Fluid element, package, drug delivery device, biomolecular testing device, and method for forming a fluid channel.

Abstract

To provide a flow channel element that can be manufactured with a simple and minimal number of steps. [Solution] The flow channel element comprises a substrate, a film formed on the substrate, and a modified portion of the film that extends linearly along the substrate. A first flow channel is formed between the substrate and the film, which are peeled off on both sides of the modified portion, along the modified portion.

Description

Technical Field

[0001] The present disclosure relates to a flow path element, a package, a drug delivery device, a biomolecule inspection device, and a flow path formation method.

Background Art

[0002] Methods for manufacturing flow path elements (also referred to as "flow path devices" or "flow path structures") having fine flow paths such as micro flow path elements and nano flow path elements have been proposed (see, for example, Non-Patent Documents 1-3 and Patent Document 1). Flow path elements are expected to be applied in a wide range of fields such as analysis of biomolecules and synthesis of minute amounts of substances. In particular, in the field of nanofluidics, focused ion beam (FIB), electron beam lithography (EBL), ultraviolet (UV) and deep ultraviolet lithography, etc. are often used to form flow path structures with dimensions in the range of several tens to several hundreds of nanometers. Furthermore, direct laser writing of nanochannels using lasers such as femtosecond lasers is expected as a method for forming extremely fine flow paths (see, for example, Non-Patent Documents 2 and 3).

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Non-Patent Documents

[0004]

Non-Patent Document 1

[0005] However, there are areas for improvement in conventional methods for manufacturing fluidic elements. For example, in conventional methods, a pattern of a fluid channel with an open top is first formed on the substrate. Processing methods such as electron beam lithography or focused ion beam milling are used to form this pattern. Photolithography and etching are used to form wider channels. After forming channels with open tops on the substrate in this way, a process is carried out to seal the formed channels. As a method for sealing the channels, for example, a method such as anodic bonding, in which a glass plate is directly bonded to the substrate, is employed (see, for example, Non-Patent Document 1 and Patent Document 1). Thus, the manufacturing of fluidic elements is complex and requires many steps, and therefore has the problem of being costly.

[0006] Therefore, the purpose of this disclosure, with regard to these points, is to provide a method for manufacturing a flow channel element in a simple and few-step process, as well as a flow channel element manufactured by said method, and an apparatus using said flow channel element, such as a package, a drug delivery apparatus, and a biomolecular testing apparatus. [Means for solving the problem]

[0007] The key points of this disclosure are as follows: [1] A flow channel element comprising a substrate, a film formed on the substrate, and a modified portion of the film that extends linearly along the substrate, wherein a first flow channel is formed between the substrate and the film, with the modified portion being peeled off on both sides of the modified portion. [2] The fluid channel element according to [1], wherein the altered portion has a lower mass density than the film. [3] The fluid element according to [1] or [2], wherein the film includes a layer on the substrate side that has a higher absorption rate of light of a predetermined wavelength than other parts of the film. [4] The substrate is a glass substrate, as described in any of [1] to [3]. [5] The flow channel element according to any one of [1] to [4], wherein the film is a diamond film. [6] The fluid element according to [5], wherein the altered portion comprises non-diamond carbon. [7] The flow channel element according to any one of [1] to [6], wherein the thickness of the film is in the range of 145 nm to 1000 nm. [8] The flow channel element according to any one of [1] to [7], wherein the width of the altered portion is in the range of 0.5 μm to 5 μm. [9] The channel element according to any one of [1] to [8], wherein the dimension of the first channel perpendicular to the substrate is in the range of 5 nm to 200 nm.

[10] The flow channel element according to any one of [1] to [9], wherein the width of the first flow channel in the direction along the substrate is in the range of 1 μm to 4 μm.

[11] A flow channel element according to any one of [1] to

[10] , further comprising two second flow channels having a larger dimension than the first flow channel, each connected to a reservoir capable of storing fluid, wherein the first flow channel connects the two second flow channels. A package comprising a flow channel element as described in any of [1] to

[11] , wherein the first flow channel connects an internal space of the package on which an electronic component can be arranged with an external space of the package. A drug delivery device comprising a flow channel element described in any of

[13] , [1] to

[11] , wherein the first flow channel is used as a flow channel for drug delivery. A biomolecular testing apparatus comprising a flow channel element described in any of [1] to

[11] , and a plurality of electrodes provided at a distance from each other along a first flow channel of the flow channel element.

[15] A method for forming a channel, comprising the steps of forming a film on a substrate and irradiating the film with laser light to form a linear altered portion in a part of the film, wherein the altered portion causes delamination between the substrate and the film on both sides of the altered portion, and a first channel is formed between the substrate and the film along the altered portion.

[16] The channel formation method according to

[15] , wherein a part of the film irradiated with the laser light expands to become the altered portion, causing delamination between the substrate and the film on both sides of the altered portion.

[17] The fluid element according to

[15] or

[16] , wherein the film comprises a layer adjacent to the substrate that has a higher absorption rate of the laser light than other parts of the film.

[18] The method for forming a channel according to any one of

[15] to

[17] , wherein the substrate is a glass substrate.

[19] The method for forming a channel according to any one of

[15] to

[18] , wherein the film is a diamond film.

[20] A method for forming a channel according to any one of

[15] to

[19] , wherein the laser light is irradiated onto the film as a focused beam that converges at the interface between the substrate and the film. [twenty one] The laser light has a pulse width of 10 -15 From 10 seconds -12The channel formation method according to any one of

[15] to

[20] , which is pulsed laser light within the range of seconds.

