Non-contact dispenser and related method

Abstract

Non-contact dispensers and related methods are disclosed. In particular implementations, an apparatus includes a plate receptacle, a reagent reservoir receptacle, and a non-contact dispenser. The non-contact dispenser includes a reagent reservoir receptacle that receives a reagent reservoir containing a reagent, and the non-contact dispenser includes an inlet, an upstream valve, a syringe pump, a downstream valve, and an outlet. The syringe pump has a barrel and a hollow plunger movably disposed within the barrel. A flow path is defined between the inlet and the outlet and passes through the upstream valve, the cartridge, the hollow plunger, and the downstream valve. The cartridge is located in fluid communication between the upstream valve and the downstream valve. The plate receptacle is for receiving a well plate having a well, and the non-contact dispenser is for dispensing the reagent from the reagent reservoir into the well of the plate.

Description

[0001] Related patent applications

[0002] This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63 / 316,715, filed on March 4, 2022, the contents of which are incorporated herein by reference in their entirety and for all purposes. Background Art

[0003] A workflow can be used to prepare a DNA library to allow the sample to be sequenced. A contact dispenser (such as a pipette) is often used in this workflow. Summary of the invention

[0004] By providing a contactless dispenser and related methods, the disadvantages of the prior art can be overcome and the beneficial effects described later in this disclosure can be achieved. Various specific implementations of the device and method are described below, and these devices and methods (including and excluding the additional specific implementations listed below) can overcome these disadvantages and achieve the beneficial effects described herein in any combination (provided that these combinations are not inconsistent).

[0005] In a first specific implementation, a device has a plate receptacle, a reagent reservoir receptacle and a non-contact dispenser. The reagent reservoir receptacle is used to receive a reagent reservoir, which contains a reagent, and the non-contact dispenser includes an inlet, an upstream valve, a syringe pump, a downstream valve and an outlet. The syringe pump has a barrel and a hollow plunger movably disposed in the barrel. A flow path is defined between the inlet and the outlet and passes through the upstream valve, the barrel, the hollow plunger and the downstream valve. The barrel is fluidically connected between the upstream valve and the downstream valve. The plate receptacle is used to receive an orifice plate having a hole, and the non-contact dispenser is used to distribute the reagent from the reagent reservoir to the hole of the plate.

[0006] In a second specific implementation, an apparatus includes an inlet, an upstream valve, a syringe pump, a downstream valve, and an outlet. The syringe pump has a barrel and a hollow plunger movably disposed in the barrel. A flow path is defined between the inlet and the outlet and passes through the upstream valve, the barrel, the hollow plunger, and the downstream valve. The barrel is fluidically connected between the upstream valve and the downstream valve.

[0007] In a third embodiment, a method includes positioning an upstream valve of a touchless dispenser in an open position, positioning a downstream valve of the touchless dispenser in a closed position, and flowing a reagent into an inlet of the touchless dispenser and through the upstream valve and a hollow plunger of a syringe pump.

[0008] In a third implementation, an apparatus includes a touchless dispenser having a syringe pump having a barrel and a hollow plunger movably disposed within the barrel.

[0009] Further according to the aforementioned first specific implementation, second specific implementation, third specific implementation and / or fourth specific implementation, the device and / or method may also include or contain any one or more of the following:

[0010] In a specific implementation, the device includes an actuator for actuating the hollow plunger.

[0011] In another specific implementation, the touch-free dispenser includes a nozzle including the outlet.

[0012] In another specific implementation, the apparatus includes a fluid line coupled to the upstream valve and the hollow plunger.

[0013] In another specific implementation, the hollow plunger includes an upstream facing fitting, and the fluid line is coupled to the upstream facing fitting.

[0014] In another specific implementation, the upstream valve and the downstream valve each include a diaphragm valve having a diaphragm.

[0015] In another specific implementation, each of the diaphragm valves has a valve seat and an inner curved surface, the valve seat and the inner curved surface defining a space therebetween to allow the diaphragm of the corresponding diaphragm valve to move.

[0016] In another specific implementation, the upstream valve has a first opening to allow pressure to be applied to the diaphragm of the upstream valve to actuate the upstream valve, and the downstream valve defines a second opening to allow pressure to be applied to the diaphragm of the downstream valve to actuate the downstream valve.

