Microfilter with high recovery rate and method

Abstract

The invention relates to the technical field of experimental equipment, and provides a high-recovery-rate microfilter and a method, and the high-recovery-rate microfilter comprises a conical pipe body, a filtering membrane assembly, a pressure adjusting interface and a collecting pipe. The tapered channel of the conical tube body can guide samples to naturally converge under the action of centrifugal force, so that the dead volume of the cavity is greatly reduced; the filtering membrane assembly adopts the combination of a pre-filtering membrane and a fine filtering membrane, so that the filtering precision is ensured, and meanwhile, blockage is prevented; the key point is that a pressure adjusting interface is arranged at the upper opening end, an external pressure source is allowed to be connected after centrifugation, controllable positive pressure is applied to the top space, and final liquid drop residues caused by membrane surface tension are actively overcome. A collecting ridge is arranged at the bottom of the collecting pipe, so that trace filtrate can be conveniently collected and sucked. The method provided by the invention can realize a recovery rate of more than 99% for 10-200 [mu] L of samples, and is especially suitable for pretreatment of precious and limited trace samples.

Description

Technical Field

[0001] This invention belongs to the field of experimental equipment technology, specifically relating to a high-recovery-rate micro-filter and its method. Background Technology

[0002] In cutting-edge scientific fields such as biomedical research and development, clinical diagnostics, proteomics, metabolomics, and nanomaterial analysis, it is often necessary to process extremely precious or limited-volume liquid samples. These samples typically range in volume from tens to two hundred microliters. When filtering these trace samples to remove particulate impurities, precipitates, bacteria, or cell debris, a long-standing technical challenge becomes apparent: traditional needle filters or small filter columns exhibit extremely low sample recovery rates after filtration.

[0003] Traditional filters often have cylindrical internal cavities or significant unproductive spaces, with the filter membrane typically positioned horizontally in the center. When a trace sample is added, some liquid passes through the membrane under gravity or positive pressure, but a considerable portion remains on the walls of the inlet chamber, the upstream surface of the membrane, and at the connection point with the outlet structure. This residual volume is highly proportional to the total volume of the trace sample, resulting in a significantly lower actual recovered filtrate volume than the loaded sample. Experimental data show that using a conventional needle filter to treat a 50 μL aqueous solution typically yields a recovery rate of only 70%-85%; for extremely small samples of 10 μL, the recovery rate can be as low as below 60%. This unacceptable loss is fatal for samples that are difficult to source, expensive, or have extremely low concentrations.

[0004] Several existing technologies aim to improve filtration efficiency or throughput. For example, Chinese patent CN213433865U discloses a needle filter with a multi-layered membrane structure. This filter, using a four-layer structure consisting of a GFC membrane, a GF10 membrane, a PP membrane, and a microporous membrane, aims to progressively trap particles, prevent excessive membrane clogging, and increase filtration capacity. However, this design focuses on throughput and lifetime when processing relatively large samples, without optimizing the chamber structure to minimize dead volume or considering the specific mechanical conditions required to drive trace amounts of liquid through the multi-layered membrane. Therefore, it fails to address the core problem of low recovery rates for trace samples.

[0005] Therefore, there is an urgent need in this field for a completely new micro-filter design that cannot be simply a miniaturization of existing filters. Instead, it needs to rethink its structure and operation from a physical perspective, actively address the problems of dead volume residue and liquid film retention, and thus provide a reliable tool for micro-sample processing with a recovery rate close to 100%. Summary of the Invention

[0006] This invention aims to overcome the aforementioned deficiencies of the prior art and provide a high-recovery-rate micro-filter and its usage method. This invention breaks away from the traditional filter design paradigm, employing a unique conical converging design combined with pressure-assisted drive to forcibly guide almost all trace samples through the filter membrane, achieving an unprecedentedly high recovery rate.

[0007] To achieve the above objectives, the present invention provides the following technical solution: In a first aspect, the present invention provides a high-recovery-rate micro-filter, comprising: A tapered tube with an upper open end, a lower open end, and a tapering channel connecting the two. A filter membrane assembly is fixedly disposed in the lower middle part of the tapered channel, dividing the tapered channel into an upper top space and a lower outflow channel; A pressure regulating interface, located at the upper opening end, is used for a sealed connection to an external pressure control device to selectively regulate the pressure within the top space; and A collection tube, detachably and sealingly connected below the lower opening, is used to receive the filtered liquid; The tapered structure of the tapered channel, the location of the filter membrane assembly, and the pressure regulating interface are configured to allow trace samples to pass through the filter membrane assembly with a high recovery rate under the drive of centrifugal force and / or controlled air pressure.

