WO2024019200A1 - Biopuce de commande de fluide à base optique, et procédés de fabrication et de commande de fluide associés - Google Patents

Biopuce de commande de fluide à base optique, et procédés de fabrication et de commande de fluide associés Download PDF

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Publication number
WO2024019200A1
WO2024019200A1 PCT/KR2022/010934 KR2022010934W WO2024019200A1 WO 2024019200 A1 WO2024019200 A1 WO 2024019200A1 KR 2022010934 W KR2022010934 W KR 2022010934W WO 2024019200 A1 WO2024019200 A1 WO 2024019200A1
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WIPO (PCT)
Prior art keywords
port
biochip
fluid
ports
light
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PCT/KR2022/010934
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English (en)
Korean (ko)
Inventor
김동현
이홍기
성종환
유하준
서광명
변인섭
가석현
고관휘
임성민
문귀영
이현웅
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연세대학교 산학협력단
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Publication of WO2024019200A1 publication Critical patent/WO2024019200A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0678—Facilitating or initiating evaporation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks

Definitions

  • the disclosed embodiments relate to a biochip and its manufacturing and fluid control method, and to an optical-based fluid control biochip and its manufacturing and fluid control method.
  • Biochips are designed to allow various experiments and tests that could previously only be performed using various equipment in a laboratory to be performed in a small chip size. They have the advantage of being able to be used at high speeds with a small amount of material, so they have recently been used in many fields. It is becoming. In particular, biochips in the form of rapid antigen tests and diagnostic kits that can identify specific diseases are widely distributed and used, and research and development on biochips are currently being conducted continuously.
  • biochips are controlled by using the pressure when the fluid is first injected to push the fluid until it reaches the main location of the biochip, or by using an external pump pressure to push the fluid, or by using gravity to move the entire chip.
  • a method of controlling the flow of fluid within a biochip is used, such as by moving the fluid.
  • this method has the limitation that it is difficult to locally control the flow of fluid in the biochip.
  • the purpose of the disclosed embodiments is to provide a biochip capable of locally finely controlling the flow of fluid using light, and a method for manufacturing the same and controlling the fluid.
  • the disclosed embodiments include a biochip that forms a metal layer on each port of the biochip and precisely controls the flow of fluid based on changes in the amount of fluid evaporation that occur by irradiating light to the formed metal layer, and a method for manufacturing and controlling the fluid.
  • the purpose is to provide.
  • the purpose of the disclosed embodiments is to provide a biochip capable of controlling fluid flow to multiple ports with a single light using an optical mask, and a method for manufacturing the same and controlling the fluid.
  • a biochip includes a substrate having a plurality of ports through which at least one raw material sample in a fluid state can be supplied and a flow channel connecting the plurality of ports; and a metal structure formed at the same height as the lower surface of the flow channel, wherein the metal structure generates heat by either light or current applied to the area where at least one port among the plurality of ports is formed.
  • the flow of fluid is controlled by controlling the amount of fluid evaporation in the port.
  • the metal structure When light is irradiated to an area where at least one port is formed, the metal structure generates heat through a photothermal effect, thereby controlling the amount of evaporation of fluid in the port.
  • the metal structure may adjust the speed at which the fluid flows by adjusting the heat generated according to the intensity or wavelength of light irradiated to each area where the at least one port is formed.
  • the biochip may further include an optical mask in which at least one hole is formed so that light emitted from a single light source is emitted only to at least one designated port among the plurality of ports.
  • the optical mask may have different sizes and patterns of the at least one hole so that light of a single wavelength and single intensity emitted from the single light source is applied to each port at different intensities.
  • the optical mask may be formed by filling the at least one hole with one of glass, a lens, or a phase shift filter so that light emitted from the single light source is applied to each port at different intensities or wavelengths.
  • the metal structure may be formed on the entire area of the substrate at the same height as the lower surface of the flow channel.
  • the metal structure may be formed of a plurality of individual metal bodies disposed at each position of the plurality of ports spaced apart from each other.