[22] The energy of the laser light is selected from the range of energy that causes alteration in the part of the film by the laser light but does not remove the film, and is the channel formation method according to any one of

[15] to

[21] .

[23] The channel formation method according to any one of

[15] to

[22] , further including the step of filling the first channel with a liquid for corroding the substrate and expanding the first channels on both sides of the altered part to form a single third channel.

Advantages of the Invention

[0008] According to the present disclosure, a channel element can be manufactured by a simpler method compared to the prior art.

Brief Description of the Drawings

[0009] [Figure 1] It is a plan view of a channel element according to an embodiment. [Figure 2] It is a cross-sectional view taken along line A-A of the channel element in FIG. 1. [Figure 3] It is a diagram for explaining a method of manufacturing a channel element. [Figure 4] It is a flowchart showing a method of manufacturing a nanofluid device as a channel element according to an embodiment. [Figure 5A] It is a plan view of a glass substrate used for manufacturing a nanofluid device. [Figure 5B] It is a partial cross-sectional view taken along line B-B of the glass substrate in FIG. 5A. [Figure 6A] It is a plan view of a glass substrate after applying a seed crystal of nanodiamond. [Figure 6B] It is a partial cross-sectional view taken along line C-C of the glass substrate in FIG. 6A. [Figure 7A] It is a plan view of a nanofluid device during manufacturing in which a polycrystalline diamond film is grown. [Figure 7B] It is a partial cross-sectional view taken along line D-D of the nanofluid device during manufacturing in FIG. 7A. [Figure 8A]This is a plan view of a nanofluidic device in the manufacturing process after pattern formation. [Figure 8B] Figure 8A is a partial cross-sectional view of the EE (Energy Extraction) of a nanofluidic device during the manufacturing process. [Figure 9A] This is a plan view of a nanofluidic device in the manufacturing process, where a polycrystalline diamond film has been further grown. [Figure 9B] Figure 9A is a partial cross-sectional view of the FF (Fluid-Fissured) device during the manufacturing process. [Figure 10A] This is a plan view of a nanofluidic device in the manufacturing process after microchannel formation. [Figure 10B] Figure 10A is a partial cross-sectional view of the GG region of a nanofluidic device during the manufacturing process. [Figure 11A] This is a plan view of the manufactured nanofluidic device. [Figure 11B] Figure 11A is a partial cross-sectional view of the HH portion of a nanofluidic device. [Figure 12A] This is a plan view of the nanofluidic device after the channel has been filled with liquid. [Figure 12B] Figure 12A is a partial cross-sectional view of the nanofluidic device II. [Figure 13] This is an electron microscope image of the end face of a cleaved nanofluidic device. [Figure 14] This is the height profile of the laser writing structure relative to the laser output. [Figure 15A] This is a plan view of a package using a flow channel element. [Figure 15B] Figure 15A is a cross-sectional view of the package. [Figure 16A] This is a plan view of a drug delivery device using flow channel elements. [Figure 16B] Figure 16A is a cross-sectional view of the rag delivery device. [Figure 17] This is a plan view of a biomolecular testing device using a flow channel element. [Figure 18A] This is a cross-sectional view of a fluid element containing nanochannels. [Figure 18B] This is a fluid channel element containing a microchannel, manufactured from the fluid channel element shown in Figure 18A. [Modes for carrying out the invention]

[0010] The embodiments of this disclosure will be described below with reference to the drawings.

[0011] (Flow channel element) As shown in Figures 1 and 2, a flow channel element 10 according to one embodiment of the present disclosure includes a substrate 11, a film 12 formed on the substrate 11, and a modified portion 13 of the film 12 that extends linearly along the substrate 11. A flow channel 14 is formed between the peeled substrate 11 and the film 12 along the modified portion 13.

[0012] The substrate 11 is a flat, plate-shaped component. The substrate 11 can be made of a transparent material, such as glass, that is transparent to visible light. However, the substrate 11 is not limited to a transparent material.

[0013] The film 12 is formed on the substrate 11 using any suitable formation method. The formation method for the film 12 includes vapor phase growth and liquid phase growth. Vapor phase growth methods include, for example, chemical vapor deposition (CVD), vapor deposition, and sputtering. Liquid phase growth methods include, for example, plating, sol-gel method, and spin coating.

[0014] The film 12 has an upper layer with low absorption of light at the wavelength of the laser light 16 (described later) and a lower layer with higher absorption than the upper layer. Here, the upper layer is the layer on the opposite side of the substrate 11, and the lower layer is the layer on the substrate 11 side. For example, the absorption of light at the wavelength of the laser light 16 of the film 12 may gradually change in the thickness direction so that it is highest on the substrate 11 side. For example, the film 12 may be composed of a material whose optical properties can be adjusted by controlling the defect density. The film 12 may also be formed from multiple layers with different absorption rates of light at the wavelength of the laser light 16. Any combination of materials that exhibit different behaviors for laser light of a specific wavelength and / or intensity can be used to fabricate the nanochannels of this disclosure. Preferably, the film 12 has high chemical and thermal robustness, as well as biocompatibility. Compared to the substrate 11, the film 12 may be composed of a material that is more susceptible to degradation by laser light 16.

