TWI461230B - Filtration film for filtrating the blood serum and method for manufacturing the same and filtration device - Google Patents

Description

Filter film for filtering serum, manufacturing method thereof and filtering device

The present invention relates to a filter film, a method for producing the same, and a filter device, and more particularly to a filter film for filtering serum, a method for producing the same, and a filter device.

There are three kinds of conventional blood filtration methods: 1. Separating blood cells from serum by means of a centrifuge; 2. Separating by microelectromechanical process using dielectrophoresis principle; and 3. Blood cell serum by non-contact high-wavelength laser Separation.

The first method of separating the blood cells from the serum by the rotation of the centrifuge is to place the whole blood in a test tube, place it on a centrifuge, and separate the blood cells by the specific gravity of the blood. However, the disadvantage of this method is that the consumption of drugs and samples is large, and the processing time required is also rather lengthy.

The second method of separating the microelectromechanical process using the principle of dielectrophoresis is to use the dielectrophoretic force to generate a non-uniform alternating electric field according to the different conductivity and dielectric constant between the particle and the external solution. A symmetric polarization phenomenon in which a particle is moved by an electric field force to a high or low electric field strength. Using the principle of dielectrophoresis, particles with different particle sizes or different surface charge levels can be separated, but the required process is cumbersome and the required equipment is expensive.

The third method uses a non-contact high-wavelength laser to separate blood cells from the blood. Due to the principle of laser light focusing, a stable energy trap can be formed by using the opposite direction light pressure, and the tiny particles can be clamped. The operation of particles in fluid devices, and is a non-contact, non-invasive tool, so the use of laser light clamps to capture, move and manipulate particles can also be used for blood separation, but expensive laser optics is the study The biggest difficulty.

The above conventional methods require multiple steps to filter the product, the sample consumption is large, the time is long, the process is cumbersome, and the equipment is expensive.

Therefore, it is necessary to provide an innovative and progressive filter film for filtering serum, a method for producing the same, and a filtering device to solve the above problems.

The invention provides a filter film for filtering serum, comprising: a plurality of filter holes, a first surface and a second surface. The first surface has a plurality of arc faces, and the filter holes are between the arc faces. The second surface has a plurality of recessed regions relative to the first surface, and the recessed regions correspond to filter holes.

The invention further provides a method for manufacturing a filter film for filtering serum, comprising the steps of: (a) providing a substrate; (b) forming a photoresist layer on a surface of the substrate; and (c) forming the photoresist layer. a plurality of photoresist patterns and exposing a portion of the surface of the substrate; (d) forming an alloy layer on the photoresist pattern and the substrate; and (e) separating the alloy layer and the photoresist pattern and the substrate to form a The filter film comprises: a plurality of filter holes, a first surface and a second surface, the first surface having a plurality of arc faces, wherein the arc faces are between the filter holes, the second surface corresponding to The first surface has a plurality of recessed regions, and the recessed regions correspond to filter holes.

The invention further provides a filtering device for filtering serum, comprising: a first substrate and at least one filtering film. The first substrate has a first through hole. The at least one filter film is disposed at a position opposite to the first through hole of the first substrate, the filter film has a plurality of filter holes, a first surface and a second surface, the first surface having a plurality of curved surfaces, Between the equal arc faces are the filter holes, and the second surface corresponds to the first surface, and has a plurality of recessed regions, and the recessed regions correspond to the filter holes.

Therefore, the separated serum can be quickly obtained by the filtering device of the present invention, and the consumption of the sample to be inspected can be greatly reduced, the amount of the sample required can be greatly reduced, and the complicated processing procedure can be eliminated. In addition, the filtering device of the present invention is easy to erect, and can be erected in a general laboratory, and experiments can be performed without expensive instruments, which can reduce the experiment cost and reduce the device cost. The filtering device of the present invention utilizes the principle of multi-layer filtration and pushes whole blood with a driving device, thereby providing a fast, convenient, low-cost and miniaturized filtering platform.

In addition, by using the arc surface design of the filter film, the blood to be filtered flows from the arc surface to the filter holes, and the blood to be filtered is filtered by the pore diameter of the filter holes. Multi-layer filter membranes can be used with a filtration range of 2 μm to 8 μm, which can sequentially filter large particles to smaller particles to improve filtration efficiency without blocking.

