Separating particles from a sample

Abstract

Separating Particles from a Sample There is provided a method of separating particles from a sample. The method comprises introducing S1 a first fluid at a proximal end of a channel (110) via a first inlet (111) such that a flow of the first fluid in the channel (110) is laminar. The first fluid has a first fluid density. The method comprises introducing S2 a second fluid at the proximal end of the channel (110) via a second inlet (112), below the first inlet (111), such that a flow of the second fluid in the channel is laminar (110). The second fluid has a second fluid density that is greater than the first fluid density, thereby providing a density gradient in the channel (110). The method comprises introducing S3 a sample comprising particles of a first particle density into the channel (110) via a sample inlet (113). The sample inlet (113) is substantially perpendicular to a longitudinal axis of the channel (110). The method comprises receiving S3 a first output comprising particles of the first particle density via a first outlet (114) at a distal end of the channel (110). The first outlet (114) extends from the channel (110) and is configured to convey the first fluid from the channel (110). The first output has a first concentration of particles of the first particle density. The method comprises receiving S4 a second output comprising particles of the first particle density via a second outlet (115) at a distal end of the channel (110). The second outlet (115) extends from the channel (110) and is configured to convey the second fluid from the channel (110). The second output has a second concentration of particles of the first particle density. The second concentration is different to the first concentration.

Description

[0001] Separating Particles from a Sample

[0002] The present disclosure relates to a method and a device of separating particles from a sample.

[0003] BACKGROUND

[0004] The ability to separate particles, particularly microparticles, from a solution has long been important in the field of biotechnology. For example, point-of-care (POC) devices may depend on selective separation of microparticles to provide critical diagnostic information. Further, the ability to separate microparticles from a solution has enabled greater understanding of various diseases and supports personalized medicine.

[0005] However, in some applications particle separation technology is limited by throughput. In other words, conventional biotechnological methods and devices for separating microparticles from a solution may only be practicable for small volumes of liquids, though in some applications (e.g., liquid biopsy) it is necessary to analyze large volumes of liquids (e.g., blood).

[0006] An increasingly significant application of particle separation technology is focused on water treatment processes (e.g., to remove harmful microparticles from drinking water), where high throughput is also required. Therefore, as alluded to, conventional particle separation technology used in the field of biotechnology is typically not applicable in water treatment. Further, some particle separation technologies presently used in water treatment typically precipitate fragmentation of particles and may not remove the smallest microparticles (e.g., < 20 pm). Filters can be used, but filters have the drawback of being prone to clogging, which hinders continuous processing.

[0007] Hence, there is a need for a method and a device that facilitate effective separation of microparticles from a sample with increased throughput such that the method and device may be used in a wide range of applications (e.g., in the treatment of drinking water, cleaning appliances, industrial and domestic decontamination systems).SUMMARY

[0008] According to a first aspect, there is provided a method of separating particles from a sample. The method comprises introducing a first fluid at a proximal end of a channel via a first inlet such that a flow of the first fluid in the channel is laminar. The first fluid has a first fluid density. The method comprises introducing a second fluid at the proximal end of the channel via a second inlet, below the first inlet, such that a flow of the second in the channel is laminar. The first fluid and the second fluid having laminar flows causes the fluids to remain separated in the channel. The second fluid has a second fluid density that is greater than the first fluid density, thereby providing a density gradient in the channel. The method comprises introducing a sample comprising particles of a first particle density into the channel via a sample inlet. The sample inlet is substantially perpendicular to a longitudinal axis of the channel. The method comprises receiving a first output comprising particles of the first particle density via a first outlet at a distal end of the channel. The first outlet extends from the channel and is configured to convey the first fluid from the channel. The first output has a first concentration of particles of the first particle density. The method comprises receiving a second output comprising particles of the first particle density via a second outlet at a distal end of the channel. The second outlet extends from the channel and is configured to convey the second fluid from the channel. The second output has a second concentration of particles of the first particle density. The second concentration is different to the first concentration.

[0009] The sample may comprise particles of a second particle density greater than the first particle density. The first output may comprise particles of the second particle density. The first output may have a third concentration of particles of the second particle density. The second output may comprise particles of the second particle density. The second output may have a fourth concentration of particles of the second particle density. The second concentration may be less than the first concentration, and the fourth concentration may be greater than the third concentration.