[0015] The film 12 can be made of a material that is transparent to visible light. By making the substrate 11 and the film 12 from materials that are transparent to visible light, it becomes possible to observe the inside of the channel 14 formed in the channel element 10 from outside the channel element 10. The film 12 can be, for example, a diamond thin film.

[0016] The altered portion 13 includes the material of the film 12 that has been altered by irradiation with laser light 16 during the manufacturing process of the flow channel element 10. The altered portion 13 may further include the material of the substrate 11. In Figure 2, the altered portion 13 is located only on the substrate 11 side of the film 12, but the altered portion 13 may exist throughout the entire thickness direction of the film 12. Unlike in Figure 2, the boundary between the altered portion 13 and the film 12 is often not clear. Also, the degree of alteration of the film 12 may differ depending on its location within the altered portion 13. In other words, the altered portion 13 does not need to be uniformly altered. The altered portion 13 may be most altered from the material of the film 12 on the side in contact with the substrate 11.

[0017] The typical width of the altered portion 13 is in the range of 0.5 μm to 5 μm. This width of the altered portion 13 is approximately the same as the size of the focused spot 16a of the laser beam 16. In practice, it is difficult to make the size of the focused spot 16a less than 0.5 μm. Using a laser beam 16 with a larger focused spot 16a size results in an unnecessarily large altered area 13 and increased energy consumption. The width of the altered area 13 can be increased by increasing the laser beam intensity. However, beyond a certain laser beam intensity, the film 12 is completely removed. The width of the altered area 13 is not limited to the 0.5 μm to 5 μm range mentioned above. If the focused spot 16a of the laser beam 16 can be made smaller, the width of the altered area 13 can be made smaller than 0.5 μm. Also, the width of the altered area 13 can be made larger than 5 μm, as long as the film 12 is not removed by the laser beam 16.

[0018] The interatomic bonding state of the material of the film 12 contained in the altered portion 13 is different from the interatomic bonding state of the material contained in the film 12. For example, in the altered portion 13, the crystalline material of the film 12 may be partially changed to an amorphous state. As an example, if the film 12 is a diamond film, the altered portion 13 may contain non-diamond carbon. Therefore, when a part of the film 12 is altered into the altered portion 13 during the manufacturing of the flow channel element 10, the volume of the altered portion 13 expands compared to the film 12 before alteration. As a result, the mass density of the altered portion 13 becomes lower than the mass density of the film 12.

[0019] As shown in Figure 3, during the manufacturing of the flow channel element 10, laser light 16 from the objective lens 15 is irradiated onto the flow channel element 10 before the flow channel 14, which has a film 12 formed on the substrate 11, to form a linear altered portion 13. Here, "linear" indicates that the position where the laser light 16 is irradiated onto the flow channel element 10 moves relative to it in a linear fashion. Furthermore, the shape of the portion irradiated by the laser light 16 is not limited to a straight line, but also includes curves.

[0020] The objective lens 15 is positioned to irradiate the flow channel element 10 with laser light 16 from the laser light source as a focused beam. The laser light 16 may be irradiated toward the film 12 as a focused beam that converges near the interface between the substrate 11 and the film 12. The optical axis of the objective lens 15 may be oriented perpendicular to the substrate 11. The distance of the objective lens 15 from the substrate 11 may also be adjusted so that the laser light 16 is focused at or near the interface between the substrate 11 and the film 12. Furthermore, as mentioned above, the absorption rate of the laser light 16 by the film 12 may be higher on the substrate 11 side. As a result, the alteration of the film 12 occurs closer to the substrate 11.

[0021] The laser light 16 can be pulsed laser light emitted from a pulsed laser. The pulsed laser may be an ultrashort pulsed laser, such as a femtosecond laser. The ultrashort pulsed laser has a pulse width of 10 -15 From 10 seconds -12 The laser may be a pulsed laser within a few seconds. By using an ultrashort pulsed laser, it becomes possible to pinpoint the laser beam 16 onto the fluid element 10 without damaging the peripheral portion of the film 12. In particular, photons generated by a femtosecond laser transfer energy to the material on a shorter timescale than the timescale of thermal diffusion. As a result, only the material properties near the spot where the photons are focused are converted. Note that the laser beam 16 is not limited to a pulsed laser but may also be laser beam from a continuous wave (CW) laser. The wavelength of the laser beam 16 is a predetermined wavelength. The predetermined wavelength may mean a range of specific wavelengths. When irradiating the film 12 with laser beams 16 of multiple different wavelengths, the predetermined wavelength may include multiple wavelengths. When using a femtosecond laser, the wavelength of the laser beam 16 is usually in the range of 1 μm to 1.1 μm.

[0022] When the laser beam 16 is irradiated, at least a portion of the energy of the laser beam 16 is absorbed by the film 12. As a result, the portion of the film 12 irradiated with the laser beam 16 is altered and becomes an altered portion 13 that extends linearly along the substrate 11. Due to the expansion of the altered portion 13, a portion of the film 12 is pushed away from the substrate 11 by the altered portion 13. As a result, delamination occurs between the substrate 11 and the film 12 along the altered portion 13 on both sides of the altered portion 13. This delamination forms a channel 14 on both sides of the altered portion 13, surrounded by the substrate 11, the film 12, and the altered portion 13.

