External Fluidics for Flow Cytometers
By designing an external fluid system, using pipe fittings, pumps, measuring devices and controllers to connect with the flow cytometry system, the automatic monitoring and management of sheath fluid or waste fluid is achieved, and the sheath fluid consumption in the portable flow cytometry system is solved. The problem of exhaustion or waste container overflow extends experiment time and reduces interruptions.
Patent Information
- Application Number
- CN201980091597.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Priority Date
- 2018-12-10
- Filing Date
- 2019-12-06
- Publication Date
- 2025-02-11
- Estimated Expiration
- 2039-12-06
AI Technical Summary
Portable flow cytometry systems are prone to depleting sheath fluid or overflowing the waste container during the experiment, resulting in interruption of the experiment, and refilling or replacing the container takes time and effort.
An external fluid system is designed to connect with the existing flow cytometer system through pipe fittings, pumps, measuring devices and controllers to realize automatic monitoring and management of sheath or waste liquid to avoid container depletion or overflow.
The system can automatically detect the amount of sheath or waste liquid without interrupting the normal operation of the flow cytometer system, and adjust the operating conditions of the pump to extend the service time of the container and reduce the possibility of experiment interruption.
Smart Images

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Abstract
Description
[0001] CROSS-REFERENCE TO RELATED APPLICATIONS
[0002] This application claims priority to U.S. patent application serial number 16 / 214,674, filed on December 10, 2018, the entire contents of which are incorporated herein by reference. Background Art
[0003] Flow cytometers can be used to analyze sample fluids having cells or particles and identify the characteristics of the cells or particles contained in the fluid. These cells or particles can be biological samples or physical samples collected for analysis and / or separation. The sample is mixed with a sheath fluid to transport the cells or particles through the flow cytometer. The particles can include biological cells, calibration microbeads, physical sample particles, or other particles of interest.
[0004] Figure 1 A schematic diagram of a typical flow cytometer is shown. Figure 1 , the fluid is usually passed through a flow chamber (e.g., a small nozzle) to produce a narrow fluid stream. As cells and particles in the sample stream pass through, a light beam such as a laser beam illuminates the cells and particles in the sample stream. Photodetectors and color detectors 1 and 2 are positioned to detect scattered light and fluorescence. This information is collected by a computer and then used by the flow cytometer to identify particles or particle characteristics in the fluid. Figure 2 The hydrodynamic focusing process of a flow cell of a flow cytometer is shown. When the sheath fluid passes through the hydrodynamic focusing region of the flow cell, a set of particles is generated in the flow cytometer system for analysis and characterization. The sheath fluid is typically buffered saline or deionized (DI) water, but the sheath fluid can be any suitable fluid to hydrodynamically focus the sample fluid.
[0005] As flow cytometer systems become smaller and more portable, sheath fluid containers and waste containers have correspondingly become smaller and more portable. As a result, portable flow cytometer systems may run out of sheath fluid supplies or overflow the waste container during an experiment. While refilling or replacing the sheath fluid container and emptying the waste container requires a certain amount of time and effort, the user must continually pause the experiment to ensure that the sheath fluid does not completely run out and the waste container does not overflow. If the sheath fluid container becomes empty, the data collected from the time the sheath fluid is exhausted or before and after the sheath fluid is exhausted may be compromised. Therefore, the user will generally have to provide new sample material and perform a new experiment to ensure the accuracy of the data. Similarly, if the waste container overflows, the user will inevitably have to pause the experiment to clean and disinfect the area. Since the samples analyzed by flow cytometers vary from relatively benign to less benign, overflowing of the waste container can cause serious delays and even dangerous situations. Summary of the invention
[0006] In view of the problems in the related art, there is a need for an improved flow cytometer system that is suitable for determining the volume of sheath fluid or waste fluid during operation and can expand the storage capacity of the sheath fluid or waste fluid without causing any interruption in the normal operation of the running flow cytometer system.
[0007] Embodiments of the present invention provide systems and methods for connecting an external fluid system to an existing flow cytometer-based system (e.g., as a hot-swap option) to expand the storage capabilities of the flow cytometer-based system with only minimal changes to the flow cytometer-based system.
[0008] In one embodiment, the fluid system may include: a container; a tubing configured to be connectable to a flow cytometer-based system; a second pump; a measuring device; and a controller in operative communication with the second pump and the measuring device. The controller of the fluid system may be configured to operate the fluid system to supply fluid to the flow cytometer-based system or to extract fluid from the flow cytometer-based system. The flow of sheath fluid or waste fluid may be automatically switched between the fluid system and an internal waste fluid system of the flow cytometer-based system without causing any interruption to normal operation of the running flow cytometer-based system.
[0009] In another embodiment, a method of using a fluid system is provided. The fluid system may include tubing connecting the fluid system to a flow cytometer-based system having a first pump, a measuring device, a second pump, and a controller in operative communication with the second pump and the measuring device. The container contains a first fluid, which is a sheath fluid flowing to the flow cytometer-based system or a waste fluid flowing out of the flow cytometer-based system. The method includes: when the first fluid is the sheath fluid, the controller operates the fluid system to supply the first fluid from the container to the flow cytometer-based system, and when the first fluid is the waste fluid, the controller operates the fluid system to extract the first fluid from the flow cytometer-based system and provide it to the container.
[0010] In another embodiment, a system for cell / particle characterization or separation may include: a flow cytometer including a first pump; a fluid system operably connected to the flow cytometer. The fluid system may include: a container; a tube connected to the flow cytometer; a second pump; a measuring device; and a controller operably communicating with the second pump and the measuring device, wherein the controller is configured to operate the fluid system based on the condition of the flow cytometer.
[0011] In some embodiments, the measuring device measures the property of the sheath fluid or the waste fluid in the container and transmits the measurement result to the controller. The controller determines whether the received measurement result is greater than or equal to a predetermined threshold value and adjusts the operating conditions of the second pump to guide the fluid flow direction according to the determination result.
[0012] In certain embodiments, the fluidic system performs its function independently of any signal communication with a flow cytometer-based system. In alternative embodiments, the fluidic system performs its function based on signal communication with a flow cytometer-based system. BRIEF DESCRIPTION OF THE DRAWINGS
[0013] Figure 1 is a schematic diagram of a flow cytometer system of the prior art.
[0014] Figure 2 Schematic diagram of the hydrodynamic focusing process of cells / particles to produce a single stream in a prior art flow cytometer system.
[0015] Figure 3 is a schematic diagram of an external waste system coupled to an internal waste system of a flow cytometer-based system in accordance with an embodiment of the present invention.
[0016] Figure 4 is a diagram showing an embodiment according to the present invention Figure 3 A flow chart of the operation of the waste system is shown in FIG.
[0017] Figure 5 is a schematic diagram of an external sheath fluid system coupled to an internal sheath fluid system of a flow cytometer-based system in accordance with an embodiment of the present invention.
[0018] Figure 6 is a diagram showing an embodiment according to the present invention Figure 5 A flow chart of the operation of the sheath fluid system is shown in FIG.
[0019] Figure 7 is a schematic diagram of a user interface of a control panel according to an embodiment of the present invention. DETAILED DESCRIPTION
[0020] Embodiments of the present invention relate to advantageous external fluid systems, methods of operating the external fluid systems, and methods of using the external fluid systems. The external fluid systems can be easily connected to existing flow cytometer systems to expand the fluid storage capabilities of the existing flow cytometer systems with only minimal modifications to the existing flow cytometer systems.
