Three-dimensional electrode microfluidic chip based on dielectric wetting for in vitro diagnostics

Abstract

The present invention discloses a three-dimensional electrode microfluidic chip applied to in vitro diagnosis based on dielectric wetting, and its manufacturing comprises: on a lower insulating substrate provided with a driving electrode array, in accordance with the design requirements of the in vitro diagnostic instrument application scenario, at one or more designated copper-clad plate electrode positions, a copper-embedded block electrode with a groove is embedded into the lower insulating substrate by a copper block embedding process; on the designated copper-clad plate electrode, a fence, slice, groove or / and enclosure with a three-dimensional structure is directly constructed by a metal additive process, and then a dielectric layer is coated on the lower insulating substrate to cover the driving electrode array and the fence, slice, groove or / and enclosure. The present invention constructs three-dimensional structure electrodes, fences, slices, grooves or / and enclosures on the lower substrate through metal additive or / and metal subtractive measures, which meets the design requirements of various application scenarios of in vitro diagnostic instruments.

Description

Technical Field

[0001] The present invention relates to a microfluidic chip applied to an in vitro diagnostic instrument based on dielectric wetting technology, and in particular to a three-dimensional electrode microfluidic chip applied to in vitro diagnosis based on dielectric wetting technology. Background Art

[0002] Microfluidic chips based on electrowetting on dielectrics (EWOD) technology employ two types of droplet actuation structures: an open dielectric wetting actuation structure consisting of a lower substrate; and a dielectric wetting actuation structure composed of upper and lower substrates. The upper substrate comprises an upper insulating substrate, a common electrode, and an upper hydrophobic layer stacked in sequence from top to bottom; the lower substrate comprises a lower insulating substrate, a driving electrode array, a dielectric layer, and a lower hydrophobic layer stacked in sequence from bottom to top. The driving electrode array, located within the dielectric layer, comprises multiple electrodes arranged along predetermined microchannels.

[0003] EWOD-based microfluidic chips, depending on the project of use, will have a structural design and construction of the lower substrate of the microfluidic chip. For example, to enhance the wettability of droplets, a microstructure that can enhance surface wettability can be distributed according to a certain pattern on the surface of the lower substrate. This structure is made into a microstructure of a certain shape, size, and distribution on a silicon wafer through ICP (inductively coupled plasma) or wet etching. A layer of metal platinum is then deposited on the silicon wafer. After being coated with a dielectric layer and a hydrophobic layer, the droplets are finally driven. For example, in order to separate liquids, the height of the gap between the upper and lower substrates is set, and then large droplets are distributed into small droplets. Both examples require careful design to achieve the corresponding functions.

[0004] However, in the application of in vitro diagnostic instruments, in order to achieve certain functions such as liquid separation, droplet fixation, and rapid droplet temperature rise / fall, it is necessary to construct functional electrodes with grooves and three-dimensional structures such as fences, enclosures, and slices in the specified area of the substrate under the microfluidic chip, thereby realizing the functional design of microfluidic chips for in vitro diagnostic instruments. However, there are no relevant reports yet. Summary of the Invention

[0005] The present invention aims to provide a three-dimensional electrode microfluidic chip based on dielectric wetting applied to in vitro diagnosis, so as to meet the application of dielectric wetting microfluidic chips in the field of in vitro diagnosis.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] The three-dimensional electrode microfluidic chip based on dielectric wetting for in vitro diagnosis of the present invention comprises the following steps:

[0008] Step 1: On a lower insulating substrate provided with a driving electrode array, in accordance with the design requirements of the in vitro diagnostic instrument application scenario, a copper block electrode with a groove is embedded into the lower insulating substrate at one or more designated copper-clad plate electrode positions using a copper block embedding process (metal subtractive method);

[0009] Step 2: coating a dielectric layer on the lower insulating substrate to cover the driving electrode array;

[0010] Step 3: coating a hydrophobic layer on the dielectric layer.

[0011] When the droplets (IVD reagent or test droplets or mixed droplets thereof) are driven to the groove position of the embedded copper block electrode through dielectric wetting, the positioning and position fixation of the droplets are achieved.

[0012] At the same time, the embedded copper block electrode helps to cool the droplets, increases the surface area of contact between the droplets and the electrodes, accelerates heat transfer, and also helps to cut off the droplets and perform other functions.

[0013] Optionally, the step 2 also includes step 2.1, according to the design requirements of the in vitro diagnostic instrument application scenario, directly constructing a fence, slice, groove or / and enclosure with a three-dimensional structure on the specified copper-clad electrode through a metal additive process, and then coating a dielectric layer on the lower insulating substrate to cover the driving electrode array and the fence, slice, groove or / and enclosure.

[0014] When the droplets are driven to the fence position through dielectric wetting, it prevents the test droplets or other mixed droplets from contacting with the IVD reagents, thereby avoiding cross contamination.

[0015] When the droplets are driven to the slicing position through dielectric wetting, the droplets are segmented and reassembled.