[0010] The method may further comprise introducing the sample at a confluence of the first inlet and the second inlet.

[0011] The method may further comprise introducing the first fluid, the second fluid and the sample simultaneously.The method may further comprise coating the particles with a magnetic material before introducing the sample into the channel and applying a magnetic field substantially perpendicularly to the longitudinal axis of the channel after coating the particles.

[0012] The method may further comprise introducing the first fluid and the second fluid using a syringe pump.

[0013] The particles may be microplastic particles.

[0014] The particles may be spherical.

[0015] At least one of the first fluid, the second fluid and the sample may be an aqueous solution.

[0016] The first fluid and the second fluid may have densities of between 0.08 and 22400 kg / m3.

[0017] The first fluid and the second fluid may be introduced with a flow rate of between 5 pL / min and 50 L / min (e.g., less than 0.1 L / min, such as between 30 and 110 pL / min).

[0018] The first fluid and the second fluid may have viscosities of less than 1.5 Pa.s (e.g., between 2.24 x 10'4and 1.5 Pa.s).

[0019] The Reynolds number of the first fluid and the second fluid in the channel may be less than 4000, preferably less than 2300.

[0020] According to a second aspect, there is provided a device for separating particles from a sample. The device comprises a channel having a first inlet, a second inlet, a third inlet, a first outlet and second outlet. The device is configured to receive a first fluid at a proximal end of the channel via the first inlet such that a first flow of the first fluid in the channel is laminar. The first fluid has a first fluid density. The device is configured to receive a second fluid at the proximal end of the channel via the second inlet, which is, in use, below the first inlet, such that a flow of the second fluid in the channel is laminar. The second fluid has a second fluid density greater than the first fluid density, thereby providing a density gradient in the channel. The device isconfigured to receive a sample comprising particles of a first particle density into the channel via the sample inlet. The sample inlet is substantially perpendicular to a longitudinal axis of the channel. The device is configured to supply a first output comprising particles of the first particle density via the first outlet at a distal end of the channel. The first outlet extends from the channel and is configured to receive the first fluid from the channel. The first output has a first concentration of particles of the first particle density. The device is configured to supply a second output comprising particles of the first particle density via the second outlet at a distal end of the channel. The second outlet extends from the channel and is configured to convey the second fluid from the channel. The second output has a second concentration of particles of the first particle density. The second concentration is different to the first concentration.

[0021] The device may further comprise a magnet configured to apply a magnetic field substantially perpendicularly to the longitudinal axis of the channel.

[0022] The sample inlet may be at an angle of between 80 and 90 degrees relative to the longitudinal axis of the channel.

[0023] The channel may have a circular or square cross-section.

[0024] BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Non-limiting examples of the present disclosure will be described in the following, with reference to the appended drawings, in which:

[0026] Figure 1 shows a flow chart of a method of separating particles from a fluid;

[0027] Figure 2 shows a device for separating the particles from a fluid; and

[0028] Figure 3 shows a device for separating the particles from a fluid.

[0029] DETAILED DESCRIPTION OF EXAMPLES

[0030] Figure 1 shows a flow chart of a method of separating particles from a sample. The method shown in Figure 1 is best understood in conjunction with Figures 2 and 3, which each show a device 100 configured for separating the particles from a sampleusing the method shown in Figure 1.

[0031] The method comprises introducing S1 a first fluid at a proximal end of a channel 110 of the device 100. The channel 110, which may have a circular or square crosssection, may be a conduit for fluids (i.e., liquids and / or gases and / or plasmas). The first fluid is introduced via a first inlet 111 such that a flow of the first fluid in the channel 110 is laminar. The first fluid has a bulk density herein termed a first fluid density.

