TWI498135B - Device for liquid sample filtration - Google Patents

Description

Liquid sample filter

The present invention relates to a liquid sample filtering device, and more particularly to a liquid sample filtering device adapted to apply the principle of a sweep flow.

The blood is responsible for the important work of oxygen and energy transfer in the living body, which is one of the indispensable elements for the normal operation of the living system. Based on this, various blood-centered application technologies have been developed in the field of clinical treatment and medical examination. It is hoped that the cells or substances contained in the blood can be obtained/analyzed correctly and quickly as a basis for preventing or solving the pain. The quality of human life. Under this concept, blood separation or filtration technology, which is the basis of many advanced applications, has been regarded as one of the key development projects.

At present, it is known that techniques for separating blood cells and plasma can be mainly classified into four categories. The first type is a centrifugal technique, in which the whole blood is placed in a test tube through the characteristics of a large proportion of blood cells, and the blood cells and plasma are separated by centrifugal force generated by high-speed rotation. However, because the density and deposition rate of some blood cells are very close to or even overlap with the plasma components, centrifugal techniques cannot meet the required purity in some special applications. Moreover, such technology usually consumes a large amount of samples and medicines, and the processing takes a long time, and the overall cost is high.

The second system uses the principle of dielectrophoresis force, combined with the micro-electromechanical process, provides a non-uniform alternating electric field with special instruments and equipment, and the separation effect is obtained by the different conductivity and dielectric constant between blood cells and plasma. However, this technology is still limited by the complicated steps and the expensive equipment required, and the application range is slightly narrow.

The non-contact high-wavelength laser system has developed a new technology in recent years, which uses a light source in the opposite direction to form a stable energy trap to clamp tiny particles. Although the current doctrine theory holds that this method has excellent advantages such as non-contact and non-invasiveness, the technology is very much expected, but in practice, there is still the problem that the cost of laser optical equipment cannot be overcome. It is difficult to promote.

Deep filtration is a common application among the four techniques. By driving the blood, it flows through the multilayer film structure in a vertical direction, so that solid substances such as blood cells are trapped on the surface of the film. However, the biggest problem with this technique is the formation of filter cake on the surface of the film, especially as the amount of blood increases, and the thickness of the filter cake also increases accordingly, so that it must be rinsed and removed every time period of action, which requires considerable manpower. More importantly, deep filtration tends to exert greater pressure on blood cells in the blood, causing hemolysis during the filtration process, resulting in failure of the separation operation.

In summary, it is inevitable that the technique of separating blood cells to obtain plasma has problems such as large sample consumption, expensive equipment and equipment, inconsistent application cost, long operation time, and/or complicated process steps.

Therefore, how to provide a liquid filtering device which is low in cost and simple in structure and suitable for use as a throwing liquid, and preferably, the device requires a small amount of sample, and can effectively prevent filter cake formation and hemolysis, and at the same time Avoiding contamination during separation and detection has become an important issue.

In view of the above problems, an object of the present invention is to provide a liquid filtering device which is low in cost and simple in structure and suitable for ready-to-use liquid dispensing. Preferably, the device has a rapid response, requires a small amount of sample, and is economical in operation.

Another object of the present invention is to provide a liquid filtering device suitable for filtering whole blood blood samples to separate blood cells and plasma, and more importantly, to prevent filter cake formation and hemolysis from occurring during the process.

In order to achieve the above object, a liquid sample filtering device according to the present invention includes an inner receiving portion, a filtering portion, and a collecting portion. The filter section includes a first-class channel and a filter film. The flow path is in communication with the sample receiving portion. The filter membrane has a plurality of pores, the flow channel is stacked on the filter membrane, and a liquid sample contacts the filter membrane when flowing in the flow channel. The collecting portion is disposed on the other side of the filter film corresponding to the flow channel, and communicates with the flow channel through the hole.