[0008] Furthermore, the filter membrane assembly includes at least two filter membranes with pore sizes decreasing sequentially along the liquid flow direction, wherein the nominal pore size of the downstream fine filter membrane is 0.22 μm, and the nominal pore size of the upstream pre-filter membrane is between 0.45 μm and 10 μm.

[0009] The downstream fine filtration membrane (e.g., 0.22 μm or 0.45 μm) ensures the final sterilization or particle removal precision, while the upstream pre-filtration membrane (e.g., 0.45 μm, 1 μm, 5 μm, etc.) is used to trap larger particles, protect the fine filtration membrane, and extend its service life, which is especially important for samples that may contain fine precipitates. While the multi-layer structure provides the advantages of staged filtration, the increased flow resistance it brings can be overcome by the pressure-assisted drive mechanism unique to this invention.

[0010] Furthermore, the filter membrane assembly also includes a porous support layer or a flow guiding layer located between the at least two filter membrane layers.

[0011] Furthermore, the pressure regulating interface includes a valve structure that can seal the top space in a closed state and connect the top space to the external environment or pressure source in an open state.

[0012] Furthermore, the tapered channel of the tapered tube has a cone angle between 5° and 30°, and the filter membrane assembly is positioned at a distance of 1 / 4 to 1 / 2 of the total height of the tapered tube from the lower opening end.

[0013] This angle range is the optimal range found in experiments: if the cone angle is too small, the aggregation effect is not obvious and the reduction in dead volume is limited; if the cone angle is too large, it may cause sample dispersion in the early stage of filtration and is not conducive to processing and pressure sealing. The filter membrane assembly is preferably set at a position of about one-third of the total height of the conical tube from the lower opening end. This provides sufficient aggregation space for the sample and makes the outflow channel short enough to reduce filtrate retention.

[0014] Furthermore, the inner bottom center of the collection tube is provided with an upwardly protruding collection ridge or collection cone, which is used to form collected droplets when collecting trace amounts of liquid.

[0015] This ingenious design allows the micro-level filtrate to spontaneously gather at the bottom of the tube, forming droplets that are easy to contact and aspirate with a micropipette tip, avoiding the difficulty of aspiration and residue caused by the filtrate spreading at the bottom of the tube.

[0016] Furthermore, it also includes a detachable annular support, in which the filter membrane assembly is fixed, and the outer wall of the annular support is press-fitted with the inner wall of the tapered channel or sealed by a sealing ring.

[0017] Furthermore, the tapered tube and the collecting tube are connected in a detachable sealed manner through threads, Luer lock joints, or snap-fit ​​structures.

[0018] Furthermore, in the initial storage state, the top space and the pores of the filter membrane assembly are filled with a storage liquid, which is a non-volatile solvent with a viscosity greater than that of water or an aqueous solution composed thereof.

[0019] Secondly, the present invention proposes a method for filtering trace samples, the method being implemented based on the high-recovery-rate trace filter, the method comprising the following steps: Preparation steps: Provide the high-recovery microfilter, ensuring that its filter membrane assembly is wetted; Sample loading step: Inject a sample to be filtered with a volume of less than 200 μL into the top space of the conical tube; Sealing step: Seally connect the pressure regulating interface to a pressure control device; Driven filtration step: The sample is driven to pass completely through the filter membrane assembly into the collection tube by centrifugation and / or by adjusting the pressure of the top space through the pressure control device; Collection step: Separate the collection tube and obtain the filtrate.