[0021] In some embodiments, the external fluid system can be configured and / or used to extract waste fluid. Figure 3, the external waste liquid system 200 for waste extraction may include: an external waste pump 210, which extracts waste liquid from the optional internal waste liquid system 100 of the existing flow cytometer-based system and pumps the extracted waste liquid into a bulk container 220 connected to the external waste pump 210 through an optional valve 230; a pressure sensor 250, which is connected to the connecting pipe between the external waste pump 210 and the valve 230 to sense the pressure of the bulk container 220; a platform / load sensor 225, which is connected to the bulk container 220 to measure a primary parameter (such as volume) of the fluid contained in the bulk container 220; a float sensor 280, which is connected to the bulk container 220 to measure a secondary parameter (such as liquid level) of the fluid contained in the bulk container 220; and a power / control unit 260, which is connected to the external waste pump 210, the pressure sensor 250, the float sensor 280 and the platform / load sensor 225 to implement the control function of the external waste liquid system 200. The external waste system 200 may include an exhaust filter 240 connected to the bulk container 220 to filter the exhaust of the bulk container 220 and a power source (not shown) connected to the external waste system 200 to power the external waste system 200. The external waste system 200 may include connecting tubing and / or couplings such as a dry-disconnect connector 270 to connect to an existing flow cytometer-based system, but may alternatively connect to any suitable system.
[0022] An existing flow cytometer-based system to which the external waste system 200 can be connected may include an internal waste system 100. The internal waste system 100 (if present) may include an internal waste emptying pump 110 to extract waste liquid from an internal waste bottle 120 containing waste liquid generated by the operation of the flow cytometer-based system and pump the extracted waste liquid into an internal bulk waste tank 140. An internal waste valve 130 (e.g., a waste valve that can control which internal waste tank the waste enters, such as a 1 / 2 valve in the Bio-Rad ZE5 system) and an internal waste tee connector 150 are provided between the internal waste emptying pump 110 and the internal bulk waste tank 140. The external waste system 200 may be connected to the internal waste system 100 through the internal waste tee connector 150.
[0023] The bulk container 220 can be used to hold waste generated by the flow cytometer-based system and used as additional storage in addition to the internal bulk waste tank 140 of the internal waste system 100, thereby expanding the ability of the flow cytometer-based system to store waste when the external waste system 200 is connected to the flow cytometer-based system. The bulk container 220 can be, for example, a vented tank having a volume of approximately 20 L, and the bulk container 220 can alternatively be any suitable container of any capacity.
[0024] In addition, the external waste system 200 can be used to extract fluids other than waste liquids. For example, after the analysis operation of the flow cytometer-based system is completed, the external waste pump 210 can be used to extract bleach from the bleach container of the internal waste system 100 into the bulk container 220. As another example, after the analysis operation of the flow cytometer-based system is completed, the external waste pump 210 can extract a cleaning agent (e.g., a detergent or antimicrobial agent) from the cleaning agent container of the flow cytometer-based system into the bulk container 220.
[0025] The external waste pump 210 may be a peristaltic pump or alternatively any other suitable type of pump.The external waste pump 210 may have a known ratio of flow rate to pump speed, such that control of the speed of the external waste pump 210 corresponds to control of the flow rate of the waste fluid.
[0026] Reference again Figure 3 , valve 230 is connected to the external waste pump 210 at one end and to the bulk container 220 at the other end, and serves to facilitate the control of the waste flow. The optional valve 230 can be a check valve, such as a spring-loaded check valve, but can alternatively be any suitable valve, such as a bypass valve, a throttle valve, and / or a shut-off valve.
[0027] The platform / load cell 225 is a measuring device used to measure the key parameters of the waste liquid contained by the bulk container 220. Figure 3 , the platform / load sensor 225 is preferably arranged so that it does not directly contact the waste liquid in the bulk container 220. In one embodiment, the platform / load sensor 225 includes one or more capacitive sensors disposed on or near the bulk container 220. The capacitive sensors can sense: (1) the discrete presence or absence of the bulk container 220; (2) the discrete presence or absence of the waste liquid in the bulk container 220; or (3) the volume of the waste liquid in the bulk container 220. Alternatively, the platform / load sensor 225 can include one or more sensors to measure the weight, optical properties, acoustic properties, etc. of the waste liquid, and then calculate the volume of the waste liquid in the bulk container 220 based on the measurement results.
[0028] like Figure 3As shown, float sensor 280 measures a second parameter (e.g., liquid level) of the waste liquid contained by bulk container 220 and is connected to power / control unit 260. If platform / load sensor 225 fails, power / control unit 260 can determine that bulk container 220 is full based on the measurement of liquid level provided by float sensor 280 in order to stop overflow of bulk container 220. In other words, float sensor 280 can operate as a backup sensor in addition to the primary sensor of platform / load sensor 225 to inhibit or prevent overflow of waste liquid that may include biohazards (e.g., carboys) from bulk container 220. Figure 3 The illustrated pressure sensor 250 measures the pressure of the bulk container 220 and provides the measurement to the power / control unit 260, thereby allowing the power / control unit 260 to detect whether the pressure of the bulk container 220 exceeds a predetermined threshold (e.g., reaches a level high enough to cause an explosion or other safety issue). If the pressure does exceed the predetermined threshold, the operation of the external waste pump may be suspended or shut down.
[0029] The power / control unit 260 of the external waste system 200 can be connected to the external waste pump 210, the pressure sensor 250, the float sensor 280, and the platform / load sensor 225. In one embodiment, the power / control unit 260 sets or adjusts the pump speed of the external waste pump 210 to set or adjust the flow rate of the waste from the flow cytometer-based system to the external waste system 200. Alternatively, the power / control unit 260 can set or adjust operating parameters of the external waste pump 210 other than the pump speed, such as power, pressure, or pump head, etc., to set or adjust the flow rate of the waste from the flow cytometer-based system to the external waste system 200.
[0030] The power / control unit 260 may include a proportional integral derivative (PID) controller, but may alternatively be a proportional integral (PI) controller, a proportional derivative (PD) controller, a proportional (P) controller, or any other suitable type of controller. The power / control unit 260 may include an input device for receiving input, the input device including a keyboard, a mouse, a touch panel user interface, or other types of suitable input devices. In addition, the power / control unit 260 may include a display device including a display screen, a printer, or other types of suitable display devices for displaying the output signal of the power / control unit 260 for viewing by the user. Therefore, the user may send a command input such as a predetermined pump speed value to the power / control unit 260 via an input device. When receiving a command input from the user, the power / control unit 260 sets or adjusts the external waste pump 210 of the external waste liquid system 200 to operate at a predetermined pump speed value requested by the user.
[0031] In another embodiment, the user can send a command inputted via an input device to the power / control unit 260 to request the power / control unit 260 to automatically determine the optimal pump speed for the external waste pump 210 to operate so as to achieve the goal of allowing waste fluid from the flow cytometer-based system to flow through the internal waste tee connector 150 to the bulk container 220 of the external waste system 200.
[0032] Figure 4 It is configuration Figure 3 A flow chart of an example process for extracting waste from a flow cytometer-based system to the external waste system 200 is shown. Figure 4 , at step S100 , when the flow cytometer-based system operates under normal conditions for analyzing samples, the power / control unit 260 starts the external waste liquid system 200 including the external waste pump 210 .
