CN109513354A - Filtration syringe and method - Google Patents

Abstract

The present invention provides a kind of syringe filtration system and method, including a cylindrical drum, piston, piston rod, at least one outlet, the end cap at least one entrance, the motor controlled by microcontroller, filter membrane, circular hole and stop lid.Piston is configured in cylindrical drum inner shaft to sliding up and down.Liquid is received by the entrance on end cap, mixing, filtering and collection.

Description

Filtration syringe and method

Cross reference to related applications

This application claims the priority for the U.S. Provisional Application serial number 62/614,292 that on January 5th, 2018 submits, complete Portion's content is hereby incorporated by reference.

Technical field

The present invention relates to syringe filter devices and method.

Background technique

The filter process of biological sample and colloid is in research laboratory, biotechnology, has in pharmacy and food industry very wide General application.Some examples applied in this way disclose in pervious patent: US4018752A, US4341801A, US4680122A, US4897465A, US5342863A, US6417251B1 and US6582385B2.In filtering, in sample solution Solute and cosolvent by its size by semi-permeable membrane separate.According to the aperture of film, filter process is divided into microfiltration (~0.1-10 Micron), hyperfiltration (~1-100) nanometer) and nanofiltration (~0.1-1 nanometers).It has invented applied to the various of filtering Semi-permeable membrane, such as US3133137A, US3567810A, US3580841A, US3607329A, US4125462A, US4749487A, US5522991A, US6113794A, US6833073B2 and US8820540B2.

Usually there are two types of methods in traditional filtering instrument filter membrane, i.e. end-filtration and transverse stream filtering is arranged, such as Patent US4789482A and US5256294A.It is that a collection of sample is sent into the one of the solution room sealed by semi-permeable membrane in terminal setting End.Under the pressure gap of cross-film, filtrate will transmit through film and the component in solution greater than semi-transparent membrane aperture will be retained in solution In room.On the contrary, Cross-flow filtration system generates a main sample solution flow, along semi-permeable membrane tangential flow.Film two sides Pressure difference driving filtrate flows through film.Therefore, transverse stream filtering is also referred to as tangential flow filtration.

End-filtration and cross flow filtration process respectively have advantage and disadvantage.Terminal installation can be easily used for sample concentration and Exchange of solvent.During the filtration process, sample solution volume constantly reduces.After solution is sufficiently concentrated, i.e., usually about initial After 1/10th of volume, novel solvent can be added into sample room again.The process in triplicate or more time after, exchange of solvent is just It is realized in a manner of through diafiltration.One of end-filtration close to the high concentration of filter membrane surface accumulation common problem encountered is that due to retaining Solute and form " filter cake ", so as to cause film blocking.Therefore, traditional end-filtration system needs constantly mechanical during filtering Agitating solution.But mechanical stirring inherently may cause the degradation or assembly of fragile biological cell and macromolecular.

Transverse stream filtering setting significantly reduces accumulation of the retention on film due to introducing tangential solution flowing.Cause This, lateral streaming system is suitable for extensive filtering, and more faster than traditional end-filtration.But a significant disadvantage is exactly Sample concentration after transverse stream filtering is usually less than the sample concentration after end-filtration, and which limits it in preparation high concentration sample Application on product.

Filter device needs pressure source to provide the normal pressure between the sample side of film and filtrate/waste liquid side.This pressure There are four types of common methods to generate: compressed gas, centrifugal filtration, vacuum and hydraulic pump.At present used in the laboratory environment Widest end-filtration device is produced by EMD MilliporeBlender.These device uses come from The compressed nitrogen of laboratory air bottle is as pressure source.But Ignitable gas devices disadvantage be exactly additional cost and Specific safety regulation relevant to the storage of compressed gas and transport.In addition, the cell and protein in sample are easier in gas The degradation of liquid interface.

End-filtration can also rotate the rotating device equipped with filter membrane by high speed centrifugation to realize.But this filtering Method is by sample volume and whether has limitation workable for supercentrifuge.Vacuum is used from filtrate/waste liquid side of diaphragm Absorption can also be used for driving filtering.But be about 1 bar or 15 pounds per square inch using the maximum transmembrane pressure that vacuum generates, this It is too low for typical hyperfiltration and nanofiltration application.Most of cross flow filtration systems using hydraulic pump generate with The tangent solution stream of film and filtrate through the membrane stream.Transverse stream filtering generally requires pressure more higher than end-filtration.

