A new method for fabricating a combination of optical tweezers and digital microfluidic chip structure

Abstract

The application relates to the technical field of microfluidic chips and optical tweezers, in particular to a novel combination of an optical tweezers and a digital microfluidic chip structure manufacturing method, which comprises an upper chip substrate and a lower chip substrate; the upper chip substrate and the lower chip substrate are matched to form an optical tweezers functional area and a digital microfluidic functional area, and the optical tweezers functional area and the digital microfluidic functional area complete planar processing; the upper chip substrate comprises a hydrophobic layer, an insulating layer, an electrode layer and a glass layer; liquid crystal is arranged between the upper chip substrate and the lower chip substrate, and the liquid crystal contains cells. The application combines the optical tweezers and the digital microfluidic chip structure and the manufacturing method thereof, so that the photoelectric current control chip can be reused, the cost is reduced, the liquid phase separation capacity of small substances in microdroplets is improved, the problems of cell liquid phase separation, fixed time culture and detection can be solved, and the two technologies are not conflicted on the chip.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of microfluidic chips and optical tweezers, and particularly relates to a novel manufacturing method combining optical tweezers and digital microfluidic chip structure. BACKGROUND

[0002] The core principle of the existing photoelectric tweezers technology is based on the interaction between light and matter. An optical potential well (optical trap) is generated by focusing a laser beam, thereby realizing the capture and manipulation of micro objects. The force generation can realize high-throughput and high-stability precise manipulation of micro robots in a complex environment coupled by fluid field, photoelectric field and biological force field.

[0003] In the existing digital microfluidic technology for realizing droplet separation, the chip is disposable, which has the problem of high cost. The voltage may be too large to cause loss of biological cells, and it is difficult to realize precise separation of micro substances in the droplet. The problems of cell liquid phase separation, timed culture and detection can be realized. Therefore, we provide a novel manufacturing method combining optical tweezers and digital microfluidic chip structure. SUMMARY

[0004] In view of the above-mentioned shortcomings of the prior art, the first purpose of the present application is to provide a novel manufacturing method combining optical tweezers and digital microfluidic chip structure to solve the problems in the background art.

[0005] To achieve the above-mentioned purpose, the present application provides the following technical scheme:

[0006] A novel manufacturing method combining optical tweezers and digital microfluidic chip structure comprises an upper chip substrate and a lower chip substrate;

[0007] The upper chip substrate and the lower chip substrate are matched to form an optical tweezers functional area and a digital microfluidic functional area, and the optical tweezers functional area and the digital microfluidic functional area complete planar processing;

[0008] The upper chip substrate comprises a hydrophobic layer, an insulating layer, an electrode layer and a glass layer;

[0009] The upper chip substrate and the lower chip substrate are provided with liquid crystals, and the liquid crystals contain cells;

[0010] The upper chip substrate and the lower chip substrate are provided with a laser, and the laser is controlled by a PC end;

[0011] The lower chip substrate comprises a hydrophobic layer, a metal layer, an insulating layer, an electrode layer and a glass layer.

[0012] The chip-on-substrate glass layer uses a transparent material, and the thickness is 0.55-1.1 microns; an ITO layer or other conductive coating layer is arranged on the glass layer, and the manufacturing method can be front plating, etching of a corresponding image, or photolithography development and sputtering of an ITO coating pattern into a size-uniform and shape-different pattern.

[0013] The chip-on-substrate glass layer is mixed by doping a corresponding electrode layer in an insulating layer, the chip-on-substrate is mixed by the insulating layer and the electrode layer, and the thickness of the mixed layer is 0.2-0.5 microns.

[0014] The mixed layer of the chip-on-substrate is mixed by the insulating layer and the electrode layer, and a hydrophobic layer is arranged on the side away from the glass layer, the thickness of the hydrophobic layer is 0.3-1.2 microns.

[0015] The chip-on-substrate and the chip-off-substrate differ in that the chip-off-substrate is provided with a metal layer between the hydrophobic layer and the mixed layer of the insulating layer and the electrode layer of the chip-on-substrate, and the metal layer is used to facilitate the finding of the laser point after the laser is turned off.