[0033] Next, in step S200, the power / control unit 260 sets the external waste pump 210 to operate at a pump speed higher than the pump speed of the internal waste emptying pump 110 of the internal waste liquid system 100 in response to input from the user, or alternatively, automatically determines the optimal pump speed for the operation of the external waste pump 210.
[0034] Next, in step S300, the external waste pump 210 is operated at the pump speed set in step S200. Since the pump speed of the external waste pump 210 is set higher than the pump speed of the internal waste emptying pump 110, a pressure difference is generated between the external waste liquid system 200 and the internal waste liquid system 100, so that the waste liquid of the flow cytometer-based system flows to the bulk container 220 of the external waste liquid system 200.
[0035] For example, the external waste pump 210 and the internal waste evacuation pump 110 can be operated simultaneously at pump speeds within the same pump speed range of 0-100%. When the internal waste evacuation pump 110 operates at 20% of the pump speed range under normal operating conditions of the flow cytometer-based system and operates at 50% of the pump speed range under certain special operating conditions, the power / control unit 260 can set or adjust the external waste pump 210 to operate at a pump speed greater than 50% of the pump speed range.
[0036] Since the internal waste emptying pump 110 and the external waste pump 210 operate in parallel and compete with each other, when the external waste pump 210 operates at a higher pumping speed than the internal waste emptying pump 110, a net suction force is generated and applied to the tubing leading to the internal bulk waste tank 140, thereby sucking out the waste liquid generated by the flow cytometer-based system and flowing it through the internal waste tee connector 150 of the internal waste liquid system 100 to the bulk container 220 of the external waste liquid system 200.
[0037] Next, at step S400, the platform / load sensor 225 having one or more sensors senses or measures the volume of the waste liquid in the bulk container 220, the float sensor 280 can measure the level of the waste liquid, and the pressure sensor 250 can measure the pressure of the bulk container 220. The measurements of volume, waste liquid level, and pressure are transmitted to the power / control unit 260. In some cases, only one measurement is made (e.g., the volume measured by the platform / load sensor 225), and it is sent out if the measured value is outside the normal operating range. In some cases, only two measurements are made (e.g., the volume measured by the platform / load sensor 225 and one of the waste liquid level measured by the float sensor 280 or the bulk container pressure measured by the pressure sensor 250), and if any one of the measured values is outside the normal operating range, it is sent out.
[0038] Next, at step S500, the power / control unit 260 determines whether the volume of the waste liquid is greater than or equal to a predetermined threshold value upon receiving the measurement result. If it is determined that the measured volume is greater than or equal to the predetermined threshold value, then in order to avoid overflow of the bulk container 220, at step S600, the power / control unit 260 pauses or shuts down the operation of the external waste pump 210. As a result, there is no pump competing with the operating internal waste emptying pump 110. Therefore, the net suction between the external waste liquid system 200 and the internal waste liquid system 100 causes the waste liquid of the flow cytometer-based system to flow only to the internal bulk waste tank 140 of the internal waste liquid system 100, and not to the external waste liquid system 200.
[0039] If it is determined in step S500 that the measured volume is less than the predetermined threshold, then in step S510, the power / control unit 260 determines whether the level of the waste liquid is greater than or equal to the predetermined threshold of the level or whether the pressure of the bulk container 220 is greater than or equal to the predetermined threshold of the pressure. If it is determined that the measured level is greater than or equal to the predetermined level threshold or the measured pressure is greater than or equal to the predetermined pressure threshold, then in step S600, the power / control unit 260 pauses or shuts down the operation of the external waste pump 210 in order to avoid overflowing the bulk container 220 or to avoid a dangerous condition in the bulk container 220. In some cases, only one of these measurements is performed; if the measured value exceeds the threshold, the operation may be stopped, and the other measurement may not need to be performed at this time.
[0040] On the other hand, if it is determined in step S510 that the measured liquid level is less than the predetermined liquid level threshold and the measured pressure is less than the predetermined pressure threshold, then in optional step S520, the difference between the measured volume and the predetermined volume threshold is calculated and compared with a predetermined delta value. In optional step S540, if it is determined that the difference is greater than or equal to the predetermined delta value, the power / control unit 260 reduces the pump speed of the external waste pump 210 to reduce the inflow of waste liquid into the external waste liquid system 200 and simultaneously sends an alarm signal to the user to predict overflow at the bulk container 220. If it is determined in optional step S520 that the difference is less than the predetermined delta value, then in step S560, the power / control unit 260 maintains the external waste pump 210 at the set pump speed until the measurement result is greater than or equal to the predetermined threshold.
[0041] Alternatively, at step S510, if it is determined that the measured liquid level is less than a predetermined liquid level threshold and the measured pressure is less than a predetermined pressure threshold, and if optional steps S520 and S540 are not performed, then at step S560, the power / control unit 260 may keep the external waste pump 210 running at a set pump speed until the measurement result is greater than or equal to the predetermined threshold. In one embodiment, the external waste liquid system 200 operates independently of any signal / input from the flow cytometer-based system. In other words, there is no intentional signal communication between the external waste liquid system 200 and the flow cytometer-based system. Even if the system is connected and is in an operable communication or operating state at least through a pipe (or other connecting device), there is no intentional sending or receiving of signals (e.g., electrical / electronic signals, magnetic signals, optical signals, pressure signals, pneumatic signals, or strain signals) between the systems. Therefore, the external waste liquid system 200 performs its function without any signal communication with the flow cytometer-based system.
[0042] In another embodiment, the external waste system 200 can operate in signal communication with a flow cytometer-based system. In other words, the external waste system 200 responds to input or request signals from an existing flow cytometer-based system and performs its functions by transmitting output or feedback signals to the existing flow cytometer-based system.
[0043] Figure 5 Schematic diagram of an external sheath fluid system connected to an (optional) internal sheath fluid system of a flow cytometer-based system according to an embodiment of the present invention. Figure 5, an external sheath fluid system 500 for supplying sheath fluid may include: an external sheath pump 510, which supplies sheath fluid to the (optional) internal sheath fluid system 400 of an existing flow cytometer-based system, and pumps the sheath fluid from a bulk container 520 connected to the external sheath pump 510 through an optional valve 530; a pressure sensor 550, which is connected to a connecting tube between the external sheath pump 510 and the valve 530 to sense the pressure of the external sheath pump 510; a platform / load sensor 525, which is connected to the bulk container 520, for measuring parameters of the fluid contained in the bulk container 520; a power / control unit 560, which is connected to the external sheath pump 510, the pressure sensor 550 and the platform / load sensor 525 to implement the control function of the external sheath fluid system 500.
[0044] The external sheath fluid system 500 includes a pressure regulator (not shown) or a power source (not shown) connected to the external sheath fluid system 500 to supply power to the external sheath fluid system 500 . Figure 5 The external sheath fluid system 500 may include connecting tubing and / or connectors such as dry-disconnect connector 570 to connect to an existing flow cytometer-based system, but may alternatively connect to any suitable system.
