TWI809755B - Wafer structure for holding biochips and method for cleaning biochips using the same - Google Patents

Abstract

A wafer structure for holding biochips includes a first wafer, a second wafer, and a connecting component. The second wafer is disposed on the first wafer. The connecting component fixes the second wafer on the first wafer. The second wafer has at least one through-hole that penetrates from an upper surface of the second wafer to a lower surface of the second wafer. The through-hole includes a first hole and a second hole. The first hole has a first aperture. The second hole is located below the first hole and communicated with the first hole. The second hole has a second aperture, and the second aperture is larger than the first aperture.

Description

Wafer structure carrying biochip and method for cleaning biochip using the wafer structure

The present disclosure relates to a wafer structure carrying a biochip and a method for cleaning the biochip using the wafer structure.

There are nucleic acid or protein probes on the biochip, and these probes can be combined with the corresponding gene sequence or protein in the sample, and then the content of the analyte in the sample can be quantified by the detection instrument. However, discarding the used biochip directly will cause environmental pollution. The traditional method of cleaning the biochip may damage the substrate of the biochip and reduce the ability of the probe to bind to the analyte again. Repeated cleaning will cause the detection effect of the biochip to deteriorate. In the end, it had to be discarded and could not be used for a long time.

The present disclosure relates to a wafer structure for carrying a biochip. In some embodiments, the wafer structure includes a first wafer, a second wafer, and connecting elements. The second wafer is disposed on the first wafer. The connecting element fixes the second wafer on the first wafer, wherein the second wafer has at least one through hole, and the at least one through hole penetrates 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, the first hole having a first diameter. The second hole is located under the first hole and communicates with the first hole. The second hole has a second diameter, wherein the second diameter is larger than the first diameter.

In some embodiments, the connection element includes a bonding layer disposed between the first wafer and the second wafer.

In some embodiments, the connection element includes a clamp that clamps the first wafer and the second wafer to each other.

In some embodiments, the first wafer has a substantially planar upper surface.

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

The disclosure relates to a method of cleaning a biochip, the method comprising 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; The second wafer is fixed on the first wafer by connecting elements to hold the biochip; and the wafer structure is rotated and a cleaning solution is passed into the first hole of the second wafer to clean the biochip.

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

In some embodiments, after rotating the wafer structure and passing the cleaning solution into the first hole of the second wafer, further comprising rotating the wafer structure and passing deionized water into the first hole of the second wafer , to clean the biochip.

In some embodiments, after rotating the wafer structure and passing the cleaning solution into the first hole of the second wafer, further comprising rotating the wafer structure and passing an inert gas with a surface tension lower than about 73 mN/m A liquid or combination thereof is injected into the first hole of the second wafer to clean the biowafer.

In some embodiments, the inert gas is nitrogen and the liquid having a surface tension below about 73 mN/m is isopropanol.

It is to be understood that both the foregoing general description and the following specific description are exemplary and explanatory only and are intended to provide further explanation of the present disclosure.

Different embodiments are provided below to illustrate different features of the present disclosure. To simplify the present disclosure, specific examples of components and configurations are described below. Of course, these are examples only and are not intended to be limiting. For example, the description below that the first feature is formed above the second feature may include the embodiment that the first feature and the second feature are formed in direct contact, and may also include other features formed between the first feature and the second feature, so that the first feature An embodiment that is not in direct contact with the second feature.

In addition, spatially relative terms, such as below and above, etc., may be used conveniently herein to describe one element or feature's relationship to another element or feature in the figures. The spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. The device may be otherwise oriented (rotated 90 degrees or in other orientations) and the use of spatially relative descriptions herein may likewise be construed accordingly. In the discussion herein, unless otherwise stated, the same reference numbers in different drawings refer to the same or similar elements formed using the same or similar materials by the same or similar methods.

In the embodiment of the present disclosure, the biochip will be placed in the wafer structure of the present disclosure, and the function of cleaning the biochip can be achieved by rotating the wafer structure and injecting solution and/or gas.