[0032] The method comprises introducing S2 a second fluid at the proximal end of the channel 110. The second fluid is introduced via a second inlet 112 such that a flow of the second fluid in the channel 110 is laminar. The first fluid and the second fluid having laminar flows causes the fluids to remain separated within the channel 110. In the example shown in Figure 2, the second inlet 112 is below the first inlet 111. In other words, in use, the device 100 is orientated such that the longitudinal axis of the channel 110 is substantially parallel with a surface on which the device 100 is resting (e.g., an angle between the longitudinal axis of the channel 110 and the surface on which the device 100 is resting is less than 10 degrees), and the second inlet 112 is closer to this surface than the first inlet 111. The second fluid has a bulk density herein termed a second fluid density. The second fluid density is greater than the first fluid density.

[0033] The relative densities of the first fluid and the second fluid combined with the relative positions of the first inlet 111 and the second inlet 112 via which the first and second fluids are introduced facilitate efficient provision of a density gradient in the channel 110. A density gradient is present in the channel 110 when densities of fluids therein are stratified from lower to higher density with respect to the direction of gravity. Therefore, by introducing S1 the less dense first fluid via the first inlet 111 and introducing S2 the denser second fluid via the second inlet 112, wherein the second inlet 112 is below the first inlet 111, the density gradient is, advantageously, realized efficiently.

[0034] The method comprises introducing S3 a sample comprising particles of a first particle density into the channel 110 via a sample inlet 113. In other words, a first set of particles is introduced, and each of the particles of this first set of particles is characterized by having a first particle density.The sample inlet 113 is substantially perpendicular to the longitudinal axis of the channel 100. For example, the sample 113 inlet may be at an angle of between 80 and 90 degrees relative to the longitudinal axis of the channel 110. Advantageously, the sample inlet 113 being substantially perpendicular to the longitudinal axis may avoid particles becoming lodged in the sample inlet 113 rather than dropping into the channel 110.

[0035] The density gradient described above facilitates efficient separation of particles (e.g., the particles of the first particle density). Once particles are introduced into the channel 110, they diffuse depending on their density and the gradient density. In other words, based on the density of the particles and the gradient density, the particles diffuse in the channel 110. According to their density relative to the gradient density, the particles reach an equilibrium height or isopycnic point (i.e., a height in the channel 110 at which the particles cease to move vertically), which can be exploited for their separation. Without the presence of the density gradient (i.e., in a fluid of uniform density), separation diffusion of the particles would be based solely on their density and would occur over longer timescales. Consequently, advantageously, the density gradient facilitates increased throughput. Separation of particles based on density, advantageously, is more reliable than separation of particles based on shape, for example, because density is a more stable physical property than shape.

[0036] The method comprises receiving S4 a first output comprising particles of the first particle density via a first outlet 114 at a distal end of the channel 110. The distal end of the channel 110 is opposite to the proximal end of the channel 110. The first outlet 114 extends from the channel 110 and is configured to convey the first fluid from the channel 110. For example, the first outlet 114 may be substantially vertically aligned with the first inlet 111. In other words, the first outlet 114 is aligned with an equilibrium height of the particles of the first particle density such that the particles of the first particle density preferably leave via the first outlet 114.

[0037] The method comprises receiving S5 a second output comprising particles of the first particle density via a second outlet 115 at a distal end of the channel 110. The second outlet 115 extends from the channel 110 and is configured to convey the second fluid from the channel 110. For example, the second outlet 115 may be substantially vertically aligned with the second inlet 111 (i.e., below the first outlet 114).The first output has a first concentration of particles of the first particle density, and the second output has a second concentration of particles of the first particle density. The second concentration is different to the first concentration because of the aforementioned density-based separation of the particles. The second concentration may be less than the first concentration. For example, the 90% of the particles of the first particle density introduced via the sample inlet 113 may leave via the first outlet 114, and 10% of the particles of the first particle density introduced via the sample inlet 113 may leave via the second outlet 115. Advantageously, therefore, harmful particles may be reduced in, for example, a water supply.

[0038] The sample may also comprise particles of a second particle density greater than the first particle density. In other words, the sample may comprise a second set of particles, and each of the particles of this second set of particles is characterized by having a second particle density greater than the first particle density.