[0045] Existing flow cytometer-based systems to which the external sheath fluid system 500 can be connected may include an internal sheath fluid system 400. The internal sheath fluid system 400 is optional, although the internal bulk sheath tank 440 is usually present in most cases. The internal sheath fluid system 400 (if present) includes an internal sheath pump 410 to supply sheath fluid from the internal bulk sheath tank 440 to the internal sheath bottle 420. An internal sheath valve 430 (e.g., a sheath valve that can control which internal sheath tank the sheath fluid is directed to, such as a 1 / 2 valve in the Bio-Rad ZE5 system), an internal sheath tee connector 450, and an external source valve 455 may be provided between the internal sheath pump 410 and the internal bulk sheath tank 440. The external sheath fluid system 500 may be connected to the internal sheath fluid system 400 via the internal sheath tee connector 450 and the external source valve 455.
[0046] When the level of sheath fluid in the internal bulk sheath tank 440 is below a predetermined level (e.g., less than half full), the external source valve 455 can be configured to allow the internal bulk sheath tank 440 to be filled by the bulk container 520; when the level of sheath fluid in the internal bulk sheath tank 440 reaches a predetermined level (e.g., 75% full), the external source valve 455 can be configured to close to stop filling the internal bulk sheath tank 440 from the bulk container 520. The bulk container 520 can be used to hold sheath fluid supplied to the flow cytometer-based system and used as additional storage in addition to the internal bulk sheath tank 440 of the internal sheath fluid system 400, thereby increasing the capacity of the flow cytometer-based system for storing sheath fluid when the external sheath fluid system 500 is connected to the flow cytometer-based system. The bulk container 520 can be, for example, a tank with a volume of approximately 20 L, and the bulk container 520 can alternatively be any suitable container having any capacity.
[0047] In addition, the external sheath fluid system 500 can be used to supply fluids other than sheath fluid. For example, after the analysis operation of the flow cytometer-based system is completed, the external sheath pump 510 can be used to supply bleach from the bulk container 520 to the bleach container of the internal sheath fluid system 400. As another example, after the analysis operation of the flow cytometer-based system is completed, the external sheath pump 510 can supply a cleaning agent (e.g., a detergent or antimicrobial agent) from the bulk container 520 to the cleaning agent container of the flow cytometer-based system.
[0048] The external sheath pump 510 may be a peristaltic pump or alternatively any other suitable type of pump. The external sheath pump 510 may have a known ratio of flow rate to pump speed, such that control of the speed of the external sheath pump 510 corresponds to control of the flow rate of the sheath fluid.
[0049] Reference again Figure 5 , valve 530 is connected to the external sheath pump 510 at one end and to the bulk container 520 at the other end, and serves to facilitate control of the sheath flow. The optional valve 530 may be a check valve, such as a spring-loaded check valve, but may alternatively be any suitable valve, such as a bypass valve, a throttle valve, and / or a shutoff valve.
[0050] The platform / load sensor 525 is a measuring device for measuring a parameter of the sheath fluid contained by the bulk container 520. The platform / load sensor 525 can be arranged so as not to be in direct contact with the sheath fluid in the bulk container 520. In one embodiment, the platform / load sensor 525 includes one or more capacitive sensors disposed on or near the bulk container 520. The capacitive sensors can sense: (1) the discrete presence or absence of the bulk container 520; (2) the discrete presence or absence of the sheath fluid in the bulk container 520; or (3) the volume or level of the sheath fluid in the bulk container 520. Alternatively, the platform / load sensor 525 can include one or more sensors to measure the weight, optical properties, acoustic properties, etc. of the sheath fluid and then calculate the volume or level of the sheath fluid in the bulk container 520 based on the measurement results.
[0051] The power / control unit 560 of the external sheath fluid system 500 can be connected to the external sheath pump 510, the pressure sensor 550, and the platform / load sensor 525. In one embodiment, the power / control unit 560 sets or adjusts the pump speed of the external sheath pump 510 to set or adjust the flow rate of the sheath fluid supplied from the external sheath fluid system 500 to the flow cytometer-based system. Alternatively, the power / control unit 560 can set or adjust operating parameters other than the pump speed of the external sheath pump 510, such as power, pressure, or pump head, etc., to set or adjust the flow rate of the sheath fluid supplied from the external waste fluid system 500 to the flow cytometer-based system.
[0052] The power / control unit 560 may include a proportional-integral-derivative (PID) controller, but may alternatively be a proportional-integral (PI) controller, a proportional-derivative (PD) controller, a proportional (P) controller, or any other suitable type of controller. The power / control unit 560 may include an input device for receiving input, including a keyboard, a mouse, a touch panel user interface, or other types of suitable input devices. In addition, the power / control unit 560 may include a display device for displaying the output signal of the power / control unit 560 for viewing by a user, including a display screen, a printer, or other types of suitable display devices. Thus, a user may send a command input such as a predetermined pump speed value to the power / control unit 560 via an input device. Upon receiving a command input from a user, the power / control unit 560 sets or adjusts the external sheath pump 510 of the external sheath fluid system 500 to operate at the predetermined pump speed value requested by the user.
[0053] In another embodiment, the user can send a command input to the power / control unit 560 via an input device to request the power / control unit 560 to automatically determine the optimal pump speed for the external sheath pump 510 to operate in order to achieve the purpose of supplying sheath fluid from the bulk container 520 of the external sheath fluid system 500 through the internal sheath three-way connector 450 to the flow cytometer-based system.
[0054] When the flow cytometer-based system is operating under normal conditions for analyzing samples, the internal sheath pump 410 continues to operate to supply sheath fluid from the internal bulk sheath tank 440 to the internal sheath bottle 420. When the level of sheath fluid in the internal bulk sheath tank 440 drops below a first predetermined level (e.g., 50% full), the external source valve 455 is configured to open, thereby causing Figure 5 The external sheath fluid system 500 shown in FIG. 5 supplies sheath fluid from a bulk container 520 to a flow cytometer-based system.
[0055] Figure 6 is a flow chart of an example process for configuring an external sheath fluid system 500 to supply sheath fluid to a flow cytometer-based system. Figure 6 In step S700 , when the power / control unit 560 senses that the external source valve 455 is opened, causing the pressure of the external sheath fluid system 500 to change, the power / control unit 560 starts the external sheath pump 510 .
[0056] Next, in step S800, the power / control unit 560 sets the external sheath pump 510 to operate at a pump speed to generate a pressure of the external sheath fluid system 500 that is substantially higher than the pressure of the internal sheath fluid system 400 in response to the input, or alternatively, automatically determines an optimal pump speed for the external sheath pump 510 to operate.
[0057] Next, in step S900 , the external sheath pump 510 is operated at the pump speed set in step S800 . Due to a sufficiently high pressure difference between the external sheath fluid system 500 and the internal sheath fluid system 400 , the sheath fluid contained in the bulk container 520 is pumped to the internal bulk sheath tank 440 .
[0058] Next, at step S1000, the platform / load cell 525 having one or more sensors senses or measures the volume of the sheath fluid in the bulk container 520, and the pressure sensor 550 senses or measures the pressure of the external sheath fluid system 500. The volume and pressure measurements are sent to the power / control unit 560.
[0059] Next, at step S1100, the power / control unit 560 determines whether the measured volume is less than a predetermined volume threshold upon receiving the measurement result. If it is determined that the measured volume is less than the predetermined threshold of the volume, then in order to avoid pumping from the empty bulk container 520, at step S1200, the power / control unit 560 pauses or shuts down the operation of the external sheath pump 510. As a result, no external sheath fluid flows to the internal bulk sheath tank 440. Therefore, the flow cytometer-based system continues to operate with the internal sheath fluid system 400, so that the sheath fluid is supplied only from the internal bulk sheath tank 440 of the internal sheath fluid system 400, and not from the external sheath fluid system 500. If it is determined in step S1100 that the measured volume is greater than or equal to the predetermined threshold of the volume, then, at step S1150, the power / control unit 560 determines whether the measured pressure is greater than the predetermined threshold of the pressure.