Filter process is especially more than filtered and nanofiltration may need a few hours that could complete.Typical exchange of solvent and Sample concentration application is usually directed to up to five filter cycles.Sample solution and new is manually added between each filter cycle Solvent takes time and effort very much.

Syringe generally includes cylindrical drum, and front is with one outlet and one for exporting aspirating/dispensing by this The piston of liquid medium.By connecting filter assemblies in exit, this syringe has been used for forcing in a manual fashion Liquid medium carries out the aseptic filtration of cleaning or a small amount of liquid by filter.In operation, pass through the outlet first for liquid In body sample or other medium inhalation syringe cylinders, filter assemblies are then connected to exit, liquid to be filtered or its He is moved inward by piston and is forced past filter assemblies medium.This syringe application is difficult to automate.Firstly, filtering Device is easy to be blocked.Secondly, the process of repetitive operation is pretty troublesome, and it is limited to low pressure applications.

The present invention provides a kind of injection device, system and method so that filter process is more effective, and solves existing The limitation of filter device.It is an object of the present invention to provide a kind of injection device, end cap contains one (or multiple) Entrance for introducing liquid medium (sample or individual solvent) between piston and filter membrane and allow solvent after film By outlet.Injection device according to the present invention is suitable for building automated system, and the arrival end of this system is connected to more Port selector valve, outlet end to solenoid valve or check-valves, piston to motor and programmable electronic controller.

This syringe pump filtration system provides significant improvement to existing apparatus.Syringe pump is this new in filter device Grain husk is applied while application of the syringe pump in end-filtration and tangential flow filtration is utilized.Syringe pump can be in various filtration applications Used in work under constant pressure or constant current fast mode, and easily switch between both of which.They can also easily be connected It is controlled by it to computer, tablet computer, mobile phone or circuit control panel.This feature makes the automatic of syringe pump filter device Change it is more economical, more simply.Compared to traditional air pressure and centrifugal filtration system, the end-filtration system based on syringe pump does not have air Interface between solution, this is a considerable advantage to the filtering of biological sample, because living cells and protein may be Air and solution interface degradation.

It is a further object to provide a kind of new methods and design, so that effectively mixing during the filtration process Sample solution, to prevent the blocking of filter membrane and the assembly of potential sample molecule.According to the present invention, this purpose is to pass through The entrance that injector end covers tilted to filter membrane and deviates its center to realize.Syringe cavity is newly introduced by entrance The solvent of body is splashed to filter membrane by being directed toward the power that the fluidization tower of film generates to knock out solute of any accumulation on film.This Outside, partial center fluidization tower generates vorticla motion (i.e. stirring rod effect, but do not have stirring rod) in injecting cavity to have further strengthened Effect mixing, prevents the formation of " filter cake ".There can be more than one such entrance with more for the filter membrane of larger size, on end cap Further enhance the validity of features described above.

The present invention is placed on filter membrane the upper end of sample solution and piston to benefit by the way that syringe to be inversely installed Above-mentioned purpose is further realized with gravity.When filtering, gravity will prevent solute concentrate close to filter membrane, therefore allow more It mixes well.

It is a further object to provide a kind of end-filtration system of automation and use the method for this system. This purpose is by connection syringe pump input end to multiport selector valve, outlet end to solenoid valve or check-valves, piston to electricity Motivation, programmable electronic controller and preconfigured protocol procedure are realized.Filter is integrated with each step, packet Starting is included, initial concentration, exchange of solvent circulation is final to be concentrated, sample recycling and cleaning systems.Entire filter process be it is complete from Dynamic.This no intervention operation is very suitable to long filter process, reduces the risk of mistake.

