METHOD AND APPARATUS FOR SORTING PARTICLES
20190015841 · 2019-01-17
Inventors
Cpc classification
Y10S209/932
GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
B03B5/00
PERFORMING OPERATIONS; TRANSPORTING
F15C5/00
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
G01N15/149
PHYSICS
F16K99/0061
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
B01L3/5027
PERFORMING OPERATIONS; TRANSPORTING
B07C5/34
PERFORMING OPERATIONS; TRANSPORTING
F16K99/0046
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
F16K99/0028
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
F16K99/0001
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
Y10S209/906
GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
F16K2099/0084
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
International classification
B03B5/00
PERFORMING OPERATIONS; TRANSPORTING
F15C5/00
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
B07C5/34
PERFORMING OPERATIONS; TRANSPORTING
Abstract
A method and apparatus for sorting particles moving through a closed channel system of capillary size comprises a bubble valve for selectively generating a pressure pulse to separate a particle having a predetermined characteristic from a stream of particles. The particle sorting system may further include a buffer for absorbing the pressure pulse. The particle sorting system may include a plurality of closely coupled sorting modules which are combined to further increase the sorting rate. The particle sorting system may comprise a multi-stage sorting device for serially sorting streams of particles, in order to decrease the error rate.
Claims
1. A microfluidic system for sorting particles, the microfluidic system comprising: a first microfluidic flow channel formed in a particle processing component substrate having an upstream inlet configured to introduce a fluidic stream having a plurality of particles into the first microfluidic flow channel and downstream outlets configured to output portions of the fluidic stream of particles; a detection region located downstream of the inlet, the detection region configured to allow a particle having a predetermined characteristic to be sensed, the sensed particle being one of the plurality of particles in the fluidic stream; and a switching device located downstream of the detection region, the switching device operatively coupled to the first microfluidic flow channel to deliver a transient pressure pulse in a direction substantially perpendicular to a flow direction of the fluidic stream of particles, wherein the transient pressure pulse displaces and separates a selected single sensed particle from the fluidic stream of particles, wherein the selected particle is displaced and separated from the fluidic stream of particles in a switching region, wherein the fluidic stream of unselected particles flows into a first downstream outlet configured to output a first portion of the fluidic stream of particles, wherein the selected particle flows into a second downstream outlet configured to output a second portion of the fluidic stream of particles, wherein the transient pressure pulse is not generated downstream of the switching region, wherein the switching device, when activated, does not block or partially block flow of the fluidic stream of particles, and wherein the particle processing component substrate includes a reservoir adapted for dampening or absorbing the transient pressure pulse propagated across the microfluidic channel.
2. The microfluidic system of claim 1: wherein the switching device is integrally provided on the particle processing component substrate, and wherein the switching device is configured to be activated by a first external actuator.
3. The microfluidic system of claim 2, further comprising a second actuator, external to and operatively associated with the first microfluidic flow channel, for processing the sample on a particle-by-particle basis.
4. The microfluidic system of claim 3, wherein the first external actuator is adapted for directing particles into a first of the one or more downstream outlets and the second external actuator is adapted for directing particles into a second of the one or more downstream outlets
5. The microfluidic system of claim 1, wherein the particle processing component substrate includes a reservoir operatively associated with the switching device and adapted for originating the transient pressure pulse.
6. The microfluidic system of claim 1, wherein, the switching device introduces liquid into the microfluidic flow channel such that the transient pressure pulse is a transient hydraulic pressure pulse
7. The microfluidic system of claim 1, wherein the switching device further includes first and second side channels in fluid communication with the first microfluidic flow channel, the second side channel positioned opposite to the first side channel.
8. The microfluidic system of claim 1, further including an actuator for activating the switching device and wherein the actuator is a piezoelectric actuator.
9. The microfluidic system of claim 1, further including an actuator for activating the switching device and wherein the actuator is an electromagnetic actuator.
10. The microfluidic system of claim 1, further including an actuator for activating the switching device and wherein the actuator is a thermopneumatic actuator.