[0020] The beneficial effects of this invention are as follows: The conical cavity design fundamentally reduces the physical dead volume and utilizes centrifugal force to achieve active liquid convergence, resulting in high filtration efficiency. The introduction of a precisely controllable pressure regulation interface actively intervenes at the filtration endpoint, overcoming passive residue caused by surface tension and capillary force, which is key to achieving ultra-high recovery rates. The device can operate independently using centrifugal force (suitable for most samples) or be connected to a pressure source for more precise control, and is compatible with existing laboratory centrifuges and micro-manipulation equipment. The combination of a multi-layer membrane structure and pressure-assisted drive ensures high recovery rates while protecting the fine filter membrane through pre-filtration, making it suitable for complex samples containing small particles. The optimized bottom design of the collection tube greatly facilitates the recovery of trace amounts of filtered liquid, further improving the efficiency and reliability of the overall process. For samples of 10-200 μL, the recovery rate is consistently above 99%, solving the industry problem of high filtration loss of precious trace samples. The method of this invention employs a strategy of centrifugation first, followed by pressure sweeping: firstly, centrifugal force is used to complete the efficient filtration of most of the liquid; then, after the centrifuge stops or through a pressure control device connected to the outside of the centrifuge, a slight and controllable positive pressure (e.g., 5-15 kPa) is applied to the top space. This pressure is sufficient to push the extremely thin liquid film or droplets remaining on the upstream surface of the membrane and in the corners of the cavity, which cannot be driven by centrifugal force, through the membrane pores, thereby achieving near-complete recovery. Attached Figure Description

[0021] Figure 1 This is a schematic diagram of the high recovery rate micro-filter of the present invention; Figure 2 for Figure 1 A schematic diagram of its decomposed structure.

[0022] In the figure: 1-conical tube, 2-upper open end, 3-lower open end, 4-gradient channel, 5-filter membrane assembly, 51-pre-filter membrane, 52-fine filter membrane, 53-porous support layer, 6-collection tube, 7-top space, 8-pressure regulating interface, 81-sealing plug, 82-valve structure, 83-pressure regulating tube, 9-ring bracket, 10-collection ridge. Detailed Implementation

[0023] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0024] Please see Figure 1 and Figure 2 The high-recovery-rate microfilter provided by this invention is based on the core design concept of minimizing ineffective sample residue during the filtration process through a carefully designed conical converging structure combined with pressure assistance. The entire device is mainly composed of four functional modules working together: conical tube 1, filter membrane assembly 5, pressure regulating interface 8, and collection tube 6.

[0025] The conical tube 1 is an active converging fluid channel and forms the skeleton of the entire filter. It is usually made of a biocompatible and chemically stable material (such as medical-grade polypropylene). It has a larger diameter upper opening 2 at the top and a smaller diameter lower opening 3 at the bottom, which are connected by a smooth, tapering channel 4.

[0026] When a trace sample (e.g., 10-200 μL) is injected, the liquid flows through the converging channel 4 under the influence of gravity or subsequent centrifugal force, resulting in a continuously decreasing flow cross-section. This produces two positive effects: first, the liquid flow is guided and converges in the central region at the bottom of the channel, flowing towards the filter membrane assembly 5; second, due to the downward contraction of the channel cross-section, the contact area between the liquid and the tube wall is smaller than that of a traditional cylindrical cavity, and the liquid film is thinned during downward flow, which physically minimizes the static dead volume that may adhere to the sidewalls. Simply put, the conical structure acts like a funnel-shaped racetrack guiding the liquid to its destination, rather than a reservoir where liquid may easily remain.

[0027] The filter membrane assembly 5 is fixedly mounted in the lower middle part of the tapered channel 4 by an annular support 9 (e.g., approximately 1 / 3 to 1 / 2 of the total height of the tube body from the lower opening end). An elastic sealing ring is typically embedded on the outer side of the annular support 9, which presses against the inner wall of the tapered tube 1 to form a reliable seal, ensuring that all liquid must pass through the filter membrane assembly 5. This assembly divides the internal space into an upper top space 7 (accommodating the sample to be filtered) and a lower outflow channel.

[0028] like Figure 2 As shown, the filter membrane assembly 5 is preferably a composite multilayer structure, which takes into account filtration accuracy, flux and service life.

[0029] The pre-filter membrane 51 of the filter membrane assembly 5 is located upstream and has a relatively large pore size (e.g., 0.45 μm, 1 μm, or 5 μm). The material can be polyethersulfone (PES) or a mixture of cellulose esters. Its main function is to trap larger particles, protein aggregates, or fibers that may be present in the sample, acting as a front to protect the downstream fine filter membrane from rapid clogging.

[0030] The fine filter membrane 52 of the filter membrane assembly 5 is located downstream and is the core component for achieving the final filtration accuracy. It has a nominal pore size of 0.22 μm (or 0.45 μm) and can be made of hydrophilic polyvinylidene fluoride (PVDF) or nylon. It ensures that the filtrate meets the requirements of sterility or removal of extremely small particles.

