MICROFILTER, MANUFACTURING METHOD AND MICROFILTRATION UNIT

Abstract

A microfilter, a manufacturing method thereof, and a microfiltration unit for holding the microfilter are provided. The microfilter has: a non-epoxy based microfilm; and a plurality of microholes provided on the surface of the non-epoxy based microfilm and penetrating therethrough via UV laser ablation, wherein the surface of the non-epoxy based microfilm is patterned into predetermined sections for locating isolated targets and quick enumeration.

Claims

1. A microfilter, comprising: a non-epoxy based microfilm; and a plurality of microholes provided on the non-epoxy based microfilm and penetrating therethrough via laser ablation, wherein the surface of the non-epoxy based microfilm is patterned into predetermined sections for locating isolated targets and enumeration.

2. The microfilter of claim 1, wherein the material of the non-epoxy based microfilm is a transparent plastic material.

3. The microfilter of claim 2, wherein the transparent plastic material comprises polyimide, polycarbonate, polyethylene, polyethylene terephthalate, polyethylene naphthalate, polymethyl methacrylate and polystyrene.

4. The microfilter of claim 1, wherein the surface of the non-epoxy based microfilm further comprises a thin film to facilitate filtration function.

5. The microfilter of claim 1, wherein the microholes are circular microholes.

6. The microfilter of claim 5, wherein the mean diameter of each of the microholes is less than or equal to 10 μm.

7. The microfilter of claim 1, wherein the microholes are rectangular microholes or hexagonal microholes.

8. The microfilter of claim 1, wherein the microholes have cylindrical walls feeding through the non-epoxy based microfilm.

9. The microfilter of claim 1, wherein the microholes have tapered walls feeding through the non-epoxy based microfilm.

10. The microfilm of claim 1, wherein the thickness of the non-epoxy based microfilm ranges from 5 to 25 μm.

11. The microfilter of claim 1, wherein the number of the microholes in the non-epoxy based microfilm is more than 50,000.

12. The microfilter of claim 1, wherein the distance between two adjacent microholes is at least 15 μm.

13. The microfilter of claim 1, wherein the number of the patterned predetermined sections on the surface of the non-epoxy based microfilm is 16 sections.

14. A method for fabricating a microfilter, comprising the following steps of: using laser ablation in a non-epoxy based microfilm to form microholes in a predetermined pattern; and patterning the surface of the non-epoxy based microfilm into predetermined sections.

15. The method of claim 14, wherein the material of the non-epoxy based microfilm is a transparent plastic material.

16. A method of claim 14, wherein the laser is a UV laser.

17. The method of claim 14, wherein the non-epoxy based microfilm is exposed and perforated by the UV laser.

18. The method of claim 14, wherein the number of the patterned predetermined sections on the surface of the non-epoxy based microfilm is 16 sections.

19. A microfiltration unit, comprising: an upper frame, including an inlet orifice on the top side, an upper side wall, and a side module which includes a flexible stripe with one end thereof connected with and extended from the lower part of the upper side wall of the upper frame, and a transforming inlet head connected with the other end of the flexible stripe and having one end to be engaged with the top side of the upper frame and the other end to be connected to a sample inlet orifice of an external sample inlet syringe; and a lower frame, including an outlet orifice and a lower cylindrical side wall, wherein the upper frame and the lower frame are connected with each other through screw coupling, a perforated non-epoxy based microfilter is sandwiched between the upper frame and the lower frame, and the transforming inlet head is replaceable with a different inlet head so as to correspondingly engage with the external sample inlet syringe having a different sample inlet orifice, thereby providing a linear passage of the sample injected from the external sample inlet syringe and flowing through the inlet orifice of the upper frame to the outlet orifice of the lower frame.

20. The microfiltration unit of claim 19, wherein the upper side wall and the side module, including the flexible stripe and the transforming inlet head, are integrated into one piece.

21. The microfiltration unit of claim 19, wherein the flexible stripe is removably engaged with the lower part of the upper side wall or removably engaged with the transforming inlet head.