[0023] The dimension of the channel 14 perpendicular to the substrate 11 is preferably in the range of 5 nm to 200 nm, and more preferably in the range of 5 nm to 80 nm. This is because the fluid confined within the channel 14 exhibits behavior not seen in larger channels, and molecules such as biomolecules ranging in size from several nanometers to tens of nanometers can be handled one by one within the channel. Channels smaller than such dimensions may be difficult to manufacture due to variations in the optical properties of the film 12, variations in the energy of the laser light 16, and variations in the position of the focused spot 16a of the laser light 16. Furthermore, since the channel 14 is a delaminate portion between the substrate 11 and the film 12, the width of the channel 14 in the direction along the substrate 11 is several tens of times larger than the dimension perpendicular to the substrate 11. Typically, when the dimension perpendicular to the substrate 11 is 5 nm to 80 nm, the width of the channel 14 in the direction along the substrate 11 is preferably in the range of 1 μm to 4 μm. Furthermore, when the dimension perpendicular to the substrate 11 is between 5 nm and 200 nm, the width of the channel 14 in the direction along the substrate 11 is preferably in the range of 1 μm to 10 μm.

[0024] Furthermore, by irradiating the flow channel element 10 with laser light 16 in a manner that traces multiple lines, it is possible to form more than two flow channels 14 in the flow channel element 10. In addition, by shifting the irradiation position of the laser light 16 at an appropriate pitch, the positions where the flow channels 14 are formed can be overlapped. This makes it possible to form three or more odd numbers of flow channels 14.

[0025] As described above, the flow channel element 10 can be easily formed by irradiating a film 12 formed on a substrate 11 with laser light 16. Since the flow channel 14 of the flow channel element 10 formed by irradiation with laser light 16 is surrounded by the substrate 11, the film 12, and the altered portion 13, the process of sealing the flow channel required in the conventional technology is not necessary. Furthermore, by using a femtosecond laser as the light source for the laser light 16 to form the flow channel 14, it becomes possible to form fine flow channels with a width of 1 μm to 4 μm and a height of 5 nm to 80 nm. Moreover, when glass is used as the material for the substrate 11 and polycrystalline diamond is used as the material for the film 12, the flow channel element 10 is composed of transparent materials, so the flow channel 14 can be observed from the outside by optical means. Glass and diamond are advantageous in that they are thermally and chemically robust and biocompatible. Furthermore, since glass and diamond are made of elements that are abundant on the Earth's surface, they are sustainable materials.

[0026] (Nanofluidic devices) The term "fluidic element" can be rephrased as "fluidic device" or "fluidic structure." The fluidic element 10 may further include other components. The fluidic element 10 may also be incorporated into other devices. Below, a nanofluidic device 20 will be described as an example of the fluidic element 10 of this disclosure. First, the manufacturing method of the nanofluidic device 20 will be described with reference to the flowchart in Figure 4 and the diagrams related to each step of the flowchart in Figure 4.

[0027] First, as shown in Figures 5A and 5B, a glass substrate 21 for manufacturing the nanofluidic device 20 is prepared (Step S1). A flat and uniform glass substrate 21 can be used.

[0028] As shown in Figures 6A and 6B, a nanodiamond seed crystal 22 is coated onto the glass substrate 21 (step S2). Nanodiamonds are nanoparticles that have the crystalline structure of diamond. Nanodiamonds possess the excellent properties of diamond, such as high light transparency. Figures 6A and 6B show magnified views of the nanodiamond seed crystal 22 coated on the glass substrate 21.

[0029] As shown in Figures 7A and 7B, diamonds are grown on these nanodiamond seed crystals 22 by chemical vapor deposition until a polycrystalline diamond (PCD) film 23 of a first thickness (e.g., d = 60 nm) is formed (step S3). The PCD film 23 formed on the glass substrate 21 has a uniform thickness. In one embodiment, the polycrystalline diamond (PCD) film may be a nanocrystalline diamond (NCD) film.

[0030] As shown in Figures 8A and 8B, a pattern 24 is formed on the PCD film 23 by directly laser writing to remove a portion of the PCD film 23 (step S4). Since the PCD film 23 is kept relatively thin, patterning can be performed with a relatively low laser power to minimize damage to the glass substrate 21. The pattern 24 includes two pairs of concentric reservoir portions 24a and microchannel portions 24b extending linearly from the reservoir portions 24a. The two reservoir portions 24a are located apart from each other. The two microchannel portions 24b are arranged to face each other parallel to each other.

[0031] As shown in Figures 9A and 9B, the PCD film 23 is grown to a second thickness (e.g., d = 300 nm) by chemical vapor deposition (step S5). The second thickness must be large enough to avoid the PCD film 23 being removed by laser irradiation. To obtain channels 14 perpendicular to the substrate 11 in the range of 5 nm to 80 nm, the second thickness is preferably in the range of 280 nm to 320 nm. The second thickness is not limited to this range. The second thickness can also be in the range of 145 nm to 1000 nm.

[0032] As shown in Figures 10A and 10B, the glass substrate 21 is etched with a hydrofluoric acid (HF)-based mixture. This forms a reservoir 25 capable of storing fluid at the location of the reservoir portion 24a of the pattern 24, and forms an open-top microchannel 26 below the microchannel portion 24b of the pattern 24 (step S6). The microchannel 26 corresponds to a second flow path. Diamond does not react with hydrofluoric acid. Therefore, a wider area of ​​the glass substrate 21 than the pattern 24 formed on the PCD film 23 is removed on the underside of the PCD film 23. Each microchannel 26 is connected to one reservoir 25.

