Brand-new manufacturing method for combining optical tweezers and digital micro-fluidic chip structure

Abstract

The invention relates to the technical field of micro-fluidic chips and optical tweezers, in particular to a brand new manufacturing method of a structure combining optical tweezers and a digital micro-fluidic chip, and the structure comprises a chip upper substrate and a chip lower substrate; the chip upper substrate and the chip lower substrate are attached and 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 plane treatment; the chip upper substrate comprises a hydrophobic layer, an insulating layer, an electrode layer and a glass layer; liquid crystal is arranged between the chip upper substrate and the chip lower substrate, and the liquid crystal contains cells. The optical tweezers and digital micro-fluidic chip structure and the manufacturing method thereof are combined, so that the reutilization of the photofluidic chip is realized, the cost is reduced, the liquid-phase separation capability of tiny substances in micro-droplets is improved, the problems of liquid-phase separation and fixed-time culture and detection of cells can be solved, and two technologies are applied to the chip and do not conflict with each other.

Description

Technical Field

[0001] The invention relates to the technical field of microfluidic chips and optical tweezers, and in particular to a method for manufacturing a completely new structure combining optical tweezers and a digital microfluidic chip. Background Art

[0002] The core principle of the existing optoelectronic tweezers technology is based on the interaction between light and matter. By focusing the laser beam to generate an optical potential well (light trap), tiny objects can be captured and manipulated. The generation of force can accurately control micro-robot targets with high throughput and high stability in a complex environment where fluid fields, optoelectronic fields, and biological force fields are coupled.

[0003] The existing digital microfluidics technology for droplet separation uses disposable chips, which is expensive, may cause the loss of biological cells due to excessive voltage, and is difficult to achieve accurate separation of tiny substances in droplets, cell liquid phase separation, timed culture and detection. Therefore, we provide a new method for making a chip structure that combines optical tweezers and digital microfluidics. Summary of the invention

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

[0005] To achieve the above object, the present invention provides the following technical solutions:

[0006] A new method for manufacturing a chip structure combining optical tweezers and digital microfluidics, including an upper substrate and a lower substrate;

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

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

[0009] Liquid crystal is arranged between the upper substrate of the chip and the lower substrate of the chip, and the liquid crystal contains cells;

[0010] A laser is provided between the upper chip substrate and the lower chip substrate, and the laser is controlled by the PC end;

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

[0012] The present invention is further configured as follows: the glass layer of the substrate on the chip uses a transparent material, and the thickness is 0.55um to 1.1um; an ITO layer or other conductive coating is arranged on the glass layer, and the manufacturing method can be front-side coating, etching the corresponding image, or photolithography, development, sputtering and degumming. The ITO coating pattern is a figure of uneven size and various shapes.

[0013] The present invention is further configured as follows: the mixed layer on one side of the glass layer on the substrate on the chip is made by mixing the insulating layer with the corresponding electrode layer doped in the insulating layer, and the thickness of the mixed layer of the substrate on the chip, which is made by mixing the insulating layer and the electrode layer, is 0.2um to 0.5um.

[0014] The present invention is further configured as follows: a hydrophobic layer is provided on the side of the mixed layer formed by mixing the insulating layer and the electrode layer on the substrate on the chip away from the glass layer, and the thickness of the hydrophobic layer is 0.3um to 1.2um.

[0015] The present invention is further configured as follows: the difference between the on-chip substrate and the under-chip substrate is that a metal layer is provided on the under-chip substrate between the hydrophobic layer of the on-chip substrate and the mixed layer of the insulating layer and the electrode layer, and the function of the metal layer is to make it easier for the laser to find the location of the laser point after the laser is shot down.

[0016] The present invention is further configured as follows: the thickness of the metal layer in the substrate under the chip is 0.3um to 1um; the metal layer is arranged correspondingly following the wavelength of the laser, and the material of the metal layer is usually chromium.

[0017] The present invention is further configured as follows: the layer height between the chip upper substrate and the chip lower substrate is fixedly spaced 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.

[0018] The present invention is further configured as follows: after the upper substrate and the lower substrate of the chip are set in height, the liquid crystal balls with cells can be nested in the flow channel between the upper substrate and the lower substrate of the chip, and then the laser can be controlled by using the PC end.

