CN112113906A - Sample detection device and manufacturing method thereof - Google Patents
Sample detection device and manufacturing method thereof Download PDFInfo
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Abstract
The sample detection device with a flow channel of the present invention comprises: an optical signal detecting device for receiving and detecting an incident optical signal, which includes a plurality of image sensor chip units formed in the same substrate; the flow channel device is arranged on the upper surface of the optical signal detection device and comprises a shell, at least one sample inflow port and at least one sample outflow port are formed in the shell, at least one flow channel is formed between the lower surface of the shell and the upper surface of the optical signal detection device, and each flow channel corresponds to at least one sample inflow port and at least one sample outflow port and at least one image sensor chip unit; the flow channels and the corresponding sample flow inlets and sample flow outlets are arranged such that a biological sample can flow into its corresponding one of the flow channels via each of the sample flow inlets, reach the corresponding surface of the image sensor chip unit, and can flow out from the corresponding sample flow outlet.
Description
Technical Field
The present disclosure relates to biochemical detection devices, and more particularly, to a sample detection device with a flow channel and a method for manufacturing the same.
Background
In the field of in-vitro diagnostics (IVD), real-time detection using bioluminescent signals is a very common technique. Currently mainstream detection technologies, such as immunodetection technologies, molecular (nucleic acid) detection technologies (e.g., PCR), and genetic sequencing technologies, require real-time quantitative detection, reading, and analysis by means of bioluminescent signals.
Taking the field of immunodetection as an example, the immunofluorescence analysis technology has become a common rapid analysis technology in the current biomedical inspection, and has wide application prospect in the fields of microorganism, virus antigen or antibody detection, hormone detection, tumor marker detection and drug (including heroin, morphine, ecstasy, ketamine and the like) detection. In immunofluorescence analysis, substances of immunoreaction are generally required to be subjected to fluorescence labeling, the fluorescence intensity characterizes the strength of specific immunoreaction, and information such as the concentration of an object to be detected can be obtained by detecting the fluorescence intensity. In the field of molecular detection, the emergence of real-time fluorescence quantitative PCR technology greatly simplifies the quantitative detection process and truly realizes the absolute quantification of nucleic acid. The fluorescent quantitative PCR technology has been widely applied in the fields of nucleic acid quantitative analysis, gene expression difference analysis, SNP detection, pathogen detection and the like.
Most of traditional fluorescence detection and analysis products need an external optical detection element (such as a CMOS, a CCD or a PMT, etc.) and a customized optical path system to amplify, read and analyze a fluorescence signal, so that the volume of a detection instrument is additionally increased, the instrument cost is increased, and the time required by detection is increased, so that the requirements of partial medical scenes, especially basic medical scenes on portability, rapidness and low-cost detection cannot be met. In order to achieve miniaturization of products, the commonly adopted means is to simplify the external optical path, shorten the liquid path or reduce the volume of fluid. These measures can certainly reduce the volume of the instrument to some extent, but have limited effectiveness.
In order to further improve the integration level, Microfluidics (Microfluidics) technology is adopted in the prior art, which can manipulate fluid in sub-millimeter and sub-micron scale space, so as to shrink the basic functions of laboratories of fluid, biology, chemistry, etc. to a chip (such as a CMOS image sensor chip) of several square centimeters or even several square millimeters, thereby implementing a lab-on-a-chip. In this apparatus, a biological or chemical substance sample is transferred and fixed on the surface of an image sensor chip, fluorescence emitted from the sample is received and detected by the image sensor, and information related to the biological or chemical substance sample can be judged according to the intensity and color of the detected light signal.
However, such prior art products typically require the use of specially designed CMOS image sensors, and have the following problems:
firstly, a detection device only comprises a CMOS image sensor chip, the number of pixel units is limited, so that the designed detection flux is fixed, the detection device cannot meet the requirement for the condition that the detection requirement exceeds the designed detection flux, and if the detection flux requirement is low, the detection capability of the chip is wasted.
Secondly, the CMOS image sensor chip used in the detection device is a customized product, which is expensive to manufacture, and further results in high use cost.
