1. Field of the Invention
The present invention relates to pumps and, in more particularly, to a magnetostrictive pump that relies on the expansion and contraction of a primary magnetostrictive rod for volumetric displacement of a pumping chamber, and additional magnetostrictive elements for gating of inlet and outlet valves.
2. Description of the Background
Conventional positive displacement pumps pump liquids in and out of a pumping chamber by changing the volume of the chamber. Typically these pumps are bulky, require a source of mechanical power such as a motor or engine, and have numerous moving parts such as mechanical linkages, gearboxes, etc.
Magnetostrictive fluid pumps are quite different. Rather than a conventional piston, they rely on expanding rods that serve as actuators. The rods are made of magnetostrictive material that changes dimensions in the presence of a magnetic field. Thus, the rods move in and out of a pumping chamber like a solenoid, thereby changing the volume of the chamber. The rods may be moved within a range of several tens of microns. There are no moving parts at all, and so magnetostrictive pumps can run reliably over a long period of time.
Numerous magnetostrictive materials are known. For example, European Patent Application No. 923009280 discloses many such materials. A commercially available magnetostrictive material is Terfenol-D® by Etrema Corporation, of Ames, Iowa.
Examples of magnetostrictive pumps include U.S. Pat. No. 5,641,270, which uses a magnetostrictive element to compress a single pumping chamber. The rod produces a single pumping compression stroke for each cycle of contraction and expansion of the magnetostrictive material. Single-stroke pumps are inherently prone to pressure fluctuations. In many applications such as laboratory settings, constant pressures and flow rates are critical.
United States Patent Application 20050147506 by Dooley published Jul. 7, 2005 shows a multi pumping chamber magnetostrictive pump that facilitates higher flow rates, and smoother fluid delivery. A single magnetorestrictive actuator drives multiple pumping chambers, such as two inline pumping chambers by the linear expansion of the actuator at both ends. A pump assembly having multiple pumps each including a magnetostrictive element is also disclosed.
While the Dooley application suggests multi-chambered pumps, it fails to suggest how multiple magnetostrictive elements can be used for precision dispensing applications in a clean room environment. This requires a valved-intake port for fluid or air induction, and a valved-output port for dispensing into container, syringes or vials, etc.
For example, there is a large demand for cost effective cell sorting of stem and other cell types. Sorted isolated cell populations are used for transplantation into myeloablated cancer patients. There are currently about 100,000 such transplantations a year in the US. Cell sorting ideally needs to take place in a closed consumable container where hematopoeitic stem and progenitor cell populations are sorted from peripheral blood, umbilical cord blood, and bone marrow. Automated cell sorting techniques are becoming indispensable for both research and clinical applications. However, current cell sorters require constant parameter adjustments, use open flow sorting technology which is susceptible to contamination and these sorters can cost in excess of $250,000. These devices detect the properties of cells, and implement the physical separation of cells of interest at high speed. The detection of cells are done using optical techniques such as fluorescence and light scattering followed by separation of the cells of interest using electrostatic or other physical separation methods. Conventional cell sorters utilize a single channel that operates at sorter rates of up to 60,000 cells per second. The sorting is done using an open fluid flow system that creates an aerosol environment. This open fluid flow environment creates a high potential for contamination. A magnetostrictive pump can close the flow environment, resulting in an isolated fluid system.
It would be greatly advantageous to provide a positive displacement pump design that employs a magnetostrictive fluid pump in combination with magnetostrictive gates for high-throughput and high-accuracy filling and dispensing applications, with particular utility as a cell sorter having a closed disposable consumable portion that removes the risk of contamination.
Accordingly, it is an object of the present invention to provide a positive displacement pump design that employs a magnetostrictive fluid pump in combination with magnetostrictive gates for high-throughput and high-accuracy filling and dispensing applications.
It is another object to provide a positive displacement pump design for high-accuracy filling and dispensing applications that can be micromachined, creating a disposable pump consumable.
It is another object to provide a positive displacement pump design as described above that has particular utility as a cell sorter.