It is a further object to provide a kind of automatic tangential flow and with the filtration system of end-filtration function With the method for using the system.This target is realized by the following method: being introduced the sample into pump and is connected to multiport choosing Valve is selected, is then attached to an injection pump intake, and flow back into syringe pump from another entrance (sample export) to realize sample Continuous flowing.In this case, syringe piston is fixed on some position, sample solution by sample introduce pump continuously by Syringe cylinder is introduced, is flowed out after being horizontally through film from another entrance.Some solvents are since pressure is filtered, through filter membrane It is flowed out by outlet.Other than tangential flow, the entry design for also tilting to filter membrane provides further hitting power, To prevent any solute to be sticked on film；Its off-centered design generates vortex, it is further provided preferably mixing, filter membrane are dredged Logical and high-efficiency quick-filtering benefit.After tangential flow filtration, syringe pump can be started before sample collection with further concentrating sample, The advantage for being better than current tangential flow filtration system is provided.

Summary of the invention

In a variant, syringe filtration system includes: a cylindrical drum, and construction accommodates piston and piston rod；One A end cap includes first entrance, this lid end has the first circular hole, the second circular hole；One stop lid；One be placed at the top of lid end and Filter membrane between the portion of stop base；One first outlet；One provides the motor of power for syringe；And it is configured to control The microcontroller of motor processed.Piston is configured to slide axially along piston rod.First circular hole is arranged to be connected to cylinder The top of body, the second circular hole are configured to receive filter membrane.First entrance is configured to introduce solution example to below filter membrane.Filtering Film is configured to that the filtered fluid in fluid sample is allowed to pass through, and the component for being greater than filtering membrane aperture in sample is prevented to pass through.Export position In the top of filter membrane, it is configured to that the filtered fluid for having passed through filter membrane is allowed to flow out.

In another modification, the partial center position at an angle with the top surface of first circular hole is arranged in first entrance.

In another modification, entrance receives fluid sample from valve.

In another modification, the bottom surface of the second circular hole is configured as receiving O-ring, filter membrane and stop lid.

In another modification, valve receives the fluid sample from pump.

In another modification, entrance includes the first partial center liquid fluidization tower and the second radial fluid sample fluidization tower.

In another modification, second entrance is arranged in partial center position.

In another modification, second entrance is arranged in radial position.

In another modification, first outlet is configured to connect to solenoid valve or check-valves to receive solvent from outlet.

In another modification, selector valve is disposed for the liquid that selection enters syringe.

In another modification, a kind of filter method, including receive liquid；Syringe is drawn liquid by first entrance Carry out first time filtering；Liquid is filtered by the filter membrane of syringe；And power is provided for syringe by motor.

In another modification, new film is installed at the top of end cap before filtration.

In another modification, entrance is drawn liquid into scheduled flow velocity.

In another modification, closes selection valve and open solenoid valve or check-valves starts to filter.

In another modification, after the completion of filtering, closes solenoid valve or check-valves and open selection valve.

In another modification, the filtration cycle of preset cycle-index is repeated.

It, will be in preset a certain amount of solvent inhalation syringe after each filter cycle in another modification.

In another modification, liquid is introduced from each entrance.

In another modification, liquid is introduced from the entrance being arranged at a certain angle.

In another modification, liquid is discharged from the entrance of partial center position.

Detailed description of the invention

Fig. 1 shows the side view of the syringe with an entrance and one outlet.

Fig. 2 a shows that the side view of end cap, the end cap include a partial center position and have entering for tilt angle with film surface Mouthful.

Fig. 2 b shows that the top view of end cap, the end cap include a partial center position and have entering for tilt angle with film surface Mouthful.

Fig. 3 a shows that the side view of end cap, the end cap include a partial center position and have entering for tilt angle with film surface Mouthful, there are two fluidization tower, a radial direction and a partial centers for tool.

Fig. 3 b shows that the top view of end cap, the end cap include a partial center position and have entering for tilt angle with film surface Mouthful, there are two fluidization tower, a radial direction and a partial centers for tool.

Fig. 4 a shows that the side view of the end cap including two entrances, each entrance are in partial center position, both with film Surface is at tilt angle.

Fig. 4 b shows that the top view of the end cap including two entrances, each entrance are in partial center position, both with film Surface is at tilt angle.

Fig. 5 a shows that the side view of the end cap including two entrances, an entrance are in partial center position, another is in Radial position, both with film surface at tilt angle.

