Biochip, biological sample detection apparatus, and a method for detecting biological samples

Abstract

A biochip includes a chip unit and an elastic pad disposed on the chip unit. The chip unit includes an upper substrate and a lower substrate, and has a plurality of spaced-apart liquid inlets. A gap is formed between the upper substrate and the lower substrate to accommodate a detection liquid. The liquid inlets are formed on the upper substrate and communicate with the gap. The elastic pad includes a plurality of spaced-through injection ports and a plurality of suction ports. The injection ports correspond to the liquid inlets. The suction ports correspond to the upper substrate and provide an adsorption force to the upper substrate, thereby maintaining the gap height and preventing deformation of the biochip that would affect detection accuracy. This invention also provides a biological sample detection device including the biochip, and a biological sample detection method using the biological sample detection device.

Description

Technical Field

[0001] This invention relates to a biochip, and more particularly to a biochip that can reduce deformation under stress. Prior Technology

[0002] Biochips are high-tech components designed using principles of microelectronics, microfluidics, molecular biology, biotechnology, gene detection, and analytical chemistry. They are made using silicon wafers, glass, or polymers as substrates and combined with microelectromechanical automation or other precision processing technologies. They have the ability to perform rapid, accurate, and low-cost biological analysis and testing.

[0003] Generally, biochips need to be used in conjunction with a liquid injection system. In existing equipment, the liquid injection system moves vertically up and down, pressing against the biochip to inject the liquid, and then moves upwards to separate from the biochip after injection. As shown in Figure 10, a traditional biochip 90 includes an upper substrate 91 and a lower substrate 92, with a gap G between them. However, when the liquid injection system presses against the biochip, it generates a pressure P1. During the process of injecting the test liquid into the gap G through the injection hole 93, the downward pressure P1 applied by the liquid injection system causes the biochip to deform, shortening the gap G between the upper substrate 91 and the lower substrate 92. Simultaneously, it deforms the liquid droplets injected by the system, potentially causing the droplets to overflow into other flow channels or movement paths within the biochip, resulting in residual liquid that affects detection accuracy. Summary of the Invention

[0004] Therefore, the object of the present invention is to provide a biochip that can overcome the deformation problem.

[0005] This invention relates to a biochip, comprising a chip unit and an elastic pad disposed on the chip unit. The chip unit includes an upper substrate and a lower substrate, and has a plurality of spaced-apart liquid inlets. A gap is formed between the upper substrate and the lower substrate to accommodate a detection liquid. The liquid inlets are formed on the upper substrate and communicate with the gap. The elastic pad has an upper surface and a lower surface, the lower surface being adhered to the chip unit. The elastic pad includes a plurality of injection ports and a plurality of suction ports spaced apart and penetrating the upper and lower surfaces of the elastic pad. The injection ports correspond to the liquid inlets of the chip unit, and the suction ports correspond to the upper substrate of the chip unit. The suction ports provide an adsorption force to the upper substrate to maintain the gap height.

[0006] Another technical aspect of the present invention is that the wafer unit further includes an adhesive layer disposed between the upper substrate and the lower substrate, the adhesive layer forming the gap between the upper substrate and the lower substrate, wherein the adhesive layer has a generally annular surrounding portion and a plurality of latitudinal and spaced-apart gate portions extending laterally inward from the surrounding portion, and each of the liquid inlets of the wafer unit is located between two adjacent latitudinal gate portions.

[0007] Another technical aspect of the present invention is that the wafer unit further includes an adhesive layer disposed between the upper substrate and the lower substrate, and a rigid spacer disposed between the upper substrate and the lower substrate. The hardness of the rigid spacer is greater than that of the adhesive layer. The adhesive layer and the rigid spacer are arranged side by side, and the adhesive layer is closer to the edge of the wafer unit than the rigid spacer.

[0008] Another technical aspect of the present invention is that the wafer unit further includes two adhesive layers disposed between the upper substrate and the lower substrate, and a rigid spacer disposed between the two adhesive layers, wherein the hardness of the rigid spacer is greater than the hardness of the adhesive layers.

[0009] Another technical aspect of the present invention is that the elastic pad further includes a plurality of spaced protruding docking portions, which correspond to and communicate with the injection port and the suction port of the wafer unit, respectively.