According to the present invention, the above-described and other objects are accomplished by providing a positive displacement pump design that employs a magnetostrictive fluid pump in combination with magnetostrictive gates. The pump generally comprises a pump housing defining an internal fluid chamber, an inlet port to the fluid chamber, an outlet port from the fluid chamber, a magnetostrictive positive displacement piston in the fluid chamber, and magnetostrictive gates (valves) selectably blocking the inlet port to the fluid chamber and the outlet port from the fluid chamber. All pump and gate actuators include rods formed of magnetostrictive material with a stainless steel, ceramic or polymer tip that is seated in the housing that comes in contact with the fluid, and coil windings for electrical excitation to produce a magnetic field that varies the length of the rods. The pump is operated under electric control according to a pumping sequence comprising a fluid induction step wherein the positive displacement piston is actuated to retract within the pump housing, thereby inducting fluid. The outlet actuator rod remains in its normally extended position that closes the outlet port. Once the positive displacement mechanism is fully retracted and fluid has filled the chamber, the inlet valve is actuated to be closed, the outlet valve is actuated to be open and the positive displacement mechanism is deactivated, allowing the magnetostrictive rod material to expand and return the piston to its normally-extended position, thereby pushing a pulse of fluid through the outlet port of the pump. After moving the pulse of fluid out of the pump housing the outlet valve is deactivated to close the outlet valve, and the inlet valve is deactivated to open the inlet valve. The cycle may repeat.
The positive displacement pump is shown in the context of a cell sorter system for sorting desired cells from undesired matter. The cell sorter includes a precision magnetostrictive pump for pumping cell-containing fluid into a capillary detection and gating region and controlling positions of said cells in said detection/gating region, an optical detection system for measuring a cell characteristic, and a pair of capillary outlets each controlled by a magnetostrictive gate that causes a desired cell to pass through a cell selection port or a normal position port for unwanted material. The select gate, pump and detection system can be controlled and synchronized by a microprocessor. Optical detection can be based on fluorescence, scattered light or both. Other detection techniques such as absorbance are also included in this application.
Other objects, features, and advantages of the present invention will become more apparent from the following detailed description of the preferred embodiment and certain modifications thereof when taken together with the accompanying drawings in which:
The present invention is a multi-magnetostrictive pump that employs a magnetostrictive positive displacement element in combination with multiple magnetostrictive valves for high-throughput and high-accuracy filling and dispensing applications. The multi-valved magnetostrictive pump has particular utility in the context of a cell sorter (and an embodiment as such is disclosed), though one skilled in the art should understand that the pump may find application in many other high speed dispensing applications. The pump employs a magnetostrictive gating mechanism comprising magnetostrictive rods coupled to flow ports for selection thereof.
The positive displacement mechanism 2 generally comprises a piston actuator rod 12 formed of magnetostrictive material with a permanent magnet bias, and a stainless steel, plastic or ceramic tip that is seated in a pump housing 8. The piston actuator rod 12 extends into a fluid chamber 26, and is sealed therefrom by a distal seal 24 which may be an O-ring seal. Alternately, the sealing system can be a sealless system such as described in SP&S U.S. Pat. No. 6,739,478. The magnetostrictive piston actuator rod 12 is actuated by a coil winding 10 for positive displacement pumping between a normally-extended (unexcited) home position and an extended position. The magnetostrictive gating mechanism 4 is derived from the same fluid chamber 26, and generally comprises a capillary inlet port 22 gated by an inlet valve, and a capillary outlet port 23 gated by an outlet valve. The inlet valve comprises an inlet valve actuator rod 16 formed of magnetostrictive material with either a stainless steel, plastic or ceramic tip, seated in pump housing 8. The inlet valve actuator rod 16 is actuated by coil winding 20 between a normally-retracted (unexcited) open position and an extended closed position, and is in fluid communication with capillary inlet port 22. The outlet valve likewise comprises an outlet valve actuator rod 14 formed of magnetostrictive material and seated in pump housing 8. The outlet valve actuator rod 14 is actuated by coil winding 18 between a normally-extended (unexcited) closed position and an retracted open position, and is in fluid communication with capillary outlet port 23.
In general operation, a voltage is applied to coil winding 10, thereby actuating magnetostrictive piston actuator rod 12 to retract. The magnetostrictive piston actuator rod 12 is excited with a magnetic field that originates outside the fluid chamber 26 and capillary port region. There is no physical contact between the magnetic field generation means and the flow region. The magnetostrictive piston actuator rod 12 and tip, by virtue of its magnetostrictive properties and permanent magnet bias, physically retracts when excited by the externally applied magnetic field induced by coil winding 10, thereby inducting fluid through capillary inlet channel 22. Once the magnetostrictive piston actuator rod 12 is fully retracted and fluid has filled the chamber 26, the inlet valve is actuated to be closed, the outlet valve is actuated to be open, and the positive displacement pump 2 is deactivated, pushing a pulse of fluid through the outlet port of the pump. The outlet valve actuator rod 14 is deactivated and returns to its normally-closed position, and the inlet valve is deactivated to open the inlet valve. The cycle may repeat.