[0017] In another specific implementation, the apparatus includes a pressure source coupled to an actuation port of the upstream valve and an actuation port of the downstream valve.

[0018] In another specific implementation, the apparatus includes a pressure source for actuating the upstream valve and the downstream valve.

[0019] In another specific implementation, the hollow plunger carries a seal and the barrel has an inner surface that sealingly engages the seal.

[0020] In another specific implementation, the seal includes Teflon.

[0021] In another specific implementation, the hollow plunger carries a pair of spaced-apart seals, and the barrel has an inner surface sealingly engaged with the seals.

[0022] In another specific implementation, the apparatus includes a shaft coupled to the hollow plunger and having an end.

[0023] In another specific implementation, the apparatus includes an actuator connected to the end portion to actuate the hollow plunger.

[0024] In another specific implementation, the shaft has the end defining a groove, and the actuator has a gripper assembly having an arm movable between a closed position and an open position. The arm is received in the groove of the shaft to couple the actuator to the shaft.

[0025] In another specific implementation, the end of the shaft including the groove forms a knob.

[0026] In another implementation, the gripper assembly has a spring positioned between the arms to bias the arms toward the closed position.

[0027] In another specific implementation, the apparatus includes a shaft coupled to the hollow plunger and extending from the barrel.

[0028] In another specific implementation, the shaft defines a side opening. The apparatus includes a fluid line coupled to the upstream valve, passing through the side opening and coupled to the hollow plunger.

[0029] In another specific implementation, the shaft has a side fitting defining a port and a passage. The flow path is defined through the side fitting and the passage. The apparatus also includes a fluid line coupled to the upstream valve and the side fitting.

[0030] In another specific implementation, the hollow plunger is self-sealing.

[0031] In another specific implementation, the hollow plunger has an inner surface that tapers outwardly.

[0032] In another specific implementation, the method includes filling the barrel of the syringe pump with the reagent.

[0033] In another specific implementation, the method includes moving the hollow plunger away from the outlet of the touchless dispenser while filling the barrel of the syringe pump with the reagent.

[0034] In another specific implementation, moving the hollow plunger away from the outlet of the touchless dispenser includes using the force of the agent to move the hollow plunger.

[0035] In another specific implementation, moving the hollow plunger away from the outlet of the touch-free dispenser includes moving the hollow plunger using an actuator.

[0036] In another specific implementation, the method includes positioning the upstream valve in a closed position, positioning the downstream valve in an open position, and moving the hollow plunger toward an outlet of the touchless dispenser to dispense the agent from the outlet.

[0037] In another specific implementation, the method includes positioning the upstream valve in an open position and dispensing the agent from an outlet of the touchless dispenser.

[0038] In another specific implementation, the method includes flowing a wash buffer through the contactless dispenser.

[0039] In another specific implementation, the method includes flowing a second reagent through the touchless dispenser.

[0040] In another specific implementation, flowing the second agent through the non-contact dispenser includes opening the downstream valve, opening the upstream valve, and dispensing the second agent from an outlet of the non-contact dispenser.

[0041] In another specific implementation, flowing the second reagent through the touchless dispenser includes placing the downstream valve and the upstream valve in an open position.

[0042] In another specific implementation, flowing the second agent through the touchless dispenser includes positioning the upstream valve in an open position, positioning the downstream valve in an open position, and moving the hollow plunger toward an outlet of the touchless dispenser to dispense the second agent from the outlet.

[0043] In another specific implementation, allowing the second reagent to flow through the non-contact dispenser includes: positioning the upstream valve of the non-contact dispenser in the open position, positioning the downstream valve of the non-contact dispenser in the closed position, and allowing the second reagent to flow into the inlet of the non-contact dispenser and through the upstream valve and the hollow plunger of the syringe pump.

[0044] In another specific implementation, the method includes positioning the upstream valve of the non-contact dispenser in the open position, positioning the downstream valve of the non-contact dispenser in the closed position, and flowing a second reagent into the inlet of the non-contact dispenser and through the upstream valve and the hollow plunger of the syringe pump.