Disclosure of Invention
In order to solve the above problems in the prior art, the present invention provides a sample detection device with a flow channel, comprising: an optical signal detecting device for receiving and detecting an incident optical signal, which includes a plurality of image sensor chip units formed in the same substrate; the flow channel device is arranged on the upper surface of the optical signal detection device and comprises a shell, at least one sample inflow port and at least one sample outflow port are formed in the shell, at least one flow channel is formed between the lower surface of the shell and the upper surface of the optical signal detection device, and each flow channel corresponds to at least one sample inflow port and at least one sample outflow port and at least one image sensor chip unit; the flow channels and the corresponding sample flow inlets and sample flow outlets are arranged such that a sample can flow into its corresponding one of the flow channels via each of the sample flow inlets, reach the corresponding surface of the image sensor chip unit, and can flow out from the corresponding sample flow outlet.
In one embodiment of the present invention, the flow channel device includes a single flow channel, at least one sample inlet port, and at least one sample outlet port, the flow channel corresponds to a plurality of image sensor chip units, and the flow channel and the sample inlet port and the sample outlet port are disposed such that a sample can flow into the flow channel via the sample inlet port, reach the surfaces of the corresponding plurality of image sensor chip units, and can flow out from the sample outlet port.
In one embodiment of the present invention, the flow channel device comprises a single flow channel, and the number of the image sensor chip units is 2 to 100.
In another embodiment of the present invention, the flow channel device includes a plurality of independent flow channels that are not communicated with each other, and a plurality of sample flow inlets and a plurality of sample flow outlets respectively corresponding to the plurality of independent flow channels, each independent flow channel corresponds to at least one sample flow inlet, at least one sample flow outlet, and at least one image sensor chip unit, and each independent flow channel and the corresponding sample flow inlet and sample flow outlet are disposed such that a sample can flow into the corresponding independent flow channel through the sample flow inlet, reach a surface of the corresponding image sensor chip unit, and can flow out from the corresponding sample flow outlet.
In one embodiment of the present invention, the number of the independent flow channels is 2 to 10, and each independent flow channel corresponds to one sample inflow port and one sample outflow port.
In an embodiment of the invention, the flow channel device includes a plurality of independent flow channels that are not communicated with each other, and the number of the image sensor chip units corresponding to each independent flow channel is 1 to 100.
In one embodiment of the present invention, the image sensor chip unit is a CMOS image sensor chip unit.
The present invention further provides a method for manufacturing the sample detection device with a flow channel, comprising the following steps:
(1) preparing an image sensor wafer, wherein the wafer comprises a plurality of image sensor chip units manufactured in the same substrate, and the light receiving surface of each image sensor chip unit is the upper surface of the image sensor wafer; (2) preparing a disc with the same diameter as the image sensor wafer, wherein the disc is provided with an upper surface and a lower surface, a plurality of grooves for forming flow channels are formed in the lower surface of the disc, each groove is provided with a continuous side wall, and at least one through hole is formed in each groove at the position of two opposite sides in the length direction and penetrates through the disc; (3) combining the upper surface of the image sensor wafer with the lower surface of the disc, so that each groove covers at least one image sensor chip unit, and the disc is hermetically combined with the upper surface of the image sensor wafer at the position of the side wall of the groove; (4) and packaging and cutting the combination formed by the image sensor wafer and the circular disc so as to form a plurality of sample detection device units, wherein each sample detection device unit comprises at least one groove and a plurality of image sensor chip units.
In one embodiment of the manufacturing method of the present invention, the number of the grooves on the lower surface of the disk is 5 to 500, and the grooves are formed by etching or molding.
In an embodiment of the manufacturing method of the present invention, the disk is hermetically bonded to the upper surface of the image sensor wafer at the position of the sidewall of the groove by laser bonding or anodic bonding.
In an embodiment of the manufacturing method of the present invention, the method further includes a step of applying a protective film to an upper surface of the disk to prevent contamination inside the groove during the step of packaging and dicing the combination of the image sensor wafer and the disk.
