Wafer structure carrying biological chip and method for cleaning biological chip using the wafer structure

Abstract

A wafer structure for carrying a biochip comprises a first wafer, a second wafer, and a connecting element. The second wafer is disposed on the first wafer. The connecting element secures the second wafer to the first wafer. The second wafer has at least one through-hole extending from the upper surface of the second wafer to the lower surface of the second wafer. The through-hole comprises a first hole and a second hole. The first hole has a first aperture. The second hole is located below the first hole and is connected to the first hole, and the second hole has a second aperture that is larger than the first aperture. The biochip is cleaned by placing the biochip in the wafer structure, rotating the wafer structure, and introducing a solution and / or gas.

Description

Technical Field

[0001] The present invention relates to a wafer structure for carrying a biochip and a method for cleaning the biochip using the wafer structure. Background Art

[0002] Biochips contain probes containing nucleic acids or proteins. These probes bind to corresponding gene sequences or proteins in the sample, allowing detection instruments to quantify the amount of the analyte in the sample. However, simply discarding a used biochip can cause environmental pollution. Traditional methods of cleaning biochips can damage the biochip substrate, reducing the ability of the probes to rebind with the analyte. Repeated cleaning can lead to poor detection performance, ultimately forcing the biochip to be discarded and unusable for extended periods. Summary of the Invention

[0003] The present invention relates to a wafer structure for carrying a biochip. In some embodiments, the wafer structure includes a first wafer, a second wafer, and a connecting element. The second wafer is disposed on the first wafer. The connecting element secures the second wafer to the first wafer, wherein the second wafer has at least one through hole, and the at least one through hole extends from the upper surface of the second wafer to the lower surface of the second wafer. The at least one through hole further includes a first hole and a second hole, wherein the first hole has a first aperture. The second hole is located below the first hole and is connected to the first hole, and the second hole has a second aperture, wherein the second aperture is larger than the first aperture.

[0004] In some embodiments, the connecting element includes a bonding layer disposed between the first wafer and the second wafer.

[0005] In some embodiments, the connecting element includes a clamp that clamps the first wafer and the second wafer to each other.

[0006] In some embodiments, the first wafer has a substantially flat upper surface.

[0007] In some embodiments, the second wafer further includes a protruding portion protruding toward the first hole.

[0008] The present invention relates to a method for cleaning a biochip, which includes placing the biochip between a first wafer and a second wafer of a wafer structure, wherein the biochip is located in a second hole of the second wafer; fixing the second wafer on the first wafer by a connecting element to clamp the biochip; and rotating the wafer structure and passing a cleaning solution into the first hole of the second wafer to clean the biochip.

[0009] In some embodiments, the cleaning solution is an acidic solution or an alkaline solution.

[0010] In some embodiments, after rotating the wafer structure and introducing the cleaning solution into the first holes of the second wafer, the method further includes rotating the wafer structure and introducing deionized water into the first holes of the second wafer to clean the biochip.

[0011] In some embodiments, after rotating the wafer structure and passing the cleaning solution into the first hole of the second wafer, the method further includes rotating the wafer structure and passing an inert gas, a liquid with a surface tension lower than about 73 mN / m, or a combination thereof into the first hole of the second wafer to clean the biological chip.

[0012] In some embodiments, the inert gas is nitrogen and the liquid having a surface tension less than about 73 mN / m is isopropyl alcohol.

[0013] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are intended to provide further explanation of the invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] When reading the accompanying drawings of the present invention, it is recommended that the following description be used to understand various aspects of the present invention. It should be noted that, in accordance with standard industry practice, various feature dimensions are not drawn to scale. For clarity of discussion, various feature dimensions may be arbitrarily increased or decreased.

[0015] Figure 1 Cross-sectional views of wafer structures are illustrated according to some embodiments of the present invention.

[0016] Figure 2 A cross-sectional view of a wafer structure including a bonding layer is illustrated according to some embodiments of the present invention.