[0033] As shown in Figures 11A and 11B, the microchannels 26 are connected by direct laser writing of the nanochannels 28 (step S7). By irradiating with laser light, nanostrips 27 (altered parts) are formed mainly on the PCD film 23 side of the interface between the glass substrate 21 and the PCD film 23. Due to the expansion when the PCD film 23 is altered into nanostrips 27, delamination occurs between the glass substrate 21 and the PCD film 23, and nanochannels 28 are formed. As shown in Figures 11A and 11B, by using the channel formation method of this disclosure, it is possible to form a large number of nanochannels that are parallel to each other.

[0034] Next, as shown in Figures 12A and 12B, the reservoir 25 is filled with liquid (step S8). The liquid is, for example, water. Due to capillary action, the microchannels 26 and nanochannels 28 are filled with liquid. Experiments conducted by the inventors have shown that if only one reservoir 25 is filled with liquid, the liquid will not flow into all of the microchannels 26 and nanochannels 28. In order to fill all of the microchannels 26 and nanochannels 28 with liquid, both reservoirs 25 must be filled with liquid. In this way, the liquid to be tested or observed can be introduced into the nanochannels 28.

[0035] In steps S4 and S7, a femtosecond laser can be used for direct laser writing. The inventors used a pulsed laser beam with a laser pulse frequency of 756 kHz, pulse width of 270 fs, writing speed of 200 mm / s, and wavelength of 1033 nm, and focused the laser beam to a spot with a radius of approximately 1 μm to fabricate a nanofluidic device 20.

[0036] The above description illustrates a method for directly writing nanochannels 28 to the interface between the PCD film 23 and the glass substrate 21 using a femtosecond laser. Laser writing converts a portion of the PCD film 23 into a nanostrip 27, which is an altered portion 13. The nanostrip 27 is surrounded by two nanochannels 28 formed by the peeling of the PCD film 23. For a PCD film 23 with a thickness d = 300 nm, the average height and width of the nanochannels 28 are approximately 30 nm and 2 μm, respectively, and these dimensions can be adjusted.

[0037] Our experiments indicate that the nanostrip 27 is composed of PCD, non-diamond carbon, and glass particles, which may have been mixed by laser ablation. This leads to the conclusion that material expansion forms the nanostrip 27, causing delamination and the formation of nanochannels 28. Such expansion occurs, for example, during the conversion from diamond to non-diamond carbon.

[0038] Since ablation of the bare glass substrate does not occur unless the pulse energy is considerably higher than that used for nanochannel writing, it is presumed that the formation of the nanostrip 27 is initiated in the PCD film 23 near the interface between the PCD film 23 and the glass substrate 21. The source of this phenomenon may be the presence of low-quality PCD in that location, which absorbs more light than high-quality PCD.

[0039] Due to their biocompatibility and chemical, mechanical, electrical, optical, and quantum properties, PCDs are attractive materials for applications in nanofluidic devices. Low-cost diamond films can be grown using microwave plasma-assisted chemical vapor deposition (MWPACVD). PCD films can be realized on large-area substrates using methane gas diluted with hydrogen molecules as a precursor mixture after seeding of nanodiamonds. Adding oxygen to the mixture typically improves film quality, can induce seed etching, and enables low-temperature deposition. PCDs can also be doped to make them conductive, opening up a variety of applications.

[0040] Inexpensive, transparent, and chemically inert glass is ideal for micro and nanofluidics research. The properties of glass are also easily tunable. For example, glass can be fabricated with a coefficient of thermal expansion (CTE) similar to that of silicon, and relatively close to that of diamond. Therefore, glass can be used to fabricate structures with relatively low residual stress. Since PCD is inert to hydrofluoric acid (HF), the PCD film 23 acts as an etching stop during HF etching of the glass. The manufacturing method of the nanofluidic device 20 described above relies on this property.

[0041] Figure 13 shows a scanning electron microscope (SEM) image of a structure created by cleaving a sample of the nanofluidic device 20 immediately after film growth (d=300nm) and then laser writing across the cleaved edge with a laser pulse energy E=36.4nJ. This image shows the presence of a nanostrip 27 surrounded by two nanochannels 28 formed by the exfoliation of the PCD film 23. Laser ablation of the bare glass substrate occurs at a laser pulse energy E>190nJ, which is higher than the value of the laser pulse energy E used for nanochannel writing, so it is presumed that nanostrip formation is initiated in the PCD film 23. The nanodiamond seed crystal 22 is highly defective, and the quality of the diamond improves as the PCD film 23 grows, so under the deposition conditions used in this process, the density of non-diamond material in the PCD film 23 increases toward the film-substrate interface. Such material is more likely to absorb laser light than diamond. As a result, the portion of the PCD film 23 closest to the glass substrate 21 is most easily converted by laser writing. When irradiated with a laser, a rapid structural change occurs in the portion of the PCD film 23 closest to the glass substrate 21, causing a decrease in mass density. As a result, the formed nanostrip 27 has a lower mass density than the PCD film 23. Because the mass density of the irradiated portion decreases, the peripheral portions on both sides are pushed and peel off from the glass substrate 21, forming nanochannels 28. The PCD film 23 may be replaced with a film made of another material that has a low absorption rate of laser light at the top and a high absorption rate at the bottom. The other material is preferably chemically and thermally robust, biocompatible, and its optical properties can be adjusted by controlling the defect density.