[0010] Another object of the present invention is to provide a biological sample detection device, comprising a biochip as described above, and an operating device. The operating device includes an injection module and an adsorption module spaced between the injection module and the injection module. The injection module corresponds to the injection port of the biochip, and the adsorption module corresponds to the aspiration port of the biochip. The adsorption module provides an adsorption force to the substrate to maintain the gap height of the biochip.

[0011] Another technical aspect of the present invention is that the liquid injection module, the adsorption module, and the elastic pad of the biochip are in planar contact.

[0012] Another object of the present invention is to provide another type of biological sample detection device, comprising a biochip as described above, and an operating device. The operating device includes a liquid injection module and an adsorption module spaced between the liquid injection module and the biochip. The liquid injection module corresponds to the injection port of the biochip, and the adsorption module corresponds to the aspiration port of the biochip. The liquid injection module has a plurality of downwardly extending and tapering liquid injection connectors, and the adsorption module has a plurality of downwardly extending and tapering adsorption connectors. The liquid injection connectors and the adsorption connectors extend into corresponding mating portions of the elastic pad.

[0013] Another objective of this invention is to provide a biological sample detection method, which comprises the operating steps of the aforementioned biological sample detection device.

[0014] The biological sample detection method sequentially includes an alignment step, an adsorption step, and a liquid injection step. The alignment step involves bringing the manipulator and the biochip closer together until the manipulator contacts the biochip, and the manipulator applies a downward pushing force to the biochip. The adsorption step involves the adsorption module of the manipulator providing an upward attractive force to the upper substrate of the biochip through the aspiration port of the biochip to maintain the gap. The liquid injection step involves the liquid injection module of the manipulator injecting the liquid to be tested through the injection port of the biochip.

[0015] Another technical aspect of the present invention is that the biological sample detection method further includes a termination step, which involves first stopping the liquid injection step and then stopping the adsorption step.

[0016] Another technical aspect of the present invention is that before the alignment step is performed, the gap of the biochip has a first height; when the alignment step is performed, due to the pushing force applied by the operating machine to the upper substrate of the biochip, the gap of the biochip has a second height, which is smaller than the first height.

[0017] Another technical aspect of the present invention is that, during the adsorption step, due to the attractive force exerted by the adsorption module on the substrate of the biochip, the gap of the biochip has a third height, which is greater than the second height.

[0018] The advantage of the biochip of the present invention is that, during the liquid injection process, it can provide an adsorption force to the upper substrate of the chip unit through the suction port of the elastic pad, thereby maintaining the height of the gap between the chip units, avoiding deformation of the biochip, and thus improving detection accuracy and detection efficiency. Simple Explanation of the Diagram

[0019] Figure 1 is a perspective view of the first preferred embodiment of the biochip of the present invention; Figure 2 is a partial cross-sectional view to help illustrate the internal structure of the biochip in Figure 1; Figure 3 is a partial cross-sectional view, showing a preferred embodiment of the biological sample detection device of the present invention; Figure 4 is a flowchart illustrating a preferred embodiment of the biological sample detection method of the present invention; Figure 5 is a partial side sectional view illustrating another implementation of the guide channel. Figure 6 is an exploded perspective view of the second preferred embodiment of the biochip of the present invention; Figure 7 is a partial cross-sectional view to help illustrate the internal structure of the biochip in Figure 6; Figure 8 is a schematic diagram illustrating a third preferred embodiment of the biochip of the present invention; Figure 9 is a schematic diagram showing another configuration of the third preferred embodiment; and Figure 10 is a schematic diagram illustrating the deformation of the test liquid droplets caused by the traditional biochip injection process. Implementation

[0020] The features and technical content of the related patent applications of this invention will be clearly presented in the following detailed description of the preferred embodiments with reference to the accompanying drawings. Before proceeding with the detailed description, it should be noted that similar elements are represented by the same numbers. Furthermore, the directional terms mentioned in the following embodiments, such as up, down, left, right, front, back, bottom, and top, are only for reference to the accompanying drawings. Therefore, the directional terms used are for illustrative purposes and not for limiting the invention.