[0017] Figure 3 A cross-sectional view of a wafer structure including a chuck is illustrated according to some embodiments of the present invention.

[0018] Figure 4 A top view of a wafer structure is illustrated according to some embodiments of the present invention.

[0019] Figure 5 A bottom schematic diagram of a second wafer in a wafer structure is described according to some embodiments of the present invention.

[0020] Figure 6 A top view of a first wafer in a wafer structure is illustrated according to some embodiments of the present invention.

[0021] Figure 7 A schematic diagram illustrating cleaning a biochip using a wafer structure according to some embodiments of the present invention.

[0022] Figure 8 According to some embodiments of the present invention, a flow chart of cleaning a bio-wafer using a wafer structure is described. DETAILED DESCRIPTION

[0023] The following provides various embodiments to illustrate various features of the present invention. To simplify the present invention, specific examples of components and configurations are described below. Of course, these are merely examples and are not intended to be limiting. For example, a description below of a first feature being formed above a second feature may include embodiments in which the first and second features are directly in contact with each other, or may include embodiments in which other features are formed between the first and second features, preventing direct contact between the first and second features.

[0024] In addition, spatially relative terms, such as below and above, may be used to facilitate describing the relationship of one element or feature to another element or feature in the figure herein. In addition to the orientations depicted in the figures, spatially relative terms are intended to encompass different orientations of the device during use or operation. The device may be positioned in other ways (rotated 90 degrees or in other orientations), and the spatially relative descriptions used herein should be interpreted accordingly. In the discussion herein, unless otherwise indicated, the same reference numbers in different figures refer to the same or similar elements formed using the same or similar materials by the same or similar methods.

[0025] In an embodiment of the present invention, the biochip is placed in the wafer structure of the present invention, and the wafer structure is rotated and solution and / or gas are introduced to clean the biochip.

[0026] In an embodiment of the present invention, a wafer structure for supporting a biochip includes a first wafer, a second wafer, and a connecting element. The connecting element fixes the first wafer and the second wafer so that the second wafer is arranged above the first wafer. The second wafer includes at least one through hole, for example, a plurality of through holes, which extend from the upper surface of the second wafer to the lower surface of the second wafer. These through holes include a first hole with a first aperture and a second hole with a second aperture. The second hole is located below the first hole and is connected to the first hole. The second aperture of the second hole is larger than the first aperture of the first hole. Various aspects of the wafer structure will be described below using multiple embodiments.

[0027] Figure 1According to some embodiments of the present invention, a cross-sectional view of a wafer structure 100 is described. The wafer structure 100 includes a first wafer 101 and a second wafer 102. The material of the first wafer 101 and the second wafer 102 can be any material that does not damage the first wafer 101 and the second wafer 102 after the cleaning solution and / or gas are passed into the wafer structure 100, such as an acid-resistant or alkali-resistant material. In some embodiments, since most biological wafers to be cleaned are made of the same or similar silicon dioxide material as silicon wafers, the first wafer 101 and the second wafer 102 can be silicon wafers, which facilitates the selection of solutions and / or gases for cleaning biological wafers, simplifies the selection process, and does not damage the biological wafers while also not damaging the first wafer 101 and the second wafer 102. In some embodiments, the materials of the first wafer 101 and the second wafer 102 independently include silicon carbide, gallium nitride or gallium arsenide, etc. In some embodiments, the second wafer 102 is connected to the silicon wafer 101 by a connecting element (not shown in the figure). Figure 1 , please refer to the following Figures 2 to 3 ) is fixed on the first wafer 101 so that the lower surface 102L of the second wafer 102 is as shown Figure 1 As shown, the second wafer 102 is in direct contact with the upper surface 101U of the first wafer 101. In other embodiments, the lower surface 102L of the second wafer 102 is not in direct contact with the upper surface 101U of the first wafer 101, but rather an additional connecting element is disposed therebetween. The details of the connecting element securing the first and second wafers 101, 102 are described below.