  • the metal structure generates heat due to the Joule heat effect when a current is applied to at least one individual metal body among a plurality of individual metal bodies, thereby controlling the amount of evaporation of fluid in the corresponding port.
  • the biochip operates when the metal structure generates heat at the location of the port to which the fluid is supplied among the plurality of ports, the supplied fluid flows and is transferred to another port through the flow channel, and the port to which the fluid is not supplied flows. If the metal structure generates heat at the position, the flow of fluid transmitted from other ports can be suppressed.
  • the biochip may have the plurality of ports arranged in a matrix form, and the flow channel may be formed to connect all of the ports arranged adjacent to each other among the plurality of ports arranged in the matrix form.
  • the metal structure may be implemented by applying metal, attaching a pre-fabricated metal plate, or containing metal nanoparticles in some areas of the substrate.
  • a biochip manufacturing method includes forming a plurality of ports spaced apart from each other on a substrate through which at least one raw material sample in a fluid state can be supplied; forming a flow channel connecting the plurality of ports on a substrate; and heat is generated by either light or current applied to the area where at least one of the plurality of ports is formed at the same height as the lower surface of the flow channel, thereby controlling the amount of evaporation of the fluid in the port, thereby controlling the flow of fluid. and forming a metal structure that allows this to be controlled.
  • the fluid control method of a biochip includes a plurality of ports and a flow channel connecting the plurality of ports, and a metal structure formed at the same height as the lower surface of the flow channel. Supplying at least one raw material sample in a fluid state to at least one port among the plurality of ports; And by applying light or current to the metal structure through an area where a port selected according to the path through which the raw material sample should be transmitted through the flow channel is formed, the amount of fluid evaporated from the port is increased by heat generated by the metal structure. and controlling the flow of fluid by regulating it.
  • the biochip and its manufacturing and fluid control method according to the embodiment form a metal layer at each port of the biochip, and locally finely control the flow of fluid based on the change in the amount of fluid evaporation that occurs by irradiating light to the formed metal layer. can be controlled properly.
  • the flow of fluid not only can the flow of fluid be controlled more precisely by adjusting the wavelength or intensity of the irradiated light, but also the fluid flow for multiple ports can be controlled locally and precisely with a single light by using an optical mask. .
  • Figure 1 is a diagram to explain the concept in which fluid flow is induced according to differences in the evaporation amount of fluid in a biochip.
  • FIG. 2 is a diagram illustrating the configuration and operation of a biochip that controls the flow of fluid by inducing a difference in the evaporation amount of fluid using light according to an embodiment.
  • Figures 3 and 4 are diagrams for explaining a method of synthesizing and testing materials using the biochip of an example.
  • Figure 5 shows the configuration of a biochip according to another embodiment.
  • Figure 6 shows another example of the photo mask of Figure 5.
  • Figure 7 shows a biochip manufacturing and fluid control method according to an embodiment.
  • ... unit refers to a unit that processes at least one function or operation, which is hardware, software, or hardware. and software.
  • Figure 1 is a diagram to explain the concept in which fluid flow is induced according to differences in the evaporation amount of fluid in a biochip.
  • FIG. 1 shows a cross-sectional view of the biochip 10.
  • the biochip 10 can be divided into an upper substrate 11 and a lower substrate 12.
  • a plurality of ports P1 and P2 through which the fluid 16 is supplied are formed on the upper substrate 11 and spaced apart from each other.
  • a flow channel 13 may be formed in the upper substrate 11 or the lower substrate 12, which is a path through which the fluid 16 supplied to at least one port among the plurality of ports P1 and P2 moves to another port. there is.
  • the flow channel 13 is formed in the shape of a groove in at least one of the upper substrate 11 or the lower substrate 12, and the upper substrate 11 and the lower substrate 12 are combined to form a path through which fluid flows. there is. That is, in FIG. 1 , as an example, the flow channel 13 is shown as being formed in the upper substrate 11, but the flow channel 13 may also be formed in the lower substrate 12.