[0016] When the liquid droplets are driven to the groove positions through dielectric wetting, the liquid droplets are fixed.

[0017] When the droplets are driven to the blocking position through dielectric wetting, the droplets are prevented from flowing out of the designated electrode position and the volatilization of the droplets can be slowed down.

[0018] Optionally, the metal additive process includes:

[0019] Metal printing ink technology, 3D printing technology, metal deposition technology, laser sintering technology, fused deposition modeling technology and / or lamination manufacturing technology.

[0020] Optionally, the groove of the embedded copper block electrode is prepared by an etching process or a machining process, and the height of the embedded copper block electrode is greater than the heights of other electrodes of the driving electrode array.

[0021] Optionally, the dielectric wetting microfluidic chip comprises an upper substrate and a lower substrate spaced apart from each other; the upper substrate is composed of an upper insulating substrate, a common electrode, and an upper hydrophobic layer stacked in sequence from top to bottom; the lower substrate is composed of a lower insulating substrate, a driving electrode array, a dielectric layer, and a lower hydrophobic layer stacked in sequence from bottom to top; the driving electrode array is composed of a plurality of copper-clad electrodes arranged according to the design requirements of the application scenario of the in vitro diagnostic instrument.

[0022] The present invention constructs three-dimensional structure electrodes, fences, slices, grooves and / or enclosures on the lower substrate through metal addition and / or metal subtraction measures, meeting the design requirements of various application scenarios of in vitro diagnostic instruments. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is a schematic structural diagram of an open microfluidic chip with a groove and a copper block electrode embedded therein.

[0024] Figure 2 It is a schematic diagram of the structure of an open microfluidic chip with three grooves and copper block electrodes according to the present invention.

[0025] Figure 3 It is a schematic diagram of the structure of an open microfluidic chip provided with the fence of the present invention.

[0026] Figure 4 It is a schematic diagram of the structure of an open microfluidic chip provided with the slice of the present invention.

[0027] Figure 5 It is a plan view of an open microfluidic chip provided with the embedded copper block electrode, fence, enclosure and slice of the present invention.

[0028] Figure 6 The invention is a schematic structural diagram of a microfluidic chip having a groove with a copper block electrode embedded therein and consisting of an upper and a lower substrate.

[0029] Figure 7 The invention is a schematic structural diagram of a microfluidic chip having three grooves with copper block electrodes embedded therein and consisting of an upper and lower substrate.

[0030] Figure 8 It is a schematic structural diagram of the microfluidic chip of the present invention provided with the fence and composed of upper and lower substrates.

[0031] Figure 9 It is a schematic structural diagram of the microfluidic chip of the present invention provided with the slice and composed of upper and lower substrates. DETAILED DESCRIPTION

[0032] The following describes an embodiment of the present invention in detail with reference to the accompanying drawings. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and specific operation process. However, the protection scope of the present invention is not limited to the following embodiment.

[0033] It should be noted that, in the present invention, unless otherwise expressly specified or limited, the terms "installed," "connected," and "connected" should be understood in a broad sense. For example, they may refer to fixed, detachable, or integral connections; mechanical or electrical connections; direct or indirect connections through an intermediate medium; and internal communication between two components. Those skilled in the art will understand the specific meanings of the above terms in the present invention based on specific circumstances.

[0034] like Figure 1-4 As shown, the open microfluidic chip composed of the lower substrate is taken as an example to be described in detail:

[0035] The three-dimensional electrode microfluidic chip based on dielectric wetting for in vitro diagnosis of the present invention comprises the following steps:

[0036] Step 1: On a lower insulating substrate 1 provided with a driving electrode array, according to the design requirements of the in vitro diagnostic instrument application scenario, at one or more designated copper-clad plate electrode positions, an embedded copper block electrode 3 with a groove 2 on the upper surface is embedded into the lower insulating substrate 1 through a copper block embedding process (subtractive measure); the groove 2 of the embedded copper block electrode 3 is prepared by an etching process or a mechanical processing process; or a groove 2 with a three-dimensional structure can be directly constructed on the designated copper-clad plate electrode through a metal additive process.

[0037] The driving electrode array is composed of multiple copper-clad electrodes 3.1, which are arranged on the lower insulating substrate 1 according to the design requirements of the in vitro diagnostic instrument application scenario;

[0038] Step 2: coating a dielectric layer 4 on the lower insulating substrate 1 to cover the driving electrode array and the embedded copper block electrode 3;

[0039] Step 3: coating a hydrophobic layer 5 on the dielectric layer 4.

[0040] Beneficially or exemplarily, as Figure 2 As shown, the height of the embedded copper block electrode 3 is greater than the height of the other copper-clad electrodes 3.1 of the driving electrode array; according to the design requirements of the application scenario, two, three or more grooves 2 can be opened on the upper surface of the embedded copper block electrode 3, with no limit on the number, and the depth of the groove 2 is determined according to the design requirements of the application scenario.