[0045] It should be understood that all combinations of the foregoing concepts and the additional concepts discussed in more detail below (provided that these concepts are not mutually inconsistent) are contemplated as being part of the subject matter disclosed herein and / or can be combined to achieve the specific benefits of the specific aspects described herein. In particular, all combinations of the claimed subject matter appearing at the end of this disclosure are contemplated as being part of the subject matter disclosed herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 A schematic diagram of a specific implementation of a system according to the teachings of the present disclosure is shown.

[0047] Figure 2 It can be used to implement Figure 1 A schematic cross-sectional view of a specific implementation of a touchless dispenser of a touchless dispenser.

[0048] Figure 3 It can be used to implement Figure 1 A contactless dispenser and a contactless dispenser that can be used to implement Figure 1 A side view of a specific implementation of an actuator of an actuator.

[0049] Figure 4 yes Figure 3 A partial cross-sectional view of a touchless dispenser with the knob removed from the shaft.

[0050] Figure 5 yes Figure 3 Detailed view of a touch-free dispenser showing the outwardly tapered interior surface of the hollow plunger and the coupling between the fluid line and the upward facing fitting of the hollow plunger.

[0051] Figure 6 It can be used to implement Figure 1 A partial cross-sectional view of another contactless dispenser of a contactless dispenser.

[0052] Figure 7 A flow chart describing a process of using a touchless dispenser or any of the other implementations disclosed herein is shown. DETAILED DESCRIPTION

[0053] Although the following text discloses a detailed description of a specific implementation of the method, apparatus and / or article of manufacture, it should be understood that the legal scope of the property rights is defined by the text of the claims set forth at the end of this patent. Therefore, the following detailed description should be understood to be merely exemplary and does not describe every possible specific implementation, because it is impractical, if not impossible, to describe every possible specific implementation. Many alternative specific implementations can be implemented using current technology or technology developed after the filing date of this patent. It is contemplated that such alternative specific implementations will still fall within the scope of the claims.

[0054] At least one aspect of the present disclosure relates to a system that automates a library preparation process, a sample preparation process, or other similar processes and uses fewer consumables, thereby reducing the footprint of the system and the amount of solid waste generated. The disclosed system uses a non-contact dispenser that has an in-line and relatively straight fluid path that reduces the presence of corners, allows the non-contact dispenser to be easily rinsed, and reduces manufacturing complexity. The non-contact dispenser can be switched between dispensing different reagents, so that the same non-contact dispenser is used, and those reagents do not interact adversely with each other. Using the disclosed specific implementation will also reduce the dead volume of reagents.

[0055] Some disclosed non-contact dispensers have an inlet, an upstream valve, a syringe pump, a downstream valve, and an outlet. The syringe pump includes a barrel and a hollow plunger movably disposed within the barrel. A flow path is defined between the inlet and the outlet and passes through the upstream valve, the barrel, the hollow plunger, and the downstream valve. Passing the flow path through the hollow plunger allows the flow path to be relatively straight and easy to flush the non-contact dispenser.

[0056] By positioning the upstream valve in the open position, positioning the downstream valve in the closed position, and allowing the reagent to flow into the inlet of the non-contact dispenser and flowing through the hollow plunger of the upstream valve and syringe pump, the non-contact dispenser can be used to distribute a small volume of reagent with high accuracy. When the hollow plunger moves away from the outlet of the non-contact dispenser, the barrel of the syringe pump is filled with reagent. In some specific implementations, the reagent is distributed from the non-contact dispenser in the following manner: the upstream valve is positioned in the closed position, the downstream valve is positioned in the open position, and the hollow plunger is moved toward the outlet of the non-contact dispenser. By positioning both the upstream valve and the downstream valve in the open position, the non-contact dispenser can be used to distribute a larger volume of reagent with high accuracy. Before switching between reagents, the non-contact dispenser can be rinsed with washing buffer.

