Patent Application
20220347699
This invention relates to fluidic separation of particles suspended in a liquid supernatant. In particular, separation of whole blood into plasma and blood cell components, using a centrifugal system. Other biological samples containing cells or particulates may also be separated by such a centrifugal system.
Typically, blood or other similar biological samples should be tested immediately or within four hours of centrifugation, depending on which analyte is being studied. Current processes often result in shipment at the end of a business day with a batch of samples collected throughout the day in a meticulously assembled package. This process decreases the quality of samples taken earlier in the day and increases the opportunity for human error.
Described are various embodiments of a portable centrifugation device comprising a rotor, a motor, a set of batteries, a housing, and a lid, and methods of using such embodiments to separate whole blood into plasma or serum and blood cells. It is of note that any fluid sample initially comprising a mixture of a light fraction and a heavy fraction may be similarly separated. The rotor may have an axis of rotation, and may be configured to rotate in a direction of rotation.
Embodiments described herein may include low-cost materials. For example, the housing may include a packaging material. The portable centrifugation device may be capable of being used as a sealed shipping container. The portable centrifugation device may meet shipping regulations for biological samples. For example, the centrifugation device may further comprise a liquid absorbent material, and the housing and the lid may form an airtight cavity when mated. The centrifugation device optionally may lack certain features of a conventional centrifuge such as a circuit board or buttons or hard materials in the housing. The centrifugation device may include an on-board power source such that the device is powered by such a power source. The power source may include, but is not limited to a single cell battery. As a non-limiting example, the centrifugation device may be powered by a single AAA battery.
In certain embodiments, the rotor may include a hollow disk-shape cartridge with a closed circumference configured to contain whole blood and/or other fluid samples. The axis of rotation may be centered within the disk-shaped cartridge. The disk-shaped cartridge may comprise a ring-shaped distal cavity, a central cavity configured to accept whole blood and to retain plasma or serum after separation, and a narrow separation channel positioned between the distal cavity and the central cavity. Embodiments of this invention are configured to separate between 10 and 5000 microliters of blood. The invention may also be configured to separate between 20 and 750 microliters of blood. Preferably, the invention may be configured to separate between 50 and 500 microliters of blood.
In various embodiments, the rotor may include a structure configured to hold one or more tubes. The rotor may have an axis of rotation. Preferably, the rotor may be configured to hold only one tube. The rotor configured to hold only one tube may further comprise a counterweight. The counterweight may be configured such that a combined apparatus comprising the one tube and the rotor has a centroid close to the axis of rotation, when the one tube is filled with a volume of the sample. For example, the centroid could be less than 2 mm from the axis of rotation. The counterweight may further be aerodynamically shaped. For example, a cross-section of the counterweight may present a smooth, wedge shaped, or tear-drop profile in the direction of rotation.
Various other benefits and advantages may be realized with the systems and methods provided herein, and the aforementioned advantages should not be considered limiting.
The specification makes reference to the following appended figures, in which use of like reference numerals in different figures is intended to illustrate like or analogous components.
The embodiments described herein may allow for shipment of biological samples for diagnostic testing by incorporating the regulatory shipping requirements for potentially biohazardous materials as part of the processing and separation devices themselves, which may comprise inexpensive parts. The benefits of a portable or ready-to-ship centrifuge include little to no shipment processing time, optimal diagnostics testing intervals for each sample, and more accurate results for patients. The systems described herein may be compatible with various liquids as desired, including but not limited to whole blood, urine, and/or a collection of non-fluidic cells, such as cell culture or organ cells, that become liquefied in solution.
By enabling shipment of liquid samples, the concentration of the target analyte may be sufficient to undergo canonical assays for detection and quantification. Although dried samples require less of a biological sample to be extracted, for example a dried blood spot, the concentration of an analyte of interest may be too low for precise detection. In addition, dried blood spots require elution through several hours of soaking in a solute particular to each individual analyte. As a result, compatible devices that might be utilized for diagnostic testing following centrifugation are typically designed for liquid samples. Most commonly, biological liquid samples may include whole blood or urine. It is also possible that some biological mixtures start as a collection of non-fluidic cells, such as cell culture or organ cells, and become liquefied in solution. These types of liquids may also be compatible with the invention.