In one embodiment, the liquid sample filtering device further includes a waste liquid portion, and the waste liquid portion is in communication with the flow path.

In one embodiment, the sample receiving portion is disposed on a first structural layer, the filtering portion is disposed on a second structural layer, and the collecting portion is disposed on a third structural layer.

In an embodiment, the first structural layer is disposed directly on the second structural layer, and the second structural layer is disposed directly on the third structural layer.

In one embodiment, the filter film is sandwiched between the second structural layer and the third structural layer.

In an embodiment, the liquid sample filtering device further includes an upper cover. The upper cover covers the sample receiving portion, and the outer surface of the upper cover has an injection port, and the injection port communicates with the sample receiving portion.

In an embodiment, the sample receiving portion has an accommodating space corresponding to the injection amount of the liquid sample.

In one embodiment, the flow channel is helical or spiral.

In one embodiment, the filter film has a first surface and a second surface. The first surface has a plurality of curved surfaces, the holes are disposed between the curved surfaces, and the second surface corresponds to the holes, and has a plurality of recessed regions.

In an embodiment, the liquid sample filtering device further includes a driving unit. The sample receiving portion has a driving through hole, and the driving unit is connected to the driving through hole, and the driving through hole does not contain a liquid sample.

In one embodiment, the liquid sample filtration device is for filtering blood cells and the liquid sample is a blood sample.

In an embodiment, the collecting portion has a plurality of capillary flow passages and a confluence region, and the capillary flow passages are connected to the confluence region.

In an embodiment, the shape of the collecting portion includes a claw shape, a fork shape, a broom shape, a comb shape or a grid shape.

According to the above, the injected liquid sample is sequentially received through the sample receiving portion, the filtering portion separates the liquid portion and the suspended matter or particles in the sample, and the filtered portion is collected by the collecting portion, and the liquid sample filtering device according to the present invention The filtration separation operation can be completed independently, and the structure is simple, and no complicated parts assembly is required, which is advantageous for reducing cost and mass production.

In particular, the flow path of the apparatus is superposed on a filter film having a plurality of holes so that the liquid sample can come into contact with the filter film as it flows. Through the interaction between the two, not only the filtration of the liquid sample can be completed, but also the problem of blockage can be avoided. When applied to whole blood filtration, it can effectively reduce the formation of filter cake, reduce blood cell blocking holes, and even hemolysis.

Preferably, the liquid sample filtering device of the present invention can design the main portions in different structural layers so that the device can have better internal space utilization, so that the sample receiving portion can be adapted to be sampled in one time. The amount of space, and the filter section can use a better flow path shape to extend the filtration time and improve the effect. Therefore, the operation and erection of the device are relatively simple, and only a small amount of samples can be implemented during filtration, which has the advantage of reducing the consumption of the sample.

Compared with the prior art, the present invention is not only simple in structure, but also easy in process, and can be widely applied to liquid filtration containing suspended substances or particles. In addition, the device is easier to produce in the form of a bio-wafer, which not only has the advantage of convenient transportation, but also requires less sample consumption per operation, which is beneficial to various grades of medical institutions or research units. In addition, based on the novel composition and structure, the liquid sample filtering device of the present invention has the advantages of ready-to-use, no need for cleaning and special pre-treatment, and avoids the problem of cross-contamination of samples such as the conventional blood separation method.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, a liquid sample filtering device according to a preferred embodiment of the present invention will be described with reference to the accompanying drawings, wherein the same elements will be described with the same reference numerals.