The pump housing 8 defines a gated fluid chamber 26 driven at one end by piston actuator rod 12 to operate as a positive displacement pump, the fluid chamber 26 having a capillary inlet port 22 leading therein, and a capillary outlet port 23 leading therefrom. The ported fluid chamber 26 may be formed as a cylinder having internal dimensions to provide a smooth inflow and outflow of the fluid during the actuation periods. The piston actuator rod 12 enters the fluid chamber 26 from its own chamber, and is distally sealed by the O-ring seal 24 encircling rod 12 at the lower end. The O-ring seal may be made of rubber, Teflon, or other suitable material to assure a proper seal against the operating pressures.
The two valve actuator rods 14, 16, sealed to the housing as in rod 12, are used to gate the capillary inlet port 22 and capillary outlet port 23. The inlet valve actuator rod 16 is actuated by coil winding 20, and is in fluid communication with a capillary inlet port 23. The outlet valve actuator rod 14 is actuated by coil winding 18, and is in fluid communication with a capillary outlet port 23. Normally, the inlet valve is under pressure from a supply pressure head and the outlet valve is under static loading of fluid trapped in the fluid chamber 26. The supply pressure head could be as simple as a reservoir at a sufficient head.
All three magnetostrictive actuator rods 12, 14, 16 are formed of magnetostrictive material such as Terbium alloy, Dysprosium, and Iron that is commercially available in the form of rods, tubes, washers, and particles. For example, all of the magnetostrictive rods 12, 14, 16 may be formed of Terfenol-D particles that are 50 to 300 microns in size, distributed uniformly in a polymeric host material. These particles are preferably magnetically oriented in a desired direction by applying an orientation magnetic field during fabrication. This results in a composite Terfenol-D rod, the crystalline structure of which is such that all the magnetic domains produce maximum moments when excited in the preferred direction. Such magnetostrictive components may be made in bulk form or can be made of magnetostrictive particulate composite. Although the magnetostrictive particulate composite rods are less efficient compared to the bulk rods, they can be shaped to almost any shape. Also, the magnetostrictive particulate composite rods have higher bandwidth. The magnetostrictive rods will elongate by up to 2000 parts per million, and the frequency response of rods can be as high as 10 kHz. The magnetostrictive piston actuator rod 12 is preferably about 2 mm diameter, and is preferably biased with a permanent magnet to facilitate bi-directional actuation. Rods 14 and 16 may be the same size or 1 mm or smaller magnetostrictive rods. The rods may also contain an internal bore so that a preload stress can be applied to the actuator.
In operation, each of the magnetostrictive elements are operated in a cycle comprising a fluid induction step and fluid dispensing step under the following preferred conditions:
Step 1: Fluid Induction
Piston Actuator Rod 12 is normally extended with no field using a bias permanent magnet;
Inlet valve actuator rod 16 is retracted with no field,
Outlet valve actuator rod 14 is extended using a bias permanent magnet with no field
Thus, the fluid dispensing sequence is explained as follows:
Simultaneously and synchronously, the inlet valve actuator coil 20 is not excited, the inlet valve actuator rod 16 is retracted, and the capillary inlet port 22 remains open. The outlet valve actuator rod 14 is normally extended and closed while the inlet valve actuator rod 16 is normally open. The piston element coil 10 is excited, whereby piston actuator rod 12 retracts causing fluid to be sucked into the fluid chamber 26 via inlet port 22. Fluid chamber 26 completely fills.
Fluid Dispensing:
The next step of each discrete pump cycle is the fluid dispensing step. First the inlet valve actuator rod 16 is actuated to close the inlet port 22. The outlet valve actuation coil 18 is excited to retract the outlet valve actuator rod 14, thereby opening the capillary outlet passage 23. Next, the coil winding 10 is deactivated, thereby extending the piston actuator rod 12, causing the piston actuator rod 12 to positively displace fluid from fluid chamber 26 (pushing the fluid into the capillary outlet 23.
The cycle then repeats as described above, as the outlet valve actuation coil 18 is deenergized causing the outlet valve to be closed and moving more fluid into capillary 23. The inlet valve actuation coil 20 is deenergized leaving the inlet valve in an open status.