Another embodiment of the present invention further provides a method for manufacturing the sample detection device with a flow channel, comprising the following steps:
(1) preparing an image sensor wafer, wherein the wafer comprises a plurality of image sensor chip units manufactured in the same substrate, and the light receiving surface of each image sensor chip unit is the upper surface of the image sensor wafer; (2) preparing a disk having the same diameter as the image sensor wafer and having an upper surface and a lower surface, and forming a plurality of sets of through holes at predetermined positions of the disk, each set of through holes including at least two through holes spaced apart from each other; (3) preparing a bonding layer with the same diameter as the image sensor wafer and a certain thickness, and forming a plurality of flow passage holes with preset shapes at preset positions of the bonding layer; (4) clamping the bonding layer between the upper surface of the image sensor wafer and the lower surface of the disc, and combining the bonding layer, the upper surface of the image sensor wafer and the lower surface of the disc into a whole in a pressing mode, so that each group of through holes are positioned in one flow channel hole, at least one through hole is arranged at any end of the flow channel hole in the length direction, each flow channel hole comprises at least one image sensor chip unit, and the disc is hermetically combined with the upper surface of the image sensor wafer through the bonding layer, so that a combined body is formed; (5) and packaging and cutting the combination formed by the image sensor wafer, the bonding layer and the disc to form a plurality of sample detection device units, wherein each sample detection device unit comprises at least one flow channel hole and a plurality of image sensor chip units.
In one embodiment of the above manufacturing method of the present invention, the bonding layer has a thickness of 5 to 500 μm, and the number of the flow channel holes is 5 to 500.
In an embodiment of the above manufacturing method of the present invention, the material of the bonding layer is a thin film of a polymer material, and the polymer material is selected from one of Polyimide (Polyimide), Polydimethylsiloxane (PDMS), Acrylate (Acrylate), Polyester (Polyester), or Resin material (Resin).
In an embodiment of the above manufacturing method of the invention, the pressing manner is a hot pressing manner.
In an embodiment of the above manufacturing method of the present invention, the step of packaging and cutting the combined body further includes a step of applying a protective film to an upper surface of the circular disc to prevent the flow channel holes from being contaminated.
As described above, according to the sample detection device with flow channels of the present invention, a single flow channel and a corresponding plurality of image sensor chip units may be included in one detection device unit, or a plurality of independent flow channels may be included, and each of the independent flow channels may include the same or different number of image sensor chip units. The difference in the number of chip units corresponds to different detection fluxes. In practical use, different independent flow channels can be used separately or simultaneously for detection. Therefore, different application scenes can be flexibly met according to different detection flux requirements. The method can meet the detection requirement in high flux and avoid the waste of detection capability under the requirement of low flux.
Furthermore, the sample detection device of the present invention can use the already large-scale commercial CMOS image sensor, and does not need to be customized specially, so the manufacturing period is short, and the manufacturing cost and the use cost are low.
The manufacturing method of the sample detection device with the flow channel is used for processing on the basis of the image sensor chip wafer instead of processing on the basis of a single chip as in the prior art, so that the process is simpler and the manufacturing cost is lower.
Drawings
FIG. 1a is a perspective view of one embodiment of a sample detection device unit with a flow channel according to the present invention, FIG. 1B is a longitudinal sectional view taken along the dotted line A-A 'in FIG. 1a, and FIG. 1c is a transverse sectional view taken along the dotted line B-B' in FIG. 1 a.
Fig. 2a, 2b and 2c are schematic plan views of a combination of a flow channel and an image sensor chip unit according to different embodiments of the invention.
FIG. 3a is a schematic perspective view of one embodiment of a method for manufacturing a sample detection device according to the present invention, and FIG. 3b is a schematic flow chart of the embodiment.
FIG. 4a is a schematic view of another embodiment of the method for manufacturing a sample detection device according to the present invention, and FIG. 4b is a schematic flow chart of the embodiment.
FIGS. 5a and 5b are schematic views showing the packaging and cutting steps of one embodiment of the method for manufacturing a sample testing device according to the present invention.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
Embodiments of the present invention are described below with reference to the drawings.
Reference will now be made in detail to the exemplary embodiments, examples of which are illustrated in the accompanying drawings. When the following description refers to the accompanying drawings, like numbers in different drawings represent the same or similar elements unless otherwise indicated. The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present application. Rather, they are merely examples of apparatus and methods consistent with certain aspects of the present application, as detailed in the appended claims.
The terminology used in the present application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used in this application and the appended claims, the singular forms "a", "an", and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It should also be understood that the term "and/or" as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items. The word "comprising" or "comprises", and the like, means that the element or item listed as preceding "comprising" or "includes" covers the element or item listed as following "comprising" or "includes" and its equivalents, and does not exclude other elements or items.