1 is an exploded perspective view of a liquid sample filtering device according to a preferred embodiment of the present invention, and FIG. 2 is a partial assembled view of each structural layer shown in FIG. 1. In the present embodiment, the liquid sample filtering device 1 is used to filter a liquid sample, which is, for example, a flowable substance containing suspended particles, particles, particles or other small solid matter. Although the liquid sample is not limited to a specific type, for the sake of clarity, in the following, the liquid sample is represented by whole blood or blood containing blood cells, and red blood cells collectively called blood cells and various white blood cells are suspended therein. And / or platelets. In addition, it should be specially stated that the term "filtration" as used herein means the passage of existing pores to limit the size of specific suspended particles, particles or other small solid materials in the passage of liquid. , stagnant or trapped at one end of the hole, and separated from the liquid component that circulates to the other end of the hole. In addition, "filtering" is not limited to complete separation, but covers errors that are allowed due to manufacturing defects, a few special conditions, or the doctrine of the doctrine.

According to the foregoing definition, the liquid sample filtering device 1 of the present embodiment can arrest or trap blood cells including red blood cells, various white blood cells and/or platelets at one end of the hole, and the blood-free blood portion at the other end of the access hole ( That is, plasma) is separated. Of course, in other embodiments, the liquid sample filtering device can also be used to filter an aqueous solution in which colloidal particles are suspended, such as an aqueous solution containing a pharmaceutical composition, and the present invention is not limited thereto.

Referring to FIG. 1, in the present embodiment, the liquid sample filtering device 1 may be a micro device such as a micro biochip. In terms of the main functional composition, the liquid sample filtering device 1 includes the same housing portion 11, a filtering portion 12, and a collecting portion 13 in order from top to bottom. The sample housing portion 11 is disposed on the same first layer 15 . The filter unit 12 is disposed on a filter layer 17 and includes a first-class track 121 and a filter film 122. The lower end of the flow path 121 is originally open, and is closed by being combined with the filter film 122.

In the present embodiment, the liquid sample filtering device 1 further includes an upper cover body 14 which is directly disposed on the sample layer 15 so as to cover above the sample receiving portion 11. The outer surface of the upper cover 14 has an injection port 141 which communicates with the sample receiving portion 11 for injecting a liquid sample and guiding the liquid sample into the sample receiving portion 11.

Referring to FIG. 2, in the embodiment, the structure of the liquid sample filtering device 1 can be further divided into a first structural layer A, a second structural layer B and a third structural layer C. The first structural layer A includes a sample layer 15 provided with a sample receiving portion 11 and an upper cover 14; the second structural layer B includes a separation layer 16 and a filter layer 17; and the third structural layer C includes a collection portion 13 Lower the cover 18. In detail, the first structural layer A is directly disposed on the second structural layer B, and the second structural layer B is directly disposed on the third structural layer C to achieve a clear structure and easy to manufacture. However, in the other embodiments, the structures of the liquid sample filtering device may also change the order relationship of the settings, or may include other structures between or outside the structures. The invention is not limited thereto.

Further, the sample layer 15 is provided with a communication portion 151 which is also a pipe defined by the upper cover 14 and the separation layer 16. The filter layer 17 is provided with a waste liquid portion 171. The upper and lower ends of the waste liquid portion 171 are respectively closed by the partition layer 16 and the lower cover body 18, and the waste liquid portion 171 has a relatively large inner diameter, which can be collected and filtered. Part to avoid leakage or exposure to the outside of the device, reducing pollution. As for the duct formed by the communication portion 151, there is a function of introducing the liquid sample that has passed through the filter portion 12 but not collected into the waste liquid portion 171 for storage. Further, the filter film 122 is a portion of the filter portion 12, and its position is substantially disposed between the second structure layer B and the third structure layer C.

The layer structure of the liquid sample filtering device 1 may be an integrally formed or separated block, and the sizes may be the same or different, and even the liquid sample filtering device 1 may be processed by a single block, which has the effect of simplifying the process steps more. The invention is not limited thereto. In this embodiment, the first structural layer A, the second structural layer B, and the third structural layer C are three parts made separately, but the length, width, and height are respectively 3 cm, 3 cm, and 0.3. Centimeters. After the formation of each structural layer, the liquid sample filtering device 1 can be formed by sealing bonding. Of course, the size of each structural layer can also be adjusted as needed by the application, which is not a limitation.