[0060] In the internal sheath fluid system 400, when the level of the sheath fluid in the internal bulk sheath tank 440 reaches a second predetermined level (e.g., 75% full) greater than the first predetermined level, the external source valve 455 is configured to close. At step S1150, when the power / control unit 560 senses that the pressure of the external sheath fluid system 500 rises to a level greater than a predetermined threshold of the pressure due to the closing of the external source valve 455, in order to avoid the pump from operating ineffectively due to a leak condition in the external sheath fluid system 500, at step S1160, the power / control unit 560 pauses the operation of the external sheath pump 510 and only turns the external sheath pump 510 back on when it is determined that the measured pressure is less than or equal to the predetermined threshold of the pressure. On the other hand, if it is determined in step S1150 that the measured pressure is less than or equal to the predetermined threshold of the pressure, the power / control unit 560 keeps the external sheath pump 510 running at the set pump speed.
[0061] The process of filling the internal bulk sheath tank 440 with sheath fluid from the bulk container 520 by starting and pausing the external sheath pump 510 is repeated until the volume of sheath fluid in the bulk container 520 is less than a predetermined threshold of the volume (e.g., until the bulk container 520 becomes empty). In one embodiment, the external sheath fluid system 500 operates independently of any signal / input from the flow cytometer-based system. In other words, there is no intentional signal communication between the external sheath fluid system 500 and the flow cytometer-based system. Even if the systems are connected and are in operable communication or operation at least through tubing (or other connecting means), there is no intentional sending or receiving of signals (e.g., electrical / electronic signals, magnetic signals, optical signals, pressure signals, pneumatic signals, or strain signals) between the systems. Therefore, the external sheath fluid system 500 performs its functions without any signal communication with the flow cytometer-based system.
[0062] In another embodiment, the external sheath fluid system 500 can operate using signal communication with a flow cytometer-based system. In other words, the external sheath fluid system 500 responds to an input or request signal from an existing flow cytometer-based system and performs its function by transmitting an output or feedback signal to the existing flow cytometer-based system.
[0063] In some embodiments, different colored caps may be used on various components to help easily distinguish different containers (e.g., bulk containers, internal bulk sheath tanks, etc.) and / or different valves or pumps from one another.
[0064] Figure 7 Provided are illustrations of user interfaces for control panels (e.g., electromechanical control switches) of certain embodiments of the present invention. It should be understood that Figure 7 The user interface shown is for illustrative purposes only and should not be construed as intended to limit how and in what manner the external fluidic system or flow cytometer-based system may perform its functions.
[0065] like Figure 7 As shown, the user interface of the control panel may include: a system on / off button for turning on or off an external waste pump or an external sheath pump; a system run LED indicating the status of the above pumps, wherein when the system run LED is on, it indicates that the pump is on and running; a system stop LED indicating the status of the pump, wherein when the system stop LED is on, it indicates that the pump has stopped. In addition, the user interface of the control panel may include a silent alarm button, which, when pressed and then immediately released, silences an alarm indicating a dangerous condition of the external fluid system (e.g., a bulk container is full of waste liquid). In addition, when the silent alarm button is pressed and held for a long time (e.g., 5 seconds), the volume of the alarm sound can be adjusted. For example, when the silent alarm button is pressed and held for more than 5 seconds, the volume of the alarm sound increases until the maximum volume is reached. If the silent alarm button is pressed and held for more than 5 seconds after reaching the maximum volume, the alarm sound can be silenced or the volume can be gradually reduced until it is silent. Distinguishable color caps can be used for the buttons of the control panel user interface to distinguish the different functions of these buttons.
[0066] The user interface of the control panel may also include a full LED indicator (e.g., when the bulk container for holding the waste fluid is full, the indicator may be green for an external sheath fluid system, and may turn red and flash for an external waste fluid system). An empty LED may be included (e.g., when the bulk container for holding the sheath fluid is empty, the LED may be green for an external waste fluid system, and may turn red and flash for an external sheath fluid system). A set of level LEDs may also be included to indicate different levels of fluid contained in the bulk container (e.g., 1 / 4 full, 1 / 2 full, or 3 / 4 full).
[0067] In addition, the user interface of the control panel may include one or more hidden buttons that are not marked or otherwise labeled and are intended to be accessible only to authorized personnel for service use. One of the hidden buttons may be an empty calibration button for calibrating an empty bulk container during maintenance. For example, when the empty calibration button is pressed and held for more than 5 seconds, certain parameter values of the empty bulk container will be stored in a storage device such as flash memory of a controller board (e.g., a microcontroller or FPGA controller). Another hidden button may be a full calibration button for calibrating a full bulk container. For example, when the full calibration button is pressed and held for more than 5 seconds, certain parameter values of the full bulk container may be stored in a storage device such as flash memory of a controller board (e.g., a microcontroller or FPGA controller).
[0068] The methods and processes described herein may be embodied as code and / or data. The software codes and data described herein may be stored on one or more machine-readable media (e.g., computer-readable media), which may include any device or medium that can store code and / or data for use by a computer system. When a computer system and / or processor reads and executes the code and / or data stored on a computer-readable medium, the computer system and / or processor executes the methods and processes embodied as data structures and codes stored in the computer-readable storage medium.
[0069] It will be understood by those skilled in the art that computer-readable media include removable and non-removable structures / devices that can be used to store information (such as computer-readable instructions, data structures, program modules, and other data used by computing systems / environments). Computer-readable media include, but are not limited to, volatile memory, such as random access memory (RAM, DRAM, SRAM); non-volatile memory, such as flash memory, various read-only memories (ROM, PROM, EPROM, EEPROM), magnetic and ferromagnetic / ferroelectric memories (MRAM, FeRAM), and magnetic and optical storage devices (hard drives, tapes, CDs, DVDs); network devices; or other media now known or later developed that can store computer-readable information / data. Computer-readable media should not be understood or interpreted as including any propagated signals. The computer-readable medium of the present invention can be, for example, a compact disc (CD), a digital video disc (DVD), a flash memory device, a volatile memory, or a hard disk drive (HDD), such as an external HDD or a HDD of a computing device, but the embodiments are not limited thereto. The computing device can be, for example, a laptop, a desktop computer, a server, a mobile phone, or a tablet computer, but the embodiments are not limited thereto.
[0070] The present invention includes, but is not limited to, the following exemplary embodiments.
[0071] Embodiment 1. A fluid system capable of being connected to a main system, the fluid system comprising:
[0072] a (at least one) container;
[0073] a (at least one) pipe fitting configured to be connected (or coupled) to a host system;
[0074] Second pump;
[0075] Measuring devices; and
[0076] A controller is in operable communication with the second pump and the measuring device.
[0077] Embodiment 2. The fluidic system of embodiment 1, wherein the host system comprises a flow cytometer-based system, and wherein the fluidic system is configured such that, in operation:
[0078] The container contains a first fluid, which is a sheath fluid flowing to the flow cytometer-based system or a waste fluid flowing out of the flow cytometer-based system.