[0057] Figure 1The schematic diagram of the specific implementation of the system 100 according to the teaching content of the present disclosure is shown.For example, the system 100 can be used for automatically, easily and efficiently preparing the DNA library for sequencing application.In some specific implementations, the system 100 can perform a DNA library preparation workflow, which includes an amplification process, a cleaning process, a library standardization process and / or a merging process.The system 100 can perform a workflow, such as a whole genome sequencing (WGS) workflow, a DNA and RNA enrichment workflow, a methylation workflow, a separation pool amplicon workflow and / or an amplicon workflow, etc. The DNA library preparation workflow can be performed on any number of samples, such as between a sample and twenty-four samples, forty-eight samples, ninety-six samples or more samples.The system 100 therefore allows variable batch processing.However, other uses of the system 100 can prove to be suitable.In the specific implementation shown, the system 100 includes a working area 102 and a reagent reservoir receptacle 104 for receiving a reagent reservoir 106, which accommodates a reagent 108.The reagent reservoir receptacle 104 can be alternatively positioned above the working area 102.

[0058] The work area 102 includes a plate receptacle 110 that receives a plate 114 having holes 116 and a non-contact dispenser 118 that dispenses reagents 108 from the reagent reservoir 103 into the holes 116 of the plate 114. The plate 114 may have any number of holes 116, such as twenty-four holes. However, another number of holes 116 is suitable.

[0059] The non-contact dispenser 118 is fluidly coupled to the reagent reservoir 106. The non-contact dispenser 118 may alternatively use, for example, a tip to aspirate the reagent 108 from the reagent reservoir 106 and dispense the reagent 108 into the wells 116 of the plate 114. In such an implementation, the non-contact dispenser 118 may not be fluidly coupled to the reagent reservoir 106.

[0060] The non-contact dispenser 118 has an inlet 120, an upstream valve 122, a syringe pump 124, a downstream valve 126 and an outlet 128. The syringe pump 124 includes a barrel 130 and a hollow plunger 132 movably disposed in the barrel 130. A flow path 133 is defined between the inlet 120 and the outlet 128 and passes through the upstream valve 122, the barrel 130, the hollow plunger 132 and the downstream valve 126. The flow path 133 shown is in-line and relatively straight, and therefore has limited or no corners and / or areas that inhibit flushing. Therefore, the non-contact dispenser 118 can be easily flushed and / or cleaned. The barrel 130 is positioned between the upstream valve 122 and the downstream valve 126 in fluid communication. The system 100 also includes an actuator 134 that actuates the hollow plunger 132. The actuator 134 can be a voice coil. However, other types of actuators 134 are suitable.

[0061] The non-contact dispenser 118 can be used to dispense smaller volumes of reagents 108 and larger volumes of reagents 108. The wash buffer 136 can flush the non-contact dispenser 118 to allow the non-contact dispenser 118 to dispense different reagents 108.

[0062] By positioning the upstream valve 122 in an open position to fill the non-contact dispenser 118 with the first reagent 135 when the downstream valve 126 is in a closed position, the non-contact dispenser 118 can dispense a smaller volume of the first reagent 135. The first reagent 135 flows into the inlet 120 and flows through the upstream valve 122 and the hollow plunger 132, and the reagent 108 fills the cartridge 130. While the cartridge 130 is filled with the reagent 108, the hollow plunger 132 is moved away from the outlet 128. The first reagent 135 can exert a force acting on the hollow plunger 132 that moves the hollow plunger 132 away from the outlet 128 of the non-contact dispenser 118. The hollow plunger 132 can be moved away from the outlet 128 using the actuator 134 in addition or alternatively.

[0063] When dispensing a smaller volume of reagent 108, the upstream valve 122 is in a closed position; the downstream valve 126 is in an open position, and the hollow plunger 132 moves toward the outlet 128 of the non-contact dispenser 118. The non-contact dispenser 118 can dispense a larger volume of the first reagent 135 by positioning both the upstream valve 122 and the downstream valve 126 in an open position and allowing the first reagent 135 to flow into the inlet 120 and through the upstream valve 122, the hollow plunger 132, and out of the outlet 128. When the non-contact dispenser 118 dispenses a larger volume, the hollow plunger 132 can be in a lowered position. However, the hollow plunger 132 can be in other positions.

[0064] The non-contact dispenser 118 can flow a wash buffer 136 through the non-contact dispenser to flush the first reagent 135 out of the non-contact dispenser 118, thereby allowing the non-contact dispenser 118 to dispense a second reagent 137 through the non-contact dispenser 118. Thus, the non-contact dispenser 118 can dispense any number of reagents for any library preparation workflow, and can perform flushing / cleaning before switching between reagents. The non-contact dispenser 118 can also be used to dispense fluids for other reasons, including reasons not associated with a library preparation workflow.