[0021] Referring to Figures 1 and 2, a first preferred embodiment of the biochip 2 of the present invention is shown, comprising a chip unit 21 and an elastic pad 22 disposed on the chip unit 21. As shown in Figure 2, the chip unit 21 includes an upper substrate 211 and a lower substrate 212. The chip unit 21 has a plurality of spaced-apart liquid inlets 213. A gap 210 is formed between the upper substrate 211 and the lower substrate 212 to accommodate detection liquid. The liquid inlets 213 are formed on the upper substrate 211 and communicate with the gap 210. The elastic pad 22 has an upper surface 221 and a lower surface 222, and the lower surface 222 is attached to the chip unit 21. The elastic pad 22 includes a plurality of spaced-apart injection ports 223 and a plurality of suction ports 224 that penetrate the upper surface 221 and the lower surface 222 of the elastic pad 22. The injection port 223 corresponds to the liquid inlet 213 of the wafer unit 21, and the suction port 224 corresponds to the upper substrate 211 of the wafer unit 21. More specifically, the suction port 224 corresponds to the position of the wafer unit 21 where the liquid inlet 213 is not formed. Therefore, the suction port 224 can adhere to the upper substrate 211 and provide an adsorption force to the upper substrate 211, thereby maintaining the height of the gap 210. Through the above structural design, during the liquid injection process, the suction port 224 of the elastic pad 22 can provide an adsorption force to the upper substrate 211 of the wafer unit 21, preventing the wafer unit 21 from deforming due to the downward pressure of the liquid injection. This maintains the height of the gap 210 between the upper substrate 211 and the lower substrate 212 of the wafer unit 21, preventing deformation of the biochip 2, and thus improving detection accuracy and efficiency. For example, in this embodiment of Figure 1, the injection port 223 of the biochip 2 is arranged along the four sides, and at least one suction port 224 is provided on each side; in other embodiments, as shown in Figure 6, the suction port 224 may be located at a corner position between the four sides.

[0022] Referring to Figure 3, a preferred embodiment of the biological sample detection device of the present invention is shown, comprising the biochip 2 and an operating platform 3. The operating platform 3 includes a liquid injection module 31 and an adsorption module 32 spaced apart from the liquid injection module 31. The liquid injection module 31 corresponds to the injection port 223 of the biochip 2, and the adsorption module 32 corresponds to the suction port 224 of the biochip 2. The adsorption module 32 provides an adsorption force to the substrate 211 to maintain the height of the gap 210 of the biochip 2. For example, the biological sample detection device of the present invention uses electromagnetic technology to control the movement and mixing of the liquid to be tested and the reagent. Therefore, maintaining the height of the gap 210 between the upper substrate 211 and the lower substrate 212 of the biochip 2 not only avoids the situation where the liquid to be tested and the reagent are easily gathered near the injection port after being injected into the biochip 2 and cannot flow smoothly to the chip operation area; but also avoids the liquid mixing outside the chip operation area, causing unexpected mixing. Therefore, the biological sample detection device of the present invention helps to improve detection accuracy and detection efficiency. The following describes the biological sample detection method of the present invention through the biological sample detection device of FIG. 3. Referring to FIG. 4, the detection method sequentially includes an alignment step 41, an adsorption step 42, and a liquid injection step 43. It should be noted that in FIG. 4, the structure of the biochip 2 and the operating platform 3 is shown schematically. The alignment step 41 involves bringing the manipulator 3 and the biochip 2 closer together until the manipulator 3 touches the biochip 2, and applying a downward pushing force F1 to the biochip 2. The adsorption step 42 involves the adsorption module 32 of the manipulator 3 providing an upward attractive force F2 to the upper substrate 211 of the biochip 2 through the suction port 224 of the biochip 2 to maintain the gap 210. The liquid injection step 43 involves the liquid injection module 31 of the manipulator 3 injecting the liquid to be tested through the injection port 223 of the biochip 2. Because the manipulator 3 exerts a downward pushing force F1 on the upper surface 221 of the biochip 2 when it touches the biochip 2, the upper substrate of the biochip 2 is easily deformed and concave downward (as shown in the alignment step 41), causing the gap 210 between the upper substrate 211 and the lower substrate 212 to narrow, making it difficult for the injected liquid to be tested to move according to the command. Therefore, when the liquid injection module 31 contacts the biochip 2 and applies a downward pushing force F1 to the upper substrate of the biochip 2, the upward attraction F2 of the adsorption module 32 to the upper substrate can reduce the deformation of the upper substrate, thereby keeping the gap 210 space unchanged.