22. The microfiltration unit of claim 19, wherein the side module of the upper frame is allowed to adjust the sample inlet orifice from a wider opening to a narrower opening.

23. The microfiltration unit of claim 19, wherein the upper frame further comprises an upper gasket disposed at an inner peripheral wall thereof, the lower frame further comprises a lower gasket disposed at an inner peripheral wall thereof, and the microfilter is sandwiched between the two gaskets.

24. The microfiltration unit of claim 19, further comprising two gaskets respectively placed below and above the microfilter to avoid sample leakage and to hold the microfilter in place.

25. The microfiltration unit of claim 19, wherein the side module is integrated with the sample inlet syringe.

26. The microfiltration unit of claim 19, wherein the diameter of the microfilter is 13 mm and the diameter of a filtration area is 9 mm.

27. The microfiltration unit of claim 19, further comprising a controlled suction pump for applying a negative pressure to the outlet orifice such that the linear passage of the sample is directed by a pressure difference.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0023] FIG. 1 shows a diagram of a microfilter. FIG. 1(a) shows a microfilter structure having a microfilm with a diameter of 13 mm and a filtration area with a diameter of 9 mm. FIG. 1(b) shows the partial enlarged view of the microfilter showing perforated microholes designed to penetrate through the microfilm.

[0024] FIG. 2(a) shows the overall structure of the microfiltration unit of the invention. FIG. 2(b) shows the upper frame of the microfiltration unit of the invention. FIG. 2(c) shows the lower frame of the microfiltration unit of the invention, wherein the microfilter is sandwiched between an upper gasket and a lower gasket by screw coupling of the frames. FIG. 2(d) shows the cross-sectional side view of the microfilter unit, illustrating an assembly of the upper frame and the lower frame. FIG. 2(e) shows an assembly of the microfiltration unit of the invention when in use.

EXAMPLES

[0025] The present invention may be implemented in many different forms and should not be construed as limited to the examples set forth herein. The described examples are not limited to the scope of the present invention as described in the claims.

[0026] As shown in FIG. 1, the microfilter of the present invention comprised a microfilm which was composed of a transparent polymer without an epoxide chain. Therefore, the microfilm was a non-epoxy based microfilm, and the material of the non-epoxy based microfilm was a transparent plastic material. FIG. 1(a) shows a microfilter structure having a microfilm with a diameter of 13 mm and a filtration area with a diameter of 9 mm. The surface of the microfilm of the microfilter was patterned into predetermined sections, for example, 16 sections (as shown in FIG. 1(a)), to locate the isolated targets and quickly enumerate the number of the isolated targets. In addition, the microfilm was further coated with a thin film to facilitate the filtration process. The thickness of the non-epoxy based microfilm was less than or equal to 25 μm.

[0027] FIG. 1(b) shows the perforated microholes designed to penetrate through the microfilm. The perforated microholes were used for filtering or isolating targets. Therefore, the diameter of the perforated microholes depended on the size of the screening targets. The target was isolated on the surface of the microfilm.

[0028] There was a plurality of circular perforated microholes with a diameter of approximately 7 μm in the microfilm. In addition, the shape of the perforated microholes was rectangular or hexagonal, depending on the screening targets. The perforated microholes were patterned in a uniform array in a straight, staggered or hexagonal geometry in the microfilm. The perforated microholes in the microfilm had the cylindrical walls or the tapered walls.

[0029] The number of the perforated microholes was at least 50,000, and the gap between two adjacent perforated microholes was optimized at about 20 μm. A number of perforated microholes was distributed into different sections.

[0030] The microfiltration unit was operated by applying negative pressure at the bottom. The sample passed through a top inlet of the microfiltration unit to a bottom outlet of the microfiltration unit due to a pressure difference. There was a microfilter in the microfiltration unit, wherein the microfilter was a thin film with multiple perforated microholes. The molecules in a sample having larger size than the microholes in the microfilter were isolated at the surface of the microfilter while smaller molecules were filtered through the microholes to the outlet. The negative pressure was applied by using a controlled suction pump.