The material of each structural layer of the liquid sample filtering device 1 may include, for example, polymethylmethacrylate (PMMA), poly-dimethylsiloxane (PDMS), epoxy resin (Epoxy), metal or Glass, of course, other polymeric materials with better mechanical strength and high biocompatibility properties can also be applied. In the present embodiment, the material of each structural layer of the liquid sample filtering device 1 is exemplified by polymethyl methacrylate (PMMA), which is not cytotoxic and is suitable as a material for contact with a living biological sample. In addition, polymethyl methacrylate has good light transmittance and is easy to observe and other characteristics.

The main components of the liquid sample filtering device 1 will be further explained below from a functional perspective.

The sample receiving portion 11 can have an accommodating space 111, and the upper and lower ends thereof are open. When the sample layer 15 is combined with the upper cover 14 and the partition layer 16, the accommodating space 111 can form a cavity after blood injection. Of course, the size of the accommodating space 111 can be adjusted according to requirements, so as to adjust the difference between the blood injection amount and the amount of the flow path 121, and the operation convenience is improved. In the present embodiment, the shape and size of the accommodating space 111 are substantially equal to the sample accommodating portion 11, but in other embodiments, the design and adjustment may be made according to the amount of the liquid sample to be injected, which is not a limitation.

Referring to FIG. 1 , in the embodiment, the sample receiving portion 11 has a driving through hole H and a driving unit P. The drive through hole H is provided on the side of one end of the sample accommodating portion 11 and, in detail, on the side where the sample accommodating portion 11 communicates with the injection port 141. The drive unit P is connected to the drive through hole H, preferably connected to the open end of the drive through hole H by a Teflon bridge joint. Since the sample receiving portion 11 is a minute structure, and the influence of the air pressure and the viscosity of the liquid sample, the liquid sample does not flow into the driving through hole H after being injected into the liquid sample filtering device 1, in other words, the driving through hole H is driven. There is no liquid sample inside.

The drive unit P can be a micro injection pump or a micro motor. The driving unit P squeezes the air in the driving through hole H to push the liquid sample in the accommodating space 111 to flow. In this embodiment, since the driving through hole H does not contain the liquid sample, the driving unit P does not substantially contact with the liquid sample, thereby effectively reducing the possibility of contamination. However, the present invention is not limited thereto. In other embodiments, The drive through hole H can also be made in a simple manner such that a part of the liquid sample may be contained therein, but this does not affect the actuation of the drive unit P. In addition, the drive unit P mentioned here is used to drive the fluid and control the flow rate. According to this condition, the drive unit P can of course be other power-providing modules or components, such as an aspirator, a manually operated syringe. Or other similar devices.

The flow path 121 has openings 123 and 124 at opposite ends thereof, and corresponding to the two through holes 161 and 162 of the partition layer 16 respectively, thereby connecting the sample housing portion 11 and the communication portion 151. The opening 123 of the flow path 121 is an inflow port into which the liquid sample is input, and the other opening 124 is an outflow port of the output. The overall path of the flow path 121 is not limited in shape. Here, the spiral path or the spiral shape is taken as an example, and a liquid passage having a long distance can be formed within a certain area, which is advantageous for the filtration operation to exert a better effect. However, in other embodiments, the flow channel 121 may also be in a simple straight or serrated shape, depending on the filtration requirements and the components contained in the liquid sample, to be able to reliably separate the specified particles, particles or suspended matter from the liquid. in principle. In the present embodiment, the flow path 121 is provided in the filter layer 17 in a manner of potting. In detail, the polydimethyl methoxy alkane having a fluid colloidal property may be used to cover the master mold, and after the colloid is solidified, the portion formed by the polydimethyl siloxane is separated from the master mold to form a set. The filter layer 17 of the flow channel 121.