  • the upper substrate 11 and the lower substrate 12 may be made of various plastic or acrylic materials that do not react with the fluid 16 supplied to the port, and may be made of transparent materials.
  • a general biochip 10 is shown in which the upper substrate 11 and the lower substrate 12 are individually manufactured and connected to each other to facilitate forming a plurality of ports (P1, P2) and flow channels 13.
  • the biochip 10 may be implemented on a single substrate in which the upper substrate 11 and the lower substrate 12 are not distinguished.
  • the biochip 10 is implemented so that the two ports (P1, P2) are connected to each other through the flow channel 13, and the fluid 16 is supplied to the first port (P1) in a relatively large size.
  • Fluid droplets may be formed, and relatively small-sized fluid droplets may be formed in the second port (P2).
  • pressures of different sizes are applied to fluid droplets of different sizes formed in the first and second ports (P1, P2) due to surface tension.
  • a relatively small pressure is applied to the fluid droplet formed in the first port P1, which has a large radius of curvature due to its large size, while the second port has a small radius of curvature due to its small size.
  • a relatively large pressure is applied to the fluid droplet formed in (P2).
  • the fluid 16 flows from the second port (P2) through the flow channel 13 to the first port (P1). It flows in the direction of port (P1).
  • the fluid droplets in the first port (P1) which have a relatively large size, quickly evaporate the fluid (16) due to their large surface area
  • the fluid droplets in the second port (P2) have a relatively small surface area. (16) evaporates slowly.
  • the reduction in the size of the fluid droplets due to the flow of the fluid 16 occurs more significantly than the reduction in the size of the fluid droplets due to evaporation. . Therefore, the flow of fluid 16 in the direction of the first port P1, as shown in (a) of FIG. 1, is caused by surface tension because the radii of curvature of the fluid droplets formed in the first and second ports P1 and P2 are the same. It only occurs for a certain period of time until the pressure is equalized.
  • the size of the fluid droplets in the first port (P1) quickly decreases due to the large evaporation amount due to the large surface area, while the fluid droplets in the second port (P2) have a small evaporation amount due to the small surface area, causing the fluid droplets to drop.
  • the fluid 16 flows from the first port P1 to the second port P2 through the flow channel 13.
  • the biochip 10 can locally control the flow of the fluid 16 according to the amount of fluid evaporation generated from the plurality of ports P1 and P2.
  • the flow of fluid 16 in Figure 1 is generated depending on natural evaporation supplied to the ports P1 and P2, it cannot be seen as controlling the fluid 16 to flow in the direction desired by the user. In particular, the speed at which the fluid 16 flows cannot be adjusted. Therefore, it is very difficult to use the biochip 10 of FIG. 1 for material synthesis and testing.
  • FIG. 2 is a diagram illustrating the configuration and operation of a biochip that controls the flow of fluid by inducing a difference in the evaporation amount of fluid using light according to an embodiment.
  • FIG. 2 also shows a cross-sectional view of the biochip 20.
  • the biochip 20 according to the embodiment also has an upper substrate 21 and a lower substrate 21, similar to the biochip 10 of FIG. 1, and the upper substrate 21 has A plurality of ports P1 and P2 are formed, and a flow channel 23 is formed in the upper substrate 21 or the lower substrate 22.
  • the biochip 20 of the embodiment has a plurality of ports (P1, P2) corresponding to each port (P1, P2) at each position where the plurality of ports (P1, P2) are formed on the lower surface of the flow channel 23.
  • the metal structures 24 and 25 are formed.
  • the metal structures may be formed in the form of a metal plate as shown in (a) of FIG. 2 or have a regular or irregular pattern as shown in (b) of FIG. 2. , it can be implemented to have a nanoscale or larger scale size.
  • the metal structure ((MP1, MP2), (MP3, MP4)) may be implemented by applying metal, or may be implemented by manufacturing and attaching a nano-scale structured metal plate (metal layer) or nano-pattern.
  • the lower substrate 22 may be implemented with nanoparticle metal.