Fig. 5 b shows that the top view of the end cap including two entrances, an entrance are in partial center position, another is in Radial position, both with film surface at tilt angle.

Fig. 6 a shows that the side view of the end cap including two entrances, each entrance are in partial center position, each has Radial fluidization tower and partial center fluidization tower, two entrances are all with film surface at tilt angle.

Fig. 6 b shows that the top view of the end cap including two entrances, each entrance are in partial center position, each has Radial fluidization tower and partial center fluidization tower, two entrances are all with film surface at tilt angle.

Fig. 7 a shows the side view of the end cap including three entrances, and two entrances are in partial center position, and third is in diameter To position, three entrances are all with film surface at tilt angle.

Fig. 7 b shows the top view of the end cap including three entrances, and two entrances are in partial center position, and third is in diameter To position, three entrances are all with film surface at tilt angle.

Fig. 8 a shows the side view of the end cap including four entrances, and two entrances are in partial center position, and two are in diameter To position, and film surface is at tilt angle.

Fig. 8 b shows the top view of the end cap including four entrances, and two entrances are in partial center position, and two are in diameter To position, and film surface is at tilt angle.

Fig. 9 a shows the top view of the piston with small notch, and one of surface is towards entrance.

Fig. 9 b shows the side view of the piston with small notch, and one of surface is towards entrance.

Figure 10 shows the syringe pump filtration system with an entrance.

Figure 11 shows the syringe pump filtration system with two entrances.

Figure 12 shows the flow chart of filter process.

Figure 13 shows the continuous flowing syringe pump filtration system that pump is introduced with sample.

Figure 14 shows that another introduces the continuous flowing syringe pump filtration system example of pump with sample.

Figure 15 shows the flow chart that the continuous flowing sample filtering program of pump is introduced including sample.

It is intended to indicate that the reference number of the element in figure and in description below:

10 syringes, 15 cylindrical drums, 20 pistons, 25 piston rods, 30 end caps, 32 top circular holes, 35 circular holes, 40 partial centers enter Mouthful, 40a radial direction entrance, 45 filter membranes, 50 partial center fluidization towers, 50a radial direction fluidization tower, 52 conical tapers, 55 stop lids, 60 motors, 65 final sample collectors, 70 selector valves, 75 solenoid valves or check-valves, 80 outlets, 85 microcontrollers, 90 samples introduce pump, 95O Shape circle, 100 small notch.

Specific embodiment

In a variant, referring generally to Fig. 1 to Figure 15, syringe 10 is connected to a cylindrical drum 15 and one The piston 20 of piston rod 25, piston 20, which is assembled into, to be suitable for sliding axially in cylindrical drum 15.End cap 30 has circular hole 35 in bottom, It is snugly fit inside in cylindrical drum 15 in the airtight and close mode of liquid.Top circular hole 32 is for receiving O-ring 95, filter membrane 45 With stop lid 55.Circular hole 35 has the cone 52 of taper.

In another modification, as illustrated in figures 2 a-2b, side of the end cap 30 below filter membrane surface 45 is inclined with one Central inlet 40.Entrance 40 is inclined at an angle to filter membrane surface 45.When 20 slide downward of piston, due to entrance 40 Obliquity, fluid sample or solvent are pumped into from entrance 40, and splash filter membrane 45, and since its partial center designs, come from into The liquid of mouth 40 generates vorticla motion in cylindrical drum 15.This design plays the role of two: washing away and is sticked to filter membrane surface 45 On any solute and generate a liquid eddying motion, so that liquid is better mixed.Splashing power and rotation speed are by horse Up to 60 speed control.

In another modification, as shown in Figure 3 a-3b, end cap 30 have one with film surface 45 have inclination angle entrance 40 and Two shunting columns: a deviation center (partial center) 50 and another radial (being directed toward center) 50a.In addition to it is above-mentioned partially in Except the function of heart fluidization tower 50, radial fluidization tower 50a assaults the main target central area and keeps characteristics mentioned above more efficient.