Fig. 1a schematically shows a sample detection device unit 1 with a flow channel according to an embodiment of the present invention, fig. 1B is a cross-sectional view taken along a broken line a-a 'in fig. 1a, and fig. 1c is a cross-sectional view taken along a broken line B-B' in fig. 1 a.
As shown in the figure, the sample detection device unit 1 of the present invention includes an optical signal detection device 2 and a flow channel device 3. The optical signal detection device 2 may employ a CMOS image sensor chip. As shown in the drawing, the optical signal detection device 2 in this embodiment includes two sets of five image sensor chip units 2-1 each connected in a row. The flow channel device 3 comprises a shell 3-1, the shell 3-1 is arranged on the upper surface of the optical signal detection device 2, the shell 3-1 is tightly fit with the upper surface of the optical signal detection device 2 at the position of a side wall 3-5 of the shell, and the side wall 3-5 is continuous, so that a cavity is defined as the flow channel 3-2. The housings 3-1 at both ends in the longitudinal direction of the flow channel 3-2 are respectively provided with a through hole as a sample inflow port 3-3 and a sample outflow port 3-4.
As shown in FIGS. 1a and 1c, the sample-detecting device unit 1 has two independent flow paths 3-2 and corresponding sample-inflow ports 3-3 and sample-outflow ports 3-4. Each individual flow channel 3-2 covers and corresponds to a group of five image sensor chip units 2-1 connected in a row.
As shown, the width of the flow channel 3-2 should be the same as or slightly larger than the width of the image sensor chip unit 2-1, and the length of the flow channel 3-2 is about the length of five image sensor chip units 2-1 or slightly larger, so that the flow channel 3-2 can cover the five image sensor chip units 2-1 corresponding to the flow channel 3-2. The flow channel 3-2 is formed to have a shape gradually narrowed at both ends in the longitudinal direction, which is advantageous in that the liquid sample introduced into the flow channel 3-2 from the sample inflow port 3-3 can reach all the surfaces of the five image sensor chip units 2-1 covered by the flow channel 3-2 and can completely flow out from the sample outflow port 3-4 without remaining in the flow channel, although it is impossible to use the liquid sample because a part of the surfaces of the image sensor chip units 2-1 at both ends of the flow channel 3-2 are covered by the side walls 3-5. Of course, the flow channel 3-2 may also be formed in other suitable shapes to achieve the same effect.
The upper surface of the image sensor chip unit 2-1 is typically subjected to a biological or chemical treatment to adsorb the sample flowing across the surface for image detection and analysis.
FIGS. 2a to 2c are top plan views of different embodiments of the sample detection device unit 1 according to the present invention.
In the embodiment shown in fig. 2a, ten image sensor chip units 2-1 are included, and the shape of the flow channel 3-2 is schematically shown, which has a width slightly larger than the width of two chip units 2-1, a length of about five chip units 2-1, and two ends gradually narrowed to the sample inlet 3-3 and the sample outlet 3-4, so as to facilitate the flow of the sample liquid into the flow channel, to the surface of the five chip units 2-1 covered by the flow channel, and to allow the whole flow to exit without residue. FIG. 2b shows the embodiment of FIG. 1a, wherein the sample detection device unit 1 comprises two independent flow channels 3-2, each flow channel covering five image sensor chip units 2-1. Fig. 2c shows a further embodiment of the present invention, wherein the sample detection device unit 1 comprises five mutually independent flow channels 3-2, each flow channel covering two image sensor chip units 2-1.
Although the sample detection device unit 1 in the above embodiment includes 2 to 5 different flow channels, and the number of the chip units covered by each flow channel is the same, the sample detection device unit 1 of the present invention can be made to include more flow channels, for example, 10 flow channels, and each flow channel can be made to cover different number of chip units, for example, the number can be 1 to 100.
FIG. 3a is a schematic view showing an embodiment of a method for manufacturing a sample detection device according to the present invention, and FIG. 3b is a partial cross-sectional view schematically showing a manufacturing process of the sample detection device according to the present invention, which will be described below with reference to the two drawings.