  • Each of the plurality of metal structures may be implemented with various metals such as gold, silver, platinum, aluminum, or copper, which can cause a photothermal effect when light is applied.
  • At least one metal structure light (L1, L2) among the plurality of metal structures (MP1, MP2) is used to control the flow of the fluid 26 through the flow channel 23. investigate.
  • the first metal structure MP1 to which the first light L1 is applied When applying the first light L1 to the first metal structure MP1 corresponding to the first port P1 in (a) of FIG. 2, the first metal structure MP1 to which the first light L1 is applied ) generates heat due to the photothermal effect, and the heat generated by the photothermal effect improves the evaporation rate of the fluid droplets formed in the first port (P1). Accordingly, the radius of curvature of the fluid droplet formed in the first port (P1) becomes smaller faster and is subjected to greater pressure due to surface tension. As a result, the movement speed of the fluid 26 flowing from the first port (P1) to the second port (P2) through the flow channel 23 increases.
  • the second metal structure MP2 when the second light L2 is applied to the second metal structure MP2 formed at a position corresponding to the second port P2, the second metal structure MP2 generates heat and the second port P2 ) of the fluid 26 is evaporated, but since the fluid droplets in the first port (P1) have a larger surface area and have a large natural evaporation amount, the fluid 26 is evaporated from the first port (P1) to the second port (P2). ), or if it does flow, it only flows in a very small amount. That is, when the second light L2 is applied to the second metal structure MP2, flow of the fluid 26 from the first port P1 to the second port P2 due to natural evaporation can be suppressed.
  • the flow speed of the fluid 26 can be precisely controlled by adjusting the wavelength or intensity of the first and second lights L1 and L2.
  • the metal structures MP1 and MP2 may generate heat differently depending on the intensity or wavelength of the applied light L1 and L2.
  • the metal structures MP1 and MP2 can generate more heat as the intensity of light becomes stronger, and as light with a matching wavelength is applied to the metal, more heat can be generated. Therefore, applying light of a stronger intensity to the metal structures (MP1, MP2) or applying light of a wavelength matching the type of metal implemented by the metal structures (MP1, MP2) will increase the amount of evaporation of the fluid 26. This allows not only the speed at which the fluid 26 flows to be faster or slower, but also the direction in which the fluid 26 flows can be changed. That is, the flow of the fluid 26 can be finely controlled using the intensity and wavelength of the light L1 and L2.
  • the first and second lights (L1, L2) irradiated to the metal structures (MP1, MP2) may be irradiated from a light source (not shown), and the light source may be implemented as a laser module (not shown), in this case.
  • the first and second lights L1 and L2 may be laser lights.
  • the light (L1, L2) since the light (L1, L2) must be independently applied to the first and second metal structures (MP1, MP2), the light (L1, L2) is irradiated to each metal structure (MP1, MP2).
  • a plurality of light sources may also be provided. For example, a number of light sources may be provided corresponding to the number of ports P1 and P2.
  • the flow channel 23 is formed only between the two ports (P1 and P2) in the biochip 20, so that the fluid 26 flows through the first port (P1) and the second port (P2). It could only flow between them. However, multiple ports may be formed in the biochip 20, and the flow channel 23 may be formed to connect multiple ports.
  • the flow channel 23 is formed to connect a plurality of ports in addition to the first and second ports P1 and P2. In this case, when the first light L1 is applied to the first metal structure MP3 among the first and second metal structures MP3 and MP4, the fluid 26 flows through the second port ( P2) as well as other ports (not shown).
  • the fluid 26 flows along all movement paths formed by the flow channel 23 in the first port P1.
  • the fluid 26 may not flow in the direction of the second port P2 but may only flow in the other port direction.
  • the fluid supplied to the first port (P1) is It does not flow in the direction of port (P2), but can only flow in the direction of other ports.
  • first and second metal structures MP3 and MP4 are formed in nanopatterns, but they may also be implemented in the form of a metal plate as shown in Figure 2(a).