[0079] Embodiment 3. The fluidic system of embodiment 2, wherein the host system comprises a flow cytometer-based system, and wherein the fluidic system is configured such that, during operation:
[0080] The second pump is operated to supply the first fluid from the container to the flow cytometer-based system when the first fluid is a sheath fluid, and to extract the first fluid from the flow cytometer-based system and provide it to the container when the first fluid is a waste fluid.
[0081] Embodiment 4. The fluid system of any one of embodiments 2-3, wherein the fluid system is configured such that, during operation:
[0082] The measuring device measures a property of the first fluid in the container and sends the measurement result to the controller.
[0083] Embodiment 5. The fluid system of embodiment 4, wherein the fluid system is configured such that during operation:
[0084] When receiving the measurement result, the controller determines whether the measurement result is greater than or equal to a predetermined threshold.
[0085] Embodiment 6. A fluid system according to embodiment 5, wherein the fluid system is configured so that during operation: when the controller determines that the measurement result is greater than or equal to a predetermined threshold, if the first fluid is a sheath fluid, the controller adjusts the operating state of the second pump to pause or stop supplying the first fluid from the container to the flow cytometer-based system; if the first fluid is a waste fluid, the controller adjusts the operating state of the second pump to pause or stop extracting the first fluid from the flow cytometer-based system and providing it to the container.
[0086] Embodiment 7. A fluid system according to any one of embodiments 5-6, wherein the system is configured so that in operation: when the controller determines that the measurement result is less than a predetermined threshold, the controller maintains the operating condition of the second pump unchanged.
[0087] Embodiment 8. A fluid system according to any one of embodiments 1-7, wherein the main system includes a flow cytometer-based system having a first pump, and wherein operation of the fluid system by a controller includes: when the container contains waste liquid flowing out of the flow cytometer-based system, setting or adjusting the second pump by the controller to operate at a pump speed higher than the pump speed at which the first pump operates.
[0088] Embodiment 9. A fluid system according to any one of embodiments 1-8, wherein the main system includes a flow cytometer-based system, and wherein the controller is configured to perform operations of the fluid system based on the status of the flow cytometer-based system without any signal communication with the flow cytometer-based system.
[0089] Embodiment 10. A fluid system according to any one of embodiments 1-9, wherein the host system includes a flow cytometer-based system, and wherein the fluid system is configured to be hot-swappable to the flow cytometer-based system during operation.
[0090] Embodiment 11. A method of using a fluid system comprising a (at least one) container, a (at least one) tubing connecting the fluid system to a flow cytometer-based system having a first pump, a measuring device, a second pump, and a controller in operable communication with the second pump and the measuring device,
[0091] wherein the container contains a first fluid, the first fluid being a sheath fluid flowing to a flow cytometer-based system or a waste fluid flowing out of a flow cytometer-based system, and
[0092] Among them, the method includes:
[0093] When the first fluid is a sheath fluid, the fluid system operated by the controller supplies the first fluid from the container to the flow cytometer-based system, and when the first fluid is a waste fluid, the fluid system operated by the controller extracts the first fluid from the flow cytometer-based system and provides it to the container.
[0094] Embodiment 12. The method according to embodiment 11, further comprising:
[0095] measuring a property of a first fluid in the container by a measuring device and transmitting the measurement result to a controller; and
[0096] The controller determines whether the received measurement is greater than or equal to a predetermined threshold.
[0097] Embodiment 13. The method according to embodiment 12 further comprising:
[0098] When the controller determines that the measurement result is greater than or equal to the predetermined threshold, the operation state of the second pump is adjusted by the controller to pause or stop supplying the first fluid from the container to the flow cytometer-based system when the first fluid is a sheath fluid, and to pause or stop extracting the first fluid from the flow cytometer-based system and providing it to the container when the first fluid is a waste fluid.
[0099] Embodiment 14. The method according to any one of embodiments 12-13, further comprising:
[0100] When the controller determines that the measurement result is less than the predetermined threshold, the operating condition of the second pump is maintained unchanged by the controller.
[0101] Embodiment 15. A method according to any one of embodiments 11-14, wherein operating the fluid system includes: when the container contains waste fluid flowing out of the flow cytometer-based system, the controller sets or adjusts the second pump to operate at a pump speed higher than the pump speed of the first pump.
[0102] Embodiment 16. The method of any one of embodiments 11-15, wherein operation of the second pump is performed by the controller without any signal communication with the flow cytometer-based system.
[0103] Embodiment 17. A method according to any one of embodiments 11-16, wherein the fluidic system is configured to be hot-swappable during operation to a flow cytometer-based system.
[0104] Embodiment 18. A system for cell / particle characterization or separation, the system comprising:
[0105] A flow cytometer comprising a first pump; and
[0106] a fluidic system in operable communication with the flow cytometer,
[0107] The fluid system includes:
[0108] a (at least one) container;
[0109] One (at least one) piece of tubing connected to a flow cytometer;
[0110] Second pump;
[0111] Measuring devices; and
[0112] A controller is in operable communication with the second pump and the measurement device, wherein the controller is configured to operate the fluidic system based on a condition of the flow cytometer.
[0113] Embodiment 19. The system of embodiment 18, wherein the fluid system is configured such that, during operation:
[0114] The container contains a first fluid, which is a sheath fluid flowing into the flow cytometer or a waste fluid flowing out of the flow cytometer.
[0115] Embodiment 20. The system of embodiment 19, wherein the fluid system is configured such that, during operation:
[0116] When the first fluid is a sheath fluid, the second pump is operated to supply the first fluid from the container to the flow cytometer, and when the first fluid is a waste fluid, the second pump is operated to extract the first fluid from the flow cytometer and provide it to the container.
[0117] Embodiment 21. The system of any one of embodiments 19-20, wherein the fluid system is configured such that, in operation:
[0118] The measuring device measures a property of the first fluid in the container and sends the measurement result to the controller.
[0119] Embodiment 22. The system of embodiment 21, wherein the fluid system is configured such that, during operation:
[0120] When receiving the measurement result, the controller determines whether the measurement result is greater than or equal to a predetermined threshold.
[0121] Embodiment 23. A system according to embodiment 22, wherein the fluid system is configured so that during operation: when the controller determines that the measurement result is greater than or equal to a predetermined threshold, the controller adjusts the operating conditions of the second pump so that when the first fluid is a sheath fluid, the supply of the first fluid from the container to the flow cytometer is paused or stopped, and when the first fluid is a waste fluid, the extraction of the first fluid from the flow cytometer and its provision to the container is paused or stopped.
[0122] Embodiment 24. A system according to any one of embodiments 22-23, wherein the fluid system is configured so that in operation: when the controller determines that the measurement result is less than a predetermined threshold, the controller maintains the operating condition of the second pump unchanged.
[0123] Embodiment 25. A system according to any one of embodiments 18-24, wherein the operation of the fluid system by the controller based on the condition of the flow cytometer includes: when the container contains waste fluid flowing out of the flow cytometer-based system, the controller sets or adjusts the second pump so that it operates at a pump speed higher than the pump speed at which the first pump operates.
[0124] Embodiment 26. A system according to any one of embodiments 18-25, wherein the controller is configured to perform operations of the fluid system based on signal communication with a flow cytometer-based system.
[0125] Embodiment 27. A method according to any one of embodiments 18-26, wherein the fluid system is configured to be hot-swapped to the flow cytometer system during operation.
