Point-of-care diagnostic biochip having microfluidic channel formed using laser, and manufacturing method therefor

Abstract

A point-of-care diagnostic biochip is provided. The point-of-care diagnostic biochip may comprise: a substrate having a predetermined volume; and a microfluidic channel formed inside the substrate by a laser composed of multiple photons having energy exceeding the bandgap energy of the substrate.

Description

Point-of-care diagnostic biochip having microfluidic channels formed using a laser and method for manufacturing the same

[0001] The present invention relates to a point-of-care diagnostic biochip having microfluidic channels formed using a laser and a method for manufacturing the same. More specifically, the invention relates to a point-of-care diagnostic biochip having microfluidic channels formed using a laser, having high mechanical stability and flexibility, and a method for manufacturing the same that can be manufactured in a short time through a single laser process.

[0002] Microfluidic technology is a technique for precisely controlling and moving fluids at the micro and sub-micro scales, and is utilized to control or analyze fluid flow through narrow channels.

[0003] These microfluidic technologies can efficiently move fluids by utilizing physical properties such as the capillary effect at a small scale.

[0004] In particular, combined with a sensor, it performs the function of collecting bodily fluids such as saliva, tears, and sweat and delivering them to the sensor, enabling fast and accurate biomarker analysis even with small sample volumes.

[0005] Furthermore, unlike conventional laboratory-based analysis methods, microfluidic technology enables immediate detection and processing in the field, demonstrating high potential for application in areas such as Point-of-Care Testing (POCT).

[0006] Meanwhile, conventional microfluidic channel manufacturing methods have limitations, such as high production costs and the requirement for time-consuming manual labor, as they primarily utilize lithography-based processes.

[0007] In particular, in conventional microfluidic channel manufacturing methods, problems such as device contamination, misalignment, and reduced production efficiency occurred during the process of aligning and attaching the cover layer after forming the microfluidic channel.

[0008] In addition, fabrication using a 3D additive manufacturing method is also being considered, but the 3D additive manufacturing method leaves a layered pattern, which is an inherent problem of the additive manufacturing method. Therefore, when forming microfluidic channels through the 3D additive manufacturing method, it can interfere with the dynamic flow of the fluid, and as a result, there is a problem that it is unsuitable for use as a sensor.

[0009] Therefore, there is a need to introduce a new method that enables the formation of high-precision microfluidic channels while having a simple and fast manufacturing process.

[0010] One technical problem that the present invention aims to solve is to provide a point-of-care biochip having a microfluidic channel formed using a laser, having high mechanical stability and flexibility, and a method for manufacturing the same.

[0011] Another technical problem that the present invention aims to solve is to provide a point-of-care diagnostic biochip having a microfluidic channel formed using a laser, which can be manufactured in a short time through a single laser process, and a method for manufacturing the same.

[0012] Another technical problem that the present invention aims to solve is to provide a point-of-care biochip having a microfluidic channel formed using a laser, in which capillary action is maximized, and a method for manufacturing the same.

[0013] The technical problems that the present invention aims to solve are not limited to those described above.

[0014] To solve the above-mentioned technical problem, the present invention provides a biochip for field diagnosis.

[0015] According to one embodiment, the biochip for point-of-care diagnosis may include a substrate having a set volume; and a microfluidic channel formed inside the substrate by a laser composed of multiple photons exceeding the bandgap energy of the substrate.

[0016] According to one embodiment, the formation depth of the microfluidic channel can be determined according to the increase or decrease in the output of the laser.

[0017] According to one embodiment, the formation depth of the microfluidic channel becomes shallower as the output of the laser increases, while the cross-sectional size of the microfluidic channel may become smaller as the formation depth of the microfluidic channel increases.

[0018] According to one embodiment, the microfluidic channel can be formed inside the substrate by a laser focused on the surface of the substrate.

[0019] According to one embodiment, the laser composed of multiple photons may be a picosecond pulse laser.

[0020] According to one embodiment, the substrate is made of a polymer material that transmits the laser, and the polymer material may include PDMS (Polydimethylsiloxane).

[0021] According to one embodiment, the substrate comprises a first substrate; and a second substrate laminated on the first substrate, wherein the first substrate may have a relatively higher absorption rate for the laser composed of multiple photons than the second substrate.

[0022] According to one embodiment, the microfluidic channel may be formed at the interface between the first substrate and the second substrate.

[0023] Meanwhile, the present invention provides a method for manufacturing a biochip for field diagnosis.

[0024] According to one embodiment, the method for manufacturing a biochip for point-of-care diagnosis may include the steps of: preparing a substrate; focusing a laser composed of multiple photons exceeding the bandgap energy of the substrate onto the surface of the substrate; and irradiating the laser focused onto the surface of the substrate toward the substrate to form a microfluidic channel inside the substrate.

[0025] According to one embodiment, in the step of forming a microfluidic channel inside the substrate, the output of the laser can be controlled to control the depth of formation of the microfluidic channel.

[0026] According to one embodiment, in the step of preparing the substrate, a substrate consisting of a single layer is prepared, and the substrate may be made of a polymer material that transmits the laser.

[0027] According to one embodiment, in the step of preparing the substrate, a substrate composed of multiple layers is prepared, wherein the substrate composed of multiple layers comprises a first substrate; and a second substrate laminated on the first substrate, wherein the first substrate may have a relatively higher absorption rate for the laser composed of multiple photons than the second substrate.

[0028] According to an embodiment of the present invention, the invention may include a substrate having a set volume; and a microfluidic channel formed inside the substrate by a laser composed of multiple photons exceeding the bandgap energy of the substrate.

[0029] Accordingly, a point-of-care diagnostic biochip having high mechanical stability and flexibility can be provided.

[0030] That is, according to an embodiment of the present invention, since microfluidic channels are formed directly inside a substrate without an additional cover layer alignment and attachment process, high mechanical stability can be provided, and since the substrate in which the microfluidic channels are formed is made of a flexible polymer material, it can be utilized in various application fields including wearable devices.