  • a plurality of metal structures 24 are formed at positions corresponding to each of the plurality of ports P1 and P2 in the flow channel 23, and at least one of the plurality of metal structures 24 formed Not only can the flow of fluid be controlled locally by radiating light (L1, L2) independently to the metal structure, but also the direction and speed of fluid flow can be finely adjusted by adjusting the intensity or wavelength of the irradiated light.
  • the biochip 20 may control the flow of the fluid 26 by applying heat directly rather than light to each of the plurality of metal structures (MP1 to MP4). It may be configured to control the flow of the fluid 26 by allowing a current to flow through it, using the heat generated by the Joule heat effect. In this case, the amount of evaporation of the fluid 26 varies depending on the intensity of the flowing current, so that the flow of the fluid 26 can be controlled.
  • Figures 3 and 4 are diagrams for explaining a method of synthesizing and testing materials using the biochip of an example.
  • the biochip 30 of FIG. 3 includes an upper substrate 31 and a lower substrate 32. Also, a case where six ports (P11, P12, P21, P22, P31, P32) and one target port (TP) are formed on the upper substrate 31 is shown. Here, six ports (P11, P12, P21, P22, P31, P32) are arranged in a 3 x 2 matrix, and the target port (TP) is arranged separately. And the Euro Channel 33 has 6 ports (P11, P12, P21, P22, P31, P32) and 2 ports ((P11, P12), (P21, P22), (P31, P32)) per row. connection, and is commonly connected to the target port (TP).
  • the six ports supply raw material samples, such as materials for producing synthetic materials or samples for performing various tests, in a fluid state, and flow through them as light is applied. It is formed to control the flow of fluid flowing through the channel 33.
  • the target port (TP) is a port where target samples such as synthetic materials or specimens generated from raw material samples are collected when synthesizing, reacting, experimenting, testing, or measuring materials using the biochip 30. .
  • FIG. 2 it is explained that the metal structures MP1 to MP4 are formed at the positions of the corresponding ports P1 and P2, respectively.
  • FIG. 3 shows a case where a metal structure 34 in the form of a metal layer disposed between the upper substrate 31 and the lower substrate 32 is formed.
  • the metal structures (MP1 to MP4) are not formed only at positions corresponding to each port (P1, P2), but as shown in FIG. 3, the metal structures 34 are formed on the upper substrate 31 and the lower substrate 32.
  • the metal structure 34 is not formed separately at each position of the individual ports (P11, P12, P21, P22, P31, and P32) but is formed as a metal plate corresponding to the entire area as shown in FIG. 3, the biochip ( 30) As the manufacturing process is simplified, manufacturing cost and time can be reduced.
  • the first and third lights (L1, L3) are applied to the 11th port (P11) and the 31st port (P31), respectively, and the second light (L2) is applied to the 22nd port (P22). . Since the first and third lights (L1, L3) are applied to the 11th port (P11) and the 31st port (P31), respectively, but the light is not applied to the 12th port (P12) and the 32nd port (P32), The first and third raw material samples (M1, M3) supplied to the 11th port (P11) and the 31st port (P31) are delivered to the target port (TP) through the flow channel 33.
  • the second raw material sample M2 supplied to the 21st port P21 is not delivered to the target port TP. Accordingly, the first and third raw material samples (M1, M3) supplied to the 11th port (P11) and the 31st port (P31) are synthesized at the target port (TP) to obtain the target sample (TM). At this time, the flow of fluid is adjusted according to the intensity and wavelength of the first and third lights (L1, L3) applied to the 11th port (P11) and the 31st port (P31), and the target obtained at the target port (TP) The ratio of the first and third raw material samples M1 and M3 included in the sample TM may be adjusted differently.
  • the target sample (TM) may be obtained from the target port (TP) by applying light (L1, L2, L3), respectively.
  • the biochip 30 of the embodiment determines whether light is applied to each of the plurality of ports (P11, P12, P21, P22, P31, and P32) and adjusts the intensity and wavelength of the applied light to obtain a target at the target port (TP).