[0126] Embodiment 28. A fluid system according to any one of embodiments 1-10, wherein the operation of the fluid system by the controller according to the condition of the flow cytometer-based system includes: when the container contains sheath fluid flowing to the flow cytometer-based system, the controller sets or adjusts the pressure of the fluid system according to the pressure of the flow cytometer-based system.
[0127] Embodiment 29. A method according to any one of embodiments 11-17, wherein operating the fluid system according to the condition of the flow cytometer-based system includes: when the container contains sheath fluid flowing to the flow cytometer-based system, the controller sets or adjusts the pressure of the fluid system according to the pressure of the flow cytometer-based system.
[0128] Embodiment 30. A system according to any one of embodiments 18-27, wherein the operation of the fluid system by the controller according to the condition of the flow cytometer-based system includes: when the container contains sheath fluid flowing to the flow cytometer-based system, the controller sets or adjusts the pressure of the fluid system according to the pressure of the flow cytometer-based system.
[0129] In many embodiments, the external fluid system can include one or more sheath fluid containers, one or more waste fluid containers, or any combination of waste fluid containers and sheath fluid containers.
[0130] In certain embodiments, the external fluid system may include additional control functions, including but not limited to:
[0131] (1) controlling an external waste pump or an external sheath pump based on user input, bulk container level indication, pressure level, and / or indication of erroneous operation (e.g., a sensor not properly installed);
[0132] (2) alerting the user when the bulk waste container is full or the bulk sheath container is empty;
[0133] (3) controlling the alarm by temporarily stopping the alarm or adjusting the volume of the alarm after a period of time or in response to user input;
[0134] (4) using an LED display to display the liquid level information of the bulk container and causing the LED to flash when the bulk waste container is full or the bulk sheath container is empty;
[0135] (5) Calibrate the sensors of the platform / load cell; and / or
[0136] (6) If an incorrect operation occurs, an error code is displayed on the control panel.
[0137] The external fluid system may further include a mass storage device capable of storing and accessing software instructions and / or data to perform certain of the above methods and processes. In an alternative embodiment, the above methods and processes may be performed by hardware implementations, including but not limited to: application specific integrated circuit (ASIC) chips, field programmable gate arrays (FPGAs), and other programmable logic devices now known or later developed.
[0138] When an external fluid system as shown in an embodiment of the present invention is connected to an existing flow cytometer-based system, the total capacity of the waste storage or sheath storage of the existing flow cytometer-based system can be easily expanded to exceed its designed maximum capacity. Moreover, the external fluid system can be hot-plugged into an existing flow cytometer-based system for analyzing a sample or hot-plugged from an existing flow cytometer-based system for analyzing a sample. Because the external fluid system can operate without receiving intentional signals from or sending intentional signals to an existing flow cytometer-based system, the components, structures, connections, control programs, and software programs / data of the existing flow cytometer-based system do not need to be changed or reconfigured. Therefore, the external fluid system can be connected to a running flow cytometer-based system as a hot-plug connection option without interrupting the operation of the flow cytometer-based system. In addition, since the external fluid system is an independent system that can be connected to an existing flow cytometer-based system, minimal maintenance and care is required, making it very suitable for commercial applications.
[0139] As those skilled in the art of flow cytometry will recognize from the foregoing detailed description and from the accompanying drawings and claims, modifications and variations may be made to the embodiments of the present invention without departing from the scope of the invention as defined in the appended claims.
[0140] All patents, patent applications, provisional applications, and publications referenced or cited herein are hereby incorporated by reference in their entirety, including all figures and tables, to the extent they do not contradict the explicit teachings of this specification.
[0141] It should be understood that the examples and embodiments described herein are for illustrative purposes only, and various modifications or changes in view of them will be suggested to those skilled in the art and will be included within the spirit and scope of the present application.
Claims
1. A fluid system that can be connected to a main system, the main system comprising a first pump, the first pump being an internal sheath pump or an internal waste pump, the fluid system comprising: a container configured to hold a liquid; a pipe fitting configured to be connectable to a main system; a dry-disconnect connector connected to the first end of the tubing; a second pump connected to a second end of the tubing opposite the first end; a pressure sensor configured to sense a pressure of the fluid system between the second pump and the container; a measuring device connected to the container and configured to measure a signal indicative of a volume of liquid in the container; and a float sensor coupled to the container and configured to measure a level of liquid in the container; a controller in operable communication with the second pump, the pressure sensor and the measuring device, and the float sensor; and a control panel in operable communication with the second pump and comprising a system on / off button configured to turn the second pump on or off, a system operating indicator light configured to illuminate when the fluid system is operating, a system stopping indicator light configured to illuminate when the fluid system is stopped, a silent alarm button configured to sound an alarm when pressed by a user, a full indicator light configured to illuminate when the container is full, an empty indicator light configured to illuminate when the container is empty, and at least one partially full indicator light configured to illuminate when the container is filled to a level indicated by a corresponding partially full indicator light, wherein the indicator lights are LEDs, The controller is further configured to, when the container contains waste liquid flowing from the main system, stop the second pump if the float sensor indicates that the liquid level in the container is full, wherein the controller is further configured to set a pressure of the fluid system, using the pressure sensor to determine when a desired pressure of the fluid system is reached, and The controller is further configured to stop the second pump if the pressure sensor indicates that the pressure of the fluid system exceeds a predetermined threshold.
2. A fluid system according to claim 1, wherein the main system includes a flow cytometer-based system having the first pump, and wherein when the container contains waste fluid flowing out of the flow cytometer-based system, the controller is configured to cause the second pump to operate at a pump speed that is higher than the pump speed at which the first pump operates.
3. The fluid system of claim 1 , wherein the host system comprises a flow cytometer-based system, and wherein when the container contains sheath fluid flowing to the flow cytometer-based system, the controller is configured to operate the pressure of the fluid system according to the pressure of the flow cytometer-based system.
4. The fluidic system of claim 1 , wherein the host system comprises a flow cytometer-based system, and wherein the fluidic system is configured such that, in operation: The container contains a first fluid, the first fluid being a sheath fluid flowing to the flow cytometer-based system or a waste fluid flowing out of the flow cytometer-based system; when the first fluid is a sheath fluid, the second pump is operated to supply the first fluid from the container to the flow cytometer-based system, and when the first fluid is a waste fluid, the second pump is operated to extract the first fluid from the flow cytometer-based system and supply it to the container; The measuring device measures the property of the first fluid in the container and sends the measurement result to the controller; and When receiving the measurement result, the controller determines whether the measurement result is greater than or equal to a predetermined threshold.
5. The fluid system of claim 4, wherein the fluid system is configured such that, in operation: when the controller determines that the measurement result is greater than or equal to a predetermined threshold, the controller adjusts the operating conditions of the second pump so that when the first fluid is a sheath fluid, the supply of the first fluid from the container to the flow cytometer-based system is paused or stopped, and when the first fluid is a waste fluid, the extraction of the first fluid from the flow cytometer-based system and its supply to the container is paused or stopped.
6. The fluid system of claim 5, wherein the fluid system is configured such that, in operation: when the controller determines that the measurement result is less than a predetermined threshold, the controller maintains the operating condition of the second pump unchanged.
7. The fluidic system of claim 1, wherein the host system comprises a flow cytometer-based system, and wherein the controller is configured to perform operations of the fluidic system without any signal communication with the flow cytometer-based system.