[0031] In particular, according to an embodiment of the present invention, it is applicable even to devices with complex shapes, thereby providing high versatility in fields such as biochemical analysis, chemical and electrochemical sensor devices.

[0032] In addition, according to an embodiment of the present invention, a microfluidic channel is formed inside a substrate by a laser consisting of multiple photons exceeding the bandgap energy of the substrate, so that, unlike a lithography process which requires a clean room environment and proceeds with a complex manufacturing process, it can be manufactured in a short time through a simple single laser process, and as a result, production efficiency can be maximized.

[0033] In addition, according to an embodiment of the present invention, a point-of-care biochip having a microfluidic channel having an excellent surface area relative to its volume and a method for manufacturing the same may be provided.

[0034] Accordingly, capillary action can be maximized, and as a result, fluid can be delivered or mixed through microfluidic channels without external pressure, which can contribute to improving reaction and sensing efficiency in microfluidic-based devices.

[0035] In addition, according to an embodiment of the present invention, by adjusting laser parameters such as output, repetition rate, scan speed, and focus, the position of the microfluidic channel formed inside the substrate can be precisely controlled according to the user's intention, and through this, microfluidic channels can be formed at various locations, such as forming a microfluidic channel at a crosslinked interface of the substrate or forming a microfluidic channel inside the substrate.

[0036] In this case, according to an embodiment of the present invention, by providing a substrate with a multilayer structure, a complex microfluidic channel pattern can be formed inside it, and such a multilayer structure can be utilized in fields requiring complex structures, such as healthcare devices.

[0037] FIGS. 1 and FIGS. 2 are schematic diagrams for explaining a biochip for field diagnosis according to one embodiment of the present invention.

[0038] Figures 3 and 4 are the results of measuring the depth of microfluidic channel formation according to the laser output of the point-of-care diagnostic biochip for each experimental example.

[0039] FIG. 5 is a schematic diagram illustrating a biochip for on-site diagnosis according to another embodiment of the present invention.

[0040] FIG. 6 is a flowchart illustrating a method for manufacturing a biochip for field diagnosis according to one embodiment of the present invention.

[0041] Figure 7 is a schematic diagram illustrating step S110 of Figure 6.

[0042] Figure 8 is a schematic diagram illustrating step S120 of Figure 6.

[0043] Figure 9 is a schematic diagram illustrating step S130 of Figure 6.

[0044] FIGS. 10 and 11 are photographs of cross-sections of a point-of-care diagnostic biochip manufactured through a method for manufacturing a point-of-care diagnostic biochip according to an embodiment of the present invention.

[0045] FIGS. 12 to 14 are photographs taken of experiments on the fluid movement phenomenon of microfluidic channels formed inside PDMS of a point-of-care biochip manufactured through a method for manufacturing a point-of-care biochip according to one embodiment of the present invention.

[0046] FIG. 15 is a flowchart illustrating a method for manufacturing a biochip for field diagnosis according to another embodiment of the present invention.

[0047] FIG. 16 is a schematic diagram illustrating step S210 of FIG. 15.

[0048] Figure 17 is a schematic diagram illustrating step S220 of Figure 15.

[0049] FIG. 18 is a schematic diagram illustrating step S230 of FIG. 15.

[0050] FIGS. 19 and 20 are photographs of cross-sections of a point-of-care diagnostic biochip manufactured through a method for manufacturing a point-of-care diagnostic biochip according to another embodiment of the present invention.

[0051] FIGS. 21 and 22 are electron microscope images of the interface between the opaque PDMS layer and the transparent PDMS layer of a point-of-care diagnostic biochip manufactured through a method for manufacturing a point-of-care diagnostic biochip according to another embodiment of the present invention.

[0052] Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the attached drawings. However, the technical concept of the present invention is not limited to the embodiments described herein and may be embodied in other forms. Rather, the embodiments introduced herein are provided to ensure that the disclosed content is thorough and complete and to ensure that the concept of the present invention is sufficiently conveyed to those skilled in the art.

[0053] In this specification, when a component is described as being on another component, it means that it may be formed directly on the other component or that a third component may be interposed between them. Additionally, in the drawings, shapes and sizes are exaggerated for the effective illustration of the technical content.

[0054] Additionally, although terms such as first, second, third, etc., have been used to describe various components in the various embodiments of this specification, these components should not be limited by such terms. These terms are used merely to distinguish one component from another. Accordingly, what is referred to as the first component in one embodiment may be referred to as the second component in another embodiment. Each embodiment described and illustrated herein also includes its complementary embodiment. Furthermore, in this specification, "and / or" is used to mean including at least one of the components listed before and after it.

[0055] In the specification, singular expressions include plural expressions unless the context clearly indicates otherwise. Furthermore, terms such as "include" or "have" are intended to specify the existence of the features, numbers, steps, components, or combinations thereof described in the specification, and should not be understood as excluding the existence or addition of one or more other features, numbers, steps, components, or combinations thereof. Additionally, in this specification, "connection" is used to include both indirectly connecting multiple components and directly connecting them.

[0056] Additionally, terms such as “…part,” “…unit,” and “module” described in the specification refer to a unit that processes at least one function or operation, and this may be implemented in hardware, software, or a combination of hardware and software.

[0057] In addition, in describing the present invention below, if it is determined that a detailed description of related known functions or configurations could unnecessarily obscure the essence of the invention, such detailed description will be omitted.

[0058]

[0059] FIGS. 1 and FIGS. 2 are schematic diagrams for explaining a biochip for field diagnosis according to one embodiment of the present invention.

[0060]

[0061] As illustrated in FIGS. 1 and 2, a biochip (100) for field diagnosis according to one embodiment of the present invention can provide high mechanical stability and flexibility.

[0062] Accordingly, the biochip (100) for field diagnosis according to one embodiment of the present invention can be applied to devices of complex shapes, thereby providing high versatility in fields such as biochemical analysis, chemical and electrochemical sensor devices.