  • the type and ratio of the raw material samples (M1 to M3) that make up the sample (TM) can be precisely controlled.
  • the biochip 40 includes an upper substrate 41 and a lower substrate 42 and a metal structure 44 formed in the form of a metal plate in the entire area between the upper substrate 41 and the lower substrate 42.
  • the biochip 40 has 9 ports ((P11, P12, P13), (P21, P22, P23), (P31, P32, P33)) arranged in a 3 x 3 shape and 2 target ports ( A case including TP1 and TP2) is shown.
  • raw material samples (M1, M2, M3) may be supplied to each.
  • the first and second raw material samples (M1, M2) are synthesized to obtain a second target sample (TM2) in the second target port (TP2), and the second and third raw material samples are obtained in the first target port (TP1).
  • TM1 is obtained by combining (M2, M3).
  • the first raw material sample (M1) must be delivered only to the second target port (TP2)
  • the third raw material sample (M3) must be delivered only to the first target port (TP1)
  • the second raw material sample (M2) must be delivered only to the first target port (TP1).
  • light L1 to L3 is applied to the 11th port P11, the 22nd port P22, and the 33rd port P33, respectively. Since the first light L1 is applied only to the 11th port P11 in the first row, the first raw material sample M1 supplied to the 12th port P12 passes through the 13th port P13 to the second target port. It is delivered to (TP2). And in the third row, since the third light (L3) is applied only to the 33rd port (P33), the third raw material sample (M3) supplied to the 32nd port (P32) is transmitted to the first target through the 31st port (P31). It is delivered to port (TP1).
  • the second raw material sample M2 is supplied to the first and second target ports TP1, TP2) is passed on to all. Therefore, the first target sample (TM1) obtained by synthesizing the second and third raw material samples (M2, M3) can be obtained in the first target port (TP1), and the first and second raw material samples (M2, M3) can be obtained in the second target port (TP2).
  • a second target sample (TM2) obtained by synthesizing the raw material samples (M1 and M2) may be obtained.
  • the speed of the first to third raw material samples (M1 to M3) delivered to the first and second target ports (TP1 and TP2) can be adjusted by adjusting at least one of the intensity or wavelength of the first to third light.
  • the biochip 40 of FIG. 4 can simultaneously acquire two different target samples (TM1 and TM2).
  • the biochips 30 and 40 of the embodiment must be formed according to the number of raw material samples supplied, the number of target samples to be obtained, and the composition of the raw material samples to be included in the target samples.
  • the number and positions of ports and target ports can be adjusted in various ways, and flow channels can also be formed in various forms depending on the number and positions of ports and target ports.
  • Figure 5 shows the configuration of a biochip according to another embodiment.
  • the biochip 50 includes an upper substrate 51 and a lower substrate 52 and a metal structure 54 formed between the upper substrate 51 and the lower substrate 52.
  • the port configuration of the biochips 30 and 40 of FIGS. 3 and 4 is expanded to form a plurality of ports (P) arranged in a matrix form without separate ports and target ports. do.
  • the flow channel 53 is configured to connect all adjacent ports to each other.
  • the port through which the raw material sample is supplied and the raw material sample are connected to each other. Since the forwarding port and target port are not separately specified, multiple target samples can be obtained in a variety of combinations.
  • the biochip can be used universally for various purposes without having to manufacture it separately according to the purpose.
  • the number of ports is very large, so if it is desired to distinguish each of the multiple ports and irradiate light individually, not only a very large number of light sources are required, but also it is necessary to control each light source. Also, it is not easy.
  • the biochip 50 is further provided with a light mask 57.
  • the light mask 57 is formed with a plurality of holes 58 so that even if a single light L is irradiated to the biochip 50, the light can be irradiated only to the designated port so that the raw material sample can be delivered to the designated target port. And the light L is blocked in the remaining area where the hole 58 is not formed. That is, the optical mask 57 can use the plurality of holes 58 formed to designate a delivery path so that the raw material sample is delivered to the target port through the flow channel even with a single light L.