[0042] Figure 14 shows the height profiles of the air interface (i.e., the top surface of the PCD film 23) of each laser-written structure formed by varying the laser pulse energy E of the femtosecond laser during the manufacturing process of the nanofluidic device 20. In Figure 14, the horizontal axis "y" is the distance from the center in the direction (y direction) perpendicular to both the direction in which the nanostrip 27 extends (x direction) and the direction perpendicular to the glass substrate 21 (z direction). The vertical axis H is the height of the air interface in the z direction. For the nanofluidic device 20, the height "H" of the top surface of the PCD film 23 before irradiation with the femtosecond laser is set to 0. The height H is calculated by averaging atomic force microscope (AFM) data over the x direction.

[0043] As is clear from Figure 14, the higher the laser pulse energy E, the larger the maximum height profile of the nanofluidic device 20. In other words, the higher the laser pulse energy E, the greater the deformation of the PCD film 23, and thus larger nanochannels 28 are formed. When the laser pulse energy E is 36.4 nJ or higher, the deformation of the PCD film 23 is relatively large, so relatively large nanochannels 28 are formed. On the other hand, when the laser pulse energy E is less than 29.8 nJ, the deformation of the PCD film 23 is small, so it is thought that nanochannels 28 are not easily formed.

[0044] The laser pulse energy E in step S7 is selected from an energy range that causes some degree of alteration to a portion of the PCD film 23 by the laser light 16, but does not remove the PCD film 23. The appropriate magnitude of the laser pulse energy E is determined based on various conditions, including the material of the PCD film 23.

[0045] The inventors of the present invention further fabricated nanofluidic devices 20 by setting the thickness d of the PCD film 33 to various values ​​in the range of 62 nm to 320 nm, and observed the nanochannels 28 using a reflected light microscope. As a result, it was confirmed that when the thickness d is between 280 nm and 320 nm, nanochannels 28 are formed over a relatively wide range of laser pulse energies E. Furthermore, when the thickness d of the PCD film 33 is 300 nm, no film peeling due to laser irradiation was observed within an appropriate range of laser pulse energies E. Since the cost of film deposition increases with increasing thickness d, it is preferable to keep the thickness d relatively small. Another reason for keeping the thickness d relatively small is that the surface roughness of the PCD film 33 increases with increasing thickness d. Surface roughness causes light scattering, which prevents the observation of channels with an optical microscope. Therefore, it is preferable that the thickness of the PCD film 33 be within the range of 280 nm to 320 nm. The thickness d of the PCD film 33 may be outside the above-mentioned preferred range of thickness d. Experiments conducted by the present inventors confirmed that nanochannels 28 are formed when the thickness d is 145 nm or greater. Furthermore, it is estimated that light scattering due to the surface roughness of the PCD film 33 is within an acceptable range if the thickness of the PCD film 33 is up to approximately 1000 nm. Therefore, the thickness of the PCD film 33 can be within the range of 145 nm to 1000 nm. For thicker PCD films 33, additional polishing steps may be necessary to reduce scattering.

[0046] As described above, by using the channel formation method of this disclosure, a nanofluidic device 20 having a large number of parallel-arranged nanochannels 28 can be manufactured. The nanofluidic device 20 is expected to be used for research and development and analysis in fields such as medicine, biotechnology, and chemistry. Furthermore, the channel formation method of this disclosure allows for changing the size of the nanochannels 28 by changing the laser pulse energy E, etc. Therefore, a nanofluidic device 20 having nanochannels 28 of various sizes to meet diverse needs can be manufactured.

[0047] (Package for electronic components) Referring to Figures 15A and 15B, a package 30 of an electronic component comprising the flow channel element 10 of this disclosure (hereinafter referred to as "package 30") will be described.

[0048] Package 30 is formed by bonding a glass substrate 32 to the top of a package body 31 having a bottom and sides using adhesive 34. Electronic components can be placed in the hollow portion 31a, which is the internal space surrounded by the package 30 and the glass substrate 32. In addition, a via 32a is formed in the center of the glass substrate 32, penetrating the glass substrate 32.

[0049] A PCD film 33 is formed on the glass substrate 32. The PCD film 33 covers the entire upper part of the glass substrate 32, including the upper part of the via 32a. Such a PCD film 33 can be formed by a known method, for example, as described in International Publication No. 2020 / 222297. Furthermore, a nanochannel 35 (first channel) is formed between the glass substrate 32 and the PCD film 33, connecting the space inside the via 32a and the space outside the package 30. The nanochannel 35 is formed based on the manufacturing method of the channel element 10 shown in Figure 3.

[0050] As described above, the package 30 can expel gas from inside the hollow section 31a via the nanochannels 35, even if the solvent contained in the adhesive 34 vaporizes and increases the pressure inside the hollow section 31a. Furthermore, by making the nanochannels 35 hydrophobic and sufficiently small, particles from the outside space can be blocked. This makes it possible to maintain a good environment around the electronic components inside the package 30.

[0051] (Drug delivery device) A drug delivery device 40 incorporating the flow channel element 10 of this disclosure will be described with reference to Figures 16A and 16B.

[0052] The drug delivery device 40 includes a housing 41 and a glass substrate 42. The hollow portion 41a surrounded by the housing 41 and the glass substrate 42 is filled with the drug during use. A via 42a is formed in the center of the glass substrate 42, penetrating the glass substrate 42.