And 2, preparing a disc 5 which has an upper surface, a lower surface and a certain thickness, wherein the diameter of the disc is the same as that of the CMOS image sensor wafer 4. The disc 5 is processed to form a plurality of grooves 5-1 of a predetermined shape at predetermined positions of the lower surface thereof by etching or molding to form the flow channels 3-2. In the embodiment, the grooves are long strips, adjacent grooves are separated, and each groove is provided with a circle of continuous groove side walls 5-3. The number of grooves may be 5 to 500 and the depth may be 5 to 500. mu.m. And (3) punching holes at two ends of each groove in the length direction to respectively form a through hole 5-2, wherein the diameter of each through hole can be 0.2mm to 1 mm. The number of the through holes 5-2 is 10-1000, i.e., twice the number of the grooves, corresponding to the number of the grooves 5-1. The through-hole 5-2 serves as a sample inflow port 3-3 and a sample outflow port 3-4. The disc 5 may be made of glass, plastic, silicon material, etc.
And 3, attaching the upper surface of the wafer 4 and the lower surface of the disc 5 together to form a combined body, for example, a laser bonding or anodic bonding mode can be adopted, so that the grooves 5-1 are hermetically attached to the upper surface of the wafer 4 at the groove side walls 5-3, and each groove covers a predetermined number of chip units 2-1, for example, 1 to 100.
The thus formed combination of the image sensor wafer and the disk is packaged and cut to produce a plurality of sample detection device units similar to those shown in fig. 1, which will be described later with reference to fig. 5.
FIG. 4a schematically shows another embodiment of the method for manufacturing a sample detection device according to the present invention, and FIG. 4b schematically shows a manufacturing flow of the embodiment shown in FIG. 4a in a partial cross-sectional view, which will be described below with reference to the two drawings.
And 2, preparing a disc 6 with the same diameter as the image sensor wafer 4, wherein the disc 6 is provided with an upper surface and a lower surface, and a plurality of groups of through holes 6-1 are formed at preset positions on the disc 6, and each group of through holes comprises at least two through holes separated from each other. The number of vias may be 10-1000. The disc 5 may be made of glass, plastic, silicon, etc. The through-hole 6-1 serves as a sample inflow port 3-3 and a sample outflow port 3-4.
And 3, preparing a bonding layer 7 with the same diameter as the image sensor wafer, wherein the bonding layer has a certain thickness, a plurality of through flow passage holes 7-1 with preset shapes are formed at preset positions, and each flow passage hole 7-1 is provided with a circle of continuous side walls 7-2. The bonding layer may have a thickness of 5 to 500 μm, and the number of the flow channel holes may be 5 to 500. The bonding layer 7 may be made of a polymer material film, for example, Polyimide (Polyimide), Polydimethylsiloxane (PDMS), Acrylate (Acrylate), Polyester (Polyester), or Resin material (Resin). The flow channel hole 7-1 forms a flow channel 3-2.
And 4, clamping the bonding layer 7 between the upper surface of the image sensor wafer 4 and the lower surface of the disc 6, for example, by using a hot pressing process, and integrating the three in a pressing manner, so that each group of through holes 6-1 on the disc 6 is located in one flow channel hole 7-1, at least one through hole 6-1 is arranged at any end of the flow channel hole 7-1 in the length direction, each flow channel hole 7-1 contains at least one image sensor chip unit 2-1, and the disc 6 is hermetically bonded with the upper surface of the image sensor wafer 4 through the bonding layer 7, so as to form a combined body.
The joined body produced through the above steps needs to be packaged and cut to form the sample detection device unit 1 of the present invention. The packaging step is explained below with reference to fig. 5.
It should be noted that the fabrication method of the present invention basically adopts the conventional wafer packaging and dicing process. In the conventional wafer packaging and cutting step, a glass disc is adhered on the surface of the wafer in advance to serve as a support so as to prevent the wafer from cracking in the process. In the manufacturing method, a disc is attached to the surface of the wafer for manufacturing the runner device, the glass disc which needs to be bonded originally is replaced, and the wafer of the image sensor is supported in the packaging and cutting steps. However, since the disk used in the present invention has through holes, the surface of the disk needs to be temporarily sealed by a protective film in the packaging and cutting steps to prevent impurities from entering the flow channel from the through holes and damaging the surface of the image sensor chip.