[0063] In addition, the biochip (100) for on-site diagnosis according to one embodiment of the present invention can be manufactured in a short time through a simple single laser process, unlike the lithography process which requires a clean room environment and proceeds with a complex manufacturing process, and accordingly, production efficiency can be maximized.

[0064] And, a biochip (100) for field diagnosis according to one embodiment of the present invention may be provided with a microfluidic channel (120) having an excellent surface area relative to its volume, and accordingly, capillary action may be maximized, and consequently, it may contribute to improving reaction and detection efficiency in a microfluidic-based device.

[0065]

[0066] A biochip (100) for field diagnosis according to one embodiment of the present invention may include a substrate (110) and a microfluidic channel (120).

[0067]

[0068] The above-described material (110) forms the exterior of a biochip (100) for field diagnosis according to one embodiment of the present invention. The above-described material (110) may have a set volume. Accordingly, the above-described material (110) may provide an internal space in which the microfluidic channel (120) is formed.

[0069] According to one embodiment of the present invention, the substrate (110) may be made of a polymer material that transmits a laser. Additionally, the substrate (110) may be made of a polymer material having flexibility.

[0070] Accordingly, the biochip (100) for field diagnosis according to one embodiment of the present invention can have high flexibility and, through this, can be utilized in various application fields including wearable devices.

[0071] In particular, since the biochip (100) for field diagnosis according to one embodiment of the present invention has high flexibility, it can be applied to devices of complex shapes, thus providing high versatility in fields such as biochemical analysis, chemical and electrochemical sensor devices.

[0072] According to one embodiment of the present invention, the polymer material forming the substrate (110) may include PDMS (Polydimethylsiloxane).

[0073] Here, the cured PDMS can maintain structural stability and flexibility even after the microfluidic channel (120) is formed inside. Accordingly, the microfluidic channel (120) formed inside the substrate (110) made of PDMS can provide the durability required for biochemical analysis and biosensing devices.

[0074] From an optical perspective, the PDMS exhibits high transmittance across various wavelength bands, particularly in the visible and near-infrared bands. This characteristic allows a laser beam to pass through the PDMS and form precise patterns within the PDMS.

[0075] Meanwhile, the above material (110) may be made of any one of various polymer materials that provide both transparency and flexibility in addition to PDMS.

[0076] For example, any one of the polymer materials selected from polyethylene terephthalate (PET), polymethyl methacrylate (PMMA), polyurethane (PU), and polyethylene (PE) may be used as the above material (110).

[0077]

[0078] The microfluidic channel (120) may be formed inside the substrate (110). According to one embodiment of the present invention, the microfluidic channel (120) may be formed inside the substrate (110) by a laser composed of multiple photons that exceed the bandgap energy of the substrate (110).

[0079] At this time, the microfluidic channel (120) can be formed inside the substrate (110) by a laser focused on the surface of the substrate (110).

[0080] According to one embodiment of the present invention, a laser composed of multiple photons exceeding the bandgap energy of the substrate (110) may be a picosecond pulse laser.

[0081] When a picosecond pulse laser focused on the surface of the above-mentioned substrate (110) is irradiated onto a substrate (110) made of a polymer material, for example, PDMS, the picosecond pulse laser can pass through the substrate (110) and be refracted into the interior of the substrate (110).

[0082] In this way, a picosecond pulse laser refracted into the interior of the substrate (110) can transfer energy into the interior of the substrate (110) by being focused by a self-focusing phenomenon (or Kerr lens effect) as it passes a certain distance. At this time, the energy transfer can be based on a nonlinear absorption phenomenon.

[0083] The above nonlinear absorption phenomenon occurs at high laser peak intensity and transfers energy through a multiphoton absorption mechanism that absorbs multiple photons simultaneously.

[0084] At this time, the position where the laser passes through and is absorbed by the transparent substrate (110) may vary depending on the number of laser pulses and the laser fluence.

[0085] Nonlinear absorption occurs locally in the focal region, causing the laser to process material only at specific locations with high energy density.

[0086] Accordingly, laser processing technology utilizing magnetic focusing and multiple photon absorption can make it possible to form a three-dimensional microfluidic channel (120) at a desired location with high resolution inside a substrate (110) made of a polymer material.

[0087] In this way, a biochip (100) for field diagnosis according to one embodiment of the present invention may have a microfluidic channel (120) formed in a three-dimensional structure inside a substrate (110) by a laser composed of multiple photons exceeding the bandgap energy of the substrate (110).

[0088] Accordingly, a biochip (100) for on-site diagnosis having high mechanical stability and flexibility can be provided.

[0089] That is, according to one embodiment of the present invention, a microfluidic channel (120) is formed directly inside the substrate (110) by a laser consisting of multiple photons exceeding the bandgap energy of the substrate (110), for example, a picosecond pulse laser, without an additional cover layer alignment and attachment process, so high mechanical stability can be provided, and since the substrate (110) in which the microfluidic channel (120) is formed is made of a flexible polymer material, for example, PDMS, it can be utilized in various applications including wearable devices.

[0090] Accordingly, the biochip (100) for field diagnosis according to one embodiment of the present invention can be applied to devices of complex shapes, thereby providing high versatility in fields such as biochemical analysis, chemical and electrochemical sensor devices.

[0091] Meanwhile, Continuous Wave Lasers (CW) utilize a linear absorption mechanism, and absorption occurs only when the energy of a single photon exceeds the material's electronic energy bandgap (laser-induced breakdown).

[0092] However, in transparent materials with large band gaps, such as PDMS, the laser mostly passes through the material because single photons cannot exceed the band gap energy. Accordingly, processing transparent materials with CW lasers is possible only when the laser fluence is above a critical value, and a very high-output laser is required.

[0093] Energy is primarily absorbed by surface impurities, initiators, defects, etc., and heat is transferred to the surface of the material, leading to thermal pyrolysis and processing of the material.