[0028] Continue Figure 1 , the second wafer 102 further includes at least one through hole 102H extending from the upper surface 102U of the second wafer 102 to the lower surface 102L of the second wafer 102. The through hole 102H can be formed by any suitable etching method to form a through hole 102H having a first hole H1 and a second hole H2, wherein the first hole H1 is located above the second hole H2 and is connected to the second hole H2. The first hole H1 has a first aperture D1, which is exposed from the upper surface 102U of the second wafer 102, so that the first hole H1 can be used as an inlet for a cleaning solution and / or gas to enter the wafer structure; and the second hole H2 has a second aperture D2, which is exposed from the lower surface 102L of the second wafer 102, so that the second hole H2 can be used as a place for placing a biological chip (not shown in the figure). Figure 1 ). In some embodiments, the second hole H2 has a volume substantially compatible with most biochips, such as a thickness of approximately 1 mm. However, spaces of various shapes are contemplated by the present invention. For example, the shape of the second hole H2 can complement the shape of the biochip to be placed.

[0029] In some embodiments, Figure 1The second wafer 102 further has a protruding portion 102P, which protrudes toward the first hole H1, so that the first aperture D1 of the first hole H1 is smaller than the second aperture D2 of the second hole H2. Therefore, the protruding portion 102P can press the biochip (not shown) placed below in the second hole H2 from above. Figure 1 ), as a structure for fixing the bio-wafer when cleaning the bio-wafer. Since the edge of the bio-wafer is not modified with probes, pressing the edge of the bio-wafer with the protruding portion 102P does not affect the function of the wafer structure to clean the bio-wafer.

[0030] exist Figure 1 In the embodiment, the first wafer 101 located below the second wafer 102 has a substantially flat and continuous upper surface 101U, which can be aligned with the biochip (not shown) placed in the second hole H2. Figure 1 ) in direct contact. In some embodiments, the lower surface 101L of the first wafer 101 may also be as Figure 1 The substantially continuous flat surface is shown to facilitate connection of other components, such as a rotating component, below the first wafer 101. In some embodiments, the rotating component (see Figure 7 ) by adsorbing onto the flat portion of the lower surface 101L to stabilize the rotating wafer structure. Adsorption can be performed, for example, by vacuum adsorption, whereby the vacuum chuck of the rotating element is attached to the lower surface 101L of the first wafer 101, and the gas within the vacuum chuck is sucked, causing the vacuum chuck to adsorb the first wafer 101.

[0031] Figure 2 According to some embodiments of the present invention, a cross-sectional view of a wafer structure 200 including a bonding layer 103 is shown. The wafer structure 200 has substantially the same Figure 1 The structure of the wafer structure 100 is similar to that of the wafer structure 100. The reference numerals of the components in the figure can refer to the reference numerals in the previous figure and will not be repeated. As can be seen from the above, the second wafer 102 is fixed on the top of the first wafer 101 by the connecting element. Figure 2 In an embodiment, the connecting element may be a bonding layer 103. The bonding layer 103 is located between the upper surface 101U of the first wafer 101 and the lower surface 102L of the second wafer 102, and directly contacts the upper surface 101U and the lower surface 102L. In some embodiments, the bonding layer 103 is coated between the upper surface 101U and the lower surface 102L through a temporary bonding process to bond the first wafer 101 and the second wafer 102. After the biochip is cleaned, the first wafer 101 and the second wafer 102 are separated by laser or thermal stripping. In some embodiments, the bonding layer 103 is any suitable engineering tape, such as a UV tape that can be peeled off by irradiation with ultraviolet light or a thermally degradable tape that can be peeled off by heating.