11. The microfluidic system of claim 1, further including an actuator for activating the switching device and wherein the actuator is a heat pulse generator.
12. The microfluidic system of claim 1, wherein the switching device is integrally provided on the particle processing component substrate and is configured for an external actuator to operatively engage and activate the switching device.
13. The microfluidic system of claim 1, wherein the switching device is configured to direct the selected particle out of the fluidic stream of particles without generating a pressure wave that travels upstream of the switching device.
14. The microfluidic system of claim 1, wherein the fluidic stream of particles maintains a laminar flow when the selected particle is displaced and separated from the fluidic stream of particles.
15. A microfluidic method for producing a particle product from a sample having particles, the method comprising: flowing the sample as a fluidic stream of particles from an upstream inlet along a first flow path through a first microfluidic flow channel formed in a substrate of a microfluidic particle processing component; processing the sample on a particle-by-particle basis to produce a particle product; outputting a first portion of the processed sample via a first downstream outlet of the first microfluidic flow channel; and outputting a second portion of the processed sample via a second downstream outlet of the first microfluidic flow channel, wherein the step of processing includes: activating a switch component; redirecting a single selected particle out of the first flow path of the fluidic stream of particles at a switching region and into a second flow path flowing downstream into the second downstream outlet, and deactivating the switch component, wherein activating the switch component does not generate a pressure wave that travels upstream to the switching region, wherein activating the switch component does not shift the remainder of the fluidic stream of unselected particles from the first flow path flowing downstream into the first downstream outlet, and wherein activating the switch component includes using an actuator external to and operatively associated with the microfluidic particle processing component, to activate the switch component; and further comprising using a reservoir operatively associated with the first microfluidic flow channel to dampen or absorb a transient pressure pulse propagated across the microfluidic channel.
16. The microfluidic method of claim 15, wherein the step of processing further includes using a reservoir operatively associated with the first microfluidic flow channel to originate the transient pressure pulse propagated across the first microfluidic flow channel for sorting particles on a particle-by-particle basis into the second downstream outlet.
17. The microfluidic method of claim 15, wherein activating the switch component includes flexing the switch component.
18. The microfluidic method of claim 15, wherein the switch component is located in a side channel and wherein the side channel is not a flow through channel.
19. A microfluidic system for sorting particles, the microfluidic system comprising: a first microfluidic flow channel formed in a particle processing component substrate having an upstream inlet configured to introduce a fluidic stream having a plurality of particles into the first microfluidic flow channel and downstream outlets configured to output portions of the fluidic stream of particles; a detection region located downstream of the inlet, the detection region configured to allow a particle having a predetermined characteristic to be sensed, the sensed particle being one of the plurality of particles in the fluidic stream; a switching device located downstream of the detection region, the switching device operatively coupled to the first microfluidic flow channel to deliver a transient pressure pulse in a direction substantially perpendicular to a flow direction of the fluidic stream of particles, wherein the transient pressure pulse displaces and separates a selected single sensed particle from the fluidic stream of particles, wherein the selected particle is displaced and separated from the fluidic stream of particles in a switching region, wherein the fluidic stream of unselected particles flows into a first downstream outlet configured to output a first portion of the fluidic stream of particles, wherein the selected particle flows into a second downstream outlet configured to output a second portion of the fluidic stream of particles, wherein the transient pressure pulse is not generated downstream of the switching region, and further including an actuator for activating the switching device and wherein the actuator is a piezoelectric actuator, wherein the particle processing component substrate includes a reservoir adapted for dampening or absorbing the transient pressure pulse propagated across the microfluidic channel.
20. The microfluidic system of claim 19, wherein the particle processing component substrate includes a reservoir operatively associated with the switching device and adapted for originating the transient pressure pulse.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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DETAILED DESCRIPTION OF THE INVENTION
[0038] The present invention provides a particle sorting system for sorting particles suspended in a liquid. The particle sorting system provides high-throughput, low error sorting of particles based on a predetermined characteristic. The present invention will be described below relative to illustrative embodiments. Those skilled in the art will appreciate that the present invention may be implemented in a number of different applications and embodiments and is not specifically limited in its application to the particular embodiments depicted herein.