3a is a partially enlarged schematic view of the filter film shown in FIG. 1, and FIG. 3b is a schematic view of the filter film shown in FIG. 3a at a position along the line Y-Y. Referring to FIG. 3a and FIG. 3b simultaneously, in the embodiment, the filter film 122 can be a circular film having a diameter of 1 cm and having a plurality of holes 125 thereon. The filter film 122 has a first surface 126 and a second surface 127, which are the upper surface and the lower surface of the filter film 122, respectively. In the present embodiment, the first surface 126 and the second surface 127 of the filter film 122 under the macroscopic view are both approximately flat surfaces without undulations (as shown in FIG. 1 or 2). However, referring to FIG. 3b, if further viewed in a microscopic side view, the first surface 126 has a plurality of upwardly convex curved faces 128, and the holes 125 are disposed between the curved faces 128, and the second surface 127 The corresponding hole 125 has a plurality of recessed regions 129.

The above structure will be described in detail. Referring to FIG. 3a and FIG. 3b simultaneously, in the embodiment, the curved surface 128 can be, for example, a circular arc surface, and includes a top end and a bottom end. The bottom ends of the adjacent two curved surfaces 128 define a hole 125. The border. The recessed area 129 is defined by the structure of the second surface 127, which may be circular and has an area larger than the area of the hole 125, and has the effect of assisting the filtered portion to pass through the hole 125 quickly. In addition, the holes 125 are circular perforations that communicate with the first surface 126 to the second surface 127 of the filter film 122, and may have a diameter of, for example, 1 micrometer. However, in other embodiments of the present invention, the holes 125 may have other shapes and/or sizes, for example, from 1 to 50 microns, in principle, depending on the composition of the target liquid sample and the size of the suspended particles, particles, particles or solid matter. Adjustment. For example, by separating blood cells in a blood sample from whole blood by filtration, the preferred diameter of the holes 125 is 2 micrometers.

In this embodiment, the centers of the filter unit 12, the collecting portion 13, and the filter film 122 may be substantially overlapped, for example, and the filter film 122 is interposed between the flow path 121 and the collecting portion 13, in other words, the filter film 122 is also It is sandwiched between the second structural layer B and the third structural layer C. The size and configuration of the filter film 122 are not particularly limited, and in principle, the principle of the flow path 121 is matched.

The filter film 122 may be an alloy material which is manufactured through several steps including a lithography process and electroforming to form a desired microstructure. First, a substrate may be provided first, and then a photoresist layer is formed on one surface of the substrate. Subsequently, a plurality of photoresist patterns are formed on the photoresist layer and exposed on a part of the surface of the substrate. A photomask is disposed above the photoresist layer, wherein the photomask has a plurality of patterns corresponding to the photoresist patterns. Thereafter, exposure and development are performed to form a circular photoresist pattern as shown in this embodiment. An alloy layer is formed on the photoresist pattern and the substrate by electroforming. Finally, the alloy layer is separated from the photoresist pattern and the substrate to form the filter film 122 of the present embodiment.

4 is an enlarged schematic view of the collecting portion of the liquid sample filtering device shown in FIG. 1. Referring to FIG. 1 and FIG. 2 simultaneously, the collecting portion 13 is disposed on the cover body 18 under the third structural layer C, and corresponds to The flow path 121 is located on the other side of the filter film 122. The collecting portion 13 has a plurality of capillary flow passages 131 to jointly form an collection region, and the capillary flow passages 131 are circulated together in a confluence region 132. The capillary flow passage 131 is slightly inclined downward in the direction toward the confluence zone 132, whereby the liquid passing through the filtration membrane 122 can be smoothly concentrated toward the confluence zone 132, and finally exits the liquid sample filtration device 1. Preferably, as shown, the arrangement of the capillary flow passages 131 allows the collection zone, or even the collection section 13, to assume a claw shape, or in other embodiments, the shape further includes a fork, a broom, a comb or The grid shape and the like all contribute to the improvement of the collection effect, and the present invention is not limited thereto.