[0016] The thickness of the metal layer in the chip-off-substrate is 0.3-1 micron, the metal layer is arranged according to the wavelength of the laser, and the material of the metal layer is usually chromium.

[0017] The height between the chip-on-substrate and the chip-off-substrate is fixed by using UV glue and small balls, the UV glue is fixed and limited by being wrapped on the outer surface of the small balls, and then the small balls with the UV glue are embedded between the chip-on-substrate and the chip-off-substrate to fix the height.

[0018] After the height of the chip-on-substrate and the chip-off-substrate is fixed, the liquid crystal balls with cells are embedded into the flow channel between the chip-on-substrate and the chip-off-substrate, and then the laser is controlled by using a PC terminal.

[0019] The laser can extract the cells in the liquid crystal, the cells are adsorbed on the head of the laser to be extracted from the liquid crystal, and the liquid crystal after the extraction is taken out of the flow channel between the chip-on-substrate and the chip-off-substrate.

[0020] Advantages

[0021] Compared with the known prior art, the technical scheme provided by the present application has the following advantages:

[0022] 1. The application combines optical tweezers and digital microfluidic chip structure and its manufacturing method to realize the reuse of optoelectronic current control chip, reduce the cost, and improve the liquid phase separation ability of small substances in microdroplets, which can solve the problems of cell liquid phase separation, time culture and detection, and the two technologies are not in conflict with each other on the chip.

[0023] 2. The application combines the optical tweezers functional area and the digital microfluidic functional area to achieve high precision and high efficiency of cell extraction and processing, the chip-on-substrate and the chip-under-substrate form two functional areas, the setting of the laser and the help of the metal layer make the laser can accurately irradiate the cells in the liquid crystal, start the optical tweezers effect to extract the cells, and the accurate positioning of the optical tweezers area ensures the accuracy of cell extraction, avoids cell damage caused by operation error, and improves the success rate of the extraction process.

[0024] 3. The application fixes the chip-on-substrate and the chip-under-substrate through UV glue and small balls, effectively ensures the layer height and alignment between the chip-on-substrate and the chip-under-substrate, maintains the accurate chip structure, the fixed chip can be embedded in the liquid crystal small ball, carries the cells and performs fine operation, ensures that the laser can accurately act on the cells, is not affected by the layer height error, ensures the precision of laser extraction and the integrity of cells, this design greatly improves the stability and controllability of the cell extraction process, makes the whole cell extraction and processing process more efficient and repeatable. BRIEF DESCRIPTION OF DRAWINGS

[0025] Figure 1 The chip-on-substrate and the chip-under-substrate arrangement schematic diagram of the manufacturing method of the new combination of optical tweezers and digital microfluidic chip structure of the application;

[0026] Figure 2 The chip-on-substrate schematic diagram of the manufacturing method of the new combination of optical tweezers and digital microfluidic chip structure of the application;

[0027] Figure 3 The chip-under-substrate schematic diagram of the manufacturing method of the new combination of optical tweezers and digital microfluidic chip structure of the application;

[0028] Figure 4 The height between the chip-on-substrate and the chip-under-substrate schematic diagram of the manufacturing method of the new combination of optical tweezers and digital microfluidic chip structure of the application;

[0029] Figure 5 The laser schematic diagram of the manufacturing method of the new combination of optical tweezers and digital microfluidic chip structure of the application;

[0030] Figure 6A schematic diagram of a new combined optical tweezers and digital microfluidic chip structure manufacturing method according to the present application.

[0031] Legend:

[0032] 1, hydrophobic layer; 2, metal layer; 3, insulating layer; 4, electrode layer; 5, glass layer. DETAILED DESCRIPTION

[0033] In order to make the technical problems to be solved by the present application, technical solutions and beneficial effects more clear and explicit, the present application will be further described in detail below in combination with the drawings and examples. It should be understood that the described examples are only a part of the embodiments of the present application, not all the embodiments. The specific examples described herein are only used to explain the present application, and are not used to limit the present application. Based on the examples in the present application, all other examples obtained by those skilled in the art without making creative efforts fall within the scope of protection of the present application.