The above-described pump cycle may be controlled by a micro-controller, conventional personal computer or a dedicated programmable logic controller (PLC). One skilled in the art will understand that any number of inlet and/or outlet valves may be provided by adding additional actuation coils, outlet valve actuators, and capillary passages, and by maintaining proper synchronization with programming of the control computer or PLC. Thus, multi-outlet port fluid dispensing is possible for various filling and dispensing applications.
The above-described magnetostrictive pump with gated fluid inlet and outlet channels is especially well-suited for use as a cell sorter with magnetostrictive gating mechanism. Cell sorters sort cells based on desired characteristics, usually measured optically.
In operation, a pumping sequence begins with a cell induction step followed by a pumping step as defined earlier with regard to
In addition to sorting fluorescent and non-fluorescent cells, the invention can also provide multiparameter analysis, such as multicolor detection. For example, cells labeled with different color markers or dyes, or cells labeled with other detectable reagents can be sorted by the invention.
One skilled in the art will understand the choice of normally-open versus normally closed positions of the actuator rods 14, 16 and 36 are a matter of design choice. In regard to primary actuator rod 12, it should be capable of moving around 1000 parts per million or around 1 micron per millimeter. For a movement of 25-30 microns, a rod of this type would need to be around 25-30 mm long. Any rod of any material that can expand is within the scope of the present invention. The gating rods, including each of the magnetostrictive actuator rods 14, 16 and 36 as shown in
In the foregoing embodiments the motion of the positive displacement piston rod 12 under PLC control (as well as all gate rods 14, 16, 36) was presumed to be between two fixed stops, fully open and fully closed. The position of the two stops may be determined quantitatively. However, it is possible to introduce an element of feedback into the positive displacement piston rod 12 and/or to any of the gating rods 14, 16, 36 to provide for qualitative start and stop positions.
When either a fluorescence or light scatter signal (or both) indicates a cell to be sorted is in position, the pump control electronics keeps track of the time shift necessary so that the cells are properly presented to the gating mechanism (gating actuator 36 of
When a selected cell is in position in the capillary 33, the control electronics either applies the external magnetic field via coils 38, or not, depending upon which exit port 39, 40 is desired. Once the magnetic field is removed (if it had been applied), the gating actuator 36 re-aligns itself to the normal position or non-selected normal port. The speed of fluid flow from the magnetostrictive pump can be high as previously discussed. When a cell needs to be removed the incremental flow can be stopped to be carefully synchronized to the gating valve (gating actuator 36).
The present invention thus couples a precision pump, an optical cell detection system and a control channel into a closed system that can move a cell into position to be identified, identify it and make a sort decision, move the selected cell to the control gate (if not already in position), set the control gate, and pull the selected cell out into a proper exit port. The present invention can be run in a pulsed (or discrete motion) mode or it can be run with continuous flow and hence continuous cell motion. Cells are identified and classified by the optical detection system according to optical properties that are either intrinsic or can be given to the desired cells through methods well-known in the art.
The present invention allows cells to be sorted by using a dynamic gate that can be constructed using magnetostrictive or other technology to create a small capillary valve. The valve can be switched from one state to another by the application of a magnetic field. The valve can be constructed where two (or more) ports are very close together so that as one port closes, the other is opening, or it can be constructed with ports further apart so that there is a period of time when both ports are blocked. The valve system can be part of a single or multiple capillary block. Such a block can be micro-machined using laser technology.
For example,
It should now be apparent that the above-described positive displacement pump design by virtue of its combination magnetostrictive fluid pump with magnetostrictive gates offers a high-throughput and high-accuracy filling and dispensing solution for various applications, with particular utility as a cell sorter.
Having now fully set forth the preferred embodiments and certain modifications of the concept underlying the present invention, various other embodiments as well as certain variations and modifications of the embodiments herein shown and described will obviously occur to those skilled in the art upon becoming familiar with said underlying concept. It is to be understood, therefore, that the invention may be practiced otherwise than as specifically set forth in the appended claims.
The present application derives priority from U.S. Provisional Patent Application No. 60/627,383; filed: 12 Nov. 2004, and is a continuation-in-part of U.S. patent application Ser. No. 10/688,331, filed 17 Oct. 2003.
Number | Date | Country | |
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60627383 | Nov 2004 | US |
Number | Date | Country | |
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Parent | 10688331 | Oct 2003 | US |
Child | 11273583 | Nov 2005 | US |