FIGS. 5a and 5b schematically illustrate, in partial cross-sectional views, the steps of packaging and cutting in accordance with one embodiment of the method of manufacturing a sample testing device of the present invention, and the packaging step in accordance with one embodiment of the method of manufacturing the present invention is described below with reference to FIG. 5 a.
And 2, sticking a protective film on the upper surface of the disc 5 or 6 to prevent impurities from entering the flow channel through the through hole on the disc to form pollution. The combined body is turned over so that the back surface of the image sensor wafer 4 faces upward, and a conventional wafer thinning and grinding process is performed. In one embodiment, the thinned image sensor wafer 4 has a thickness of 100-300 μm.
And 3, firstly, coating photoresist on the surface of the thinned wafer, wherein the thickness of the photoresist layer can be about 1-2 μm. The exposure is then carried out with ultraviolet light, and the exposure time may vary from a few milliseconds to a few seconds. And then developing with a developing solution, wherein the developing solution generally uses a 2.38% TMAH solution, and the developing time is 60-120 seconds. This forms the photoresist layer into a predetermined pattern.
And 4, removing the protective film on the surface of the disc, and etching the surface of the wafer exposed after the photoresist layer is patterned. The etching material may be a mixed gas of a halide gas, oxygen, argon, or the like.
And 5, sticking a protective film on the surface of the disc again, and then removing the photoresist on the surface of the wafer. One of the photoresist removing methods is to burn with high-temperature oxygen and then remove the carbide residue formed by burning the photoresist with a cleaning solution. Another photoresist removing method is to soak the combined body in chemicals, dissolve the photoresist organic matter and remove it. Thus, the wafer surface is formed with a predetermined pattern.
And 6, coating photoresist on the surface of the wafer again, exposing by using ultraviolet rays, and developing by using a developing solution to form a predetermined pattern on the photoresist layer, which can be referred to as step 3.
And 7, removing the protective film on the surface of the disc, further etching the surface of the wafer exposed after the photoresist layer is patterned, and exposing the wiring metal of the chip, which can be referred to as the step 4.
And 8, attaching a protective film on the surface of the disc, and then removing the photoresist on the surface of the wafer. Reference may be made specifically to step 5.
And 9, removing the protective film, and depositing an insulating layer on the patterned wafer surface, wherein the insulating layer is made of an inorganic material such as silicon dioxide or silicon nitride, and the process method can be chemical vapor deposition, for example. As the insulating layer material, an organic compound material may be used as needed.
And step 10, coating photoresist on the surface of the wafer again, exposing and developing, and etching the insulating layer formed before to expose the wiring metal of the chip. The etching gas differs depending on the material of the insulating layer, and for example, if the insulating layer is SiO2 which is inorganic, the etching gas may be CH2Cl2 or a mixed gas of CHCl3 gas and oxygen gas. If the insulating layer is an organic material, the etching gas requires the use of another gas, such as argon.
Step 11, attaching a protective film on the upper surface of the disk to prevent foreign matters from entering the flow channel, and then removing the photoresist on the surface of the wafer, which may specifically refer to step 5, for example, soaking the wafer in chemicals to dissolve and remove organic matters.
And step 12, depositing metal on the surface of the patterned wafer by an electroplating or physical vapor deposition method, and then etching to form a metal connecting line. The metal material may be titanium, tantalum, copper, chromium, nickel, cobalt, or the like. The metal etching method is determined according to the metal material, and may be specifically classified into wet etching, dry etching, and the like, and particularly, a wet etching scheme may be adopted. Then, an insulating encapsulation and a solder ball array (BGA) are formed on the surface of the wafer. The plastic packaging material is generally made of organic resin, the coating method is a glue coating method, the glue has larger thickness, and the thickness is different according to specific embodiments, for example, the thickness can be 5-50 μm. In one embodiment, solder balls may be screen printed at predetermined locations. And finally, removing the protective film on the surface of the disc to finish the packaging step of the combined body.
Referring now to fig. 5b, the cutting step of one embodiment of the manufacturing method of the present invention is described.
And step 1, after the combined body finishes the packaging step, adhering a film for cutting on the upper surface of the disc.
And 2, cutting the combined body at a preset position, for example, cutting the combined body at the position of a vertical dotted line in the figure to form a plurality of sample detection device units. Each unit formed after cutting may contain a different number of flow channels as needed, and each flow channel may also cover a different number of image sensor chip units.