[0032] Figure 3A cross-sectional view of a wafer structure 300 including a fixture 104 is shown according to some embodiments of the present invention. The wafer structure 300 has substantially the same Figure 1 The structure of the wafer structure 100 is similar to that of the wafer structure 100. The reference numerals of the components in the figure can refer to the reference numerals in the previous figure and will not be repeated. As can be seen from the above, the second wafer 102 is fixed on the top of the first wafer 101 by the connecting element. Figure 3 In the embodiment of , this connecting element can be a clamp 104. Figure 3 In the embodiment, the clamp 104 holds the second wafer 102 and the first wafer 101 from the upper surface 102U of the second wafer 102 and the lower surface 101L of the first wafer 101. In some embodiments, the clamp 104 is made of Teflon which is acid and alkali resistant. The second wafer 102 and the first wafer 101 can be fixed by any number of clamps 104, and are not limited to Figure 3 Number of fixtures shown.

[0033] Figure 4 According to some embodiments of the present invention, a top view of a wafer structure is illustrated, wherein a cross-sectional view cut along line AA' is, for example, Figure 1 、 Figure 2 or Figure 3 The cross-sectional view of wafer structure 100, wafer structure 200 or wafer structure 300 is shown. In some embodiments, second wafer 102 and first wafer 101 are both circular wafers with substantially the same radius, and are, for example, eight-inch wafers or twelve-inch wafers. Figure 4 This is only an example and is not intended to limit the size and shape of the second wafer 102 and the first wafer 101. Any size and shape of the second wafer 102 and the first wafer 101 that can carry a biochip is within the scope of the present invention. In addition, any number of through holes 102H can be formed in the wafer structure, and is not limited to Figure 4 There are four through holes 102H shown, and the more through holes 102H there are, the more bio-wafers can be carried, thereby achieving the function of cleaning a large number of wafers at one time. Figure 4 In the top view, the dotted area shows the perspective area of ​​each through hole 102H corresponding to the first hole H1 and the second hole H2, and the protruding portion 102P of the second wafer 102 is located between the dotted areas shown by the first hole H1 and the second hole H2.

[0034] Figure 5 According to some embodiments of the present invention, a schematic diagram of the bottom surface of the second wafer 102 in the wafer structure is shown, wherein the line AA' corresponds to Figure 1 、 Figure 2 and Figure 3The position of the protruding portion 102P can be more clearly seen from the lower surface 102L of the second wafer 102, that is, between the first hole H1 and the second hole H2 shown by the dotted line.

[0035] Figure 6 According to some embodiments of the present invention, a top view of the first wafer 101 in the wafer structure is illustrated, wherein the line AA' corresponds to Figure 1 、 Figure 2 and Figure 3 The position where the wafer structure is cut. Figure 6 In the embodiment of the present invention, the upper surface 101U of the first wafer 101 is flat and continuous. The dotted area shows the projection positions of the first hole H1 and the second hole H2 on the upper surface 101U.

[0036] Figure 7 According to some embodiments of the present invention, a schematic diagram of using a wafer structure to clean a biochip 105 is described. The cleaning structure 400 includes the wafer structure 100, a liquid / gas introduction element 107, and a rotating element 106. It should be noted that, Figure 7 The wafer structure 100 may also be replaced by Figure 2 Wafer structure 200 or Figure 3 The wafer structure 300 is formed. The biochip 105 is placed in the second hole H2 of the second wafer 102. The rotating element 106 connects to the wafer structure 100 from the lower surface 101L of the first wafer 101 and rotates the wafer structure 100. The liquid / gas introduction element 107 provides a cleaning solution or gas to the first hole H1 of the second wafer 102 to clean the biochip 105 placed in the second hole H2. It should be noted that Figure 7 The placement of the biochip 105 in the second hole H2 on the right side is merely exemplary and is not intended to limit the number of biochips that can be placed on the wafer structure. Any suitable number may be used to achieve the goal of cleaning multiple biochips simultaneously. In some embodiments, a liquid / gas introduction element 107 is positioned above the center of the wafer structure 100, allowing the solution or gas introduced into the first hole H1 to be carried outward by the centrifugal force generated by the rotation, thereby cleaning multiple biochips. In some embodiments, the liquid / gas introduction element 107 can move horizontally and / or vertically above the wafer structure 100, cleaning the biochip 105 in a scanning manner, thereby improving cleaning efficiency. In some embodiments, when the biochip 105 of the present invention is placed in the second hole H2, only the front surface is exposed. This allows liquid or gas cleaning of the front surface of the biochip probe, while the sidewalls and back surface of the biochip 105 are not exposed to the liquid or gas. Compared to conventional cleaning methods that immerse the biochip in a solution, this method avoids significant damage to the biochip caused by double-sided cleaning, allowing for a greater number of reusable biochips.