[0094] However, the continuous energy transfer of a CW laser induces thermal diffusion around the processing area, resulting in a wide heat-affected zone.

[0095] On the other hand, picosecond pulse lasers induce nonlinear absorption through high peak power for a very short period of time. During picosecond pulse laser processing, energy exceeding the bandgap energy is locally delivered through multiphoton absorption, and laser energy is effectively absorbed even within the PDMS. This enables the picosecond pulse laser to precisely process the inside of the transparent material or to form a pattern, i.e., form a microfluidic channel (120), without damaging the surface.

[0096] In other words, the multiple photon absorption phenomenon concentrated at a local site by the picosecond pulse laser minimizes the effects of thermal diffusion, thereby enabling precision micro-processing with minimized thermal effects.

[0097] In this way, according to one embodiment of the present invention, a microfluidic channel (120) is formed inside the substrate (110) by a laser consisting of multiple photons that exceed the bandgap energy of the substrate (110), i.e., a picosecond pulse laser. Unlike a lithography process that requires a clean room environment and proceeds with a complex manufacturing process, the microfluidic channel (120) can be formed inside the substrate (110) in a short time through a simple single laser process, and as a result, production efficiency can be maximized.

[0098] In addition, according to one embodiment of the present invention, a microfluidic channel (120) can be formed inside a substrate (110) by a laser consisting of multiple photons exceeding the bandgap energy of the substrate (110), i.e., a picosecond pulse laser, so as to be formed into a cylindrical structure, unlike a rectangular channel produced through a conventional lithography process.

[0099] Accordingly, the microfluidic channel (120) can have an excellent surface area relative to its volume. This structural characteristic of the microfluidic channel (120) can maximize capillary action, thereby providing the advantage of being able to deliver or mix fluids without external pressure.

[0100] These microfluidic channels (120) can contribute to improving the reaction and sensing efficiency in microfluidic-based devices.

[0101] Meanwhile, according to one embodiment of the present invention, the position of the microfluidic channel (120) formed inside the substrate (110) can be controlled through laser parameter control such as output, repetition rate, scan speed, and focus.

[0102] Accordingly, the microfluidic channel (120) can be formed at various locations, i.e., various depths, inside the substrate (110) according to the user's intention.

[0103] According to one embodiment of the present invention, the formation depth of the microfluidic channel (120) can be determined by increasing or decreasing the output of a laser composed of multiple photons, for example, a picosecond pulse laser, which exceeds the bandgap energy of the substrate (110).

[0104] That is, according to one embodiment of the present invention, the depth of the microfluidic channel (120) formed inside the substrate (110) can be shallower as the output of the picosecond pulse laser increases.

[0105] Conversely, the depth of the microfluidic channel (120) formed inside the substrate (110) can be increased as the output of the picosecond pulse laser decreases.

[0106] Accordingly, according to one embodiment of the present invention, the microfluidic channel (120) can be formed at a desired or target location inside the substrate (110) without damaging the surface structure of the substrate (110) by controlling the output of a picosecond pulse laser.

[0107] At this time, according to one embodiment of the present invention, the cross-sectional size of the microfluidic channel (120) may become smaller as the formation depth of the microfluidic channel (120) increases.

[0108] That is, as the output of the picosecond pulse laser decreases, the depth of the microfluidic channel (120) formed inside the substrate (110) increases, so the cross-sectional size of the microfluidic channel (120) can be reduced as the output of the picosecond pulse laser decreases.

[0109] Conversely, according to one embodiment of the present invention, the cross-sectional size of the microfluidic channel (120) may increase as the formation depth of the microfluidic channel (120) becomes shallower.

[0110] That is, as the output of the picosecond pulse laser increases, the depth of the microfluidic channel (120) formed inside the substrate (110) becomes shallower, so the cross-sectional size of the microfluidic channel (120) can increase as the output of the picosecond pulse laser increases.

[0111] As such, according to one embodiment of the present invention, the microfluidic channel (120) demonstrates various application possibilities in that its formation location and size within the substrate (110) can be precisely controlled by controlling the output of a picosecond pulse laser.

[0112]

[0113] Experiment Example 1

[0114] A picosecond pulse laser focused on the surface of the cured PDMS was irradiated onto the cured PDMS to process a single-path microfluidic channel inside the cured PDMS once.

[0115] At this time, the picosecond pulse laser conditions were set to an output of 4 W, a repetition rate of 300 kHz, and a scan speed of 50 mm / s. Under these conditions, the peak power was measured to be 3.8 μJ and the fluence to be 1.2 J / cm².

[0116]

[0117] Experiment Example 2

[0118] A picosecond pulse laser focused on the surface of the cured PDMS was irradiated onto the cured PDMS to process a single-pass microfluidic channel inside the cured PDMS once.

[0119] At this time, the picosecond pulse laser conditions were set to an output of 6 W, a repetition rate of 300 kHz, and a scan speed of 50 mm / s. Under these conditions, the peak power was measured to be 9.2 μJ and the fluence to be 2.9 J / cm².

[0120]

[0121] Experiment Example 3

[0122] A picosecond pulse laser focused on the surface of the cured PDMS was irradiated onto the cured PDMS to process a single-pass microfluidic channel inside the cured PDMS once.

[0123] At this time, the picosecond pulse laser conditions were set to an output of 9 W, a repetition rate of 300 kHz, and a scan speed of 50 mm / s. Under these conditions, the peak power was measured to be 17.8 μJ and the fluence to be 5.7 J / cm².

[0124]

[0125] Experiment Example 4

[0126] A picosecond pulse laser focused on the surface of the cured PDMS was irradiated onto the cured PDMS to process a microfluidic channel with an open structure on the surface of the cured PDMS once.

[0127] At this time, the picosecond pulse laser conditions were set to an output of 12 W, a repetition rate of 300 kHz, and a scan speed of 50 mm / s. Under these conditions, the peak power was measured to be 32.9 μJ and the fluence to be 10.5 J / cm².