[0041] When the droplet 6 (IVD reagent or test droplet or a mixed droplet thereof) is driven to the groove 3.1 of the embedded copper block electrode 3 through dielectric wetting, the droplet 6 can be positioned and fixed in position; at the same time, due to the presence of the groove 3.1, the embedded copper block electrode 3 also helps to cool the droplet 6, increases the contact surface area between the droplet 6 and the embedded copper block electrode 3, accelerates heat transfer, and also helps to cut off the liquid flow of the droplet 6, among other functions.

[0042] Beneficially or exemplarily, as Figure 3 、 5 As shown, according to the design requirements of the application scenario, metal printing ink technology, 3D printing technology, metal deposition technology, laser sintering technology, fused deposition modeling technology or / and lamination manufacturing technology are used to directly construct a fence 7 or enclosure 7.1 with a three-dimensional structure on the specified copper-clad electrode through a metal additive process, and then a dielectric layer is coated on the lower insulating substrate to cover the driving electrode array and the fence 7 or enclosure 7.1.

[0043] Therefore, when the droplet 6 is driven to the fence 7 or the enclosure 7.1 position through the dielectric wetting effect, it prevents the test droplet or other droplets from contacting with the IVD reagent to avoid cross contamination; or prevents the droplet 6 from flowing out of the designated electrode position, and at the same time can slow down the volatilization of the droplet.

[0044] Beneficially or exemplarily, as Figure 4 、 5 As shown, according to the design requirements of the application scenario, in step 2, metal printing ink technology, 3D printing technology, metal deposition technology, laser sintering technology, fused deposition modeling technology or lamination manufacturing technology is used to directly construct a slice 8 with a three-dimensional structure on the specified copper-clad electrode, and then a dielectric layer 4 is coated on the lower insulating substrate to cover the driving electrode array and the slice 8.

[0045] Therefore, when the droplet 6 is driven to the slice 8 position through the dielectric wetting effect, the droplet is split and reassembled.

[0046] like Figure 5 , which is a schematic plan view of an open microfluidic chip constructed according to the method of the present invention and provided with an embedded copper block electrode 3, a fence 7, a barrier 7.1 and a slice 8.

[0047] like Figure 6-9 As shown, it is a schematic diagram of the structure of a microfluidic chip consisting of an upper and a lower substrate. It differs from an open microfluidic chip consisting of a lower substrate only in that an upper substrate consisting of an upper insulating substrate 9, a common electrode 10, and an upper hydrophobic layer 11 stacked in sequence from top to bottom is added. The preparation of the lower substrate is the same as that of the open microfluidic chip and will not be repeated.

Claims

1. A three-dimensional electrode microfluidic chip based on dielectric wetting for in vitro diagnostics, characterized by: The manufacturing of the three-dimensional electrode microfluidic chip includes the following steps: Step 1: On a lower insulating substrate provided with a driving electrode array, according to the design requirements of the in vitro diagnostic instrument application scenario, a copper block electrode with a groove is embedded into the lower insulating substrate at one or more designated copper-clad plate electrode positions using a metal subtractive process; Step 2: coating a dielectric layer on the lower insulating substrate to cover the driving electrode array; Step 3: coating a hydrophobic layer on the dielectric layer.

2. The three-dimensional electrode microfluidic chip based on dielectric wetting for in vitro diagnosis according to claim 1, characterized in that: The step 2 also includes step 2.1, according to the design requirements of the in vitro diagnostic instrument application scenario, directly constructing a fence, slice, groove or / and enclosure with a three-dimensional structure on the specified copper-clad electrode through a metal additive process, and then coating a dielectric layer on the lower insulating substrate to cover the driving electrode array and the fence, slice, groove or / and enclosure.

3. The three-dimensional electrode microfluidic chip based on dielectric wetting for in vitro diagnosis according to claim 2, characterized in that: The metal additive process includes: Metal printing ink technology, 3D printing technology, metal deposition technology, laser sintering technology, fused deposition modeling technology and / or lamination manufacturing technology.

4. The three-dimensional electrode microfluidic chip based on dielectric wetting for in vitro diagnosis according to claim 1 or 2, characterized in that: The groove of the embedded copper block electrode is prepared by an etching process or a mechanical processing process, and the height of the embedded copper block electrode is greater than the heights of other electrodes of the driving electrode array.

5. The three-dimensional electrode microfluidic chip based on dielectric wetting for in vitro diagnosis according to claim 1, characterized in that: The three-dimensional electrode microfluidic chip includes an upper substrate and a lower substrate spaced apart from each other; the upper substrate is composed of an upper insulating substrate, a common electrode, and an upper hydrophobic layer stacked in sequence from top to bottom; the lower substrate is composed of a lower insulating substrate, a driving electrode array, a dielectric layer, and a lower hydrophobic layer stacked in sequence from bottom to top; the driving electrode array is composed of multiple copper-clad electrodes arranged according to the design requirements of the in vitro diagnostic instrument application scenario.

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