Whole blood quickly deteriorates ex vivo, so it is typically processed within 24 hours of obtaining a sample. Separating whole blood may isolate red blood cells, platelets, and plasma. Plasma has a shelf life of up to 1 year when frozen and can be tested through a comprehensive metabolic panel or lipid panel to determine attributes of a person's overall health. Another benefit of separating whole blood into a plasma part and cell part is that it prevents diagnostic instrument clogging with blood cells. Plasma is more stable than whole blood because red blood cells within the whole blood may hemolyze and release their intracellular contents into the sample, which may interfere with analyte concentrations in diagnostic testing. Serum, the liquid left behind following the clotting of whole blood, may also undergo centrifugation with this invention, but sample processing may be delayed due to the time it takes for whole blood to clot before separation.
The invention, which is powered by an on-board power source such as one or more batteries, enables remote blood separation, especially where access to power-hungry plug-in centrifugation is limited. Without requiring an external power source, use in remote environments or emergency vehicles can be achieved. Although unpowered centrifuges, such as hand-crank operated spinners, exist, a powered centrifuge according to the embodiments described herein provide a consistent spin rate and spin time performance required by regulations and standards for diagnostic testing. Furthermore, balancing and operating a conventional centrifuge is not within the capability of most untrained users as may be common in remote or home environments. At-home testing may be facilitated by ease of use of a small, portable centrifuge that is completely or partially disposable to prevent biohazardous waste in a home where proper disposal systems are not arranged. Complete autonomous use by a user at home is therefore possible.
The inventions described herein are generally intended to facilitate separation and processing of small fluid samples in circumstances where conventional centrifuges are often insufficient or unavailable including, but not limited to: (a) processing samples between 0.02 mL and 1.00 mL in volume, (b) processing samples by untrained users, (c) processing samples in remote areas and/or without available power, (d) processing samples with limited shelf or storage space, and (e) processing samples under time pressure.
Embodiments of the inventions described herein are intended for portable centrifugation of biological samples. Embodiments may be referred to as centrifuges or centrifugal devices. In various embodiments, the centrifuges may be made from low cost and/or disposable materials. The centrifuges may be considered disposable medical devices, suitable for remote deployment. Certain embodiments may be suitable for use as both a centrifuge and as secondary packaging for shipment of biological materials.
In some embodiments, centrifuges described herein may be devices less than 75 mm in diameter. The centrifuges may include a motor, such as a small DC motor, a power source, such as one or more battery cells, and a housing. The housing optionally may include a closeable or removable and attachable lid. Optionally a printed circuit board or other suitable controller controlling the flow of current from the batteries to the motor may be included. When mated with a rotor, the centrifuge may rotate the rotor at between 2000 and 20000 RPM. Preferably, the centrifuge may rotate the rotor between 2000 and 15000 RPM. Rapid separation of blood may be achieved with rotation between 6000 and 15000 RPM.
In some embodiments, the centrifuge may be configured to automatically spin when the closable lid is shut. This may be achieved by way of a sensor, mechanical switch, or magnetic switch such as a reed switch. Other activation mechanisms or devices may be utilized as desired. In certain embodiments, the lid may irreversibly attach to the housing when closed, such as with a pressure sensitive adhesive or a ratchet mechanism. Alternately, attachment of the lid may close a circuit allowing electrical current to flow through the battery and motor.
In certain embodiments, the rotor may include a hollow disk-shaped cartridge. In some embodiments, the cartridge may have a diameter of between 10 mm and 160 mm. Preferably, the diameter of the disk-shaped cartridge may be between 15 mm and 75 mm. More preferably, the disk-shaped cartridge may be between 20 mm and 45 mm. The disc-shaped cartridge may be configured to receive blood, separate blood cells into its periphery following rotation, and separate retrievable plasma into its center.
The housing of the centrifuge may be built from disposable material such as, but not limited to, cardboard or thermoplastics. Optionally, the housing of the centrifuge may partly comprise packing materials used for shipment. The housing of the centrifuge optionally may include multiple layers of materials, such as but not limited to a liquid impermeable layer, a liquid absorbent layer, and an outer layer suitable for shipping directly by postal or courier services. The layers of material may be laminated together by adhesives or otherwise assembled as desired.