In an embodiment of the present disclosure, a wafer structure for carrying a biochip includes a first wafer, a second wafer and connecting elements. 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, such as a plurality of through holes, and the through holes penetrate from the upper surface of the second wafer to the lower surface of the second wafer. The vias include first holes with a first diameter and second holes with a second diameter. The second hole is located below the first hole and communicates with 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 with multiple embodiments.

FIG. 1 illustrates a cross-sectional view of a wafer structure 100 according to some embodiments of the present disclosure. 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 is passed to the wafer structure 100, such as acid resistance or alkali-resistant materials. In some embodiments, since most of the biowafers to be cleaned are made of the same or similar silicon dioxide material as the silicon wafers, the first wafer 101 and the second wafer 102 can be silicon wafers, which facilitates selection. The solution and/or gas for cleaning the biochip simplifies the selection process, and does not damage the biochip and also 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 SiC, GaN or GaAs. In some embodiments, the second wafer 102 is fixed above the first wafer 101 through connecting elements (not shown in Figure 1, please refer to Figures 2 to 3 below), so that the second wafer 102 The lower surface 102L of the first wafer 101 is in direct contact with the upper surface 101U of the first wafer 101 as shown in FIG. 1 . 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 another connecting element is disposed between the two. Relevant descriptions about the connection elements fixing the first wafer 101 and the second wafer 102 can be referred to below.

Following FIG. 1 , the second wafer 102 further includes at least one through hole 102H penetrating from the upper surface 102U of the second wafer 102 to the lower surface 102L of the second wafer 102 . The through hole 102H may be formed by any suitable etching method to form the through hole 102H including a first hole H1 and a second hole H2 , wherein the first hole H1 is located above the second hole H2 and communicates with 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 entrance for the cleaning solution and/or gas to enter the wafer structure; and the second hole H2 has a second hole. The second hole D2 is exposed from the lower surface 102L of the second wafer 102 , so that the second hole H2 can be used as a space for placing a biochip (not shown in FIG. 1 ). In some embodiments, the second hole H2 has a volume that is substantially compatible with most biochips, for example, the thickness is about 1 mm. However, spaces of various shapes are within the scope of the present disclosure. For example, the shape of the second hole H2 can be complementary to the shape of the biochip to be placed.

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

In Figure 1, the first wafer 101 located below the second wafer 102 has a substantially flat and continuous upper surface 101U, which can be placed in the second hole H2 with a biochip (not shown in the first figure). Fig.) direct contact. In some embodiments, the lower surface 101L of the first wafer 101 can also be a substantially continuous flat surface as shown in FIG. 1 , which is helpful for connecting other components, such as rotating components, under the first wafer 101 . In some embodiments, the rotating element (refer to FIG. 7 ) can stabilize the rotating wafer structure through adsorption on the flat portion of the lower surface 101L. The adsorption method is, for example, vacuum adsorption. The vacuum chuck of the rotating element is attached to the lower surface 101L of the first wafer 101 , and the gas in the vacuum chuck is sucked, so that the vacuum chuck absorbs the first wafer 101 .

FIG. 2 illustrates a cross-sectional view of a wafer structure 200 including a bonding layer 103 according to some embodiments of the present disclosure. The wafer structure 200 has a structure substantially similar to the wafer structure 100 of FIG. 1 . Reference numerals in the preceding figures may be referred to, and further descriptions are omitted. It can be seen from the above that the second wafer 102 is fixed on the top of the first wafer 101 by a connection element, and in the embodiment as shown in FIG. 2 , the connection element may be the bonding layer 103 . The bonding layer 103 is interposed 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, and after the biowafer is cleaned, the laser Or thermal stripping to separate the first wafer 101 and the second wafer 102 . In some embodiments, the bonding layer 103 is any suitable engineering tape, such as a UV tape that can be peeled by irradiating ultraviolet light or a pyrolytic tape that can be peeled by heating.