While the invention has been shown and described with reference to certain preferred embodiments, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention.
Claims (31)
1. A sample detection device with a flow channel, comprising:
an optical signal detecting device for receiving and detecting an incident optical signal, which includes a plurality of image sensor chip units formed in the same substrate;
the flow channel device is arranged on the upper surface of the optical signal detection device and comprises a shell, at least one sample inflow port and at least one sample outflow port are formed in the shell, at least one flow channel is formed between the lower surface of the shell and the upper surface of the optical signal detection device, and each flow channel corresponds to at least one sample inflow port and at least one sample outflow port and at least one image sensor chip unit;
the flow channels and the corresponding sample flow inlets and sample flow outlets are arranged such that a sample can flow into its corresponding one of the flow channels via each of the sample flow inlets, reach the corresponding surface of the image sensor chip unit, and can flow out from the corresponding sample flow outlet.
2. The sample detection device of claim 1, wherein the image sensor chip unit is a CMOS image sensor chip unit.
3. The sample testing device according to claim 1, wherein said flow channel means comprises a single flow channel, a sample inlet port and a sample outlet port, said single flow channel corresponds to a plurality of image sensor chip units, and said flow channel and said sample inlet port and sample outlet port are arranged so that a sample can flow into said flow channel via said sample inlet port, reach the surface of said corresponding plurality of image sensor chip units, and can flow out from said sample outlet port.
4. The sample detection device according to claim 3, wherein the number of the image sensor chip units corresponding to the single flow channel is 2 to 100.
5. The sample testing device according to claim 1, wherein said sample inflow port and said sample outflow port are circular through holes provided in said housing, at least one of each, having a diameter of 0.2mm to 1 mm.
6. The sample testing device as claimed in claim 1, wherein said flow channel device comprises a plurality of independent flow channels which are not connected to each other, each independent flow channel corresponds to a sample flow inlet, a sample flow outlet and at least one image sensor chip unit, each of said independent flow channels and its corresponding sample flow inlet and sample flow outlet are disposed such that a sample can flow into the corresponding independent flow channel via said sample flow inlet, reach the surface of the corresponding image sensor chip unit, and can flow out from the corresponding sample flow outlet.
7. The sample testing device of claim 6, wherein the number of independent flow channels is 2 to 10.
8. The sample testing device as claimed in claim 7, wherein the number of said image sensor chip units corresponding to each of said independent flow channels is 1 to 100.
9. The sample testing device as claimed in claim 1, wherein said flow channel comprises a groove formed on a lower surface of said housing, and an edge of said groove is hermetically combined with an upper surface of said optical signal testing device.
10. The sample testing device of claim 9, wherein there are a plurality of said grooves, adjacent grooves have continuous edges, and said housing is hermetically bonded to said upper surface of said optical signal testing device at the edges of the grooves, thereby forming a plurality of independent flow paths that are not connected to each other.
11. The sample testing device of claim 9, wherein the depth of said recess formed in said lower surface of said housing is 5-500 μm.
12. The sample testing device of claim 1, wherein said flow conduit device further comprises a bonding layer, said housing is hermetically bonded to the upper surface of said optical signal testing device by said bonding layer, said bonding layer has a thickness and has at least one flow conduit hole penetrating through the bonding layer, said bonding layer is hermetically bonded to the lower surface of said housing and the upper surface of said optical signal testing device in a region other than said flow conduit hole, and said flow conduit hole forms said flow conduit.
13. The sample testing device of claim 12, wherein the binding layer has a thickness of 5-500 μ ι η.
14. The sample detection device according to claim 12, wherein the number of the flow paths is 1, and the number of the image sensor chip units corresponding thereto is 2 to 100.
15. The sample detection device according to claim 12, wherein the number of the flow channels is 2 to 5, and the number of the image sensor chip units corresponding to each flow channel is 1 to 100.
16. The sample testing device of claim 13, wherein the binding layer is made of a polymeric material selected from one of Polyimide (Polyimide), Polydimethylsiloxane (PDMS), Acrylate (Acrylate), Polyester (Polyester), and Resin (Resin).