[0065] The work area 102 also includes an imaging system 138, which can be used to determine the volume of the reagent 108 dispensed from the non-contact dispenser 118. In the specific implementation shown, the imaging system 138 includes a light source assembly 139 and an imaging device 140. The light source assembly 139 generates an illumination beam 142 in operation, which is directed toward the imaging device 140 and passes through a dispensing path 144 of the non-contact dispenser 118. Therefore, the light beam 142 may encounter the dispensed reagent 108 and / or be affected by the reagent. The imaging device 140 obtains image data associated with the dispensed reagent 118, and the system 100 uses the image data to determine and / or verify the volume of the dispensed reagent 108. Alternatively, the imaging system 138 can be omitted.

[0066] The working area includes a platform 146 for moving the non-contact dispenser 118 relative to the plate receptacle 110 and a light bar 148 that can be used to degrade the oligonucleotides. The platform 146 can be an XY platform or an XYZ platform. In some specific implementations, the light bar 148 can be a high-power ultraviolet (UV) light bar that is used periodically throughout the workflow to repeatedly degrade the oligonucleotides to prevent cross contamination.

[0067] System 100 also includes drive assembly 150, extractor manifold assembly 152 and controller 154.Extractor manifold assembly 152 can be connected to the reagent reservoir 106 of corresponding quantity via reagent extractor 156.Reagent reservoir 106 can hold fluid (for example, reagent and / or another kind of reaction component, such as reagent 135,138 or washing buffer solution 136).In some specific implementations, extractor manifold assembly 152 includes a plurality of ports, wherein each port of extractor manifold assembly 152 can receive a reagent extractor in reagent extractor 156.Reagent extractor 156 can be referred to as fluid line.Extractor manifold assembly 152 also includes valve 158, and this valve can be selectively actuated, to control the fluid flow through fluid line 160. The pipette manifold assembly 152 also includes a pump 162 to selectively flow the reagent 108 from the reagent reservoir 106 , through the reagent pipette 156 , through the fluid line 160 , and out of the touchless dispenser 118 .

[0068] Valve 158 can be implemented by a rotary valve, a selection valve, a pinch valve, a flat valve, a solenoid valve, a check valve, a piezoelectric valve, etc. Other fluid control devices may prove suitable. Pump 162 can be implemented by a syringe pump, a peristaltic pump and / or a diaphragm pump. However, other types of fluid transfer devices can be used. Controller 54 is electrically and / or communicatively connected to non-contact dispenser 118, actuator 134, imaging system 138, light bar 148, drive assembly 150 and aspirator manifold assembly 152 to perform the various functions disclosed herein. Alternatively, aspirator manifold assembly 152 can be omitted or modified. For example, positive pressure can be used to push reagent 108 out of reagent reservoir 106, and pump 187 can be omitted (see Figure 6 ).

[0069] The drive assembly 150 includes a pump drive assembly 164 and a valve drive assembly 166. The pump drive assembly 164 may be adapted to connect with the pump 162 to pump fluid from the reagent reservoir 106 to the non-contact dispenser 118. The valve drive assembly 166 may be adapted to connect with the valves 122, 126, 158 to control the positions of the valves 122, 126, 158.

[0070] The controller 154 includes a user interface 168, a communication interface 170, one or more processors 172, and a memory 174 that stores instructions executable by the one or more processors 172 to perform various functions including the disclosed implementation. The user interface 168, the communication interface 170, and the memory 174 are electrically and / or communicatively coupled to the one or more processors 172.

[0071] In a specific implementation, the user interface 168 receives input from a user and provides the user with information associated with the operation of the system 100 and / or the analysis performed. The user interface 168 may include a touch screen, a display, a keyboard, a speaker, a mouse, a trackball, and / or a voice recognition system. The touch screen and / or the display may display a graphical user interface (GUI).

[0072] In a specific implementation, the communication interface 170 uses a network to implement communication between the system 100 and a remote system (e.g., a computer). The network may include an intranet, a local area network (LAN), a wide area network (WAN), the Internet, etc. Some of the communications provided to the remote system may be associated with a distribution process, an amplification process, a cleaning process, a library normalization process, and / or a merging process, etc. generated or otherwise obtained by the system 100. Some of the communications provided to the system 100 may be associated with a distribution process, an amplification process, a cleaning process, a library normalization process, and / or a merging process to be performed by the system 100.