FIG. 3 illustrates a cross-sectional view of a wafer structure 300 including a fixture 104 according to some embodiments of the present disclosure. The wafer structure 300 has a substantially similar structure to the wafer structure 100 of FIG. 1 . Refer to the reference numerals in the preceding figures, and no further description is given. It can be known from the above that the second wafer 102 is fixed on the top of the first wafer 101 by a connection element, and in the embodiment as shown in FIG. 3 , the connection element may be a clamp 104 . In FIG. 3 , jig 104 holds second wafer 102 and first wafer 101 from upper surface 102U of second wafer 102 and lower surface 101L of first wafer 101 . In some embodiments, the clamp 104 is made of acid and alkali resistant Teflon. Any number of clamps 104 can be used to fix the second wafer 102 and the first wafer 101 , not limited to the number of clamps shown in FIG. 3 .

FIG. 4 illustrates a top view of a wafer structure according to some embodiments of the present disclosure, wherein the cross-sectional view taken along the line AA' is, for example, the wafer structure 100 shown in FIG. 1 , FIG. 2 or FIG. 3 . , a cross-sectional view of the wafer structure 200 or the wafer structure 300 . In some embodiments, the second wafer 102 and the first wafer 101 are both circular wafers with substantially the same radius. The second wafer 102 and the first wafer 101 are, for example, eight-inch wafers or ten-inch wafers. 2 inch wafer. Fig. 4 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 size of the second wafer 102 and the size of the first wafer 101 that can carry biochips and shapes are all within the scope of this disclosure. In addition, any number of through holes 102H can be formed in the wafer structure, not limited to the four through holes 102H shown in FIG. It can achieve the function of cleaning a large number of wafers at one time. In the top view of FIG. 4, the dotted line area shows the perspective area of each through hole 102H corresponding to its first hole H1 and second hole H2, and the protruding portion 102P of the second wafer 102 is located between the first hole H1 and the second hole H2. between the dashed areas shown.

FIG. 5 illustrates a schematic diagram of the bottom surface of the second wafer 102 in the wafer structure according to some embodiments of the present disclosure, wherein the line AA' corresponds to the cut position of the wafer structure in FIG. 1 , FIG. 2 and FIG. 3 . . From the lower surface 102L of the second wafer 102 , the position of the protruding portion 102P can be clearly seen, that is, between the first hole H1 and the second hole H2 indicated by the dotted line.

FIG. 6 illustrates a top view of the first wafer 101 in the wafer structure according to some embodiments of the present disclosure, wherein the line AA' corresponds to the cut position of the wafer structure in FIG. 1 , FIG. 2 and FIG. 3 . . In the embodiment shown in FIG. 6 , the upper surface 101U of the first wafer 101 is flat and continuous. The dashed area shows the projected positions of the first hole H1 and the second hole H2 on the upper surface 101U.

FIG. 7 illustrates a schematic diagram of cleaning a biowafer 105 using a wafer structure 400 according to some embodiments of the present disclosure. The cleaning structure 400 includes the above-mentioned wafer structure 100 , the liquid/gas feeding element 107 and the rotating element 106 . It should be noted that the wafer structure 100 in FIG. 7 can also be replaced with the wafer structure 200 in FIG. 2 or the wafer structure 300 in FIG. 3 . The biochip 105 is placed in the second hole H2 of the second wafer 102 . The rotating member 106 connects the wafer structure 100 from the lower surface 101L of the first wafer 101 and rotates the wafer structure 100 . The liquid/gas feeding unit 107 provides 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 Fig. 7 only exemplarily places biochips 105 in the second hole H2 on the right side, and is not intended to limit the number of biochips placed in the wafer structure, any suitable number is all right, so as to achieve one-time cleaning The purpose of multiple biochips. In some embodiments, the liquid/gas introduction element 107 is placed above the center of the wafer structure 100 , so that the solution or gas introduced into the first hole H1 is carried out by the centrifugal force caused by the rotation, thereby cleaning a plurality of biowafers. In some embodiments, the liquid/gas feeding unit 107 can move horizontally and/or vertically above the wafer structure 100 to clean the biowafer 105 in a scanning manner, thereby improving cleaning efficiency. In some embodiments, when the biochip 105 of the present disclosure is placed in the second hole H2, only the front side is exposed, so that the front side of the biochip tool probe can be cleaned with liquid or gas, and the sidewall and the back side of the biochip 105 are not in contact. liquid or gas. Compared with the previous cleaning method of soaking the biological chip into the solution, it can avoid the greater damage to the biological chip caused by cleaning on both sides, so that the cleaned biological chip tool can be recycled more times.