In another modification, as shown in Fig. 4 a-8b, end cap 30 uses various forms.A kind of deformation (Fig. 4 a-4b) has Two deviation center (or partial center) entrances 40.Another deformation (Fig. 5 a-5b) has a partial center entrance 40 and a diameter To entrance 40a.The third deformation (Fig. 6 a-6b) has two entrances 40, and each entrance 40 separates two fluidization towers, a partial center A 50 and radial direction 50a, a total of four fluidization tower 50,50a.There are three entrance, two partial centers 40 and a diameters for one end cap 30 tool To 40a (Fig. 7 a-7b).There are four the end cap 30 of entrance, two partial centers 40 and two radial direction 40a (Fig. 8 a- for another variant tool 8b) entrance.These variants are useful to the syringe 10 with larger diameter film 45.

In another modification, as shown in Fig. 9 a-9b, piston 20 has a small notch 100 at the top of it, is used for final samples Product are collected.The surface that piston 20 is mounted so as to small notch 100 is parallel to cylindrical shaft, towards entrance 40.When piston 20 slides up When dynamic, final solution is forced through entrance 40 and reaches final sample receiving flask 65.Small notch 100, which allows to lose with minimal sample, to be received Collect final solution.

In another modification, with reference to Figure 10, the syringe pump according to the present invention with single entry 40 and end cap 30 filters system System.Syringe pump filtration system includes the syringe 10 for being connected to motor 60, and a multiport selector valve 70 is connected to injection The entrance 40 of device 10, a solenoid valve or check-valves 75 are connected to the outlet 80 of syringe 10 and a microcontroller 85 controls Motor 60, selector valve 70 and solenoid valve or check-valves 75 provide function for filtration system.Initial sample to be filtered, it is new molten Agent, deionized water, final concentrate collector 65, cleaning solution etc. may be coupled to the different port of selector valve 70.

In another modification, referring to Figure 11, syringe pump filtration system can be the syringe pump with more than one entrance 40 90 constructions.In this case, inlet flow is divided into two, and one enters first entrance 40, another enters second entrance 40.

In another modification, referring to Figure 12, fresh filter membrane 45 is mounted on to the top of end cap 30, all solution are put Enter in its specified container.In the typical filter operation as instantiation procedure, user selects an agreement and inputs circulation The number of filtering.Microcontroller 85, which receives, to be instructed and starts automatic fitration process.All pipelines are all ready, and are passed through Piston 20 sucks cylindrical drum 15 by entrance 40 with scheduled flow velocity to sliding below cylindrical drum 15, by a certain amount of initial soln It is interior.Selector valve 70 is closed, solenoid valve or check-valves 75 are opened.Upward sliding piston 20 come push sample solution pass through filter membrane 45 To carry out the first time filtering of sample solution.Some solvents are filtered out, and sample is just concentrated.Next, closing electricity Magnet valve or check-valves 75, and selector valve 70 is connected to new buffer pipeline.A certain amount of novel solvent is inhaled into cylindrical drum 15, And the step of repeating front, the number of the circulating filtration until reaching user's selection.Every time after circulation, sample becomes more concentrated. Inclination and partial center design, the solvent stream 50 newly introduced due to entrance firmly shoot down any solute for being deposited on film surface 45, 15 eddy motions generated in cylindrical drum of solvent stream 50 cause preferably to mix.In addition, in the syringe pump 90 being inversely installed Gravity can prevent weight solute to be adhered to filter membrane surface 45 to prevent filter membrane 45 to be blocked.

Then solenoid valve or check-valves 75 are closed, selector valve 70 is connected to final sample connecting pipeline.Final sample Product solution is to collect towards 15 top sliding plunger 20 of cylindrical drum.User, which is alerted, takes away final sample solution, then Begin to cleaning procedure.The example of the filter of foregoing description is substantially exactly the end-filtration carried out using syringe pump 90. It remains all advantages of conventional terminal filtration system, and eliminates its all disadvantage.Since syringe 10 is hermetic seal System is closed, without result in air-solution interface of sample degradation and assembly.In addition, external stirring rod is not used, to eliminate To the mechanical stress of sample.The two features are extremely important for very sensitive biological sample.