Figure 5a is an enlarged schematic view of the filter layer of the liquid sample filtering device shown in Figure 1, and Figure 5b is a schematic view of the filter layer shown in Figure 5a at a position along the line X-X. Referring to FIG. 5a and FIG. 5b simultaneously, in the embodiment, since the flow path 121 is substantially parallelly stacked on the first surface 126 (ie, the upper surface) of the filter film 122, when the liquid sample is introduced and When flowing through the flow path 121, it is inevitably in direct contact with the filter film 122, and flows through the filter film 122 in a manner substantially parallel to the filter film 122. The flow path 121 communicates with the collecting portion 13 through the hole 125 of the filter film 122. When the liquid sample flows in the flow channel 121, it will be subjected to gravity to flow from the arc surface 128 of the first surface 126 to the hole 125 (the figure is still flat due to the giant angle, and the detailed structure can be referred to FIG. 3b) The liquid substance is smoothly passed through the pores, and the suspended matter, particles, particles or solid matter containing the pore size of the liquid sample are trapped by the pores 125 to achieve the separation and filtration effect.

It should be particularly noted that with the liquid sample filtering device structure of the present invention, the liquid sample can conform to the principle of sweep filtration to generate parallel shear stress, thereby sweeping up the first surface 126 of the filter film 122 during the filtration process. Suspended matter, particles, particles or solid matter having a particle size exceeding the size of the pores, avoiding the filtration rate being affected by the accumulation of the filtered material on the pores 125, resulting in an increase in the operational resistance. In order to produce better parallel shear stress and filtration effect, the flow rate of the liquid sample ranges from about 1 mL/min to 12 mL/min, and the filtration effect obtained at a higher flow rate is better, for example, 10 mL/ Min.

Fig. 6 is a partially enlarged schematic view showing the flow path when whole blood is filtered by the apparatus of the preferred embodiment of the present invention to separate blood cells. Referring to FIG. 6, through the liquid sample filtering device, the whole blood sample BL can flow in the flow path 121 in the manner of the parallel filter film 122, and according to the above description, not only the white blood cell WC, the red blood cell RC, and the platelet PL are thus Separation from plasma SR completes the purpose of collecting plasma SR, while also effectively reducing the formation of filter cake, preventing occlusion and hemolysis.

In order to verify the feasibility of the liquid sample filtering device of the present invention, an experimental example will be described below to explain the operation of the liquid sample filtering device of the present invention to separate blood cells in a blood sample of whole blood to collect plasma.

Experimental Example 1 Filtering blood cells in a blood sample of whole blood to collect plasma

First, take 100 μL of human whole blood blood sample and dilute the blood sample ten times with 900 μL of deionized water. Take 1 mL of ten-fold diluted blood sample into the injection port, so that it is temporarily placed in the sample receiving part, and then the injection port is closed, waiting for subsequent operations. The external driving unit is used to drive the gas in the driving through hole, and the driving unit is adjusted to continuously pass the blood sample into the filtering portion with different filtering flow rates to prove that the invention can achieve different degrees of hematocrit under different flow rates. . The samples were divided into five groups of 1 mL/min, 3 mL/min, 5 mL/min, 7 mL/min, and 10 mL/min according to the filtration flow rate used, and the waste liquid containing blood cells after filtration was transmitted through the communication. The tube is contained in the waste liquid portion, and the blood sample component passing through the filter membrane having a pore size of 2 μm is collected through the capillary force flow path of the collecting portion, and is collected by the collecting region outside the discharge device. Next, the filtration result can be observed by aligning the cell counting disk with an optical microscope, and the results are shown in Figs. 7 to 8b.