[0034] It should be further pointed out that the drawings and embodiments of the present application mainly describe and explain the concept of the present application. On the basis of the concept, the specific forms and settings of some connection relationships, position relationships, power mechanisms, power supply systems, hydraulic systems and control systems may not be completely described, but those skilled in the art can realize the above-mentioned specific forms and settings by using well-known ways on the premise of understanding the concept of the present application.

[0035] When an element is referred to as being "fixed to" or "set to" another element, it can be directly on the other element or indirectly on the other element. When an element is referred to as being "connected to" another element, it can be directly connected to the other element or indirectly connected to the other element.

[0036] The terms "inner, outer" refer to the inner and outer relative to the contour of each component itself. The terms "length", "width", "upper", "lower", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer" and the like indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only used to facilitate the description of the present application and simplify the description, and do not indicate or imply that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as a limitation on the present application.

[0037] For purposes of the description hereinafter, spatially relative terms, such as "above", "below", "up", "down", "between", "within", "left", "right", "rear", "front", "upper", "lower", "horizontal", "vertical", "above", "below", "on", "under", "in", "above", "below", "over", "under" and the like, can be used where appropriate to describe the relative location or orientation of one component or feature to another in the drawings. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientations depicted in the figures. For example, if a device in the figures is inverted, then a component or feature that is described as "above" or "over" another component or feature would then be oriented "below" or "under" the other component or feature. Thus, the exemplary term "above" can encompass both an orientation of above and below. The device can be otherwise oriented (e.g., rotated 90 degrees, inverted, etc.) and the spatially relative descriptors used herein interpreted accordingly.

[0038] The terms "first", "second", "third", etc. are used only for descriptive purposes and should not be construed as implying or suggesting relative importance or an indicated number of technical features. Thus, the features defined with "first", "second" can include one or more of the features explicitly or implicitly. In the description of the present application, the meaning of "multiple" is two or more, and the meaning of "several" is one or more, unless otherwise explicitly specified.

[0039] Now a new combination of optical tweezers and digital microfluidic chip structure manufacturing method provided by the present application is described.

[0040] Example 1

[0041] As Figures 1-6 shown, the present application provides a technical solution: a new combination of optical tweezers and digital microfluidic chip structure manufacturing method, including chip on substrate and chip on substrate; characterized in that:

[0042] The chip on substrate and the chip on substrate are matched to form an optical tweezers functional area and a digital microfluidic functional area, and the optical tweezers functional area and the digital microfluidic functional area complete planar processing;

[0043] The chip on substrate includes a hydrophobic layer 1, an insulating layer 3, an electrode layer 4 and a glass layer 5;

[0044] The chip on substrate and the chip on substrate are matched to form an optical tweezers functional area and a digital microfluidic functional area, and the optical tweezers functional area and the digital microfluidic functional area complete planar processing;

[0045] A laser is provided between the chip on substrate and the chip on substrate, and the laser is controlled by the PC end;

[0046] The chip on substrate includes a hydrophobic layer 1, a metal layer 2, an insulating layer 3, an electrode layer 4 and a glass layer 5;

[0047] The glass layer 5 of the on-chip substrate uses a transparent material, and the thickness is 0.55 μm-1.1 μm; the ITO coating or other conductive coating is arranged on the glass layer 5, and the manufacturing method can be front plating, etching of the corresponding image, or photolithography development and sputtering of the ITO coating pattern to be a size-uniform and shape-different pattern;

[0048] The mixed layer on one side of the glass layer 5 of the on-chip substrate is mixed by doping the corresponding electrode layer 4 in the insulating layer 3, and the mixed layer of the on-chip substrate mixed by the insulating layer 3 and the electrode layer 4 has a thickness of 0.2 μm-0.5 μm;

[0049] The mixed layer mixed by the insulating layer 3 and the electrode layer 4 on the on-chip substrate is attached to the hydrophobic layer 1 away from the glass layer 5, and the thickness of the hydrophobic layer 1 is 0.3 μm-1.2 μm;

[0050] The difference between the on-chip substrate and the off-chip substrate is that the off-chip substrate is provided with a metal layer 2 between the hydrophobic layer 1 of the on-chip substrate and the mixed layer of the insulating layer 3 and the electrode layer 4, and the metal layer 2 is used to make it more convenient to find the position of the laser spot after the laser is turned off;