8. The fluid system of claim 1 , wherein the control panel further comprises an unmarked first hidden button and an unmarked second hidden button, wherein the first hidden button is configured to calibrate the container in an empty state, and wherein the second hidden button is configured to calibrate the container in a full state.
9. A method of using a fluid system comprising a container, a tubing connecting the fluid system to a flow cytometer-based system having a first pump, a measuring device, a second pump, a pressure sensor, a dry-break connector, a float sensor, and a controller in operable communication with the second pump, the pressure sensor, the measuring device, and the float sensor, the tubing being connected at a first end thereof to the dry-break connector and at a second end thereof to the second pump, wherein the container contains a first fluid, the first fluid being a sheath fluid flowing to a flow cytometer-based system or a waste fluid flowing out of a flow cytometer-based system, wherein the first fluid is a liquid, wherein the first pump is configured to supply fluid to the flow cytometer-based system when the first fluid is a sheath fluid, and to extract fluid from the flow cytometer-based system when the first fluid is a waste fluid, The fluid system further comprises a control panel in operable communication with the second pump and comprising a system on / off button configured to turn the second pump on or off, a system operating indicator light configured to illuminate when the fluid system is operating, a system stopping indicator light configured to illuminate when the fluid system is stopped, a silent alarm button configured to sound an alarm when pressed by a user, a full indicator light configured to illuminate when the container is full, an empty indicator light configured to illuminate when the container is empty, and at least one partially full indicator light configured to illuminate when the container is filled to a level indicated by a corresponding partially full indicator light, wherein The indicator light is LED, and Wherein, the method comprises: when the first fluid is a sheath fluid, the second pump is operated by the controller to supply the first fluid from the container to the flow cytometer-based system, and when the first fluid is a waste fluid, the second pump is operated by the controller to extract the first fluid from the flow cytometer-based system and provide it to the container; sensing the pressure of the fluid system between the second pump and the container by a pressure sensor; measuring, by a measuring device, a signal indicative of a volume of a first fluid in the container; Measuring the liquid level of the first fluid in the container by a float sensor; Setting the pressure of the fluid system by a controller, using a pressure sensor to determine when a desired pressure of the fluid system is reached; and If the float sensor indicates that the level of the first fluid in the container is full or if the pressure sensor indicates that the pressure of the fluid system exceeds a predetermined threshold, the second pump is stopped by the controller, and the stopping of the second pump causes the system stop indicator light to illuminate.
10. The method according to claim 9, further comprising: measuring a property of a first fluid in the container by a measuring device and transmitting the measurement result to a controller; and The controller determines whether the received measurement is greater than or equal to a predetermined threshold.
11. The method according to claim 10, further comprising: When the controller determines that the measurement result is greater than or equal to the predetermined threshold, the operating condition of the second pump is adjusted by the controller to pause or stop supplying the first fluid from the container to the flow cytometer-based system when the first fluid is a sheath fluid, and to pause or stop extracting the first fluid from the flow cytometer-based system and providing it to the container when the first fluid is a waste fluid.
12. The method according to claim 11, further comprising: When the controller determines that the measurement result is less than the predetermined threshold, the operating condition of the second pump is maintained unchanged by the controller.
13. The method of claim 9, wherein the controller's operation of the second pump comprises: When the container contains waste fluid from the flow cytometer-based system, setting or adjusting, by the controller, the second pump to operate at a higher pump speed than the operating pump speed of the first pump; And wherein the operation of the second pump by the controller includes: when the container contains sheath fluid flowing to the flow cytometer-based system, setting or adjusting the pressure of the fluid system to be higher than the pressure of the flow cytometer-based system by the controller.
14. The method of claim 9, wherein the operation of the fluidic system is performed by the controller without any signal communication with the flow cytometer-based system.
15. The method of claim 9, wherein the control panel further comprises an unlabeled first hidden button and an unlabeled second hidden button, wherein the first hidden button is configured to calibrate the container in an empty state, and wherein the second hidden button is configured to calibrate the container in a full state.
16. A system for cell / particle characterization or separation, the system comprising: A flow cytometer comprising a first pump and a three-way connector, wherein the first pump is an internal waste pump or an internal sheath pump; and a fluidic system in operative communication with the flow cytometer, The fluid system comprises: a container configured to hold a liquid; A tube connected to the flow cytometer via a dry-break connector, the dry-break connector being connected to a first end of the tube, the dry-break connector being further connected to a three-way connector; a second pump connected to a second end of the tubing opposite the first end; a pressure sensor configured to sense a pressure of the fluid system between the second pump and the container; a measuring device connected to the container and configured to measure a signal indicative of a volume of liquid in the container; a float sensor connected to the container and configured to measure a level of liquid in the container; a controller in operable communication with the second pump, the measuring device, and the float sensor, wherein the controller is further configured to operate the fluid system based on a condition of the flow cytometer, wherein the controller is further configured to stop the second pump if the float sensor indicates that the level of liquid in the container is full when the container contains waste liquid from the main system, wherein the controller is further configured to set a pressure of the fluid system using a pressure sensor to determine when a desired pressure of the fluid system is reached, and wherein the controller is further configured to stop the second pump if the pressure sensor indicates that the pressure of the fluid system exceeds a predetermined threshold; and a control panel in operative communication with the second pump and comprising a system on / off button configured to turn the second pump on or off, a system operating indicator light configured to illuminate when the fluid system is operating, a system stopping indicator light configured to illuminate when the fluid system is stopped, a silent alarm button configured to sound an alarm when pressed by a user, a full indicator light configured to illuminate when the container is full, an empty indicator light configured to illuminate when the container is empty, and at least one partially full indicator light configured to illuminate when the container is filled to a level indicated by a corresponding partially full indicator light, wherein the indicator lights are LEDs.
17. The system of claim 16, wherein the fluid system is configured such that, in operation: The container contains a first fluid, which is a sheath fluid flowing into the flow cytometer or a waste fluid flowing out of the flow cytometer; the second pump is operated to supply the first fluid from the container to the flow cytometer when the first fluid is a sheath fluid, and the second pump is operated to extract the first fluid from the flow cytometer and supply it to the container when the first fluid is a waste fluid; The measuring device measures a property of the first fluid in the container and sends the measurement result to the controller; and When receiving the measurement result, the controller determines whether the measurement result is greater than or equal to a predetermined threshold.
18. The system of claim 17, wherein the fluid system is configured such that, in operation: when the controller determines that the measurement result is greater than or equal to a predetermined threshold, the controller adjusts the operating conditions of the second pump so that when the first fluid is a sheath fluid, the supply of the first fluid from the container to the flow cytometer is paused or stopped, and when the first fluid is a waste fluid, the extraction of the first fluid from the flow cytometer and its supply to the container is paused or stopped.
19. The system of claim 16, wherein the control panel further comprises an unlabeled first hidden button and an unlabeled second hidden button, wherein the first hidden button is configured to calibrate the container in an empty state, and wherein the second hidden button is configured to calibrate the container in a full state.
20. The system of claim 16, wherein when the container contains waste fluid flowing from the flow cytometer, the controller is configured to set or adjust the second pump to operate at a pump speed that is higher than the pump speed at which the first pump operates; and wherein when the container contains sheath fluid flowing to a flow cytometer-based system, the controller is configured to set or adjust the pressure of the fluid system to be higher than the pressure of the flow cytometer.
Citation Information
Patent Citations
Fluid flow system of flow cytometry and control method thereof
CN107782657A