The centrifuge motor may be a DC motor. The power source may be various types of batteries. As non-limiting examples, the battery may be a disposable button cell battery or use an AAA or AA configuration. The battery may have a lithium manganese dioxide, zinc carbon, lithium ion, or alkaline chemistry. Optionally, the centrifuge may not include a printed circuit board. The centrifuge may close an electrical circuit upon closure of the lid by an operator. The centrifuge optionally may rotate until the battery is exhausted. The centrifuge may rotate for 5 seconds to 60 minutes. The centrifuge may preferably rotate for 10 seconds to 30 minutes. The centrifuge may rotate for 15 seconds to 3 minutes. In some embodiments, the centrifuge may rotate for 15 seconds to 60 seconds. Timing of the centrifugal spin may depend on the operator such that the spin is initiated when a centrifuge lid is closed and the spin may stop when the centrifuge lid is opened.
The centrifuge may have a disposable inner lining made from materials including but not limited to a layer of plastic or cardboard. The centrifuge may have a re-usable module component comprising the motor, the batteries, and a printed circuit board. The re-usable module may have a smooth and continuous outer surface suitable for disinfection. The circuit board may control the speed of the centrifuge and may count the number of runs. The circuit board may present a visible signal such as by an LED when the centrifuge has reached a maximum number of runs. The circuit board may present a visible signal if the battery reaches a minimum threshold of voltage. The centrifuge may comprise a layer of material affixed to the housing between the motor and the rotor.
The centrifuge housing may include a box made from cardboard or other materials as desired. The lid of the centrifuge housing may contain a magnet and the printed circuit board may contain a magnetic sensor such as a Hall Effect sensor. The printed circuit board may be mounted to the wall of the housing and oriented with a sensor toward a point of interface with the housing lid. The printed circuit board may be mounted to a cardboard wall by a rivet, staple, pressure sensitive adhesive, or glue.
Inner layers of the centrifuge housing may be a hollow cylindrical shape with threading around the top and the motor, and batteries inside. A cylindrical centrifuge housing may comprise metal or plastic. The lid may be circular and contain threading that interfaces with threading on the centrifuge housing. Screwing on the lid may result in completing a circuit from the battery, through the motor, and through an electrical pathway joined to the centrifuge housing and lid. Screwing on the lid may be irreversible or reversible only by squeezing portions of the lid, similar to common pharmaceutical packaging. Alternately, the centrifuge may be roughly square shaped, with a lid that opens and closes by a hinge on one side of the lid. The entire centrifuge and packaging maybe less than 100 mm in length, width, and depth. The entire centrifuge and packaging may be less than 75 mm in length, width, and depth. The centrifuge may be about 2.5 inches in length and width, and less than 2 inches in depth. In some embodiments, the centrifuge packaging may be less than 50 mm in length, width, and depth. The centrifuge may be configured for shipment by commercial methods while meeting relevant packaging standards for potentially biohazardous biological specimens.
The top side 114 defines an opening 120 providing access to the cavity 118 (see, e.g.,
In various embodiments, the bottom side 116 may include a flat or planar surface 106. In such embodiments, the flat surface 106 may allow for the tube 101 and/or the tube assembly 110 to be self-standing, and the tube 101 and/or the tube assembly 110 may be able to stand upright independently.
In certain embodiments, and as best illustrated in
Various other benefits and advantages may be realized with the tube provided herein, and the aforementioned advantages should not be considered limiting. Moreover, one or more of the aforementioned benefits or advantages may be realized with other tubes provided herein.
Referring to
In addition to the clasps 405, 406, the rotor 401 may include a counterweight 402, an extension 403, and a rib 404. In certain embodiments, the rib 404 may optionally extend downwards from the counterweight 402. Optionally, the extensions 403 may define a maximum width of the rotor 401. Said rib 404 and extension 403 may provide an aerodynamic counterweight for said aerodynamic tube 101.