FIG. 7 is a graph showing experimental results grouped according to different filtering flows. Referring to Figure 7, the tube is a total of 6 tubes and is left to right: unfiltered, 1 mL/min, 3 mL/min, 5 mL/min, 7 mL/min, and 10 mL/min. After calculation by the cell counter, the filtration rates of the five different filtration flows were 78.5%, 78.7%, 87.3%, 92.9%, and 96.2%, respectively, which represent the proportion of blood cells filtered out in the blood sample. In addition, as shown in the figure, the collected amount after filtration is 20 μL, which is in accordance with the amount of the sample required for general IgE allergic blood test, and it is confirmed that the sample receiving portion can accommodate a certain amount of injection at a time by using the present invention, and The amount of injection is used in the analysis of the sample supplied by the filter, which has the advantage of convenient operation.

Fig. 8a and Fig. 8b are respectively microscopic observation views of the experimental group using the apparatus of the present invention and setting the filtration flow rate of 10 mL/min before and after filtration. Obviously, comparing Figures 8a and 8b, there was a significant decrease in blood cells in the field of view. It can be seen from Fig. 8b that when the whole blood sample is diluted 10 times and the membrane is filtered using a nickel-palladium alloy micropore having a pore size of 2 μm, and the filtration flow rate is set to 10 mL/min, no hemolysis occurs.

It can be seen from the experimental example that with the device of the present invention, the blood cell filtration rate of the plasma collected after filtration is proportional to the filtration flow rate, that is, the larger the filtration flow rate, the better the filtration effect. Moreover, in addition to achieving high efficiency filtration, the device of the present invention can also avoid the problem of hemolysis.

In summary, the injected liquid sample is sequentially received through the sample receiving portion, the filtering portion separates the liquid portion and the suspended matter or particles in the sample, and the filtered portion is collected by the collecting portion, and the liquid sample filtering device according to the present invention The filtration separation operation can be completed independently, and the structure is simple, and no complicated parts assembly is required, which is advantageous for reducing cost and mass production.

In particular, the flow path of the apparatus is superposed on a filter film having a plurality of holes so that the liquid sample can come into contact with the filter film as it flows. Through the interaction between the two, not only the filtration of the liquid sample can be completed, but also the problem of blockage can be avoided. When applied to whole blood filtration, it can effectively reduce the formation of filter cake, reduce blood cell blocking holes, and even hemolysis.

Preferably, the liquid sample filtering device of the present invention can design the main portions in different structural layers so that the device can have better internal space utilization, so that the sample receiving portion can be adapted to be sampled in one time. The amount of space, and the filter section can use a better flow path shape to extend the filtration time and improve the effect. Therefore, the operation and erection of the device are relatively simple, and only a small amount of samples can be implemented during filtration, which has the advantage of reducing the consumption of the sample.

Compared with the prior art, the present invention is not only simple in structure, but also easy in process, and can be widely applied to liquid filtration containing suspended substances or particles. In addition, the device is easier to produce in the form of a bio-wafer, which not only has the advantage of convenient transportation, but also requires less sample consumption per operation, which is beneficial to various grades of medical institutions or research units. In addition, based on the novel composition and structure, the liquid sample filtering device of the present invention has the advantages of ready-to-use, no need for cleaning and special pre-treatment, and avoids the problem of cross-contamination of samples such as the conventional blood separation method.

1. . . Liquid sample filter

11. . . Sample housing

111. . . Housing space

12. . . Filter section

121. . . Runner

122. . . Filter film

123, 124. . . Opening

125. . . Hole

126. . . First surface

127. . . Second surface

128. . . Curved surface

129. . . Sag area

13. . . Collection department

131. . . Capillary flow channel

132. . . Confluence area

14. . . Upper cover

141. . . Note entry

15. . . Sample layer

151. . . Connecting part

16. . . Separation layer

161, 162. . . Through hole

17. . . Filter layer

171. . . Waste liquid department

18. . . Lower cover

A. . . First structural layer

B. . . Second structural layer

BL. . . Whole blood sample

C. . . Third structural layer

H. . . Drive through hole

X-X, Y-Y. . . Section line

P. . . Drive unit

PL. . . Platelet

RC. . . erythrocyte

SR. . . plasma

WC. . . leukocyte

1 is an exploded perspective view of a liquid sample filtering device according to a preferred embodiment of the present invention;