[0053] A PCD film 43 is formed on the glass substrate 42. The PCD film 43 covers the entire upper part of the glass substrate 42, including the upper part of the via 42a. Furthermore, a drug delivery channel 44 (first channel) is formed between the glass substrate 42 and the PCD film 43, connecting the internal space of the drug delivery device 40 with the external space of the drug delivery device 40. The drug delivery channel 44 is a channel used for drug delivery. The drug delivery channel 44 is formed based on the manufacturing method of the channel element 10 shown in Figure 3.

[0054] The drug delivery device 40 can release the drug filled in the hollow section 41a to the required location on the patient's body over a long period of time. The drug delivery device 40 uses a drug delivery channel 44 as a flow path for releasing the drug. The dimensions of the drug delivery channel 44 can be set to an appropriate size depending on the type of drug. The drug delivery device 40 may include a release mechanism (not shown) for releasing the drug in the hollow section 41a to the outside.

[0055] As described above, the drug delivery device 40 is configured to deliver the appropriate drug to the appropriate site in the patient at the appropriate rate over a long period of time. Furthermore, since the drug delivery device 40 is composed of diamond and glass, it has the advantage of not having any harmful effects on the human body.

[0056] (Biomolecular testing device) Referring to the plan view in Figure 17, a biomolecular testing apparatus 50 incorporating the flow channel element 10 of this disclosure will be described.

[0057] The biomolecular testing device 50 includes a flow channel element 51 and a first electrode 52a and a second electrode 52b as disclosed herein. The flow channel element 51 includes a nanostrip 53 and two nanochannels 54a and 54b. Similar to the nanofluidic devices 20 shown in Figures 4 to 13, the flow channel element 51 uses a glass substrate 11 as the substrate 11 of the flow channel element 10 and a PCD film as the film 12. The width and height dimensions of the nanochannels 54a and 54b can be tens to hundreds of nanometers. Note that the substrate 11 and film 12 of the biomolecular testing device 50 are not limited to a glass substrate and a PCD film. The substrate 11 and film 12 can be made of various materials as long as they meet the required specifications.

[0058] The first electrode 52a and the second electrode 52b may contain a conductive metallic material, such as platinum, gold, silver, or copper. The first electrode 52a and the second electrode 52b are positioned apart on both or either the upper and lower surfaces of the flow channel element 51, in a direction along the nanochannels 54a and 54b. The first electrode 52a and the second electrode 52b may be positioned at or near both ends of the nanochannels 54a and 54b. The first electrode 52a and the second electrode 52b can apply an electric field to the nanochannels 54a and 54b. The first electrode 52a and the second electrode 52b may generate electrophoretic force within the nanochannels 54a and 54b to move the biomolecules 55a and 55b located within the nanochannels 54a and 54b.

[0059] The biomolecular testing device 50 may further include a circuit for controlling the potentials of the first electrode 52a and the second electrode 52b, and an observation device for observing the biomolecules 55a and 55b trapped in the nanochannels 54a and 54b. The observation device may be, for example, an optical microscope or an atomic force microscope. The biomolecular testing device 50 may also include a light source and an optical system for irradiating the biomolecules 55a and 55b with light. The circuit, observation device, light source, etc., may not be part of the biomolecular testing device 50, but may be external devices.

[0060] With the above configuration, the biomolecular inspection device 50 can observe biomolecules one molecule at a time. For example, the biomolecular inspection device 50 can observe the behavior of biomolecules 55a and 55b in response to the application of an electric field and / or irradiation with light. Furthermore, since nanochannels 54a and 54b are smaller in size than living cells, the biomolecular inspection device 50 can reproduce the chemical reactions of proteins contained in living cells in the intracellular environment.

[0061] Furthermore, the number of nanochannels 54a and 54b in the biomolecular testing device 50 is not limited to two. The biomolecular testing device 50 may be configured to include a nanochannel array in which a large number of nanochannels are arranged in parallel.

[0062] The flow channel element 10 of this disclosure is not limited to the nanofluidic device 20, package 30, drug delivery device 40, and biomolecular testing device 50 described above, but can be applied to a variety of other applications. The flow channel element 10 can be used for the transport, mixing, reaction, and observation of minute amounts of biomolecules and / or chemical substances. Therefore, it is expected to be used in many fields, including medicine, biotechnology, drug discovery, chemistry, and materials development.

[0063] (Method for forming microchannels) Referring to Figures 18A and 18B, a method for manufacturing a fluid channel element 60A having a microchannel 64 having a width of 10 μm or more will be described, for example, of the fluid channel element 60 of the present disclosure which includes two nanochannels 63 having a width of several hundred nanometers to several micrometers. The nanochannels 63 correspond to a first fluid channel, and the microchannels 64 correspond to a third fluid channel.

[0064] The flow channel element 60, like the nanofluidic device 20 shown in Figures 4 to 13, includes a glass substrate 61 and a PCD film 62 formed on the glass substrate 61. Two nanochannels 63 are formed between the glass substrate 61 and the PCD film 62 by the flow channel formation method of this disclosure. Figure 18A is a cross-sectional view taken from a plane perpendicular to the direction in which the two nanochannels 63 extend.

[0065] A liquid that corrodes the glass substrate 61 is filled into the nanochannel 63 of the flow channel element 60. The liquid that corrodes the glass substrate 61 is, for example, hydrofluoric acid (HF). By providing a reservoir at at least one end of the nanochannel 63 and supplying hydrofluoric acid (HF) to this reservoir, the nanochannel 63 can be filled with hydrofluoric acid (HF) by capillary action.