FIG. 8 illustrates a process 500 for cleaning a biowafer using a wafer structure, according to some embodiments of the present disclosure. 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 on the first wafer by connecting elements to clamp the biochip to prevent the biochip from being thrown out due to centrifugal force during the rotation process. In step S503 , while the wafer structure is rotated, a cleaning solution is passed from the liquid/gas feeding element into the first hole of the second wafer. 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 or the like. In the past, the 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, so that the detection effect of biochips would deteriorate over time, and the biochips could not be used for a long time; , in some embodiments, the present disclosure removes the carriers on the biochip, such as genes or proteins, and removes the probes at the same time, by rotating the wafer structure carrying the biochip and passing through a suitable cleaning solution, followed by Probes are modified on biochips to enable them to detect and be reused for a long time. In some embodiments, the cleaning solution completely covers the surface of the wafer structure by adjusting the rotation speed and the flow rate. In some embodiments, in step S503 , the rotating speed of the wafer structure is 800 rpm to 2000 rpm. If the rotating speed is too small, the cleaning effect will be poor, and if the rotating speed is too high, the surface structure will be damaged or wires will fall. In step S504, after the wafer structure is rotated and the cleaning solution is introduced, deionized water is passed from the liquid/gas inlet element into the first hole of the second wafer while the wafer structure is rotated to dilute the previous steps. Added cleaning solutions, such as acidic or alkaline solutions. In some embodiments, in step S504, the rotation speed of the rotating wafer structure is 800 rpm to 2000 rpm, if the rotation speed is too low, the cleaning effect will be poor, and if the rotation speed is too high, the surface structure will be damaged or wires will fall. In some embodiments, in step S505, after the wafer structure is rotated and deionized, an inert gas (such as nitrogen) is passed from the liquid/gas feeding element into the first hole of the second wafer and Simultaneously rotate the wafer structure. In some embodiments, in step S505, a liquid (for example: isopropanol) having a surface tension lower than that of water (about 73mN/m) is passed into the first wafer of the second wafer from the liquid/gas passage element. in a hole while simultaneously rotating the wafer structure. In some embodiments, in step S505 , when the wafer structure is rotated, an inert gas is introduced into the first hole first, and then a liquid with a surface tension lower than about 73 mN/m is injected into the first hole. In some embodiments, in step S505 , when the wafer structure is rotated, a liquid with a surface tension lower than about 73 mN/m is introduced into the first hole first, and then an inert gas is injected into the first hole. In some embodiments, in step S505, the rotating speed of the wafer structure is 800 rpm to 2000 rpm. If the rotating speed is too small, the cleaning effect will be poor, and if the rotating speed is too high, the surface structure will be damaged or wires will fall. Perform step S505 to spin dry the surface of the biochip to avoid leaving water marks to affect the ability of the biochip to bind to the carrier after the probe is modified or to affect the function of the biochip after the current is passed, wherein the use of an inert gas to spin the surface of the biochip can avoid the process Unnecessary reactions occur in the process, and the use of a liquid with a surface tension lower than water (surface tension is about 73mN/m) to spin dry the surface of the biochip can speed up the volatilization of deionized water with the liquid with a surface tension lower than water. In some embodiments, steps S503 to S505 use the same rotation speed. In some embodiments, from step S503 to step S505, different rotation speeds are used in each step.

The present disclosure cleans the biochip sandwiched in the wafer structure with a cleaning solution/gas while rotating the wafer structure, so as to achieve the purpose of removing the surface carrier of the biochip, and remove the probes on the biochip at the same time. The biochip can be reused without harming the biochip substrate.

The foregoing summarizes features of some embodiments so that those of ordinary skill in the art may better understand the presently disclosed aspects. Those skilled in the art will recognize that they may at any time use this 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 presented herein. Those skilled in the art should also realize that such equivalent constructions do not depart from the spirit and scope of the disclosure, and that they can make various changes, substitutions and modifications herein without departing from the spirit and scope of the disclosure.

