsequent integration is facilitated.

The tail end of the counter electrode external connection part 802 is connected into the counter electrode transfer groove 11, and the tail end of the working electrode external connection part 602 is connected into the working electrode transfer groove 10; the isolating layer is embedded into the conductive fragment 1401, the reference electrode switching groove 9 is also embedded into the conductive fragment 1401, the two conductive fragments are overlapped to form the conductive sheet 14, and after the isolating layer is spliced with the upper cover plate 101, the tail end of the external connecting part of the reference electrode is contacted with the conductive fragment of the isolating layer.

In this embodiment, the upper cover plate 101 is made of polycarbonate, the bottom plate 102 is made of glass, the reference electrode is made of Ag, the working electrode and the counter electrode are made of Pt, the isolation layer 103 and the seal ring 1032 are made of PDMS, and the conductive sheet is made of Ag paste.

In the method of this embodiment, a solution is introduced through the first opening to fill the cavity, and then the reference electrode external connection portion 702, the working electrode external connection portion 602, and the counter electrode external connection portion 802 are connected to an external electrical signal providing apparatus, so as to obtain a corresponding test result.

If different working electrodes or different modification test results of the working electrodes need to be researched, different working electrodes are directly integrated on the bottom plate or different modifications are made on the working electrodes first, and then measurement is carried out, so that measurement parameters of different working electrodes in the same solution can be obtained, and different indexes can be obtained.

When cleaning or fluid measurement is carried out, a sample or cleaning fluid is introduced from the first opening and flows out from the second opening; or the sample or the cleaning solution is introduced from the second opening and flows out from the first opening.

Example 2

The embodiment provides a multi-impedance detection microfluidic chip, which has the specific structure shown in fig. 6 to 13:

chip body 1, chip body 1 include chip body upper surface 1a, and three first opening 2 and three second opening 3 are seted up to chip body upper surface 1a, simultaneously at first opening and second opening part design robust mouthful 15, the follow-up operation of being convenient for.

The chip body 1 adopts a split structure and sequentially comprises an upper cover plate 101, an isolating layer 103, an isolating film 12, a composite layer 13 and a bottom plate 102 which are detachably connected from top to bottom, wherein the upper cover plate 101 comprises an upper cover plate body layer 1011 and an additional layer 1012 which are stacked from top to bottom and detachably connected, the upper cover plate body layer 1011 comprises a lower surface 1011a of the upper cover plate body layer, and the bottom plate 102 comprises an upper surface 102a of the bottom plate opposite to the isolating layer 103; the isolation layer 103 comprises an isolation layer body 1031, wherein the isolation layer body 1031 is provided with four side-by-side first cavity holes 401, and every two of the four side-by-side first cavity holes are in a group; a sealing ring 1032 is arranged on the side, opposite to the bottom plate 102, of the isolation layer 103 along the periphery of the four cavity holes 401; in the present embodiment, the separator 12 is a porous membrane, a semi-permeable membrane, or a substance containing a semi-permeable membrane.

The additional layer 1012 is provided with a second cavity hole 4021, six microchannel holes and a microchannel track cavity 501; the second cavity holes 4021 correspond to the first cavity holes 401 one by one, the second cavity holes 4021 and the lower surface 1011a of the upper cover plate body layer are spliced together to form cavity slots 402, and two ends of each second cavity hole 4021 are respectively provided with a cavity opening 403; the micro-channel holes correspond to the first openings and the second openings one by one; the micro-channel track cavity 501 is branched into four branches from a micro-channel hole 201 corresponding to one first opening 2, the four branches are respectively connected with the cavity openings 403 of the four cavity grooves 402, and then two branches are combined into one branch from another cavity opening 403 of the four cavity grooves 402 to form two new branch channels, and the two branch channels are respectively connected with a micro-channel hole 301 corresponding to a second opening 3; meanwhile, the isolating layer 103 is provided with two micro-channel holes 201 corresponding to the first opening 2, the corresponding first opening 201 is a first opening 201 where the additional layer 1012 is not communicated with the micro-channel track cavity 5, and a micro-channel hole 301 corresponding to the second opening 3, and the corresponding second opening 3 is a second opening 3 where the additional layer 1012 is not communicated with the micro-channel track cavity 501.

The composite layer 13 includes a first microchannel isolation layer 1301, an intermediate composite layer 1302, and a second microchannel isolation layer 1303, which are detachably connected and stacked in this order from top to bottom. The first microchannel isolation layer 1301 has a microchannel hole and a first composite layer cavity hole 404, the microchannel hole corresponds to the microchannel hole on the isolation layer one to one, and the first composite layer cavity hole 401 corresponds to the first cavity hole 401 one to one. The middle composite layer is provided with micro-channel holes, a micro-channel track cavity 501 and a second composite layer cavity 405, the micro-channel holes are in one-to-one correspondence with the micro-flow holes of the first micro-channel isolation layer 1301, the middle composite layer 1302 is in one-to-one correspondence with the first cavity holes 401, the micro-channel track cavity 501 is branched into four branches from the micro-channel hole 301 corresponding to one second opening 3, the four branches are respectively connected with the cavity openings 403 of the four cavity grooves, every two branches are combined into one branch from the other cavity opening 403 of the four cavity grooves to form two new branch channels, and the two branch channels are respectively connected with the micro-channel hole 201 corresponding to one first opening 2. The second microchannel isolation layer 1303 is only provided with third composite layer cavity holes 406, and the third composite layer cavity holes 406 are in one-to-one correspondence with the first cavity holes 401.