[0019] The present invention is further configured such that: the laser can extract cells from the liquid crystal, and then extract the cells from the liquid crystal by allowing the cells to be adsorbed on the laser head, and then take the extracted liquid crystal out of the flow channels in the chip upper substrate and the chip lower substrate.

[0020] Beneficial Effects

[0021] Compared with the known public technology, the technical solution provided by the present invention has the following beneficial effects:

[0022] 1. The present invention combines optical tweezers with a digital microfluidic chip structure and a manufacturing method thereof to achieve the reuse of the photocurrent microfluidic chip, reduce costs, and improve the liquid phase separation capability of tiny substances in microdroplets, which can solve the problems of cell liquid phase separation and timed culture and detection. The two technologies are used on the chip without conflicting with each other.

[0023] 2. The present invention achieves high precision and high efficiency in cell extraction and processing by cleverly combining the optical tweezers functional area and the digital microfluidics functional area. The bonding of the upper substrate and the lower substrate of the chip forms two functional areas. The setting of the laser and the help of the metal layer enable the laser to accurately irradiate the cells in the liquid crystal, starting the optical tweezers to extract cells. The precise positioning of the optical tweezers area ensures the accuracy of cell extraction, avoids cell damage caused by operational errors, and improves the success rate of the extraction process.

[0024] 3. The present invention effectively ensures the layer height and alignment between the upper substrate and the lower substrate of the chip and maintains the precise chip structure through the fixing design of UV glue and small balls. The fixed chip can be embedded with liquid crystal balls to carry cells and perform fine operations, ensuring that the laser can act on the cells accurately without being affected by layer height errors, thereby ensuring the accuracy of laser extraction and cell integrity. This design greatly improves the stability of the cell extraction process and the controllability of the operation, making the entire cell extraction and processing process more efficient and repeatable. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 A schematic diagram of the arrangement of an upper substrate and a lower substrate of a chip in a method for manufacturing a new chip structure combining optical tweezers and a digital microfluidic chip according to the present invention;

[0026] Figure 2 A schematic diagram of a substrate on a chip of a new method for manufacturing a chip structure combining optical tweezers and digital microfluidic control;

[0027] Figure 3 A schematic diagram of a chip lower substrate of a new method for manufacturing a chip structure combining optical tweezers and digital microfluidic control;

[0028] Figure 4 A schematic diagram of a chip upper substrate and a chip lower substrate in a new method for manufacturing a chip structure combining optical tweezers and digital microfluidic control according to the present invention;

[0029] Figure 5 A schematic diagram of a laser for a novel method of manufacturing a combined optical tweezers and digital microfluidic chip structure according to the present invention;

[0030] Figure 6The schematic diagram of the circuit of a new manufacturing method combining optical tweezers and digital microfluidic chip structure of the present invention.

[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, technical solutions and beneficial effects to be solved by the present invention clearer, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the described embodiments are only part of the embodiments of the present application, rather than all the embodiments, and the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in the field without making creative work are within the scope of protection of this application.

[0034] It should be further explained that the drawings and implementation modes of the present invention mainly describe the concept of the present invention. On the basis of this concept, the specific forms and settings of some connection relationships, positional relationships, power mechanisms, power supply systems, hydraulic systems and control systems may not be fully described. However, on the premise that those skilled in the art understand the concept of the present invention, those skilled in the art can implement the above-mentioned specific forms and settings in a well-known manner.

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

[0036] The directional words "inside and outside" refer to the inside and outside relative to the outline of each component itself. The directions or positional relationships indicated by the terms "length", "width", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside" and "outside" are based on the directions or positional relationships shown in the drawings and are only for the convenience of describing the present invention and simplifying the description. They do not indicate or imply that the device or element referred to must have a specific direction, be constructed and operated in a specific direction, and therefore should not be understood as limiting the present invention.

[0037] For ease of description, spatially relative terms such as "above", "above", "on the upper surface of", "above", etc. may be used here to describe the spatial positional relationship between a device or feature and other devices or features as shown in the figure. It should be understood that spatially relative terms are intended to include different orientations of the device in use or operation in addition to the orientation described in the figure. For example, if the device in the accompanying drawings is inverted, the device described as "above other devices or structures" or "above other devices or structures" will be positioned as "below other devices or structures" or "below other devices or structures". Thus, the exemplary term "above" may include both "above" and "below". The device may also be positioned in other different ways, and the spatially relative descriptions used here are interpreted accordingly.