  • biochip manufactured for general use as shown in Figure 5 The same task can be easily performed repeatedly in various places or times. That is, as long as the pattern of the hole 58 formed in the mask 57 is known, the same target sample can be obtained regardless of the user or location. Therefore, it can provide very high efficiency in collaborative tasks performed by many people together.
  • Figure 6 shows another example of the photo mask of Figure 5.
  • the optical mask 57 is simply formed with a plurality of holes so that light is irradiated to port positions along the path through which the raw material sample must be delivered.
  • the path through which the raw material sample is delivered can be adjusted by using a plurality of holes 58, while the size of the holes 58 are all the same, so the speed at which the raw material sample is delivered is limited. difficult to control.
  • holes 61 to 65 of various shapes are formed in the optical mask 60, so that the intensity and wavelength of the light L irradiated to the port P through each hole 61 to 65 can be adjusted. It was allowed to happen. As shown in FIG.
  • the holes 61 and 62 may be formed in different sizes in the light mask 60, or the holes 63 and 64 may be formed in a form in which only some areas are open according to various patterns. there is. Additionally, the hole 65 may not be formed as an open structure that simply passes through the mask 60, but may be filled with another material that allows light to pass through, such as glass, a lens, or a phase shift filter.
  • the light passing through the holes 61 to 65 may have different intensities and wavelengths, and thus The speed at which each raw material sample is delivered may be different.
  • Figure 7 shows a biochip manufacturing and fluid control method according to an embodiment.
  • the biochip manufacturing and fluid control method can be broadly divided into a biochip manufacturing step 70 and a fluid control step 80.
  • the biochip manufacturing step (70) ports and flow channels are first formed on the upper and lower substrates (71).
  • the number and location of ports (including target ports) and the pattern of the flow channel connecting the ports vary depending on the number of raw material samples in fluid state, the number of target samples, and the number of raw material samples synthesized to obtain each target sample. can be adjusted accordingly.
  • a plurality of ports (P) may be arranged in a matrix form, and the flow channel 53 may be formed so that all ports (P) arranged adjacently are connected to each other.
  • a metal structure is formed (72).
  • the metal structure may be formed as a metal plate or a designated pattern at a position corresponding to each of a plurality of ports in the flow channel, as shown in FIG. 2, but as shown in FIGS. 3 to 5, the metal structure may be formed between the upper substrate and the lower substrate. It may be formed in the form of a metal layer.
  • the upper and lower substrates are combined (73). Then, the light source that will irradiate light to each port is determined (74). At this time, it may be decided to use multiple light sources to individually radiate light of different wavelengths or intensities to each of the multiple ports, or to irradiate the same light to the entire biochip using a single light.
  • a biochip is immediately obtained by combining the upper and lower substrates.
  • multiple raw material samples supplied to different ports can be delivered to at least one target port through the flow channel, ports to which light should be irradiated and ports to which light should not be irradiated.
  • An optical mask with multiple holes for distinguishing is manufactured (76). At this time, multiple holes formed in the mask may be formed in various sizes or patterns to control the intensity or wavelength of light irradiated to each port, and the holes may be filled with other materials such as glass, lenses, or phase shift filters.
  • a biochip is manufactured by combining the fabricated optical mask in the direction in which a single light will be irradiated from the combined upper and lower substrates (77).
  • the fluid control step (80) at least one raw material sample is supplied to at least one port among a plurality of ports formed on the biochip (81). Then, light is irradiated to at least one port among the multiple ports of the biochip (82). At this time, light may be irradiated only to some ports so that at least one raw material sample supplied to the port can be moved to a designated target port according to the flow of fluid generated by evaporation by the photothermal effect of the metal structure. Additionally, in order to control the flow speed of fluid, the intensity or wavelength of light irradiated to each port may be different. At this time, if a single light source is used instead of multiple light sources, the intensity or wavelength of light irradiated to each port can be adjusted by the pattern of holes formed in the light mask or the material filled in the holes.