[0031] The porous support layer 53 of the filter membrane assembly 5 is located below the fine filter membrane 52 and is typically made of high-porosity polyester or non-woven fabric. Its function is to provide robust mechanical support, preventing the fine filter membrane 52 from rupturing or excessively deforming under pressure (especially in subsequent pressure-assisted steps), thus ensuring the reliability of filtration.

[0032] The pressure adjustment port 8 located at the upper opening 2 allows the operator to actively intervene at the filtration endpoint to resolve residues caused by surface tension. This port is a multi-functional module. The sealing plug 81 is used during storage, transportation, or simple centrifugal filtration to provide a simple seal for the top space 7, preventing contamination or evaporation.

[0033] The valve structure 82 can be a check valve, a miniature rotary valve, or a push-button valve. Its core function is to controllably open the path connecting the top space 7 to the outside when needed.

[0034] The pressure regulating tube 83 serves as a bridge connecting the valve structure 82 to an external pressure control device (such as a micro-injector, syringe pump, or positive pressure controller).

[0035] Operating Logic: After the routine centrifugation step, a very small amount of liquid may remain on the membrane surface or conical tip due to capillary forces and membrane pore surface tension. At this point, the operator can open valve structure 82 and apply a gentle, controllable positive pressure (e.g., 5-15 kPa) via an external pressure control device. This precise external pressure acts on the gas in the top space 7, thereby forcing the stubborn residual droplets to completely pass through the filter membrane. This step actively disrupts the naturally formed liquid phase equilibrium at the end of the filtration process and is the key technology for achieving an ultra-high recovery rate of >99%.

[0036] The collection tube 6 is connected to the lower opening end 3 via a threaded or snap-fit ​​seal. The collection ridge 10 at its inner bottom is a thoughtful detail. For microliter-level liquids, a flat tube bottom would spread into a thin film that is difficult to completely aspirate. The collection ridge 10 (which can be annular, cross-shaped, or several dot-like protrusions) alters the microgeometry of the tube bottom, guiding the filtrate to spontaneously gather in the depressions surrounding the protruding structure under surface tension, forming thicker, more concentrated droplets. This allows for easy and near-complete filtrate recovery using standard micropipette tips, reducing losses in the final aspiration stage.

[0037] Based on the above structure, a complete ultra-high recovery rate filtration process is as follows: Preparation: If the filter is stored in a dry state, first wet the filter membrane assembly 5 with a compatible wetting solution (such as water or low concentration ethanol).

[0038] Assembly and sample loading: Connect the collection tube 6 to the conical tube 1. Use a micropipette to add 50 μL of precious protein sample along the tube wall to the top space 7. Cover with the sealing plug 81.

[0039] Centrifugation drive: Place the entire apparatus into the centrifuge adapter and centrifuge at 10,000 × g for 2 minutes. Under strong centrifugal force, the sample accelerates and converges in the converging channel 4 and penetrates the filter membrane assembly 5, with most of the filtrate entering the collection tube 6.

[0040] Pressure-assisted finishing: Remove after centrifugation. Connect the pressure regulating tube 83 of the syringe to the valve structure 82. Open the valve structure 82 and slowly push the syringe piston to inject approximately 0.3 mL of air into the top space 7, generating a positive pressure of approximately 10 kPa, which is maintained for several seconds. Observe until the last remaining liquid film or tiny air bubbles in the viewing window are pushed through the membrane.

[0041] Final recovery: Unscrew collection tube 6. The filtrate has been collected thanks to the action of collection ridge 10. All filtrate can be easily and quantitatively transferred for downstream analysis using a micropipette.

[0042] The conical structure physically minimizes the design dead volume and guides the liquid flow; the pressure regulating interface solves the problem of active discharge of residual liquid at a chemical / physical level (overcoming surface tension). These two elements are not simply superimposed, but rather a systematic solution to residual problems at different stages of the filtration process.

[0043] For extremely small samples of 10 μL, traditional filters often achieve a recovery rate of less than 70%, while this invention, through the above-described process, can consistently achieve a recovery rate of >99%. This directly makes the analysis of many trace and precious samples, which was previously impossible due to excessive losses, possible.