[0023] More specifically, before performing the alignment step 41, the gap 210 of the biochip 2 has a first height H1. During the alignment step 41, due to the pushing force F1 applied by the operating platform 3 to the upper substrate 211 of the biochip 2, the gap 210 of the biochip 2 has a second height H2, which is smaller than the first height H1. During the adsorption step 42, due to the attractive force F2 applied by the adsorption module 32 to the upper substrate 211 of the biochip 2, the gap 210 of the biochip 2 has a third height H3, which is greater than the second height H2. That is, during the alignment step 41, the pushing force F1 applied by the operating platform 3 to the upper substrate 211 of the biochip 2 will press down on the biochip 2, making the gap of the biochip 2 smaller (the second height H2 is smaller than the first height H1). During the adsorption step 42, the adsorption module 32 applies an attractive force F2 to the upper substrate 211 of the biochip 2, which pulls the upper substrate 211 upward, increasing the distance between the upper substrate 211 and the lower substrate 212, and further enlarging the compressed gap of the biochip 2 (the third height H3 is greater than the second height H2). In this way, the internal gap 210 space of the biochip 2 can be kept constant during liquid injection, thereby ensuring that the liquid droplets formed by the injected liquid to be tested do not deform and can move smoothly.

[0024] It should also be noted that the biological sample detection method includes a termination step, which involves first stopping the liquid injection step 43 and then stopping the adsorption step 42. In this way, it can be ensured that the adsorption of the biochip 2 is stopped only after the liquid injection step 43 has been completed, thus maintaining the gap 210 height of the biochip 2 during the liquid injection process.

[0025] Referring to Figure 3, the elastic pad 22 further includes a plurality of spaced-apart protrusions 225, which correspond to and communicate with the injection port 223 and the suction port 224 of the wafer unit 21, respectively. In this embodiment, the injection module 31 and the adsorption module 32 are in planar contact with the elastic pad 22 of the biochip 2. In other embodiments, as shown in Figure 5, the injection module 31 has a plurality of downwardly extending injection connectors 311 with a gradually decreasing outer diameter, and the adsorption module 32 has a plurality of downwardly extending adsorption connectors 321 with a gradually decreasing outer diameter. The injection connectors 311 and the adsorption connectors 321 extend into the corresponding docking portions 225 of the elastic pad 22. With the above structural design, if there is any deviation when the operating platform 3 and the biochip 2 are approaching each other (as shown in Figure 5), the tapered design of the liquid injection connector 311 and the adsorption connector 321 has the function of guiding the direction, so that the liquid injection connector 311 and the adsorption connector 321 can be reliably placed in the corresponding docking part 225 of the elastic pad 22, thereby improving the alignment effect.

[0026] Referring to Figures 6 and 7, a second preferred embodiment of the biochip 2 of the present invention is shown, comprising a chip unit 21 and an elastic pad 22 disposed on the chip unit 21. The chip unit 21 includes an upper substrate 211, a lower substrate 212, and an adhesive layer 214 disposed between the upper substrate 211 and the lower substrate 212. The adhesive layer 214 forms a gap 210 between the upper substrate 211 and the lower substrate 212. In this embodiment, the injection ports 223 of the elastic pad 22 are arranged along the four sides, and a suction port 224 is provided at each of the four corners. As shown in Figure 6, the adhesive layer 214 has a generally annular surrounding portion 215 and a plurality of spacer portions 216 extending laterally inward from the surrounding portion 215 and arranged at intervals. Through the design of the annular surrounding portion 215 and the spacer portions 216, the adhesive layer 214 can uniformly support the upper substrate 211 and the lower substrate 212 along the periphery, thereby ensuring the uniformity of the gap 210 of the overall biochip 2. The chip unit 21 has a plurality of spaced-apart liquid inlets 213, which are formed on the upper substrate 211 and communicate with the gap 210. Each liquid inlet 213 is located between two adjacent spacer portions 216 of the adhesive layer 214. More specifically, a channel 217 is formed between two adjacent spacer portions 216, and each channel 217 corresponds to each liquid inlet 213. The biochip 2 of this preferred embodiment can also be used with the operating device 3. When the liquid to be tested is injected through the inlet 213, it is confined within the channel 217 formed by two adjacent grid portions 216, flowing towards the operating area of ​​the chip unit 21. In this way, the adhesive layer 214 not only maintains the gap 210, but the grid portions 216 also block adjacent inlets 213, preventing overflow of liquids to be tested from different inlets 213 and ensuring the accuracy of bioreaction detection. The grid portions 216 can reduce the cavity space below the inlet 213 of the chip unit 21, ensuring that the liquid to be tested can move smoothly towards the operating area of ​​the chip unit 21 after being injected through the inlet 213, preventing liquid residue below the inlet 213, and also increasing the detection volume.