100:Wafer structure

101:First Wafer

101L: lower surface

101U: upper surface

102:Second wafer

102H: Through hole

102L: lower surface

102P:Prominent part

102U: upper surface

103: Bonding layer

104: fixture

105: Biochip

106: rotating element

107: Liquid/Gas Access Components

200: wafer structure

300: wafer structure

400: cleaning structure

500: Process

A-A': line

D1: the first aperture

D2: second aperture

H1: the first hole

H2: second hole

S501: step

S502: step

S503: step

S504: step

S505: step

When reading the accompanying drawings of this disclosure, it is suggested that various aspects of this disclosure be understood from the following descriptions. It is to be noted that, in accordance with the standard practice in the industry, the dimensions of various features are not drawn to scale. The dimensions of the various features may be arbitrarily increased or decreased for clarity of discussion. FIG. 1 illustrates a cross-sectional view of a wafer structure according to some embodiments of the present disclosure. FIG. 2 illustrates a cross-sectional view of a wafer structure including a bonding layer according to some embodiments of the present disclosure. FIG. 3 illustrates a cross-sectional view of a wafer structure including a clamp, according to some embodiments of the present disclosure. FIG. 4 illustrates a top view of a wafer structure according to some embodiments of the present disclosure. FIG. 5 illustrates a schematic bottom view of a second wafer in the wafer structure according to some embodiments of the present disclosure. FIG. 6 illustrates a top view of a first wafer in a wafer structure according to some embodiments of the present disclosure. FIG. 7 illustrates a schematic diagram of cleaning a biowafer using a wafer structure according to some embodiments of the present disclosure. FIG. 8 illustrates a flow diagram for cleaning a biowafer using a wafer structure according to some embodiments of the present disclosure.

100:Wafer structure

101:First Wafer

101L: lower surface

101U: upper surface

102:Second wafer

102H: Through hole

102L: lower surface

102P:Prominent part

102U: upper surface

D1: the first aperture

D2: second aperture

H1: the first hole

H2: second hole

Claims (9)

A wafer structure for carrying biochips, comprising: a first wafer; a second wafer, arranged on the first wafer; and a connection element, fixing the second wafer to the first wafer On the wafer, wherein the connection element includes a clamp, the clamp clamps the first wafer and the second wafer, the second wafer has at least one through hole, and the at least one through hole is formed from the second wafer An upper surface of the second wafer penetrates to the lower surface of the second wafer, and the at least one through hole includes: a first hole having a first diameter; and a second hole located under the first hole and communicating with the first hole. A hole, the second hole has a second diameter larger than the first diameter. The wafer structure as claimed in claim 1, wherein the connection element includes a bonding layer, and the bonding layer is disposed between the first wafer and the second wafer. The wafer structure as claimed in claim 1, wherein the first wafer has a substantially flat upper surface. The wafer structure as claimed in claim 1, wherein the second wafer further includes a protruding portion protruding toward the first hole. A method of cleaning a biochip, comprising: placing a biochip between the first wafer and the second wafer of the wafer structure of claim 1, wherein the biochip is located on the second wafer In the second hole; fix the second wafer on the first wafer by the connection element to hold the biochip; and rotate the wafer structure and pass a cleaning solution into the second wafer circle the first hole to clean the biowafer. The method according to claim 5, wherein the cleaning solution is an acidic solution or an alkaline solution. The method as described in claim 5, after rotating the wafer structure and passing the cleaning solution into the first hole of the second wafer, further comprising rotating the wafer structure and passing a deionized water into in the first hole of the second wafer to clean the biowafer. The method according to any one of claims 5 to 7, after rotating the wafer structure and passing the cleaning solution into the first hole of the second wafer, further comprising 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 is injected into the first hole of the second wafer to clean the biowafer. The method as described in claim item 8, wherein the inert gas is Nitrogen, the liquid with a surface tension below about 73 mN/m is isopropanol.

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