[0128]

[0129] Figures 3 and 4 are the results of measuring the depth of microfluidic channel formation according to the laser output of the point-of-care diagnostic biochip for each experimental example.

[0130] Referring to Figures 3 and 4, it was confirmed that as the output of the picosecond pulse laser focused on the surface of the cured PDMS increases, the energy density changes, and the focal position and energy absorption characteristics of the picosecond pulse laser inside the PDMS change.

[0131] That is, as in Experimental Example 1, it was confirmed that when the output of the picosecond pulse laser is low at 4 W, the focal point of the picosecond pulse laser is formed at a deep position inside the PDMS.

[0132] In addition, as shown in Experimental Examples 2 and 3, it was confirmed that as the output of the picosecond pulse laser increased to 6 W and 9 W, the focal position of the picosecond pulse laser gradually became shallower inside the PDMS.

[0133] And as in Experiment Example 4, it was confirmed that a pattern is formed on the surface of PDMS when the output of the picosecond pulse laser is high at 12 W.

[0134] At this time, it was confirmed that as the output of the picosecond pulse laser decreases, the depth of the microfluidic channels formed inside the PDMS increases and the cross-sectional size decreases.

[0135] These results suggest the possibility of precisely forming microfluidic channels at a desired depth within PDMS by controlling the picosecond pulse laser output.

[0136] In addition, it was confirmed that when processing using a low-output picosecond pulse laser, the internal structure of PDMS can be processed without damaging the surface of PDMS by changing the focal position.

[0137] Furthermore, various application possibilities were confirmed in that the location and size of microfluidic channels formed within PDMS can be precisely controlled by adjusting the output of the picosecond pulse laser.

[0138]

[0139] Hereinafter, a biochip for on-site diagnosis according to another embodiment of the present invention will be described with reference to FIG. 5.

[0140]

[0141] FIG. 5 is a schematic diagram illustrating a biochip for on-site diagnosis according to another embodiment of the present invention.

[0142]

[0143] Referring to FIG. 5, a biochip (200) for field diagnosis according to another embodiment of the present invention may include a substrate (210) and a microfluidic channel (120).

[0144]

[0145] Since another embodiment of the present invention differs from the first embodiment of the present invention only in the structure of the substrate, the same reference numerals are assigned to the remaining identical components, and a detailed description thereof is omitted.

[0146]

[0147] According to another embodiment of the present invention, the substrate (210) may include a first substrate (211) and a second substrate (212).

[0148] The first substrate (211) may form a lower layer of the substrate (210). The first substrate (211) may provide a laminated surface of the second substrate (212).

[0149] The first substrate (211) may be made of a polymer material having transparency and flexibility. For example, the first substrate (211) may be made of PDMS.

[0150] At this time, according to another embodiment of the present invention, the first substrate (211) may have a relatively higher absorption rate for a laser composed of multiple photons than the second substrate (212).

[0151] To this end, for example, a black pigment may be added to the PDMS forming the first substrate (211). However, this is merely an example, and the pigment added to the PDMS in the present invention is not necessarily limited to black.

[0152] The second substrate (212) may be laminated onto the first substrate (211). Accordingly, the second substrate (212) may form an upper layer of the substrate (210). The second substrate (212) may be made of a polymer material having transparency and flexibility. For example, the second substrate (212) may be made of PDMS.

[0153] Accordingly, according to another embodiment of the present invention, the substrate (210) may be formed by a lamination of a first substrate (211) forming an opaque layer and a second substrate (212) forming a transparent layer.

[0154] According to another embodiment of the present invention, the microfluidic channel (120) may be formed at the interface between the first substrate (211) and the second substrate (212) by a laser consisting of multiple photons focused on the surface of the second substrate (212) and having a bandgap energy exceeding that of the second substrate (212).

[0155] For example, the microfluidic channel (120) can be formed at the interface between the first substrate (211) and the second substrate (212) by a picosecond pulse laser focused on the surface of the second substrate (212).

[0156] When the self-focusing length of a picosecond pulse laser focused on the surface of the second substrate (212) is longer than the thickness of the second substrate (212) forming the transparent layer, absorption occurs at the interface between the second substrate (212) forming the transparent layer and the first substrate (211) forming the opaque layer located below it, and a microfluidic channel (120) can be formed at the interface.

[0157] This means that the degree of focusing of the picosecond pulse laser can be controlled by controlling the thickness of the second substrate (212) forming the transparent layer, and accordingly, the size of the microfluidic channel (120) formed at the interface can also be controlled.

[0158] That is, according to another embodiment of the present invention, the formation location of the microfluidic channel (120) within the substrate (210) can be determined according to the thickness of the second substrate (212) forming the transparent layer.

[0159] Meanwhile, according to another embodiment of the present invention, a picosecond pulse laser that passes through a second substrate (212) forming a transparent layer is absorbed by a first substrate (211) forming an opaque layer, and a microfluidic channel (120) can be formed at the interface between the first substrate (211) and the second substrate (212).

[0160] At this time, the microfluidic channel (120) formed at the interface between the first substrate (211) forming the opaque layer and the second substrate (212) forming the transparent layer may have a relatively larger cross-sectional size than the microfluidic channel (120 in FIG. 2) formed inside the substrate (110 in FIG. 2) forming the transparent layer.

[0161] For example, the microfluidic channel (120) formed at the interface between the first substrate (211) forming the opaque layer and the second substrate (212) forming the transparent layer may have a cross-sectional size approximately 10 times larger than the microfluidic channel (120 in FIG. 2) formed inside the substrate (110 in FIG. 2) forming the transparent layer.

[0162] This means that the cross-sectional size of the microfluidic channel (120) formed at the interface between the first substrate (211) forming the opaque layer and the second substrate (212) forming the transparent layer can be effectively controlled by adjusting the absorption rate of the picosecond pulse laser irradiated onto the second substrate (212) forming the transparent layer.