[0039]
[0040] The first side passage 24a is hydraulically connected to a compression chamber 70a in the first bubble valve 100a, so that if the pressure in this chamber is increased, the flow in the measurement duct near the side passage is displaced inwards, substantially perpendicular to the normal flow in the duct. The second side passage 24b, positioned opposite of the first side passage 24a is hydraulically connected to a buffer chamber 70b in the second bubble valve 100b for absorbing pressure transients. This second side passage 24b co-operates with the first side passage 24a to direct the before mentioned liquid displacement caused by pressurizing the compression chamber 70a, so that the displacement has a component perpendicular to the normal flow of the particles through the measurement duct.
[0041] Upon pressurizing the compression chamber 70a an amount of liquid is transiently discharged from the first side passage 24a. The resiliency of the second side passage 24b results upon a pressurized discharge, in a transient flow of the liquid in the duct into the second side passage 24a. The co-operation of the two side passages and the fluidic structures they interconnect causes the flow through the measurement duct 16 to be transiently moved sideways back and forth upon pressurizing and depressurising of the compression chamber 70a induced by the external actuator 26 in response to the signal raised by the detection means 19. This transient liquid displacement, having a component perpendicular to the normal flow in the duct, can be applied in deflecting particles having predetermined characteristics to separate them from the remaining particles in the mixture.
[0042] As shown, the measurement duct 16 branches at the branch point 21 into two branches 22a, 22b and the flow rates in these branches are adjusted so that the particles normally stream through the second of the two branches 22b. The angle between the branches 22a, 22b is between 0 and 180 degrees, preferably between 10 and 45 degrees. However, the angle can even be 0 degrees, which corresponds to two parallel ducts with a straight separation wall between them.
[0043] The particles to be sorted are preferably supplied to a measurement position in a central fluid current, which is surrounded by a particle free liquid sheath. The process of confining a particle stream is known, and often referred to as a sheath flow configuration. Normally confinement is achieved by injecting a stream of suspended particles through a narrow outlet nozzle into a particle free carrier liquid flowing in the duct 16. By adjusting the ratio of flow rates of the suspension and carrier liquid, the radial confinement in the duct as well as the inter particle distance can be adjusted. A relative large flow rate of the carrier liquid results in a more confined particle stream having a large distance between particles.
[0044] In a suspension introduced by the first supply duct 12, two types of particles can be distinguished, normal particles 18a and particles of interest 18b. Upon sensing the predetermined characteristic in a particle 18b in the measurement region 20, the detector 19 raises a signal. The external actuator 26 activates the first actuator bubble valve 100a, when signaled by the detector 19 in response to sensing the predetermined characteristic, to create a flow disturbance in the measurement duct 16 between the side passages 24a, 24b. The flow disturbance deflects the particle 18b having the predetermined characteristic so that it flows down the first branch duct 22a rather than the second branch duct 22b. The detector communicates with the actuator 26, so that when the detector 19 senses a predetermined characteristic in a particle, the actuator activates the first bubble valve 100a to cause pressure variations in the reservoir 70a of the first bubble valve. The activation of the first bubble valves deflects the meniscus 25a in the first bubble valve 100a and causes a transient pressure variation in the first side passage 24a. The second side passage 24b and the second bubble valve 100b absorb the transient pressure variations in the measurement duct 16 induced via the actuator 26. Basically, the reservoir 70b of the second bubble valve 100b is a buffer chamber having a resilient wall or containing a compressible fluid, such as a gas. The resilient properties allow the flow of liquid from the measurement duct into the second side passage 24b, allowing the pressure pulse to be absorbed and preventing disturbance to the flow of the non-selected particles in the stream of particles.