  • the synthesized target sample is obtained at the target port (83).
  • the step 77 of determining the light source and the step 77 of combining the light mask are included in the step 70 of manufacturing the biochip.
  • the biochip only requires the step 73 of combining the upper and lower substrates. It may be implemented.
  • a user who wishes to control the fluid flow to obtain a target sample may determine the light source to be used, and may individually manufacture a light mask according to the determined light source. Accordingly, in step 74 of determining the light source, the light mask may be manufactured.
  • the coupling step 77 may also be included in the fluid control step 80.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Optical Measuring Cells (AREA)

Abstract

Sont divulgués dans un mode de réalisation une biopuce, et des procédés de fabrication et de commande de fluide associés, la biopuce comprenant : un substrat comprenant une pluralité d'orifices à travers lesquels au moins un échantillon de matière première dans un état fluide peut être fourni, et un canal de trajet d'écoulement reliant la pluralité d'orifices ; et une structure métallique formée pour avoir la même hauteur que la surface inférieure du canal de trajet d'écoulement, la structure métallique générant de la chaleur au moyen de la lumière ou d'un courant appliqué à une région dans laquelle au moins un orifice de la pluralité d'orifices est formé, de façon à ajuster la quantité d'évaporation fluidique au niveau d'un orifice correspondant, ce qui permet de commander un écoulement fluidique, et ainsi un écoulement fluidique peut être commandé localement et minutieusement sur la base de changements dans la quantité d'évaporation fluidique, un écoulement fluidique peut être commandé plus précisément par ajustement de la longueur d'onde ou de l'intensité de la lumière émise, et un écoulement fluidique au niveau de la pluralité d'orifices peut être commandé localement et avec précision même avec une lumière unique au moyen d'un masque optique.
PCT/KR2022/010934 2022-07-20 2022-07-26 Biopuce de commande de fluide à base optique, et procédés de fabrication et de commande de fluide associés WO2024019200A1 (fr)

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WO1997021090A1 (fr) * 1995-12-05 1997-06-12 Gamera Bioscience Dispositifs et procedes d'utilisation de l'acceleration centripete pour commander le deplacement de liquides dans le traitement de laboratoire automatise
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KR20110056168A (ko) * 2009-11-20 2011-05-26 삼성전자주식회사 미세유동장치, 광조사장치 및 이를 포함하는 미세유동시스템과 그 구동방법
KR20150031928A (ko) * 2013-09-17 2015-03-25 국립대학법인 울산과학기술대학교 산학협력단 복사열을 이용한 비접촉 가열식 유전자증폭장치
KR20190074733A (ko) * 2017-12-20 2019-06-28 주식회사 씨디젠 검정색 열가소성 수지 밸브 및 비접촉 온도 센서를 이용한 랩온어 디스크 장치

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101911435B1 (ko) 2011-09-26 2018-10-25 삼성전자주식회사 유체 제어 장치, 이를 포함하는 필터 및 바이오칩

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997021090A1 (fr) * 1995-12-05 1997-06-12 Gamera Bioscience Dispositifs et procedes d'utilisation de l'acceleration centripete pour commander le deplacement de liquides dans le traitement de laboratoire automatise
KR100978317B1 (ko) * 2008-02-14 2010-08-26 한국과학기술원 광열효과를 이용한 미세밸브 및 이를 이용한 랩온어칩시스템
KR20110056168A (ko) * 2009-11-20 2011-05-26 삼성전자주식회사 미세유동장치, 광조사장치 및 이를 포함하는 미세유동시스템과 그 구동방법
KR20150031928A (ko) * 2013-09-17 2015-03-25 국립대학법인 울산과학기술대학교 산학협력단 복사열을 이용한 비접촉 가열식 유전자증폭장치
KR20190074733A (ko) * 2017-12-20 2019-06-28 주식회사 씨디젠 검정색 열가소성 수지 밸브 및 비접촉 온도 센서를 이용한 랩온어 디스크 장치

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