[0163] That is, according to another embodiment of the present invention, the cross-sectional size of the microfluidic channel (120) formed at the interface between the first substrate (211) forming the opaque layer and the second substrate (212) forming the transparent layer may vary depending on the content of the black pigment added to the PDMS forming the first substrate (211).

[0164]

[0165] As described above, according to another embodiment of the present invention, a microfluidic channel (120) is formed at a crosslinked interface of the substrate (210), that is, at the interface between the first substrate (211) forming the opaque layer and the second substrate (212) forming the transparent layer, by controlling the thickness of the second substrate (212) forming the transparent layer and the absorption rate of the picosecond pulse laser irradiated on the second substrate (212), and its size can also be controlled.

[0166] As such, a biochip (200) for on-site diagnosis according to another embodiment of the present invention may have a substrate (210) having a multilayer structure in which a microfluidic channel (210) is formed at the interface, and such a biochip (200) for on-site diagnosis may be utilized in fields requiring a complex structure, such as a healthcare device.

[0167]

[0168] Hereinafter, a method for manufacturing a biochip for field diagnosis according to one embodiment of the present invention will be described with reference to FIGS. 6 to 9.

[0169]

[0170] FIG. 6 is a flowchart illustrating a method for manufacturing a biochip for field diagnosis according to an embodiment of the present invention, FIG. 7 is a schematic diagram for explaining step S110 of FIG. 6, FIG. 8 is a schematic diagram for explaining step S120 of FIG. 6, and FIG. 9 is a schematic diagram for explaining step S130 of FIG. 6.

[0171]

[0172] Referring to FIG. 6, a method for manufacturing a biochip for field diagnosis according to one embodiment of the present invention may include steps S110, S120, and S130.

[0173]

[0174] S110 step

[0175] The above S110 step is a step of preparing the material (110).

[0176] Referring to FIG. 7, in step S110, a substrate (110) consisting of a single layer can be prepared.

[0177] At this time, the above-mentioned substrate (110) may be made of a polymer material that transmits a laser composed of multiple photons exceeding the bandgap energy of the substrate (110), for example, a picosecond pulse laser.

[0178] PDMS may be used as the polymer material forming the above substrate (110). Accordingly, the above substrate (110) can be prepared as a transparent and flexible single layer.

[0179] In the above S110 step, for example, a PDMS base and a curing agent can be mixed in a ratio of 20:1, poured into a Petri dish, and cured for 24 hours while maintaining a level surface. Through this, a single-layer substrate (110) made of transparent and flexible PDMS can be prepared.

[0180]

[0181] S120 step

[0182] The above step S120 is a step of focusing a laser consisting of multiple photons that exceed the bandgap energy of the substrate (110) prepared through the above step S110 onto the surface of the substrate (110).

[0183] Referring to FIG. 8, in step S120, a picosecond pulse laser can be focused on one side of the surface of a substrate (110) prepared as a transparent and flexible single layer.

[0184]

[0185] S130 step

[0186] The above step S130 is a step of irradiating a picosecond pulse laser focused on the surface of the substrate (110) through the above step S120 toward the substrate (110) which is made of a transparent layer.

[0187] Referring to FIG. 9, in step S130, a picosecond pulse laser can be irradiated while moving planarly over the substrate (110), thereby forming a microfluidic channel (120) inside the substrate (110). At this time, in step S130, a microfluidic channel (120) can be formed inside the substrate (110) within 1 minute.

[0188] Here, when a picosecond pulse laser focused on the surface of a substrate (110) is irradiated onto a substrate (110) forming a transparent layer, that is, a substrate (110) made of PDMS, the picosecond pulse laser can pass through the substrate (110) and be refracted into the interior of the substrate (110).

[0189] In this way, a picosecond pulse laser refracted into the interior of the substrate (110) can form a microfluidic channel (120) with a three-dimensional structure inside the substrate (110) through a self-focusing phenomenon and a multiple photon absorption mechanism.

[0190] At this time, the microfluidic channel (120) formed inside the substrate (110) by the picosecond pulse laser can be formed in a cylindrical structure, and accordingly, can have an excellent surface area relative to its volume, thereby maximizing capillary action. Through this, the advantage of being able to deliver or mix fluid without external pressure can be provided.

[0191] Meanwhile, in step S130 above, laser parameters such as output, repetition rate, scan speed, and focus can be controlled. Through this, microfluidic channels (1200) can be formed at various depths intended by the user within the substrate (110).

[0192] In step S130 above, the output of the picosecond pulse laser irradiated onto the substrate (110) can be increased. Through this, the depth at which the microfluidic channel (120) is formed inside the substrate (110) can be relatively shallow.

[0193] Conversely, in step S130 above, the output of the picosecond pulse laser irradiated onto the substrate (110) can be reduced. Through this, the depth at which the microfluidic channel (120) is formed inside the substrate (110) can be relatively deep.

[0194] In this way, in step S130, by controlling the output of the picosecond pulse laser irradiated onto the substrate (110), a microfluidic channel (120) can be formed at a desired location inside the substrate (110) without damaging the surface structure of the substrate (110).

[0195] At this time, the cross-sectional size of the microfluidic channel (120) can be reduced as the output of the picosecond pulse laser decreases, and can be increased as the output of the picosecond pulse laser increases.

[0196] According to one embodiment of the present invention, in step S130, the depth (formation location) and size of the microfluidic channel (120) formed inside the substrate (110) can be precisely controlled by adjusting the output of the picosecond pulse laser irradiated onto the substrate (110).

[0197]

[0198] FIGS. 10 and FIGS. 11 are cross-sectional photographs of a biochip for field diagnosis manufactured through a method for manufacturing a biochip for field diagnosis according to an embodiment of the present invention, FIG. 10 is a photograph taken at 5x magnification, and FIG. 11 is a photograph taken at 20x magnification.

[0199] Here, a picosecond pulse laser with a wavelength of 532 nm was focused on the surface of PDMS, and the laser conditions were set to an output of 9 W, a repetition rate of 300 kHz, and a scan rate of 50 mm / s to form a linear microfluidic channel with a single irradiation.