[0039] In the case that the sample also comprises particles of the second particle density, the first output comprises particles of the second particle density at a third concentration, and the second output comprises particles of the second particle density at a fourth concentration. As the second particle density is greater than the first particle density, the equilibrium height of the particles of the second particle density is lower that that of the particles of the first particle density. Consequently, if the second outlet 115 is aligned with an equilibrium height of the particles of the second particle density, the particles of the second particle density preferably leave via the second outlet 115, meaning that the fourth concentration is greater than the third concentration. For example, the 90% of the particles of the second particle density introduced via the sample inlet 113 may leave via the second outlet 115, and 10% of the particles of the second particle density introduced via the sample inlet 113 may leave via the first outlet 115.

[0040] Figure 3 shows the device 100 of Figure 2 in operation in the case that the sample also comprises particles of the second particle density. As indicated in Figure 3, the less dense particles 11 and the less dense first fluid are discharged from the upper first outlet 114, and more dense particles 12 and the denser second fluid are discharged from the lower second outlet 115. Advantageously, therefore, particles of different densities, which may be associated with different physicochemical properties, for example, may be sorted.The method may comprise introducing S3 the sample at a confluence 120 of the first inlet 111 and the second inlet 112. The confluence 120 of the first inlet 111 and the second inlet 112 is the junction at which the inlets 111, 112 merge. Introducing S3 the sample at the confluence 120, advantageously, maximizes the time during which density-based separation of the particles can occur, thereby increasing the efficacy of separation. For the same reasons, the method may comprise introducing S1, S2, S3 the first fluid, the second fluid and the sample simultaneously.

[0041] The method may comprise coating the particles with a magnetic material, assuming that the particles are not inherently magnetic. Coating the particles with a magnetic material may mean completely or partially coating an outer surface of the particles with the magnetic material. Coating the particles with a magnetic material may comprise selectively coating the particles with the magnetic material. Subsequently, after introducing S3 the particles, now coated with the magnetic material or inherently magnetic, into the channel 110 via the sample inlet 113, the method may comprise applying a magnetic field 200.

[0042] As indicated in Figure 2, the magnetic field 200 is applied substantially perpendicularly to the longitudinal axis of the channel 110. For example, the magnetic field 200 may be applied at an angle of between 80 and 90 degrees relative to the longitudinal axis of the channel 110. To this end, the device 100 may comprise a magnet configured to apply a magnetic field substantially perpendicularly to the longitudinal axis of the channel 110. Advantageously, applying the magnetic field 200 means that separation of the particles may occur over shorter time periods than solely density-based separation. Consequently, the throughput is further increased.

[0043] In the case of the device being configured as shown in Figure 2 and there being particles of the first particle density and the second particle density, coating the particles with a magnetic material may comprise selectively coating particles of the second particle density. In other words, particles to be discharged from the lower of the two outlets 114, 115 (i.e., the second outlet 115) may be selectively coated with a magnetic material, thereby facilitating increased throughput.

[0044] In Figure 2, the magnetic field is indicated as being applied toward a surface on which the device is resting (i.e., in the same direction as the direction of gravity). However, the magnetic field may be applied in the opposite direction to that shown in Figure 2, with analogous benefits. More specifically, if the magnetic field is applied inthe opposite direction to that shown in Figure 2 and the sample comprises particles of the first particle density and the second particle density, coating the particles with a magnetic material may comprise selectively coating particles of the first particle density to be discharged from the higher of the two outlets 114, 115 (i.e., the second outlet 114) with the magnetic material.

[0045] The method may comprise introducing S1, S2 the first fluid and the second fluid using one or more syringe pumps. In other words, the first inlet 111 and the second inlet 112 may be, respectively, couplable to a first syringe pump and a second syringe pump. Advantageously, the use of syringe pumps may enable precise control of the flow rate of the first fluid and the second fluid.

[0046] In one example, the particles are spherical. However, the particles are not limited to a particular shape. For instance, the particles may be ellipsoidal. The particles may be microparticles. In one example, the particles are microplastic particles. In the case that the particles are spherical microparticles, the diameter of the particles is less than 5 mm. For example, the diameter of the particles may be less than 1 mm, 100 pm or 20 pm.