[0038] The terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, "multiple" means two or more, and "several" means one or more, unless otherwise clearly and specifically defined.

[0039] A novel method for manufacturing a structure combining optical tweezers and a digital microfluidic chip provided by the present invention is now described.

[0040] Example 1

[0041] like Figure 1-6 As shown, the present invention provides a technical solution: a method for manufacturing a new structure combining optical tweezers and digital microfluidic chip, including a chip upper substrate and a chip lower substrate; characterized in that:

[0042] The upper substrate of the chip and the lower substrate of the chip are bonded together to form an optical tweezers functional area and a digital microfluidics functional area, and the optical tweezers functional area and the digital microfluidics functional area complete plane processing;

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

[0044] Liquid crystal is arranged between the upper substrate of the chip and the lower substrate of the chip, and the liquid crystal contains cells;

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

[0046] The substrate under the chip 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 substrate on the chip is made of transparent material, and the thickness is 0.55um to 1.1um. An ITO coating or other conductive coating is arranged on the glass layer 5. The manufacturing method can be front coating, etching the corresponding image, or photolithography, development, sputtering and degumming. The ITO coating pattern is uneven in size and various in shape.

[0048] The mixed layer on the glass layer 5 side of the chip substrate is made by doping the insulating layer 3 with the corresponding electrode layer 4, and the thickness of the mixed layer of the chip substrate made by mixing the insulating layer 3 and the electrode layer 4 is 0.2um to 0.5um;

[0049] A hydrophobic layer 1 is provided on the side of the mixed layer made of 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 0.3um to 1.2um;

[0050] The difference between the chip-on-chip substrate and the chip-off-chip substrate is that the chip-off-chip substrate is provided with a metal layer 2 between the hydrophobic layer 1 of the chip-on-chip 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 it is shot down;

[0051] The thickness of the metal layer in the substrate under the chip is 0.3um to 1um; the metal layer 2 is arranged correspondingly following the wavelength of the laser, and the material of the metal layer 2 is usually chromium;

[0052] 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 ball, and then the small ball with UV glue is embedded between the chip upper substrate and the chip lower substrate to fix the height;

[0053] After the chip substrate and the chip substrate are set at a certain height, the liquid crystal balls with cells can be embedded in the flow channel between the chip substrate and the chip substrate, and then the laser can be controlled by using the PC end;

[0054] The laser can extract the cells in the liquid crystal, and then extract them from the liquid crystal by allowing the cells to be adsorbed on the laser head and taking the extracted liquid crystal out of the flow channels in the chip substrate and the chip substrate.

[0055] In this embodiment: by bonding the upper substrate of the chip with the lower substrate of the chip, an optical tweezers functional area and a digital microfluidics functional area are formed, cells are entrained between the upper substrate of the chip and the lower substrate of the chip through a liquid crystal layer and controlled by a laser, and the laser beam of the laser is accurately irradiated to the cells in the liquid crystal with the help of the metal layer on the lower substrate of the chip, and the cells are extracted by the optical tweezers, UV glue and small balls fix the chip spacing to ensure accurate layer height, and the liquid crystal balls with cells are embedded in the flow channel of the chip, and the laser is controlled by the PC to perform cell extraction operations, and the liquid in the liquid crystal flow channel is taken out of the chip to complete the extraction and processing of the cells.

[0056] The present invention,

[0057] First, the chip substrate (including hydrophobic layer 1, insulating layer 3, electrode layer 4, glass layer 5) and the chip substrate (including hydrophobic layer 1, metal layer 2, insulating layer 3, electrode layer 4, glass layer 5) are bonded to form the optical tweezers functional area and the digital microfluidics functional area. The two functional areas are planarly processed, and liquid crystal (including cells) is sandwiched between the chip substrate and the chip substrate. The laser is set between the chip substrate and the chip substrate, and the laser is controlled by the PC end.