[0200] As shown in FIGS. 10 and 11, under the laser conditions, a microfluidic channel with a diameter of 34.51 μm was formed inside the PDMS without causing damage to the surface of the PDMS.

[0201] The length of the formed microfluidic channel was 20 mm, and it was confirmed that it was precisely formed at the desired location depending on the laser conditions.

[0202] In this way, it was demonstrated that the formation location of microfluidic channels within PDMS can be controlled by adjusting the laser's focus and output, and it was confirmed that the internal structure of PDMS can be designed without surface damage.

[0203]

[0204] Meanwhile, experiments utilizing capillary action were conducted to verify the fluid transport capability of the microfluidic channels formed inside the PDMS.

[0205] In this experiment, PDMS with formed microfluidic channels was immersed vertically in a solution of magenta ink mixed with water, and the movement of fluid through the microfluidic channels due to the capillary effect was observed.

[0206] FIGS. 12 to 14 are photographs of experiments on the fluid movement phenomenon of microfluidic channels formed inside PDMS of a point-of-care diagnostic biochip manufactured through a method for manufacturing a point-of-care diagnostic biochip according to an embodiment of the present invention. FIG. 12 is a photograph taken at 5x magnification with a focus on the microfluidic channel on PDMS, FIG. 13 is a photograph taken at 20x magnification with a focus on the microfluidic channel on PDMS, and FIG. 14 is a photograph taken at 20x magnification of a cross-section of a microfluidic channel confirmed after the microfluidic channel was stained.

[0207] First, as shown in FIGS. 12 to 14, it was confirmed that the inside of the microfluidic channels was stained as the solution moved through the microfluidic channels formed inside the PDMS. This demonstrated the continuity and fluid movement capabilities of the microfluidic channels formed inside the PDMS.

[0208] Experimental results confirmed that fluid moves spontaneously through microfluidic channels formed inside PDMS even without external pressure.

[0209] This demonstrates that the point-of-care diagnostic biochip manufactured through the method for manufacturing a point-of-care diagnostic biochip according to one embodiment of the present invention effectively enables microfluidic movement, proving that it is a technology suitable for microfluidic-based devices and indicating high potential for utilization in biochemical analysis and sensor applications.

[0210]

[0211] Hereinafter, a method for manufacturing a biochip for field diagnosis according to another embodiment of the present invention will be described with reference to FIGS. 15 to 18.

[0212]

[0213] FIG. 15 is a flowchart illustrating a method for manufacturing a biochip for point-of-care diagnosis according to another embodiment of the present invention, FIG. 16 is a schematic diagram for explaining step S210 of FIG. 15, FIG. 17 is a schematic diagram for explaining step S220 of FIG. 15, and FIG. 18 is a schematic diagram for explaining step S230 of FIG. 15.

[0214]

[0215] Referring to FIG. 15, a method for manufacturing a biochip for field diagnosis according to another embodiment of the present invention may include steps S210, S220, and S230.

[0216]

[0217] S210 stage

[0218] The above S210 step is a step of preparing the material (210).

[0219] Referring to FIG. 16, in step S210, a multilayer structure substrate (210) formed by stacking a first substrate (211) and a second substrate (212) can be prepared.

[0220] The first substrate (211) forming the lower layer of the above substrate (210) may be prepared as an opaque layer. Additionally, the second substrate (212) laminated on the first substrate (211) and forming the upper layer of the above substrate (210) may be prepared as a transparent layer.

[0221] To this end, in step S210, a PDMS base and a curing agent are first mixed, and then a black pigment is added to the mixture and mixed uniformly. At this time, the PDMS base and the curing agent may be mixed in a ratio of, for example, 20:1, and the black pigment may be added at 2.5 wt% to the mixture of the PDMS base and the curing agent.

[0222] Depending on the content of pigment added to the mixture of the PDMS base and the curing agent, the cross-sectional size of the microfluidic channel (120 in FIG. 18) formed at the interface between the first substrate (211) forming the opaque layer and the second substrate (212) forming the transparent layer may vary.

[0223] This means that by controlling the pigment content, the cross-sectional size of the microfluidic channel (120 in FIG. 18) formed at the interface between the first substrate (211) forming the opaque layer and the second substrate (212) forming the transparent layer can be controlled.

[0224] Next, in step S210, a mixture with added black pigment can be poured into a Petri dish and cured for 24 hours while maintaining a horizontal position. Through this, a first substrate (211) can be formed, which forms the lower layer of the substrate (210) and is provided as an opaque layer.

[0225] Next, in step S210, a mixture of PDMS base and curing agent mixed in the same ratio as the first substrate (211) can be poured onto the first substrate (211) and cured. Through this, a second substrate (212), which forms the upper layer of the substrate (210) and is provided as a transparent layer, can be laminated and formed on the first substrate (211).

[0226] At this time, in step S210, the second substrate (212) can be formed with a thickness thinner than the magnetic focusing distance of the laser used in the subsequent process so that a microfluidic channel (120) can be formed at the interface between the first substrate (211) and the second substrate (212).

[0227]

[0228] S220 stage

[0229] The above S220 step is a step of focusing a laser consisting of multiple photons that exceed the bandgap energy of the substrate (210) prepared through the above S210 step onto the surface of the substrate (110).

[0230] Referring to FIG. 17, in step S220, a picosecond pulse laser can be focused on one side of the surface of the second substrate (212) forming the transparent layer.

[0231]

[0232] S230 step

[0233] The above step S230 is a step of irradiating a picosecond pulse laser focused on the surface of the second substrate (212) through the above step S220 toward the second substrate (212) which is made of a transparent layer.

[0234] Referring to FIG. 18, in step S230, a picosecond pulse laser can be irradiated while moving planarly over the second substrate (212), thereby forming a microfluidic channel (120) at the interface between the first substrate (211) and the second substrate (212). At this time, in step S230, a microfluidic channel (120) can be formed at the interface between the first substrate (211) and the second substrate (212) within 1 minute.