[0047] In one example, the first fluid, the second fluid comprise water. The first fluid may be a first solution, and the second fluid may be a second solution. For instance, the first and second solutions may be aqueous solutions. In other words, the solvent of the first solution and the second solution may comprise water. For instance, the first and second solutions may comprise water and salt. The water may be deionized. In another example, one or both of the first solution and the second solution comprise ethylene glycol.

[0048] Introducing S1 the first fluid such that the flow of the first fluid in the channel 110 is laminar and introducing S2 the second fluid such that the flow of the second fluid in the channel 110 is laminar may be facilitated by the first fluid and the second fluid having particular densities and / or viscosities and by being introduced with particular flow rates. For example, the first fluid and the second fluid may have densities of between 0.08 and 22400 kg / m3and / or viscosities of less than 1.5 Pa.s (e.g., between 2.24 x 10'4and 1.5 Pa.s). The first fluid and the second fluid may be introduced with a flow rate of between 5 pL / min and 50 L / min (e.g., , less than 0.1 L / min, such as between 30 and 110 pL / min). Having a laminar flow may mean that the Reynolds number of the first fluid and the second fluid in the channel 110 is less than 4000.Preferably, the Reynolds number of the first fluid and the second fluid in the channel 110 is the less than 2300.

[0049] Some experimental data related to the method of Figure 1 is included in Table 1. Table 1 shows the flow rate and density of each of the first fluid, the second fluid and the sample. Table 1 shows how the first concentration and the second concentration (i.e., the percentage of particles of the first particle density and the percentage of particles of the second particle density, respectively) at the outlets 114, 115 are affected by changing the flow rate.

[0050] The first fluid was a solution of 30% water and 70% ethylene glycol, and the second fluid was 100% ethylene glycol. The channel 110 had a square cross-section with a width and height of 2.1 mm and a length of 450 mm. The viscosity of the fluidss was 8.9 x 10’4Pa.S.

[0051] Table 1 relates to a situation in which the sample comprises particles of two different densities in an aqueous solution, such that the bulk density of the sample was 1000 Kg / m3. The first set of particles had a first particle density of 1090 Kg / m3, and the second set of particles had a second particle density of 1060 Kg / m3. The particles have a size range of 200 to 300 pm.

[0052] Flow Flow Concentrations at Flow

[0053] Rate: Rate: Rate: Density: Density: Density:

[0054] First S Outlets First Second Sample econd

[0055] Sample (kg / m3) Fluid Fluid First Second Fluid Fluid (jiL / min) (kg / m3) (kg / m3) (jiL / min) (jiL / min)

[0056] 30 30 30 1000 1070 1130 18% 97%

[0057] 50 50 50 1000 1070 1130 100% 94% 70 70 70 1000 1070 1130 90% 100% 90 90 90 1000 1070 1130 88% 96% 110 110 110 1000 1070 1130 57% 93%

[0058]

[0059] Table 1

[0060] The method may comprise iteratively performing a set of the steps shown in Figure 1. Relatedly, a system for separating particles from a sample may comprise a plurality of the devices 100 arranged in a sequence or in a series, such as in a cascade. For example, an output of a first device may be received by a sample inlet (113) of a second device.

[0061] This description uses examples to disclose the invention and to enable any person skilled in the art to practice the invention, including making and using any devices orsystems and performing any incorporated methods. The patentable scope of the invention is defined by the claims and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims or if they include equivalent structural elements with insubstantial differences from the literal languages of the claims. Aspects from the various embodiments described, as well as other known equivalents for each such aspects, can be mixed and matched by one of ordinary skill in the art to construct additional embodiments and techniques in accordance with principles of this application. If reference signs related to drawings are placed in parentheses in a claim, they are solely for attempting to increase the intelligibility of the claim and shall not be construed as limiting the scope of the claim.