1 is a schematic view showing a filtration device for filtering serum according to a first embodiment of the present invention; and FIG. 2 is a schematic exploded view showing a filtration film and a substrate according to a first embodiment of the present invention. Referring to FIG. 1 and FIG. 2, the filter device 10 for filtering serum of the present invention comprises: a first substrate 111, a second substrate 112 and at least one filter film 121, 122, 123. The first substrate 111 has a first through hole 113. The second substrate 112 has a second through hole 114 opposite to the first through hole 113. The at least one filter film 121, 122, 123 is disposed at a position opposite to the first through hole 113 of the first substrate 111.

In this embodiment, the filter device 10 has three filter films: a first filter film 121, a second filter film 122, and a third filter film 123, which are sequentially disposed on the first substrate from top to bottom. 111. Each filter membrane has a plurality of filter pores. The first filter hole of the first filter film 121 (for example, having a diameter of 7 μm) is larger than the second filter hole of the second filter film 122 (for example, the diameter thereof is 4 μm), and the second filter hole of the second filter film 122 is the second filter hole. The third filter hole (for example, having a diameter of 2 μm) larger than the third filter film 123. Therefore, the filter membrane can utilize multi-layer filtration with a filtration range of 2 μm to 8 μm, which can sequentially filter large particles to smaller particle batches to improve filtration efficiency without blocking. And the filter film can be selected from a highly biocompatible alloy as a film material to avoid the possibility of immune rejection or contamination of the sample when filtering blood.

The filter device 10 of the present invention further includes a driving device 13 connected to the first through hole 113 of the first substrate 111 for driving the blood to be filtered to flow through the filtering films 121, 122, and 123. The driving device 13 can be used as a driving force for driving the microfluid to achieve the purpose of transporting the fluid, and can adjust the flow rate unit in mL/min or μL/min to suit the driving requirements of different fluids (blood to be filtered).

The filter device 10 of the present invention further includes an input connector 14 and an output connector 15 respectively disposed on the second through hole 114 of the second substrate 112 and the first through hole 113 of the first substrate 111. The input connector 14 can be used to connect to the syringe barrel to protect the sample from leaking; the output connector 15 can be used to connect to the drive unit 13. The input connector 14 and the output connector 15 are Polytetrafluoroethene (PTFE).

3 is a schematic view showing the combination of a plurality of substrates according to a second embodiment of the present invention; and FIG. 4 is a schematic exploded view showing the filter film and the substrate of the second embodiment of the present invention. Referring to FIG. 3 and FIG. 4 , the filter device 30 of the second embodiment of the present invention includes a first substrate 311 , a second substrate 312 , a third substrate 313 , and at least one filter film 32 . The first substrate 311 has a first through hole 314. The second substrate 312 has a second through hole 315 opposite to the first through hole 314 . The third substrate 313 is disposed on the second substrate 312 , and the third substrate 313 has a third through hole 316 opposite to the second through hole 315 . In this embodiment, the second through hole (for example, having a diameter of 8 mm) is larger than the third through hole (for example, having a diameter of 3 mm), and the third through hole is equal to the first through hole.

The filter device 30 of the present invention further includes a first adhesive layer 331 disposed between the filter film 32 and the second substrate 312, and further comprising a second adhesive layer 332 disposed on the third substrate 313 and the Between the second substrates 312. The first adhesive layer 331 and the second adhesive layer 332 may be double-sided adhesive materials to fix the substrates as interlayer adhesives to ensure stable filtration performance and the filter sample is not exposed.

The first substrate 311, the second substrate 312 and the third substrate 313 are polymethylmethacrylate (PMMA), poly-dimethylsiloxane (PDMS), epoxy resin (Poly-dimethylsiloxane). Epoxy), metal or glass, which has high mechanical strength and is a highly biocompatible polymer material.

The experiment used a colloidal particle aqueous solution to replace the whole blood to filter the precursor experiment, and the precursor experiment can predict the actual effect of whole blood separation. The experimental procedure is as follows: 1. Measure 5 μL of 4 μm particle size colloidal particles; Measure 5 μL of colloidal particles of 17 μm particle size; 3. Prepare colloidal particles with different sizes of colloidal particles of 4 μm and 17 μm, and mix 1 mL of deionized water to prepare colloidal particle reagents; 4. After the preparation of the colloidal particle reagent is completed, the injection syringe is placed in a 1 mL capacity; 5. The Teflon bridge connector is used to connect the injection syringe and the filter wafer; 6. With a driving force, the injection can be completed in about 1 minute; 7. The filtration results can be displayed by observing an inverted optical microscope.