[0044] Its multi-layered filter design enables it to process complex samples (such as cell lysates and serum); the pressure-assisted procedure is gentle and controllable, without damaging the delicate filter membrane; the overall design is compatible with standard laboratory centrifuges and micromanipulation equipment, making it easy to implement.

[0045] This invention directly addresses the two major pain points mentioned in the background art: dead volume residue and interfacial tension retention. The proposed solution is highly original and effective.

[0046] In summary, the high-recovery microfilter provided by this invention, through its innovative structural design and operating method, offers a novel, highly efficient, reliable, and extremely high-recovery tool for the filtration and purification of trace samples in life sciences, clinical diagnostics, and drug development. Any modifications, improvements, or combinations based on the core concept of this invention should fall within the protection scope of this invention.

[0047] The above are merely preferred embodiments of the present invention. The scope of protection of the present invention is not limited to the above embodiments. All technical solutions falling within the scope of the present invention's concept are within the scope of protection of the present invention. It should be noted that for those skilled in the art, any improvements and modifications made without departing from the principle of the present invention should also be considered within the scope of protection of the present invention.

Claims

1. A high-recovery-rate micro-filter, characterized in that, include: A tapered tube with an upper open end, a lower open end, and a tapering channel connecting the two. A filter membrane assembly is fixedly disposed in the lower middle part of the tapered channel, dividing the tapered channel into an upper top space and a lower outflow channel; A pressure regulating interface is provided at the upper opening end for sealing connection to an external pressure control device to selectively regulate the pressure within the top space; as well as A collection tube, detachably and sealingly connected below the lower opening, is used to receive the filtered liquid; The tapered structure of the tapered channel, the location of the filter membrane assembly, and the pressure regulating interface are configured to allow trace samples to pass through the filter membrane assembly with a high recovery rate under the drive of centrifugal force and / or controlled air pressure.

2. The high recovery rate micro-filter according to claim 1, characterized in that, The filter membrane assembly includes at least two filter membranes with pore sizes decreasing sequentially along the liquid flow direction, wherein the downstream fine filter membrane has a nominal pore size of 0.22 μm, and the upstream pre-filter membrane has a nominal pore size between 0.45 μm and 10 μm.

3. A high-recovery-rate micro-filter according to claim 2, characterized in that, The filter membrane assembly further includes a porous support layer or a flow guiding layer located between the at least two filter membrane layers.

4. A high-recovery-rate micro-filter according to claim 1, characterized in that, The pressure regulating interface includes a valve structure that can seal the top space in a closed state and connect the top space to the external environment or pressure source in an open state.

5. A high-recovery-rate micro-filter according to claim 1, characterized in that, The tapered channel of the tapered tube has a cone angle between 5° and 30°, and the filter membrane assembly is positioned at a distance of 1 / 4 to 1 / 2 of the total height of the tapered tube from the lower opening end.

6. A high-recovery-rate micro-filter according to claim 1, characterized in that, The inner bottom center of the collection tube is provided with an upwardly protruding collection ridge or collection cone, which is used to form collected droplets when collecting trace amounts of liquid.

7. A high-recovery-rate micro-filter according to claim 1, characterized in that, It also includes a detachable annular support, in which the filter membrane assembly is fixed, and the outer wall of the annular support is press-fitted with the inner wall of the tapered channel or sealed by a sealing ring.

8. A high-recovery-rate micro-filter according to claim 1, characterized in that, The tapered tube and the collecting tube are connected in a detachable, sealed manner via threads, Luer lock joints, or snap-fit ​​structures.

9. A high-recovery-rate micro-filter according to claim 1, characterized in that, In the initial storage state, the top space and the pores of the filter membrane assembly are filled with a storage liquid, which is a non-volatile solvent with a viscosity greater than that of water or an aqueous solution composed thereof.

10. A method for filtering trace samples, characterized in that, The method is implemented based on the high-recovery microfilter according to any one of claims 1-9, and the method includes the following steps: Preparation steps: Provide the high-recovery microfilter, ensuring that its filter membrane assembly is wetted; Sample loading step: Inject a sample to be filtered with a volume of less than 200 μL into the top space of the conical tube; Sealing step: Seally connect the pressure regulating interface to a pressure control device; Driven filtration step: The sample is driven to pass completely through the filter membrane assembly and enter the collection tube by centrifugation and / or by adjusting the pressure of the top space through the pressure control device; Collection step: Separate the collection tube and obtain the filtrate.

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