[0073] The one or more processors 172 and / or the system 100 may include one or more of a processor-based system or a microprocessor-based system. In some implementations, the one or more processors 172 and / or the system 100 include a reduced instruction set computer (RISC), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a field programmable logic device (FPLD), a logic circuit, and / or another logic-based device that performs various functions including those described herein.

[0074] The memory 174 may include one or more of a hard drive, flash memory, read-only memory (ROM), erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), random access memory (RAM), nonvolatile RAM (NVRAM) memory, a compact disk (CD), a digital versatile disk (DVD), a cache, and / or any other storage device or storage disk in which information is stored for any duration (e.g., permanently, temporarily, for an extended period of time, for buffering, for caching).

[0075] Figure 2 It can be used to implement Figure 1 FIG. 1 is a schematic cross-sectional view of a specific implementation of the touchless dispenser 200 of the touchless dispenser 118 . Figure 2 The touch-free dispenser 200 includes an inlet 120 , an upstream valve 122 , a syringe pump 124 including a barrel 130 and a hollow plunger 132 , a downstream valve 126 , and an outlet 128 . Figure 2 The touch-free dispenser 200 also has a nozzle 202 including an outlet 128 and a fluid line 204 coupled to the upstream valve 122 and the hollow plunger 132. The fluid line 204 may be a flexible tube.

[0076] The upstream valve 122 and the downstream valve 126 may each be a diaphragm valve 206 having a diaphragm 208. The upstream valve 122 has a valve seat 210, and the downstream valve 126 has a valve seat 212. The upstream valve 122 also has a first inner curved surface 214 that defines a first space 216 between the valve seat 210 of the upstream valve 122 and the first inner curved surface 214 to allow the diaphragm 208 of the upstream valve 122 to be moved in a closed position. Figure 2 The downstream valve 126 similarly has a second inner curved surface 218 that defines a second space 220 between the valve seat 212 of the downstream valve 126 and the second inner curved surface 218 to allow the diaphragm 208 of the downstream valve 126 to move between the open position and the closed position shown in FIG. Figure 2 and a closed position as shown in FIG.

[0077] The upstream valve 122 defines a first opening 222 to allow pressure to be applied to the diaphragm 208 of the upstream valve 122, thereby actuating the upstream valve 122, and the downstream valve 126 defines a second opening 224 to allow pressure to be applied to the downstream valve 126, thereby actuating the downstream valve 126. A pressure source 226 is also included, which is fluidically connected to the upstream valve 122 and the downstream valve 126. The pressure source 226 can be connected to the actuation port 227 of the upstream valve 122 and the actuation port 227 of the downstream valve 126. The pressure source 226 can be used to implement the valve drive assembly 166, and can actuate the upstream valve 122 and the downstream valve 126. The regulator 228 is positioned between the pressure source 226 and the valves 122, 126, and regulates the pressure of the gas provided to the valves 122, 126. The gas can be air, nitrogen and / or argon. Other gases may prove suitable. However, the valves 122 , 126 may be actuated in a different manner, such as using solenoids.

[0078] The hollow plunger 132 is shown carrying a seal 230, and the barrel 130 has an inner surface 232 that sealingly engages the seal 230. The seal 230 interacts with the inner surface 232 to inhibit or prevent a fluid, such as the reagent 108, from flowing between the seal 230 and the inner surface 232 of the barrel 130. The seal 230 may include Teflon. TM However, the seal 230 may include additional or alternative materials. The hollow plunger 132 may include a pair of spaced apart seals 230 that sealingly engage an inner surface 232 of the barrel 130. However, any number of seals 230 may be included.