In some embodiments, the rotor 401 may be configured for production using a straight-pull injection mold as follows: the upper clasp and lower clasp may be positioned such that no portion of the upper clasp overlaps with any portion of the lower clasp when viewed from above. The axis B-B of the aerodynamic tube 101 (i.e., the shorter width) may be positioned by the rotor such that it is positioned substantially vertically, thereby presenting a smaller cross-section for drag when rotated. Referring to
Said centrifuge case 602 may contain a motor 603. The motor hub 613 on said motor 603 may protrude out of a motor hole, and allow interfacing with said rotor 401. In certain embodiments, the motor 603 is a DC motor; however, other suitable types of motors may be utilized as desired. In various embodiments, the motor 603 interfaces with one or more damping features for vibration damping. In the embodiment illustrated, the motor 603 interfaces with a lower gasket 604, an upper gasket 611 and an O-ring 605 for vibration damping purposes. Said centrifuge case may further include one or more foot recesses 612, which may interface with a corresponding elastic foot 609 for further vibration damping purposes. The foot recess 612 may be approximately as high as the elastic foot 609 in order to minimize the height of the centrifuge 408. As a non-limiting example, the difference in height between the elastic foot 609 and the foot recess 612 may be less than 2 mm. In other embodiments, additional, fewer, and/or various other combinations of damping features may be used as desired
Said centrifuge case 602 may further comprise an on-board power source. In the embodiment illustrated in
The centrifuge case 602 optionally may include a boost converter 608. The boost converter 608 may be various suitable devices or mechanisms for taking a low input voltage from the battery 606 and yielding a higher output voltage to the motor 603. As a non-limiting example, the low input voltage may be between 0.9 V and 4 V. The higher output voltage may be between 3 V and 15 V. In one embodiment, the low input voltage may be between 0.9 V and 1.7 V and the higher output voltage may be between 3 V and 6 V. The boost converter 608 may comprise a circuit board less than 11 mm in length, width, and depth.
The centrifuge case 602 optionally may further include a magnetic (or other suitable) sensor or switch 607. In such embodiments, the centrifuge lid 601 may comprise a magnet 610, which may interact with said magnetic switch 607, thus completing the circuit and causing said motor 603 to spin. In other words, the magnet 610 and the magnetic switch 607 may allow for the centrifuge 408 to automatically start rotating the rotor 401 upon closing of the lid 601 because the electrical circuit is completed. Optionally, the sensor or switch 607 may be provided on the printed circuit board, although it need not in other embodiments. In one non-limiting example, the switch 607 is a Hall Effect sensor; however, other suitable types of sensors or switches may be utilized as desired. The centrifuge may close an electrical circuit upon closure of the lid by an operator. The centrifuge optionally may rotate until the battery is exhausted. The centrifuge may rotate for 5 seconds to 60 minutes. The centrifuge may preferably rotate for 10 seconds to 30 minutes. The centrifuge may rotate for 15 seconds to 3 minutes. In some embodiments, the centrifuge may rotate for 15 seconds to 60 seconds. Timing of the centrifugal spin may depend on the operator such that the spin is initiated when a centrifuge lid is closed and the spin may stop when the centrifuge lid is opened.
In various embodiments, the centrifuge 408 and/or components of the centrifuge 408 may be disposable, meaning that it may be constructed for a single use after which it is recycled or is disposed of as waste. As a non-limiting example, the centrifuge case 602 and/or lid 601 may be constructed from disposable material such as, but not limited to, cardboard or thermoplastics. Optionally, the case 602 and/or lid 601 of the centrifuge 408 may partly include packing materials used for shipment. The case 602 and/or lid 601 of the centrifuge optionally may include multiple layers of materials, such as but not limited to a liquid impermeable layer, a liquid absorbent layer, and an outer layer suitable for shipping directly by postal or courier services. The layers of material may be laminated together by adhesives or otherwise assembled as desired.
Optionally, the centrifuge 408 may have a re-usable module (e.g., it is partially disposable). As a non-limiting example, the re-usable module may include the motor 603, the batteries 606, and an optional printed circuit board or other controller (processor and/or memory). The re-usable module may have a smooth and continuous outer surface suitable for disinfection.
The circuit board or other controller may control the speed of the centrifuge 408 and may count the number of runs. Optionally, the circuit board may present a signal or alert when the centrifuge 408 has reached a predetermined number of runs. The signal or alert may be various types of signals as alerts as desired, including audible and/or visible signals. As a non-limiting example, the circuit board may provide a visible signal such as by an LED on the centrifuge 408 when the centrifuge 408 has reached a maximum number of runs and/or if the battery 606 reaches a minimum threshold of voltage.