Referring to Figure 5, a schematic of the results of the precursor experiment is shown. It shows a good filtering effect of the filtering device of the present invention, wherein the left side of Figure 5 shows the 4 μm and 17 μm mixed colloidal particle solutions before filtration, while the right side of Figure 5 shows the 17 μm colloidal particles larger than the filtration pore size. Filtered.

Therefore, the separated serum can be quickly obtained by the filtering device of the present invention, and the consumption of the sample to be inspected can be greatly reduced, the amount of the sample required can be greatly reduced, and the complicated processing procedure can be eliminated. In addition, the filtering device of the present invention is easy to erect, and can be erected in a general laboratory, and experiments can be performed without expensive instruments, which can reduce the experiment cost and reduce the device cost. The filtering device of the present invention utilizes the principle of multi-layer filtration and pushes whole blood with a driving device, thereby providing a fast, convenient, low-cost and miniaturized filtering platform.

Referring to Figures 6 through 10, there are shown schematic views of a method of making a filter membrane for filtering serum of the present invention. Referring first to FIG. 6, a substrate 51 is provided, and a photoresist layer 52 is formed on one surface of the substrate 51. Referring to FIG. 7 and FIG. 8, a plurality of photoresist patterns 521 are formed on the photoresist layer 52, and a part of the surface of the substrate 51 is exposed. In this embodiment, a photomask 53 is disposed above the photoresist layer 52. The photomask 53 has a plurality of corresponding patterns corresponding to the photoresist patterns 521 (shown in FIG. 7). Exposure and development are then performed to form the photoresist patterns (as shown in Figure 8). In the present embodiment, the photoresist patterns 521 are circular.

Referring to FIG. 9, an alloy layer 55 is formed on the photoresist pattern 521 and the substrate 51. In the present embodiment, the alloy layer 55 is formed by electroforming. Referring to FIG. 10, the alloy layer 55 and the photoresist pattern 521 and the substrate 51 are separated to form a filter film 55, which includes: a plurality of filter holes 551, a first surface 552, and a second surface 553. A surface has a plurality of curved surfaces 555, and the curved surfaces 555 are between the filtering holes 551. The second surface 553 corresponds to the first surface 552 and has a plurality of concave regions 556. The filter hole 551 should be waited for.

Referring to Figure 11, a schematic view of the second surface of the filter membrane is shown. With reference to FIG. 10 and FIG. 11 , in the embodiment, the arc surfaces 555 are arcuate surfaces, and the arc surface includes a top end and a bottom end, and the bottom end is disposed at the periphery of the filter holes 551 . The area of the recessed areas 556 is larger than the area of the filter holes 551. The recessed areas 556 are circular. The blood to be filtered is input from the first surface 552, and is output from the second surface 553 through the filter hole 551. By using the circular arc surface design of the filter film, the blood to be filtered flows from the circular arc surface to the filter holes 551, and the blood to be filtered is filtered by the pore diameter of the filter holes 551. A multi-layer filter membrane with a filtration range of 2 μm to 8 μm can be used to sequentially filter large particles into smaller particle batches to improve filtration efficiency without clogging. The filter film uses a highly biocompatible alloy as a film material to avoid the possibility of immune rejection or contamination of the sample when filtering blood.

However, the above embodiments are merely illustrative of the principles and effects of the invention and are not intended to limit the invention. Therefore, those skilled in the art can make modifications and changes to the above embodiments without departing from the spirit of the invention. The scope of the invention should be as set forth in the appended claims.

10. . . First embodiment filter device

13. . . Drive unit

14. . . Input connector

15. . . Output connector

30. . . Filter device of the second embodiment of the present invention

32. . . Filter film

51. . . Substrate

52. . . Photoresist layer

53. . . Mask

55. . . Alloy layer, filter film

111. . . First substrate

112. . . Second substrate

113. . . First through hole

114. . . Second through hole

121. . . First filter film

122. . . Second filter film

123. . . Third filter film

311. . . First substrate

312. . . Second substrate

313. . . Third substrate

314. . . First through hole

315. . . Second through hole

316. . . Third through hole

331. . . First adhesive layer

332. . . Second adhesive layer

521. . . Photoresist pattern

551. . . Filter hole

552. . . First surface

553. . . Second surface

555. . . Curved surface

556. . . Sag area

Figure 1 is a schematic view showing a filtration device for filtering serum according to a first embodiment of the present invention;

2 is a schematic exploded view of a filter film and a substrate according to a first embodiment of the present invention;

3 is a schematic view showing the combination of a plurality of substrates in the second embodiment of the present invention;

4 is a schematic exploded view showing a filter film and a substrate according to a second embodiment of the present invention;

Figure 5 shows a schematic diagram of the results of the precursor experiment;

6 to 10 are schematic views showing a method of manufacturing a filter film for filtering serum according to the present invention; and

Figure 11 shows a schematic view of the second surface of the filter membrane.