17. A method for manufacturing a sample detection device with a flow channel is characterized by comprising the following steps:
(1) preparing an image sensor wafer, wherein the wafer comprises a plurality of image sensor chip units manufactured in the same substrate, and the light receiving surface of each image sensor chip unit is the upper surface of the image sensor wafer;
(2) preparing a disc with the same diameter as the image sensor wafer, wherein the disc is provided with an upper surface and a lower surface, a plurality of grooves for forming flow channels are formed in the lower surface of the disc, each groove is provided with a continuous side wall, and at least one through hole is formed in each groove at the position of two opposite sides in the length direction and penetrates through the disc;
(3) combining the upper surface of the image sensor wafer with the lower surface of the disc, so that each groove covers at least one image sensor chip unit, and the disc is hermetically combined with the upper surface of the image sensor wafer at the position of the side wall of the groove;
(4) and packaging and cutting the combination formed by the image sensor wafer and the circular disc so as to form a plurality of sample detection device units, wherein each sample detection device unit comprises at least one groove and a plurality of image sensor chip units.
18. The manufacturing method of claim 17, wherein the number of the grooves is 5 to 500, and the grooves are formed on the lower surface of the disc by etching or molding.
19. The method of manufacturing of claim 17, wherein the depth of the groove is 5-500 μm.
20. The method of claim 17, wherein the disk is hermetically bonded to the top surface of the image sensor wafer at the location of the sidewall of the recess by laser bonding or anodic bonding.
21. The method of manufacturing of claim 17, further comprising the step of applying a protective film to an upper surface of the disk to prevent contamination inside the recess during the step of packaging and dicing the combination of the image sensor wafer and the disk.
22. The method of manufacturing according to claim 17, wherein the image sensor chip unit is a CMOS image sensor chip unit.
23. A method for manufacturing a sample detection device with a flow channel is characterized by comprising the following steps:
(1) preparing an image sensor wafer, wherein the wafer comprises a plurality of image sensor chip units manufactured in the same substrate, and the light receiving surface of each image sensor chip unit is the upper surface of the image sensor wafer;
(2) preparing a disk having the same diameter as the image sensor wafer and having an upper surface and a lower surface, and forming a plurality of sets of through holes at predetermined positions of the disk, each set of through holes including at least two through holes spaced apart from each other;
(3) preparing a bonding layer with the same diameter as the image sensor wafer and a certain thickness, and forming a plurality of flow passage holes with preset shapes at preset positions of the bonding layer;
(4) clamping the bonding layer between the upper surface of the image sensor wafer and the lower surface of the disc, and combining the bonding layer, the upper surface of the image sensor wafer and the lower surface of the disc into a whole in a pressing manner, so that each group of through holes are positioned in one flow channel hole, at least one through hole is arranged at any end of the flow channel hole in the length direction, each flow channel hole comprises at least one image sensor chip unit, and the disc is hermetically combined with the upper surface of the image sensor wafer through the bonding layer, so that a combined body is formed;
(5) and packaging and cutting the combination formed by the image sensor wafer, the bonding layer and the disc to form a plurality of sample detection device units, wherein each sample detection device unit comprises at least one flow channel hole and a plurality of image sensor chip units.
24. The method of manufacturing according to claim 23, wherein the image sensor chip unit is a CMOS image sensor chip unit.
25. The method of claim 23, wherein the bonding layer is a thin film of a polymer material selected from one of Polyimide (Polyimide), Polydimethylsiloxane (PDMS), Acrylate (Acrylate), Polyester (Polyester), and Resin material (Resin).
26. The method of manufacturing of claim 23, wherein the bonding layer has a thickness of 5 to 500 μ ι η.
27. The method of manufacturing of claim 23, wherein the number of the flow channel holes is 5 to 500.
28. The manufacturing method according to claim 23, wherein the pressing is performed by a hot press.
29. The method of manufacturing according to claim 23, wherein the step of packaging and cutting the combined body further comprises the step of applying a protective film to an upper surface of the circular plate to prevent the flow channel holes from being contaminated.
30. The method of claim 23, wherein each of the sample detection device units includes 1 number of flow channel holes and 2 to 100 number of image sensor chip units.
31. The manufacturing method according to claim 23, wherein each of the sample detection device units includes 2 to 10 flow channel holes, and each of the flow channel holes includes 1 to 100 image sensor chip units.
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