The printed circuit board may be mounted to the wall of the case 602 and oriented with a sensor (e.g., the magnetic (or other) switch 607) having a sensing region toward a point of interface with the lid 601. The printed circuit board may be mounted to a cardboard wall by various suitable mechanical and/or chemical mechanisms as desired, including but not limited to a rivet, staple, pressure sensitive adhesive, and/or glue. In other embodiments, the centrifuge 408 need not include a printed circuit board.
As illustrated in
Optionally, and as illustrated in
A collection of exemplary embodiments, including at least some explicitly enumerated as “Illustrations” providing additional description of a variety of example types in accordance with the concepts described herein are provided below. These embodiments are not meant to be mutually exclusive, exhaustive, or restrictive; and the invention is not limited to these example embodiments but rather encompasses all possible modifications and variations within the scope of the issued claims and their equivalents.
Illustration 1. An aerodynamic tube assembly for a centrifuge, the aerodynamic tube assembly comprising an aerodynamic tube, the aerodynamic tube comprising: a tube wall comprising a top side and a bottom side, wherein the tube wall defines a cavity, wherein the tube is elongated in a direction perpendicular to a direction extending from the top side to the bottom side.
Illustration 2. The aerodynamic tube assembly of any preceding or subsequent illustrations or combination of illustrations, wherein the top side comprises a rim extending outwards from the tube wall, and wherein the top side defines an opening to the cavity.
Illustration 3. The aerodynamic tube assembly of any preceding or subsequent illustrations or combination of illustrations, wherein the bottom side of the tube wall comprises a planar surface.
Illustration 4. The aerodynamic tube assembly of any preceding or subsequent illustrations or combination of illustrations, wherein the tube wall is tapered from the top side to the bottom side such that a width of the bottom side in the direction that the tube is elongated is less than a width of the top side in the direction that the tube is elongated.
Illustration 5. The aerodynamic tube assembly of any preceding or subsequent illustrations or combination of illustrations, wherein the tube wall is elongated as an aerofoil comprising a leading edge and a lagging edge, wherein a profile of the leading edge is different from a profile of the lagging edge.
Illustration 6. The aerodynamic tube assembly of any preceding or subsequent illustrations or combination of illustrations, wherein the lagging edge is at least 1.5 times a length of the leading edge.
Illustration 7. The aerodynamic tube assembly of any preceding or subsequent illustrations or combination of illustrations, further comprising a stopper configured to seal the cavity.
Illustration 8. The aerodynamic tube assembly of any preceding or subsequent illustrations or combination of illustrations, wherein the stopper comprises an insertion portion that is at least partially positionable within the cavity of the aerodynamic tube through the top side.
Illustration 9. A rotor for a portable centrifuge, the rotor comprising: a center portion configured to engage a motor hub of the portable centrifuge; a support location for an aerodynamic tube having a height and that is elongated in a direction perpendicular to the height of the aerodynamic tube, the support location comprising: a lower clasp extending outwards from the center portion; arms extending outwards from the center portion; and an upper clasp on the arms, wherein the lower claps and the upper clasp are configured to interface with a rim of the aerodynamic tube.
Illustration 10. The rotor of any preceding or subsequent illustrations or combination of illustrations, wherein the upper clasp and the lower clasp do not overlap in a vertical direction.
Illustration 11. The rotor of any preceding or subsequent illustrations or combination of illustrations, further comprising a counterweight extending outwards from the center portion in a direction opposite from the support location.
Illustration 12. The rotor of any preceding or subsequent illustrations or combination of illustrations, wherein the counterweight comprises a rib extending downwards from the counterweight and extensions extending outwards from the counterweight in a direction of rotation.
Illustration 13. The rotor of any preceding or subsequent illustrations or combination of illustrations, wherein the extensions define a maximum width of the rotor.
Illustration 14. A portable centrifuge comprising: a housing comprising a centrifuge case and a centrifuge lid configured to interface with the centrifuge case, wherein the housing comprises a single-use material; a centrifuge case comprising: a motor within the centrifuge case for interfacing with and rotating a rotor; a damping system with the centrifuge case; and an on-board power source within the centrifuge case; and an activation system for activating the motor based on an interfacing of the centrifuge lid with the centrifuge case.