10‧‧‧First embodiment filter device

13‧‧‧ drive

14‧‧‧Input connector

15‧‧‧Output connector

111‧‧‧First base

112‧‧‧Second substrate

Claims (20)

A filter film for filtering serum, comprising: a plurality of filter holes; a first surface having a plurality of arc faces, wherein the arc faces are between the filter holes; and a second surface opposite to the first The surface has a plurality of recessed regions, and the recessed regions correspond to the filter holes. The filter film of claim 1, wherein the arc surface is a circular arc surface, the arc surface includes a top end and a bottom end, and the bottom end is disposed at a periphery of the filter holes. The filter film of claim 1, wherein the area of the recessed area is larger than the area of the filter hole. The filter film of claim 1, wherein the recessed area is circular. The filter film of claim 1, wherein the blood to be filtered is input from the first surface, and is output through the filter hole through the second surface. The filter film of claim 1, wherein the filter film is made of an alloy. A method for manufacturing a filter film for filtering serum, comprising the steps of: (a) providing a substrate; (b) forming a photoresist layer on a surface of the substrate; and (c) forming a plurality of photoresists on the photoresist layer Patterning and exposing a portion of the surface of the substrate; (d) forming an alloy layer on the photoresist pattern and the substrate; and (e) separating the alloy layer and the photoresist pattern and the substrate to form a filter film The method includes: a plurality of filter holes, a first surface, and a second surface, the first surface having a plurality of arc surfaces, wherein the arc surfaces are between the filter holes, the second surface corresponding to the first surface There are a plurality of recessed areas, and the recessed areas correspond to filter holes. The manufacturing method of claim 7, wherein in the step (c), the method further comprises the steps of: (c1) providing a reticle above the photoresist layer, the reticle having a plurality of corresponding patterns corresponding to the light Resisting the pattern; and (c2) performing exposure and development to form the photoresist pattern. The manufacturing method of claim 7, wherein in the step (c), the photoresist patterns are circular. A filter device for filtering serum, comprising: a first substrate having a first through hole; and at least one filter film disposed at a relative position of the first through hole of the first substrate, the filter film having a plurality of a filter hole, a first surface and a second surface, the first surface having a plurality of curved surfaces, the curved surfaces being between the curved surfaces, the second surface corresponding to the first surface, having a plurality A recessed area corresponding to the filter holes. The filter device of claim 10, wherein the filter film comprises a first filter film, a second filter film and a third filter film, which are sequentially disposed on the first substrate from top to bottom, wherein the first The first filter hole of the filter film is larger than the second filter hole of the second filter film, and the second filter hole of the second filter film is larger than the third filter hole of the third filter film. The filtering device of claim 10, further comprising a driving device connected to the first through hole of the first substrate for driving the blood to be filtered to flow through the filtering film. The filter device of claim 10, further comprising a second substrate disposed on the filter film, the second substrate having a second through hole opposite to the first through hole. The filter device of claim 13, further comprising an input connector and an output connector respectively disposed on the second through hole of the second substrate and the first through hole of the first substrate. The filter device of claim 14, wherein the input connector and the output connector are Polytetrafluoroethene (PTFE). The filtering device of claim 13, further comprising a first adhesive layer disposed between the filter film and the second substrate. The filtering device of claim 13, further comprising a third substrate disposed on the second substrate, the third substrate having a third through hole opposite to the second through hole. The filtering device of claim 17, further comprising a second adhesive layer disposed between the third substrate and the second substrate. The filter device of claim 17, wherein the second through hole is larger than the third through hole, and the third through hole is equal to the first through hole. The filter device of claim 17, wherein the first substrate, the second substrate, and the third substrate are polymethylmethacrylate (PMMA), poly-dimethylsiloxane (PDMS). ), epoxy (Epoxy), metal or glass.