2 is a partial schematic view showing the combination of the structural layers shown in FIG. 1;

Figure 3a is a partially enlarged schematic view of the filter film shown in Figure 1;

Figure 3b is a schematic view of the filter film shown in Figure 3a at a position along the line Y-Y;

Figure 4 is an enlarged schematic view of the collecting portion of the liquid sample filtering device shown in Figure 1;

Figure 5a is an enlarged schematic view showing a filter layer of the liquid sample filtering device shown in Figure 1;

Figure 5b is a schematic view of the filter layer shown in Figure 5a at a position along the line X-X;

Figure 6 is a partially enlarged schematic view of the inside of the flow channel when the whole blood is filtered by the device of the preferred embodiment of the present invention to separate blood cells;

Figure 7 is a graph of experimental results grouped according to different filtered flow rates;

Fig. 8a and Fig. 8b are respectively microscopic observation views of the experimental group using the apparatus of the present invention and setting the filtration flow rate of 10 mL/min before and after filtration.

1. . . Liquid sample filter

11. . . Sample housing

111. . . Housing space

12. . . Filter section

121. . . Runner

122. . . Filter film

123, 124. . . Opening

13. . . Collection department

131. . . Capillary flow channel

132. . . Confluence area

14. . . Upper cover

141. . . Note entry

15. . . Sample layer

151. . . Connecting part

16. . . Separation layer

161, 162. . . Through hole

17. . . Filter layer

171. . . Waste liquid department

18. . . Lower cover

P. . . Drive unit

H. . . Drive through hole

Claims (12)

A liquid sample filtering device comprising: a same receiving portion; a filtering portion comprising: a first-class channel communicating with the sample receiving portion; and a filter film having a plurality of holes, the flow channel being stacked on the filter film And a liquid sample is in contact with the filter film when flowing in the flow channel; and a collecting portion, a corresponding flow channel is disposed on the other side of the filter film, and communicates with the flow channel through the holes, wherein The filter film has a first surface and a second surface. The first surface has a plurality of curved surfaces. The holes are disposed between the curved surfaces, and the second surface corresponds to the holes and has a plurality of recessed regions. The liquid sample filtering device of claim 1, further comprising: a waste liquid portion connected to the flow channel. The liquid sample filtering device of claim 1, wherein the sample receiving portion is disposed on a first structural layer, the filtering portion is disposed on a second structural layer, and the collecting portion is disposed on a third structural layer . The liquid sample filtering device of claim 3, wherein the first structural layer is directly disposed on the second structural layer, and the second structural layer is directly disposed on the third structural layer. A liquid sample filtering device according to claim 3, wherein The filter film is interposed between the second structural layer and the third structural layer. The liquid sample filtering device of claim 1, further comprising: an upper cover covering the sample receiving portion, and the outer surface of the upper cover has an injection port, the injection port and the sample receiving portion Connected. The liquid sample filtering device according to claim 1, wherein the sample receiving portion has an accommodating space corresponding to the injection amount of the liquid sample. The liquid sample filtering device according to claim 1, wherein the flow path is spiral or spiral. The liquid sample filtering device of the first aspect of the invention, further comprising: a driving unit, the sample receiving portion has a driving through hole, the driving unit is connected to the driving through hole, and the driving through hole does not contain The liquid sample. The liquid sample filtering device according to claim 1 is for filtering blood cells, and the liquid sample is a blood sample. The liquid sample filtering device according to claim 1, wherein the collecting portion has a plurality of capillary flow passages and a confluent region, and the capillary passages are connected to the confluent region. The liquid sample filtering device according to claim 11, wherein the shape of the collecting portion comprises a claw shape, a fork shape, a broom shape, a comb shape or a grid shape.