[0031] The microfilter fabricated using perforation of non-epoxy-based microfilm using different lasers such as UV, visible and Infrared lasers. The microholes were generated by using the above lasers, the shorter wavelength provided microholes with good quality and a submicron diameter. The excimer lasers such as Krf & XeBr, etc. provided a fine cylindrical microholes structure.

[0032] The microfilter was used in medical diagnosis and prognosis. It isolated larger nucleated cells from the blood. The enumeration and collection of nucleated cell indicated the disease state. The isolated cells were further utilized for downstream analysis such as culture, immunostaining, PCR (Polymer chain reaction), NGS (Next-Generation sequencing), etc.

[0033] The microfilter was used for non-invasive tumor metastasis diagnosis by identifying the circulating tumor cells (CTCs). The tumor cells were larger in size than normal cells. The tumor cells were isolated by passing the blood through the microfilter. The isolated CTCs at microfilter surface were identified and enumerated by immunofluorescent staining and observed under fluorescence microscope.

[0034] In another example of the present invention, the microfiltration unit was used for non-invasive prenatal diagnosis by collecting colony-forming cells (CFCs) from the maternal blood. The CFC cells are bigger than normal blood components. The isolated CFCs were analyzed for genetic analysis by using FISH, NGS, etc.

[0035] In another example of the present invention, the microfilter was used for separating micro aggregates from the blood. In particular, preserved blood may have micro aggregates during storage. The microfilter was used to clear the micro aggregates before blood transfusion to a patient.

[0036] Please refer to FIGS. 2(a), 2(b), 2(c), 2(d) and 2(e) together. A microfiltration unit 10, which comprised: an upper frame 11, including an inlet orifice 111 on the top side, an upper side wall 112, and a side module 113 which has a flexible stripe 1131 with one end thereof connected with and extended from the lower part of the upper side wall of the upper frame, and a transforming inlet head 1132 connected with the other end of the stripe and having one end to cover the top side of the upper frame 11 and the other end to be connected to a sample inlet orifice of an external sample inlet syringe (not shown) when in use, as shown in FIG. 2(e); and a lower frame 12, including an outlet orifice 121 and a lower cylindrical side wall 122, wherein the upper frame 11 and the lower frame 12 were connected with each other through screw coupling, a microfilter (not shown) is sandwiched between the upper frame 11 and the lower frame 12, and the transforming inlet head was replaceable with a different inlet head so as to correspondingly engage with the external sample inlet syringe with a different sample inlet orifice, thereby providing a linear passage of the sample injected from the external sample inlet syringe and flowing through the inlet orifice of the upper frame 11 to the outlet orifice of the lower frame 12. The microfilter was a non-epoxy based microfilm with a plurality of microholes.

[0037] In the microfiltration unit of the present invention, the side module 113 of the upper frame 11 allowed the sample inlet orifice to be adjusted from a wider opening to a narrower opening.

[0038] In the microfiltration unit of the present invention, the upper frame 11 further comprised an upper gasket 114 disposed at an inner peripheral wall thereof, the lower frame 12 further comprised a lower gasket 123 disposed at an inner peripheral wall thereof, and the microfilter was sandwiched between the two gaskets.

[0039] The microfiltration unit of the present invention further comprised two gaskets respectively placed below and above the microfilter to avoid sample leakage and to hold the microfilter in place, wherein the material of the gaskets was rubber.

[0040] In the microfiltration unit of the present invention, the upper frame and the side module; including the flexible stripe and the transforming inlet head, were integrated into one piece.

[0041] In one embodiment, the flexible stripe was removably engaged with the lower part of the upper side wall, or removably engaged with the transforming inlet head, wherein the engagement was performed via a male and a female pair connector (not shown), such as a magic tape or other engageable elements.

[0042] In the microfiltration unit of the present invention, the diameter of the microfilter was 13 mm and the diameter of a filtration area was 9 mm.

[0043] The microfiltration unit of the present invention further comprised a controlled suction pump (not shown) for applying a negative pressure to the outlet orifice such that the linear passage of the sample was directed by a pressure difference.