[0051] The thickness of the metal layer in the off-chip substrate is 0.3 μm-1 μm; the metal layer 2 is arranged according to the wavelength of the laser, and the material of the metal layer 2 is usually chromium;

[0052] The height of the layers between the on-chip substrate and the off-chip substrate is fixed by using UV glue and small balls, the UV glue is fixed and limited by wrapping the outer surface of the small balls, and then the small balls with UV glue are embedded between the on-chip substrate and the off-chip substrate to fix the height;

[0053] After the height of the on-chip substrate and the off-chip substrate is fixed, the liquid crystal balls with cells can be nested in the flow channel between the on-chip substrate and the off-chip substrate, and then the laser is controlled by using the PC end;

[0054] The laser can extract the cells in the liquid crystal, then the cells are adsorbed on the head of the laser to extract them from the liquid crystal, and the liquid crystal after the extraction is taken out of the flow channel in the on-chip substrate and the off-chip substrate.

[0055] In this embodiment: by adhering the on-chip substrate and the off-chip substrate, the optical tweezer functional area and the digital microfluidic functional area are formed, the cells are entrained between the on-chip substrate and the off-chip substrate through the liquid crystal layer, and the laser is controlled, the laser beam of the laser is precisely irradiated to the cells in the liquid crystal with the help of the metal layer on the off-chip substrate, the cells are extracted through the optical tweezer effect, the UV glue and the small ball fix the distance between the chips, the precise layer height is ensured, the liquid crystal small ball with cells is embedded into the flow channel of the chip, the laser is controlled through the PC end to extract the cells, the liquid in the liquid crystal flow channel is taken out of the chip, and the extraction and processing of the cells are completed.

[0056] The present application,

[0057] Firstly, the on-chip substrate (including a hydrophobic layer 1, an insulating layer 3, an electrode layer 4 and a glass layer 5) is adhered to the off-chip substrate (including a hydrophobic layer 1, a metal layer 2, an insulating layer 3, an electrode layer 4 and a glass layer 5) to form an optical tweezer functional area and a digital microfluidic functional area. The two functional areas complete planar processing, the liquid crystal (containing cells) is entrained between the on-chip substrate and the off-chip substrate, the laser is arranged between the on-chip substrate and the off-chip substrate, and the laser is controlled by the PC end.

[0058] The laser is installed between the on-chip substrate and the off-chip substrate, and the laser beam can be precisely irradiated to the cells in the liquid crystal with the help of the metal layer 2. The design of the metal layer 2 helps to position the laser spot and ensure that the laser can accurately act on the cells, so as to start the optical tweezer effect to extract the cells. The wavelength of the laser and the layout of the metal layer cooperate to enable the laser to accurately control the extraction of the cells.

[0059] The UV glue and the small ball are used to fix the layer height between the on-chip substrate and the off-chip substrate. The small ball is wrapped in the UV glue and is used to ensure the precise distance and alignment between the chips. This design ensures the fixation of the chips, so that the laser can accurately act on the cells in the liquid crystal and avoid inaccurate operation caused by layer height error.

[0060] After the layer height of the chip is fixed, the liquid crystal small ball containing cells is embedded into the flow channel between the on-chip substrate and the off-chip substrate, the laser is controlled by the PC end to extract the cells, the laser adsorbs the cells in the liquid crystal to the head of the laser through the optical tweezer effect, and the operation of extracting the cells from the liquid crystal is completed.

[0061] After the cells are extracted, the laser adsorbs the extracted cells to the head of the laser, the extraction and processing of the cells are completed, the liquid in the liquid crystal flow channel is taken out of the chip, and the whole process of cell extraction and processing is completed.

[0062] The above merely describes preferred embodiments of the present application, and is not intended to limit the present application. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present application shall fall within the scope of protection of the present application.

[0063] It is to be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments according to the present application. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and / or "comprising," when used in this specification, specify the presence of stated features, steps, operations, devices, components and / or combinations thereof, but do not preclude the presence or addition of one or more other features, steps, operations, devices, components and / or combinations thereof.