[0045] At the measurement region 20, individual particles are inspected, using a suitable sensor means 19, for a particular characteristic, such as size, form, fluorescent intensity etc. Examples of applicable sensing means, known in the art, are various types of optical detection systems such as microscopes, machine vision systems and electronic means for measuring electronic properties of the particles. Particularly well known systems in the field are systems for measuring the fluorescent intensity of particles. These systems comprise a light source having a suitable wavelength for inducing fluorescence and a detection system for measuring the intensity of the induced fluorescent light. This approach is often used in combination with particles that are labelled with a fluorescent marker, i.e. an attached molecule that upon illuminating with light of a particular first wavelength produces light at another particular second wavelength (fluorescence). If this second wavelength light is detected, the characteristic is sensed and a signal is raised.
[0046] Other examples include the measurement of light scattered by particles flowing through the measurement region. Interpreting the scattering yield information on the size and form of particles, which can be adopted to raise a signal when a predetermined characteristic is detected.
[0047] The actuator 26 for pressurizing the compression chamber of the first bubble valve may comprise an external actuator that responds to a signal from the sensor that a particle has a selected predetermined characteristic. There are two classes of external actuators that are suitable for increasing the pressure. The first class directly provides a gas pressure to the liquid in the first side passage 24a. For example, the actuator may comprise a source of pressurized gas connected with a switching valve to the liquid column in the side passage 24a. Activation of the switch connects the passage to the source of pressurized gas, which deflects the meniscus in the liquid. Upon deactivation, the switch connects the passage 24a back to the normal operating pressure.
[0048] Alternatively, a displacement actuator may be used in combination with a closed compression chamber having a movable wall. When the displacement actuator displaces the wall of the compression chamber inward, the pressure inside increases. If the movable wall is displaced back to the original position, the pressure is reduced back to the normal operating pressure. An example of a suitable displacement actuator is an electromagnetic actuator, which causes displacement of a plunger upon energizing a coil. Another example is the use of piezoelectric material, for example in the form of a cylinder or a stack of disks, which upon the application of a voltage produces a linear displacement. Both types of actuators engage the movable wall of the compression chamber 70 to cause pressure variations therein.
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[0052] This process of detecting and selective deflecting of particles may be repeated many times per second for sorting particles at a high rate. Adopting the fluid switching as described, switching operations may be executed up to around several thousand switching operations per second, yielding sorting rates in the order of million sorted particles per hour.
[0053] According to another embodiment of the invention, the actuator bubble valve 100a and the buffer bubble valve 100b may be placed in different positions. For example, as shown in
[0054] According to another embodiment, shown in
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[0060] Given that each single channel sorting process produces some error (y) rate (y is a probability less than one of a particle being selected by mistake) of mistaken selections, the hierarchical architecture produces an lower error rate of y.sup.2 for a 2-stage hierarchy as drawn or y.sup.n for an n-stage hierarchy. For example, if the single channel error rate is 1% the 2-stage error rate is 0.01% or one part in 10.sup.4.
[0061] Alternatively, the architecture could have M primary sets of N sorting channels per secondary channel. Given that the application wants to capture particles that have a presence in the input at rate z and single channel sorters have a maximum sorting rate x particles per second. The system throughput is M*N*x in particles per second. The number of particles aggregated in N channels per second is N*x*z and so N*z must be less than 1 so that all particles aggregated from N channels can be sorted by a single secondary channel. To increase throughput above N=1/z one must add parallel groups of N primary+1 secondary channels. Overall throughput then comes from M*N*x with M secondary channels.
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[0064] The present invention has been described relative to an illustrative embodiment. Since certain changes may be made in the above constructions without departing from the scope of the invention, it is intended that all matter contained in the above description or shown in the accompanying drawings be interpreted as illustrative and not in a limiting sense.
[0065] It is also to be understood that the following claims are to cover all generic and specific features of the invention described herein, and all statements of the scope of the invention which, as a matter of language, might be said to fall therebetween.