[0027] Referring to Figure 8, a third preferred embodiment of the biochip 2 of the present invention is shown. The similarities to the first preferred embodiment will not be repeated. The difference lies in that the chip unit 21 further includes two adhesive layers 214 disposed between the upper substrate 211 and the lower substrate 212, and a rigid spacer 218 disposed between the two adhesive layers 214. The rigid spacer 218 has a higher hardness than the adhesive layer 214. The rigid spacer 218 effectively enhances the overall hardness of the chip unit 21, ensuring that the chip unit 21 is not easily deformed by external forces during liquid injection. Referring to Figure 9, in some embodiments, the adhesive layer 214 and the rigid spacer 218 may be arranged with one adhesive layer 214 and one rigid spacer 218 side-by-side, and the adhesive layer 214 is closer to the edge of the chip unit 21 than the rigid spacer 218. In this way, in addition to increasing the overall rigidity of the biochip 2, the thickness of the biochip 2 can also be further reduced. It should be noted that the thickness of the adhesive layer 214 and the rigid spacer layer 218 in Figures 8 and 9 are only schematic and can be adjusted according to actual needs.

[0028] In summary, the advantage of the biochip 2 of the present invention lies in that, during the liquid injection process, it can provide an adsorption force to the upper substrate 211 of the chip unit 21 through the suction port 224 of the elastic pad 22, thereby maintaining the height of the gap 210 of the chip unit 21 and preventing the biochip 2 from deforming and causing the injected liquid to overflow, thus affecting the detection accuracy. Furthermore, the design of the rigid separator 218 further enhances the overall rigidity of the biochip 2, reducing the chance of deformation during operation, and effectively achieving the purpose of the present invention. Furthermore, in response to advancements in biomedical technology, the market is expanding, and the application scope of the biochip 2 of this invention is increasing daily. The number of liquids that need to be detected within the chip module is also increasing, thus enabling its wider application in the field of biological sample detection, such as high-throughput screening, disease diagnosis, drug development, clinical diagnosis, or environmental monitoring. Compared to traditional chip modules, the modifications to the internal structure of the biological sample detection device of this invention, as well as the changes in the shape of the fixing components within the chip module, not only solve existing problems and improve the efficiency of the chip module, but also do not add additional structural components. Only some functions and shapes are changed, which not only reduces design costs but also increases usability and improves the rate of return.

[0029] However, the above description is only a preferred embodiment of the present invention and should not be construed as limiting the scope of the present invention. Any simple equivalent changes and modifications made in accordance with the scope of the patent application and the description of the invention shall still fall within the scope of the patent of the present invention.

[0030] 2: Biochip 21: Chip Unit 210: Gap 211: Upper substrate 212: Substrate 213: Liquid inlet 214: Adhesive layer 215: Around the Ministry 216: Grille part 217: Channel 218: Rigid partition 22: Elastic Pad 221: Upper surface 222: Lower surface 223: Injection port 224: Suction port 225: Docking section 3: Operating platform 31: Liquid Injection Module 311: Liquid Injection Connector 32: Adsorption Module 321: Adsorption connector 41: Alignment Steps 42: Adsorption Step 43: Injection Procedure F1: Top Thrust F2: Attraction H1: First Height H2: Second Altitude H3: Third Height 90: Biochip 91: Upper substrate 92:Lower base plate 93: Injection Hole G: Gap P1: Downforce