[0037] Figure 8According to some embodiments of the present invention, a process 500 for cleaning a biochip using a wafer structure is described. In step S501, the biochip is placed between the first wafer and the second wafer of the wafer structure, wherein the biochip is located in the second hole of the second wafer. In step S502, the second wafer is fixed to the first wafer by a connecting element to clamp the biochip to prevent the biochip from being thrown out due to centrifugal force during the rotation process. In step S503, while rotating the wafer structure, a cleaning solution is introduced into the first hole of the second wafer from the liquid / gas introduction element. In some embodiments, the cleaning solution is an acidic solution or an alkaline solution, such as hydrofluoric acid or sulfuric acid. In some embodiments, the cleaning solution is hydrogen peroxide. In the past, cleaning of biochips only cleaned the carriers (such as genes or proteins) on the probes, which could not guarantee that the probes would not be damaged during the cleaning process, causing the detection effect of the biochip to deteriorate over time and the biochip to be unusable for a long time. In contrast, in some embodiments, the present invention rotates the wafer structure carrying the biochip and introduces a suitable cleaning solution to remove the carriers, such as genes or proteins, on the biochip and simultaneously remove the probes. The probes are then modified on the biochip to enable detection capabilities and long-term reuse. In some embodiments, the cleaning solution is adjusted to completely cover the surface of the wafer structure by adjusting the rotation speed and flow rate. In some embodiments, in step S503, the rotation speed of the wafer structure is 800 rpm to 2000 rpm. Too low a rotation speed will result in poor cleaning effect, while too high a rotation speed will cause damage to the surface structure or deformation. In step S504, after the wafer structure is rotated and the cleaning solution is introduced, deionized water is introduced into the first hole of the second wafer from the liquid / gas introduction element while the wafer structure is rotated to dilute the cleaning solution added in the previous step, such as an acidic solution or an alkaline solution. In some embodiments, in step S504, the rotation speed of the wafer structure is 800 rpm to 2000 rpm. Too low a rotation speed will result in poor cleaning effect, and too high a rotation speed will cause damage to the surface structure or reversal. In some embodiments, in step S505, after the wafer structure is rotated and deionized water is introduced, an inert gas (e.g., nitrogen) is introduced from the liquid / gas introduction element into the first hole of the second wafer while the wafer structure is rotated. In some embodiments, in step S505, a liquid (e.g., isopropyl alcohol) having a surface tension lower than that of water (approximately 73 mN / m) is introduced from the liquid / gas introduction element into the first hole of the second wafer while the wafer structure is rotated. In some embodiments, in step S505, when the wafer structure is rotated, an inert gas is first introduced into the first hole, and then a liquid having a surface tension lower than approximately 73 mN / m is introduced into the first hole. In some embodiments, in step S505 , while the wafer structure is being rotated, a liquid having a surface tension lower than about 73 mN / m is first introduced into the first holes, and then an inert gas is introduced into the first holes.In some embodiments, in step S505, the rotation speed of the wafer structure is 800 rpm to 2000 rpm. Too low a rotation speed will result in poor cleaning effect, and too high a rotation speed will cause damage to the surface structure or reversal. Step S505 can be performed to spin dry the surface of the biochip to avoid leaving water marks that affect the ability of the biochip to bind to the carrier after the modified probe or affect the function of the biochip after the current is passed through it. Using an inert gas to spin dry the surface of the biochip can avoid unnecessary reactions during the process, and using a liquid with a surface tension lower than water (surface tension is approximately 73mN / m) to spin dry the surface of the biochip can accelerate the evaporation rate of deionized water with the liquid with a surface tension lower than water. In some embodiments, steps S503 to 505 use the same rotation speed. In some embodiments, different rotation speeds are used in each step of steps S503 to 505.