[0058] The laser is installed between the chip upper substrate and the chip lower substrate, and with the help of metal layer 2, the laser beam can accurately irradiate the cells in the liquid crystal. The design of metal layer 2 helps to locate the laser point, ensuring that the laser can accurately act on the cells, thereby starting the optical tweezers effect to extract cells. The wavelength of the laser and the layout of the metal layer are coordinated, so that the laser can accurately control the extraction of cells.

[0059] UV glue and small balls are used to fix the layer height between the chip upper substrate and the chip lower substrate. The small balls are wrapped in UV glue to ensure the precise spacing and alignment between the chips. This design ensures the fixation of the chips, allowing the laser to accurately act on the cells in the liquid crystal, avoiding inaccurate operation caused by layer height errors.

[0060] After the chip layer height is fixed, the liquid crystal balls containing cells are embedded in the flow channel between the upper substrate and the lower substrate of the chip. The laser is controlled by the PC to perform cell extraction operations. The laser uses optical tweezers to adsorb the cells in the liquid crystal to the laser head, completing the operation of extracting cells from the liquid crystal.

[0061] After cell extraction, the laser adsorbs the extracted cells on its head to complete the cell extraction and processing. The liquid in the liquid crystal channel is taken out of the chip to ensure the completion of the entire cell extraction and processing process.

[0062] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

[0063] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present application. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, it indicates the presence of features, steps, operations, devices, components and / or combinations thereof.

[0064] Unless otherwise specifically stated, the relative arrangement, numerical expressions and numerical values ​​of the parts and steps described in these embodiments do not limit the scope of the present application. At the same time, it should be understood that, for ease of description, the sizes of the various parts shown in the drawings are not drawn according to the actual proportional relationship. The technology, methods and equipment known to ordinary technicians in the relevant field may not be discussed in detail, but in appropriate cases, the technology, methods and equipment should be regarded as a part of the authorization specification. In all examples shown and discussed here, any specific value should be interpreted as being merely exemplary, rather than as a limitation. Therefore, other examples of exemplary embodiments may have different values. It should be noted that similar reference numerals and letters represent similar items in the following drawings, so once a certain item is defined in an accompanying drawing, it does not need to be further discussed in subsequent drawings.

Claims

1. A new method for manufacturing a structure combining optical tweezers and digital microfluidic chip, characterized in that: The invention comprises a chip upper substrate and a chip lower substrate; the characteristics are: The chip upper substrate and the chip lower substrate are laminated to form an optical tweezers functional area and a digital microfluidics functional area, and the optical tweezers functional area and the digital microfluidics functional area are plane-processed; 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 arranged between the upper substrate of the chip and the lower substrate of the chip, and the liquid crystal contains cells; A laser is provided between the upper substrate and the lower substrate of the chip, and the laser is controlled by the PC end; The chip substrate comprises a hydrophobic layer (1), a metal layer (2), an insulating layer (3), an electrode layer (4) and a glass layer (5).

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

3. The method for manufacturing a 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 um to 0.5 um.

4. The method for manufacturing a 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 an insulating layer (3) and an electrode layer (4) on the chip substrate away from the glass layer (5), and the thickness of the hydrophobic layer (1) is 0.3 um to 1.2 um.

5. The method for manufacturing a novel structure combining optical tweezers and digital microfluidic chip according to claim 1, characterized in that: 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 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 method for manufacturing a novel structure combining optical tweezers and digital microfluidic chip according to claim 1, characterized in that: The thickness of the metal layer in the substrate under the chip is 0.3um to 1um; the metal layer (2) is arranged correspondingly following the wavelength of the laser, and the material of the metal layer (2) is usually chromium.

7. The method for manufacturing a novel structure combining optical tweezers and digital microfluidic chip according to claim 1, characterized in that: 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.

8. The method for manufacturing a novel structure combining optical tweezers and digital microfluidic chip according to claim 1, characterized in that: After the upper substrate and the lower substrate of the chip are fixed at a certain height, the liquid crystal balls with cells can be embedded in the flow channel between the upper substrate and the lower substrate of the chip, and then the laser can be controlled by using the PC end.

9. The method for manufacturing a novel structure combining optical tweezers and digital microfluidic chip according to claim 1, characterized in that: The laser can extract cells from the liquid crystal, and then extract the cells from the liquid crystal by allowing the cells to be adsorbed on the laser head, and then take the extracted liquid crystal out of the flow channels in the chip substrate and the chip substrate.

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