Claims

1. A biochip, comprising: a chip unit including an upper substrate and a lower substrate, the chip unit having a plurality of spaced-apart liquid inlets, a gap being formed between the upper substrate and the lower substrate to accommodate a detection liquid, the liquid inlets being formed on the upper substrate and communicating with the gap; and an elastic pad having an upper surface and a lower surface, the lower surface being adhered to the chip unit, the elastic pad including a plurality of injection ports and a plurality of aspiration ports spaced-apart and penetrating the upper and lower surfaces of the elastic pad; wherein... The injection ports correspond to the liquid inlets of the wafer unit, and the suction ports correspond to the upper substrate of the wafer unit. The suction ports are distributed at the corners of the upper substrate to provide an adsorption force to the upper substrate, thereby maintaining a consistent gap height between the upper substrate and the lower substrate.

2. The biochip as described in claim 1, wherein, The wafer unit also includes an adhesive layer disposed between the upper substrate and the lower substrate, the adhesive layer forming the gap between the upper substrate and the lower substrate, wherein the adhesive layer has a generally annular surrounding portion and a plurality of latitudinal and spaced-apart gate portions extending laterally inward from the surrounding portion, and each of the liquid inlets of the wafer unit is located between two adjacent latitudinal gate portions.

3. The biochip as described in claim 1, wherein, The wafer unit also includes an adhesive layer disposed between the upper substrate and the lower substrate, and a rigid spacer disposed between the upper substrate and the lower substrate. The rigid spacer has a higher hardness than the adhesive layer. The adhesive layer and the rigid spacer are arranged side by side, and the adhesive layer is closer to the edge of the wafer unit than the rigid spacer.

4. The biochip as described in claim 1, wherein, The chip unit also includes two adhesive layers disposed between the upper substrate and the lower substrate, and a rigid spacer disposed between the two adhesive layers, wherein the hardness of the rigid spacer is greater than the hardness of the adhesive layers.

5. The biochip as claimed in claim 1, wherein, The elastic pad also includes a plurality of spaced protruding mating portions, which correspond to and communicate with the injection port and the suction port of the wafer unit, respectively.

6. A biological sample detection device, comprising: a biochip as claimed in any one of claims 1 to 5; and an operating mechanism including a liquid injection module and an adsorption module spaced between the liquid injection module and the liquid injection module, the liquid injection module corresponding to the injection port of the biochip, the adsorption module corresponding to the aspiration port of the biochip, the adsorption module providing an adsorption force to the substrate to maintain the gap height of the biochip.

7. The biological sample detection device as described in claim 6, wherein, The liquid injection module and the adsorption module are in planar contact with the elastic pad of the biochip.

8. The biological sample detection device as described in claim 6, wherein, The injection module has a plurality of injection connectors that extend downward and have a gradually decreasing outer diameter, and the adsorption module has a plurality of adsorption connectors that extend downward and have a gradually decreasing outer diameter. The injection connectors and the adsorption connectors are inserted into the corresponding mating portions of the elastic pad.

9. A method for detecting biological samples, comprising the operating steps of the biological sample detection device according to any one of claims 6 to 8, comprising in sequence: an alignment step, wherein the operating platform and the biochip are brought close together until the operating platform contacts the biochip, and the operating platform applies a downward pushing force to the biochip; an adsorption step, wherein the adsorption module of the operating platform provides an upward attractive force to the upper substrate of the biochip through the suction port of the biochip to maintain the gap; and a liquid injection step, wherein the liquid injection module of the operating platform injects the liquid to be detected through the injection port of the biochip.

10. The biological sample detection method as described in claim 9 further includes a termination step, wherein the termination step is to first stop the liquid injection step and then stop the adsorption step.

11. The biological sample detection method as described in claim 9, wherein, Before the alignment step is performed, the gap of the biochip has a first height; during the alignment step, due to the pushing force applied by the operating instrument to the upper substrate of the biochip, the gap of the biochip has a second height, which is smaller than the first height.

12. The biological sample detection method as described in claim 11, wherein, During the adsorption step, due to the attraction exerted by the adsorption module on the substrate of the biochip, the gap of the biochip has a third height, which is greater than the second height.

Images