In another modification, referring to Figure 13-15, the note with single entry end cap 30 or such as Fig. 4 a-4b of double inlet caps 30 Penetrating pump filtration system can be used to continuously flow filtration system.Fluid sample to be filtered is connected to sample and introduces pump 90, so Selector valve 70 is arrived afterwards, is entered by entrance 40, in the previous case from 80 discharge (Figure 13) of syringe pump filtration system outlet, or (Figure 14) is discharged from another entrance 40 in latter situation.In both cases, solenoid valve or check-valves 75 are always on , piston 20 is fixed on certain position to keep the pressure fixing in cylindrical drum 15.Sample solution passes through 40 uninterrupted pumping of entrance Into cylindrical drum 15, solvent continues through filter membrane 45 under stress and filters and flow to outlet 80.Due to tilting and partial center The sample solution flow high speed of entry design, entrance continuously hits filter membrane surface 45 and generates vortex in cylindrical drum 15.Cause This, the solute of reservation will not be adhered in filter membrane surface 45, but be stopped in the solution.In addition, in the inversion of syringe pump 90 Under assembly, gravity stays in heavier solute in sample solution far from filter membrane surface 45.

This continuous filtration system substantially works as tangential flow filtration, but has the function of end-filtration simultaneously. After continuous filtration process, the sample retained can be further concentrated by syringe pump 90.That is, closing selector valve 70, injection pump piston 20 is moved up to filter out more solvents.

Claims (20)

1. a kind of syringe filtration system, comprising:

Cylindrical drum main body is configured to accommodate a piston and piston rod；

One end cap, including first entrance, this lid end have first circular hole, second circular hole；

One stop lid；

One filter membrane is placed on the top of end cap and the bottom of stop lid；

One first outlet；

One motor provides power to syringe；

One microcontroller, for controlling motor；

Wherein piston is configured to slide axially along piston rod；

Wherein first entrance is configured to introduce fluid sample to below filter membrane；

Wherein filter membrane is configured to that the filtered fluid in fluid sample is allowed to pass through, and prevents the component for being greater than filtering membrane aperture in sample Pass through；

Its middle outlet is located at the top of filter membrane, is configured to that the filtered fluid for having passed through filter membrane is allowed to flow out；

Wherein the first circular hole is configured to connect to the top of cylinder-shaped body；With

Wherein the second circular hole is configured to receive filter membrane.

2. syringe according to claim 1, wherein first entrance setting partial center position and with first circle The top surface in hole is at an angle.

3. syringe according to claim 1, wherein the entrance receives fluid sample from valve.

4. syringe according to claim 1, wherein the bottom surface of second circular hole is configured as receiving O-ring, mistake Filter membrane and stop lid.

5. syringe according to claim 3, wherein the valve receives the fluid sample from pump.

6. syringe according to claim 1, wherein the entrance includes the first partial center liquid flow and the second radial liquid Body sample flow.

7. syringe according to claim 2, wherein second entrance is arranged in partial center position.

8. syringe according to claim 2, wherein second entrance is arranged in radial position.

9. syringe according to claim 1, wherein the first outlet is connected to solenoid valve or check-valves connects from outlet Receive solvent.

10. syringe according to claim 3, wherein selector valve selection enters the liquid of syringe.

11. a kind of filter method, comprising:

Receive liquid；

By liquid by carrying out first time filtering in first entrance inhalation syringe；

Liquid is filtered by the filter membrane of syringe；With

Power is provided to syringe with motor.

12. method as claimed in claim 11 further includes installing new filter membrane at the top of end cap before filtration.

13. according to the method for claim 11, further including that the liquid is sucked the entrance with scheduled flow velocity.

14. according to the method for claim 11, further including closing selector valve when filtering and starting and opening solenoid valve or stop Return valve.

15. according to the method for claim 14, further including closing solenoid valve or check-valves after the completion of filtering and opening choosing Select valve.

16. according to the method for claim 11, further including repeating filtration cycle by the number of predetermined set.

17. according to the method for claim 16, further including aspirating the solvent of predetermined amount after each filtration cycle to enter injection Device.

18. according to the method for claim 11, further including introducing liquid from each entrance.

19. according to the method for claim 18, further including introducing liquid from the entrance for having certain angle.

20. according to the method for claim 18, further including discharging liquid from the entrance of partial center.