[0038] The present invention rotates the wafer structure while cleaning the biochip sandwiched in the wafer structure with a cleaning solution / gas to remove the carrier on the surface of the biochip and remove the probe on the biochip at the same time, allowing the biochip to be reused without damaging the biochip substrate.

[0039] The foregoing overview of features of some embodiments will enable those skilled in the art to better understand aspects of the present invention. Those skilled in the art will recognize that they can readily utilize the present disclosure as a basis for designing or modifying other processes and structures to achieve the same purposes and / or achieve the same advantages of the embodiments described herein. Those skilled in the art will also recognize that such equivalent constructions do not depart from the spirit and scope of the present disclosure, and that they can make various changes, substitutions, and modifications herein without departing from the spirit and scope of the present disclosure.

[0040]

Explanation of symbols

[0041] 100: Wafer structure

[0042] 101: First Wafer

[0043] 101L: Lower surface

[0044] 101U: Top surface

[0045] 102: Second wafer

[0046] 102H:Through hole

[0047] 102L: lower surface

[0048] 102P: protruding part

[0049] 102U: Upper surface

[0050] 103: bonding layer

[0051] 104: fixture

[0052] 105: Biochip

[0053] 106: Rotating element

[0054] 107: Liquid / gas inlet element

[0055] 200: Wafer structure

[0056] 300: Wafer structure

[0057] 400: Cleaning structure

[0058] 500:Process

[0059] A-A':line

[0060] D1: first aperture

[0061] D2: Second aperture

[0062] H1: First hole

[0063] H2: Second hole

[0064] S501: Step

[0065] S502: Step

[0066] S503: Step

[0067] S504: Step

[0068] S505: step.

Claims

1. A wafer structure for carrying a biochip, characterized in that: include: First wafer; A second wafer is disposed on the first wafer, A connecting element is used to fix the second wafer to the first wafer, wherein the second wafer has at least one through hole, the at least one through hole extending from the upper surface of the second wafer to the lower surface of the second wafer, and the at least one through hole comprises: a first hole having a first aperture; as well as The second hole is located below the first hole and communicates with the first hole. The second hole has a second aperture that is larger than the first aperture. 2 . The wafer structure according to claim 1 , wherein the connecting element comprises a bonding layer disposed between the first wafer and the second wafer. 3 . The wafer structure according to claim 1 , wherein the connecting element comprises a clamp, and the clamp clamps the first wafer and the second wafer together. The wafer structure according to claim 1 , wherein the first wafer has a substantially flat upper surface. The wafer structure according to claim 1 , wherein the second wafer further comprises a protruding portion protruding toward the first hole.

6. A method for cleaning a biochip, characterized in that: include: Placing a biochip between the first wafer and the second wafer of the wafer structure according to claim 1 , wherein the biochip is located in the second hole of the second wafer; Fixing the second wafer on the first wafer by the connecting element to clamp the biochip; as well as The wafer structure is rotated and a cleaning solution is introduced into the first hole of the second wafer to clean the biochip. The method according to claim 6 , wherein the cleaning solution is an acidic solution or an alkaline solution.

8. The method according to claim 6, after rotating the wafer structure and passing the cleaning solution into the first hole of the second wafer, further comprises rotating the wafer structure and passing deionized water into the first hole of the second wafer to clean the biochip.

9. The method according to any one of claims 6 to 8, after rotating the wafer structure and passing the cleaning solution into the first hole of the second wafer, further includes rotating the wafer structure and passing an inert gas, a liquid with a surface tension lower than about 73 mN / m, or a combination thereof into the first hole of the second wafer to clean the biological chip.

10. The method of claim 9, wherein the inert gas is nitrogen, and the liquid having a surface tension lower than about 73 mN / m is isopropyl alcohol.

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