[0064] The relative arrangement of parts and steps, numerical expressions, and numerical values set forth in these embodiments are not limiting to the scope of the present application unless specifically stated otherwise. It should be understood that the dimensions of the various parts shown in the drawings are not necessarily to scale as the drawings are shown for purposes of convenience and clarity. Techniques, methods, and apparatus known to those of ordinary skill in the relevant art can not be discussed in detail herein. However, the techniques, methods, and apparatus are considered to be part of the scope of the present application. In all examples shown and discussed herein, any specific value is to be interpreted as merely illustrative and not restrictive. Thus, other examples of the example embodiments can have different values. It is noted that like numbers and letters refer to like elements throughout the several views of the drawings and, as such, no further discussion with regard thereto is deemed necessary.

Claims

1. A new structure combining optical tweezers and digital microfluidic chip, characterized by: including an upper chip substrate and a lower chip substrate; The upper chip substrate and the lower chip substrate are laminated to form an optical tweezers functional area and a digital microfluidic functional area, and the optical tweezers functional area and the digital microfluidic functional area complete plane processing; The on-chip substrate comprises a hydrophobic layer (1), an insulating layer (3), an electrode layer (4) and a glass layer (5); Liquid crystal is provided between the upper chip substrate and the lower chip substrate, and cells are contained in the liquid crystal; A laser is provided between the upper chip substrate and the lower chip substrate, and the laser is controlled by the PC end; The chip lower substrate comprises a hydrophobic layer (1), a metal layer (2), an insulating layer (3), an electrode layer (4) and a glass layer (5); The thickness of the metal layer in the chip lower substrate is 0.3 μm to 1 μm; the corresponding metal layer (2) is arranged following the wavelength of the laser, and the material of the metal layer (2) is chromium; The layer height between the chip upper substrate and the chip lower substrate is fixed by using UV glue and small balls. The UV glue is fixed and limited by wrapping the outer surface of the small balls, and then the small balls with UV glue are embedded between the chip upper substrate and the chip lower substrate to fix the height.

2. A novel structure combining optical tweezers and digital microfluidic chip according to claim 1, characterized in that: The glass layer (5) of the substrate on the chip is made of transparent material and has a thickness of 0.55 μm to 1.1 μm. An ITO layer or other conductive layer is arranged on the glass layer (5). The manufacturing method is front coating, etching the corresponding image, or photolithography, development, sputtering and degumming. The ITO layer pattern is a pattern with uneven size and various shapes.

3. The novel structure combining optical tweezers and digital microfluidic chip according to claim 2, characterized in that: The mixed layer on one side of the glass layer (5) on the chip substrate is made by doping the insulating layer (3) with a corresponding electrode layer (4) for mixing. The thickness of the mixed layer of the chip substrate made by mixing the insulating layer (3) and the electrode layer (4) is 0.2 μm to 0.5 μm.

4. The novel structure combining optical tweezers and digital microfluidic chip according to claim 3, characterized in that: A hydrophobic layer (1) is provided on the side of the mixed layer formed by mixing the insulating layer (3) and the electrode layer (4) on the chip substrate away from the glass layer (5), and the thickness of the hydrophobic layer (1) is 0.3 μm to 1.2 μm.

5. The novel structure combining optical tweezers and digital microfluidic chip according to claim 1, characterized in that: The difference between the chip-on substrate and the chip-off substrate is that the chip-off substrate is provided with a metal layer (2) between the hydrophobic layer (1) of the chip-on substrate and the mixed layer of the insulating layer (3) and the electrode layer (4). The function of the metal layer (2) is to make it easier for the laser to find the location of the laser point after the laser is shot down.

6. The novel structure combining optical tweezers and digital microfluidic chip according to claim 1, characterized in that: After the chip substrate and the chip lower substrate are fixed at a certain height, the liquid crystal balls with cells are nested in the flow channel between the chip substrate and the chip lower substrate, and then the laser is controlled by using the PC end.

7. The novel structure combining optical tweezers and digital microfluidic chip according to claim 1, characterized in that: The laser extracts cells from the liquid crystal, and then extracts the cells from the liquid crystal by allowing the cells to be adsorbed on the laser head, and takes the extracted liquid crystal out of the flow channels in the chip upper substrate and the chip lower substrate.

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