A reference electrode 7 is connected with the lower surface 1011a of the upper cover plate body layer, a reference electrode testing part 701 is in contact with the lower surface 1011a of the upper cover plate body layer and corresponds to the position of the first cavity hole 401, as shown in fig. 7, the reference electrode is arranged in an "L" shape, the reference electrode testing part 701 is arranged perpendicular to a reference electrode external part 702, the reference electrode external part 702 is clamped between the upper cover plate body layer 1011 and the additional layer 1012, and the tail end of the reference electrode external part is connected to the middle 16 of the conducting strip cavity; one counter electrode 8 is connected with the upper surface 102a of the bottom plate, as shown in fig. 13, the counter electrode is also arranged in an "L" shape, the counter electrode testing part 801 is arranged perpendicular to the counter electrode external connection part 802, and the connection position of the counter electrode testing part 801 corresponds to the position of the first cavity hole 401; the four working electrodes 6 are connected with the upper surface 102a of the bottom plate, and the connecting positions of the working electrode testing parts 601 correspond to the positions of the first cavity holes 401; after the upper cover plate body layer, the additional layer, the isolation layer, the composite layer and the lower cover plate are spliced, the reference electrode testing part 701 penetrates through all cavities from the top, and the counter electrode testing part 801 penetrates through all cavities from the bottom.

One end of the upper cover plate 101, one end of the isolation layer 103 and one end of the bottom plate 102 are aligned, the other end of the upper cover plate 101 is aligned with the other end of the isolation layer 103, the other end of the bottom plate 103 is at the extending position of the other end of the isolation layer 103, the surface which is not in contact with the isolation layer 103 is an extending surface 102a1, a counter electrode transfer groove 11, a reference electrode transfer groove 9 and a working electrode transfer groove 10 which is in one-to-one correspondence with a working electrode are formed in the extending surface 102a1, and an alignment mark 102a2 is formed between the extending surface and the non-extending surface, so that alignment is facilitated during subsequent integration.

The tail end of the counter electrode external connection part 801 is connected into the counter electrode transfer groove 11, and the tail end of the working electrode external connection part 602 is connected into the working electrode transfer groove 10; the reference electrode switching groove 9 is internally provided with a conducting strip 14 which is connected with the tail end of the external connection part of the reference electrode after passing through a conducting strip cavity 16.

In this embodiment, the upper cover plate body layer 1011 is made of polycarbonate, the additional layer is OCA glue, the first microchannel isolation layer 1301, the middle composite layer 1302 and the second microchannel isolation layer 1303 are all made of PDMS, the isolation layer and the sealing ring are also made of PDMS, the bottom plate 102 is a glass plate, the isolation film is a polycarbonate film or a PEGDA film, the reference electrode is Ag, and the working electrode and the counter electrode are made of Pt.

The device of the embodiment comprises the following steps: injecting the same or different solutions into the cavities of each layer simultaneously by using the catheter as required, then switching on the working electrode, the counter electrode and an external instrument, testing the electrical impedance, and obtaining experimental data.

The device of the embodiment can be used for researching the isolating membrane and the osmosis of different solutions.

Example 3

This example provides the cyclic voltammetry curves for ascorbic acid solutions of different concentrations using the apparatus of example 1, with the following specific steps:

the operation method comprises the following steps: connecting the first opening and the second opening with a conduit, and introducing PBS solution into the first opening to connect the microfluidic channel and the cavityThe cavity is washed for many times, so that impurities existing on the electrode are prevented from interfering the experiment; ascorbic acid solutions with different concentrations are respectively introduced into the cavity of the microfluidic chip by using an injector, after standing for 1 minute, voltammetry cycle testing is started, PBS is used for washing the channel for multiple times before changing the concentration, mutual influence among samples is prevented, and the CHInstrynt 660D electrochemical workstation is connected. The specific parameters are as follows (initial potential: -0.2V, high potential: 0.6V, low potential: -0.2V, scanning speed: 0.05V/s, sampling interval: 0.001V, sensitivity 10-5) The voltammetric cycling profile is shown in FIG. 14.

The results show that: the graph shows that the oxidation peak current of the ascorbic acid in the micro-fluidic device under the static state is increased along with the increase of the concentration, so that the electrochemical electrodes can be manufactured separately through split manufacturing, and repeated operation on the same plane is avoided.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.

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