[0235] Here, in step S210, a second substrate (212) was formed with a thickness thinner than the magnetic focusing distance of the picosecond pulse laser.

[0236] Accordingly, since the magnetic focusing distance of the picosecond pulse laser irradiated on the second substrate (212) is longer than the thickness of the second substrate (212), absorption occurs in the first substrate (211) forming an opaque layer located below the second substrate (212) forming a transparent layer, and through this, a microfluidic channel (120) can be formed at the interface between the second substrate (212) forming a transparent layer and the first substrate (211) forming an opaque layer located below it.

[0237]

[0238] FIGS. 19 and 20 are cross-sectional photographs of a biochip for field diagnosis manufactured through a method for manufacturing a biochip for field diagnosis according to another embodiment of the present invention, where FIG. 19 is a photograph taken at 5x magnification and FIG. 20 is a photograph taken at 50x magnification.

[0239] Here, a picosecond pulse laser with a wavelength of 532 nm and a maximum output of 12 W was focused on the surface of PDMS, and the laser conditions were set to an output of 6 W, a repetition rate of 500 kHz, and a scan speed of 3 mm / s to form a linear microfluidic channel with a single irradiation.

[0240] At this time, the PDMS is provided with a 2.5 mm thick opaque PDMS layer in which the laser absorption rate is controlled using a black pigment, and a 3.5 mm thick transparent PDMS layer laminated on the opaque PDMS layer.

[0241] Referring to Figures 19 and 20, the maximum size of the linear microfluidic channel formed at the interface between the opaque PDMS layer and the transparent PDMS layer was measured to be 191 μm in width and 538 μm in length.

[0242] At this time, it was confirmed that a 'V'-shaped etching appeared on the surface of the transparent PDMS layer due to laser ablation, and the residual energy penetrated the transparent PDMS layer and was absorbed by the opaque PDMS layer, forming a microfluidic channel at the interface between the opaque PDMS layer and the transparent PDMS layer.

[0243]

[0244] Meanwhile, FIGS. 21 and 22 are electron microscope images of the interface between the opaque PDMS layer and the transparent PDMS layer of a point-of-care diagnostic biochip manufactured through a method for manufacturing a point-of-care diagnostic biochip according to another embodiment of the present invention.

[0245] As shown in Figures 21 and 22, it was confirmed that the gap between the opaque PDMS layer and the transparent PDMS layer in the sufficiently cured PDMS is very narrow, approximately 200 nm.

[0246] Accordingly, the phenomenon in which fluid moving through the microfluidic channel formed at the interface between the opaque PDMS layer and the transparent PDMS layer escapes the microfluidic channel and penetrates into the interface between the opaque PDMS layer and the transparent PDMS layer can be prevented.

[0247]

[0248] Although the present invention has been described in detail using preferred embodiments, the scope of the invention is not limited to specific embodiments and should be interpreted by the appended claims. Furthermore, those skilled in the art will understand that many modifications and variations are possible without departing from the scope of the invention.

Claims

1. A substrate having a set volume; and A biochip for point-of-care diagnosis comprising a microfluidic channel formed using a laser, the microfluidic channel formed inside the substrate by a laser composed of multiple photons exceeding the bandgap energy of the above-described material.

2. In Paragraph 1, A point-of-care diagnostic biochip having a microfluidic channel formed using a laser, wherein the formation depth of the microfluidic channel is determined according to the increase or decrease in the output of the laser.

3. In Paragraph 2, The formation depth of the microfluidic channel becomes shallower as the laser output increases, but, A point-of-care diagnostic biochip having a microfluidic channel formed using a laser, wherein the cross-sectional size of the microfluidic channel decreases as the formation depth of the microfluidic channel increases.

4. In Paragraph 1, A point-of-care diagnostic biochip having a microfluidic channel formed using a laser, wherein the microfluidic channel is formed inside the substrate by a laser focused on the surface of the substrate.

5. In Paragraph 1, A point-of-care diagnostic biochip having a microfluidic channel formed using a laser, wherein the laser composed of the above multiple photons is a picosecond pulse laser.

6. In Paragraph 1, The above description is made of a polymer material that transmits the laser, The above polymer material is a point-of-care biochip having microfluidic channels formed using a laser, comprising PDMS (Polydimethylsiloxane).

7. In Paragraph 1, The above description is, First description; and A second substrate laminated on the first substrate, wherein The first above-described material is a biochip for point-of-care diagnosis having a microfluidic channel formed using a laser, which has a relatively higher absorption rate for the laser composed of multiple photons than the second above-described material.

8. In Paragraph 7, The above microfluidic channel is a point-of-care biochip having a microfluidic channel formed using a laser at the interface between the first substrate and the second substrate.

9. Step of preparing materials; A step of focusing a laser composed of multiple photons exceeding the bandgap energy of the above-described material onto the surface of the above-described material; and A method for manufacturing a point-of-care biochip having a microfluidic channel formed using a laser, comprising the step of irradiating a laser focused on the surface of the substrate toward the substrate to form a microfluidic channel inside the substrate.

10. In Paragraph 9, A method for manufacturing a point-of-care biochip having a microfluidic channel formed using a laser, wherein in the step of forming a microfluidic channel inside the above-mentioned material, the output of the laser is controlled to control the depth of formation of the microfluidic channel.

11. In Paragraph 9, In the step of preparing the above-mentioned material, a material consisting of a single layer is prepared, The above description describes a method for manufacturing a point-of-care biochip comprising a microfluidic channel formed using a laser, which is made of a polymer material that transmits the laser.

12. In Paragraph 9, In the step of preparing the above-mentioned material, a multi-layered material is prepared, The above-mentioned multilayer substrate is, First description; and A second substrate laminated on the first substrate, wherein A method for manufacturing a biochip for point-of-care diagnosis comprising a first substrate having a microfluidic channel formed using a laser, wherein the absorption rate for the laser composed of multiple photons is relatively higher than that of the second substrate.

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