[0066] As shown in Figure 18B, the glass substrate 61 in contact with the nanochannel 63 is corroded by hydrofluoric acid (HF), causing the two nanochannels 63 to connect on the glass substrate 61 side, forming a single microchannel 64 that is larger in width and height than the nanochannel 63. Therefore, this channel formation method makes it possible to manufacture a channel element 60A in which a microchannel 64 is formed between the glass substrate 61 and the PCD film 62.

[0067] While embodiments relating to this disclosure have been described based on the drawings and examples, it should be noted that those skilled in the art will find it easy to make various modifications or changes based on this disclosure. Therefore, it should be noted that these modifications or changes are included within the scope of this disclosure. [Explanation of Symbols]

[0068] 10 flow channel elements 11 circuit boards 12 membrane 13. Deteriorated parts 14. Flow channel (first flow channel) 15 Objective lens 16 Laser light 16a Focusing spot 20. Nanofluidic Devices (Flow Channel Elements) 21 Glass substrate (substrate) 22 Seed crystals of nanodiamonds 23. Polycrystalline diamond film (PCD film) 24 patterns 24a Reservoir section 24b Microchannel section 25 Reservoir 26 Microchannels (Second Channels) 27 Nanostrip (altered portion) 28 Nanochannels (First channel) 30 packages 31 Package body 31a Hollow part 32 Glass substrate (substrate) 32a via 33. Polycrystalline diamond film (PCD film) 34 Adhesives 35 Nanochannels (First channel) 40 Drug delivery devices 41 Housing section 41a Hollow part 42 Glass substrate 42a Via 43. Polycrystalline diamond film (PCD film) 44. Drug delivery channel (first channel) 50 Biomolecular Analysis Devices 51 Flow element 52a First electrode 52b Second electrode 53 Nanostrip (altered portion) 54a, 54b nanochannels 55a, 55b Biomolecules 60, 60A flow channel element 61 Glass substrate 62. Polycrystalline diamond film (PCD film) 63 Nanochannels (First channel) 64 microchannels (third channel)

Claims

1. circuit board and A film formed on the substrate, A modified portion of the aforementioned film, comprising a modified portion that extends linearly along the substrate, A flow channel element comprising a first flow channel formed between the peeled substrate and the film on both sides of the altered portion along the altered portion.

2. The fluid channel element according to claim 1, wherein the altered portion has a lower mass density than the film.

3. The fluid element according to claim 1, wherein the film includes a layer on the substrate side that has a higher absorption rate of light of a predetermined wavelength than other parts of the film.

4. The flow channel element according to claim 1, wherein the substrate is a glass substrate.

5. The flow channel element according to claim 1, wherein the aforementioned film is a diamond film.

6. The fluid channel element according to claim 5, wherein the altered portion contains non-diamond carbon.

7. The flow channel element according to claim 1, wherein the thickness of the film is in the range of 145 nm to 1000 nm.

8. The flow channel element according to claim 1, wherein the width of the altered portion is in the range of 0.5 μm to 5 μm.

9. The channel element according to claim 1, wherein the dimension of the first channel perpendicular to the substrate is in the range of 5 nm to 200 nm.

10. The flow channel element according to claim 1, wherein the width of the first flow channel in the direction along the substrate is in the range of 1 μm to 4 μm.

11. The flow channel element according to claim 1, further comprising two second flow channels having a larger dimension than the first flow channel, each of which is connected to a reservoir capable of storing fluid, the first flow channel connecting the two second flow channels.

12. A package comprising the flow channel element according to claim 1, wherein the first flow channel connects an internal space of the package on which an electronic component can be arranged with an external space of the package.

13. A drug delivery device comprising the flow channel element described in claim 1, wherein the first flow channel is used as a flow channel for drug delivery.

14. The flow channel element according to claim 1, A plurality of electrodes are provided at a distance from each other along the first flow path of the flow channel element and A biomolecular testing device equipped with the following features.

15. A process of forming a film on a substrate, A step of irradiating the film with laser light to form a linear altered portion in a part of the film, wherein the altered portion causes delamination between the substrate and the film on both sides of the altered portion, and a first channel is formed between the substrate and the film along the altered portion. A method for forming a channel, including the following.

16. The method for forming a channel according to claim 15, wherein a portion of the film irradiated with the laser light expands to become the altered portion, causing delamination between the substrate and the film on both sides of the altered portion.

17. The method for forming a channel according to claim 15, wherein the film includes a layer adjacent to the substrate that has a higher absorption rate of the laser light than other parts of the film.

18. The method for forming a channel according to claim 15, wherein the substrate is a glass substrate.

19. The method for forming a channel according to claim 15, wherein the aforementioned membrane is a diamond membrane.

20. The method for forming a channel according to claim 15, wherein the laser light is irradiated onto the film as a focused beam that converges at the interface between the substrate and the film.

21. The laser light has a pulse width of 10 －１５ From 10 seconds －１２ The method for forming a channel according to claim 15, wherein the pulsed laser light is within a range of seconds.

22. The method for forming a channel according to claim 15, wherein the energy of the laser light is selected from an energy range that causes alteration to a part of the film by the laser light, but does not remove the film.

23. The method for forming a channel according to claim 15, further comprising the step of filling the first channel with a liquid that corrodes the substrate and expanding the first channels on both sides of the altered portion to form a single third channel.

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