Illustration 15. The portable centrifuge of any preceding or subsequent illustrations or combination of illustrations, wherein the activation system comprises a magnet on the centrifuge lid and magnetic switch within the centrifuge housing and connected to the on-board power source and the motor.
Illustration 16. The portable centrifuge of any preceding or subsequent illustrations or combination of illustrations, wherein the damping system comprises an upper gasket, a lower gasket, and an O-ring.
Illustration 17. The portable centrifuge of any preceding or subsequent illustrations or combination of illustrations, wherein the motor is a DC motor, and wherein the portable centrifuge further comprises a boost converter for receiving an input voltage from the on-board power source and yielding an output voltage to the DC motor.
Illustration 18. The portable centrifuge of any preceding or subsequent illustrations or combination of illustrations, further comprising a controller configured to: control a speed of the centrifuge; count a number of runs by the centrifuge; and generate an alert based on the portable centrifuge being in a predetermined condition, wherein the predetermined condition comprises at least one of a maximum number of runs or a minimum threshold of voltage of the on-board power source.
Illustration 19. The portable centrifuge of any preceding or subsequent illustrations or combination of illustrations, wherein the on-board power source comprises at least one battery.
Illustration 20. The portable centrifuge of any preceding or subsequent illustrations or combination of illustrations, wherein: the centrifuge lid comprises a lid tab; and the centrifuge case comprises: a tab notch defined in the centrifuge case and configured to receive the lid tab; and a lid rib, wherein centrifuge case and the lid rib are configured to vertically overlap the lid tab based on rotation of the centrifuge lid relative to the centrifuge case.
Descriptions, scenarios, examples and drawings are non-limiting embodiments. All references to “invention” refer to “embodiments.” Embodiments described herein are of a device intended for use in blood separation, and methods of using the device. Other embodiments have other applications. Drawings are not to scale.
Ideal, Ideally, Optimum and Preferred—Use of the words, “ideal,” “ideally,” “optimum,” “optimum,” “should” and “preferred,” when used in the context of describing this invention, refer specifically to a best mode for one or more embodiments for one or more applications of this invention. Such best modes are non-limiting, and may not be the best mode for all embodiments, applications, or implementation technologies, as one trained in the art will appreciate.
All examples are sample embodiments. In particular, the phrase “invention” should be interpreted under all conditions to mean, “an embodiment of this invention.” Examples, scenarios, and drawings are non-limiting. The only limitations of this invention are in the claims.
May, Could, Option, Mode, Alternative and Feature—Use of the words, “may,” “could,” “option,” “optional,” “mode,” “alternative,” “typical,” “ideal,” and “feature,” when used in the context of describing this invention, refer specifically to various embodiments of this invention. Described benefits refer only to those embodiments that provide that benefit. All descriptions herein are non-limiting, as one trained in the art appreciates. The phrase, “configured to” also means, “adapted to.” The phrase, “a configuration,” means, “an embodiment.”
All numerical ranges in the specification are non-limiting exemplary embodiments only. Brief descriptions of the Figures are non-limiting exemplary embodiments only.
Embodiments of this invention explicitly include all combinations and sub-combinations of all features, elements and limitation of all claims. For avoidance of doubt, any combination of features not physically impossible or expressly identified as non-combinable herein may be within the scope of the invention. Embodiments of this invention explicitly include all combinations and sub-combinations of all features, elements, examples, embodiments, tables, values, ranges, and drawings in the specification, figures, drawings, and all drawing sheets. Embodiments of this invention explicitly include devices and systems to implement any combination of all methods described in the claims, specification and drawings. Embodiments of the methods of invention explicitly include all combinations of dependent method claim steps, in any functional order. Embodiments of the methods of invention explicitly include, when referencing any device claim, a substitution thereof to any and all other device claims, including all combinations of elements in device claims.
This application claims the benefit of U.S. Provisional Patent Application No. 63/182,663, filed on Apr. 30, 2021 and entitled ULTRACOMPACT CENTRIFUGE, SPECIMEN CONTAINER AND METHODS OF USE, the content of which is hereby incorporated by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 63182663 | Apr 2021 | US |