Claims

CLAIMS1. A method of separating particles from a sample, the method comprising:introducing (S1) a first fluid at a proximal end of a channel (110) via a first inlet (111) such that a flow of the first solution in the channel (110) is laminar, wherein the first fluid has a first fluid density;introducing (S2) a second fluid at the proximal end of the channel (110) via a second inlet (112), below the first inlet (111), such that a flow of the second fluid in the channel (110) is laminar, wherein the second fluid has a second fluid density that is greater than the first fluid density, thereby providing a density gradient in the channel (110);introducing (S3) a sample comprising particles of a first particle density into the channel (110) via a sample inlet (113), wherein the sample inlet (113) is substantially perpendicular to a longitudinal axis of the channel (110);receiving (S4) a first output comprising particles of the first particle density via a first outlet (114) at a distal end of the channel (110), wherein the first outlet (114) extends from the channel (110) and is configured to convey the first fluid from the channel (110), wherein the first output has a first concentration of particles of the first particle density; andreceiving (S5) a second output comprising particles of the first particle density via a second outlet (115) at a distal end of the channel (110), wherein the second outlet (115) extends from the channel (110) and is configured to convey the second fluid from the channel (110), wherein the second output has a second concentration of particles of the first particle density, the second concentration being different to the first concentration.

2. The method of claim 1, wherein:the sample comprises particles of a second particle density greater than the first particle density;the first output comprises particles of the second particle density, wherein the first output has a third concentration of particles of the second particle density; and the second output comprises particles of the second particle density, wherein the second output has a fourth concentration of particles of the second particle density, whereby the second concentration is less than the first concentration, the fourth concentration being greater than the third concentration.

3. The method of claim 1 or 2, further comprising:introducing (S3) the sample at a confluence (120) of the first inlet (111) and the second inlet (112).

4. The method of any preceding claim, further comprising:introducing (S1, S2, S3) the first fluid, the second fluid and the sample simultaneously.

5. The method of any preceding claim, further comprising:coating the particles with a magnetic material before introducing (S3) the sample into the channel (110); andapplying a magnetic field substantially perpendicularly to the longitudinal axis of the channel (110) after coating the particles.

6. The method of any preceding claim, further comprising:introducing (S1, S2) the first fluid and the second fluid using a syringe pump.

7. The method of any preceding claim, wherein the particles are microplastic particles.

8. The method any preceding claim, wherein at least one of the first fluid, the second fluid and the sample is an aqueous solutions.

9. The method of any preceding claim, wherein the first fluid and the second fluid have densities of between 0.08 and 22400 kg / m3.

10. The method of any preceding claim, wherein the first fluid and the second fluid are introduced with a flow rate of between 5 pL / min and 50 L / min.

11. The method of any preceding claim, wherein the first fluid and the second fluid have viscosities of less than 1.5 Pa.s.

12. The method of any preceding claim, wherein the Reynolds number of the first fluid and the second fluid in the channel (110) is less than 4000, preferably less than 2300.

13. A device (100) for separating particles from a sample, the device (100) comprising a channel (110) having a first inlet (111), a second inlet (112), a sampleinlet (113), a first outlet (114) and second outlet (115), wherein the device (100) is configured to:receive a first fluid at a proximal end of the channel (110) via the first inlet (111) such that a flow of the first solution in the channel (110) is laminar, wherein the first fluid has a first fluid density;receive a second fluid at the proximal end of the channel (110) via the second inlet (112), which is, in use, below the first inlet (111), such that a flow of the second fluid in the channel (110) is laminar, wherein the second fluid has a second fluid density that is greater than the first fluid density, thereby providing a density gradient in the channel (110);receive a sample comprising particles of a first particle density into the channel (110) via the sample inlet (113), wherein the sample inlet (113) is substantially perpendicular to a longitudinal axis of the channel (110);supply a first output comprising particles of the first particle density via the first outlet (114) at a distal end of the channel (110), wherein the first outlet (114) extends from the channel (110) and is configured to convey the first fluid from the channel (110), wherein the first output has a first concentration of particles of the first particle density; andsupply a second output comprising particles of the first particle density via the second outlet (115) at a distal end of the channel (110), wherein the second outlet (115) extends from the channel (110) and is configured to convey the second fluid from the channel (110), wherein the second output has a second concentration of particles of the first particle density, the second concentration being different to the first concentration.

14. The device (100) of claim 13, further comprising:a magnet configured to apply a magnetic field substantially perpendicularly to the longitudinal axis of the channel (110).

15. The device (100) of claim 13 or 14, wherein the sample inlet (113) is at an angle of between 80 and 90 degrees relative to the longitudinal axis of the channel (110).

Images