[0079] Figure 3 It can be used to implement Figure 1 The non-contact dispenser 118 of the non-contact dispenser 300 and the non-contact dispenser 300 can be used to implement Figure 1 1 is a side view of a specific implementation of actuator 301 of actuator 134 . Figure 2The non-contact dispenser 200 includes an inlet 120, an upstream valve 122, a syringe pump 124 including a barrel 130 and a hollow plunger 132, a downstream valve 126, and an outlet 128. The non-contact dispenser 200 has a shaft 302, which is coupled to the hollow plunger 130 and has an end 304. Therefore, the shaft 302 moves with the hollow plunger 130. The actuator 301 is connected to the end 304 of the shaft 302 to actuate the hollow plunger 130. The actuator 301 can move the end 304 toward the outlet 128 to dispense the reagent 108 from the non-contact dispenser 300, and when the syringe pump 124 is filled with the reagent 108, the reagent 108 itself can move the hollow plunger 130 away from the outlet 128. Therefore, the actuator 301 can be used to dispense the reagent 108, and can not be used when the reagent 108 is sucked into the syringe pump 124. Alternatively, the actuator 301 may be used to simultaneously dispense the reagent 108 and draw the reagent 108 into the syringe pump 124 .

[0080] The end 304 of the shaft 302 defines a groove 306 and forms a knob 308, and the actuator 301 has a catcher assembly 310 having arms 312, 314 that can move between a closed position and an open position. The knob 308 can be removably coupled to the shaft 302. The arms 312, 314 have an inwardly facing catcher 316 that is received in the groove 306 of the shaft 302 to couple the actuator 301 to the shaft 302. The arms 312, 314 can move relative to a pivot 317. The catcher assembly 310 has a spring 318 positioned between the arms 312, 314 to bias the arms 312, 314 toward the closed position.

[0081] The actuator 301 is positioned within a housing 319 having a distal end 320 and is movable between a first position and a second position as shown in a direction generally indicated by arrow 321. The distal end 320 of the housing 319 engages the arms 312, 314 of the grabber assembly 310 in the first position, compressing the spring 318 and moving the arms 312, 314 to the open position. In the open position, the grabber assembly 310 can be positioned around the knob 308. The actuator 301 can extend from the distal end 320 of the housing 319 in the second position so that the arms 312, 314 of the grabber assembly 310 are spaced apart from the housing 319 and the spring 318 biases the arms 312, 314 into the closed position. The grabber assembly 310 can grab the knob 308 in the closed position.

[0082] Figure 4 yes Figure 3308 is a partial cross-sectional view of a touchless dispenser 300 with the knob 308 removed from the shaft 302. The hollow plunger 132 of the touchless dispenser 300 has an upward-facing fitting 320, and the fluid line 204 is coupled to the upstream valve 122 and the upward-facing fitting 320 of the hollow plunger 132. The shaft 302 defines a side opening 322, and the fluid line 204 is shown passing through the side opening 322 and coupled to the hollow plunger 132. The shaft 302 is shown as a separate component positioned around the hollow plunger 132. The shaft 302 can be coupled to the hollow plunger 132 by interference fittings, fasteners, and / or adhesives. Alternatively, the shaft 302 and the hollow plunger 132 can be formed from a single component.

[0083] In the illustrated embodiment, the hollow plunger 132 is self-sealing. To this end, the hollow plunger 132 has an outwardly tapered inner surface 324. The outwardly tapered inner surface 324 tapers away from the longitudinal axis 326 of the hollow plunger 132 and allows the reagent 108 contained in the syringe pump 124 to exert a radial force on the outwardly tapered inner surface 324, which urges the hollow plunger 132 against the inner surface 232 of the barrel 130. In this manner, the hollow plunger 132 interacts with the inner surface 232 to form a leak seal and / or a lip seal.

[0084] Figure 5 yes Figure 3 Detailed view of the touchless dispenser 300 of FIG. 1 showing the outwardly tapered interior surface 324 of the hollow plunger 132 and the coupling between the fluid line 204 and the upward facing fitting 320 of the hollow plunger 132. The shaft 302 is shown as a portion 328 surrounding and coupled to the hollow plunger 132. The portion 328 may include the upward facing fitting 320.

[0085] Figure 6 It can be used to implement Figure 1 A partial cross-sectional view of the touch-free dispenser 118 of the touch-free dispenser 400 . Figure 6 The contactless dispenser 400 is similar to Figure 3 The contactless dispenser 300. In contrast, Figure 6 The non-contact dispenser 400 includes a shaft 402 having a side fitting 404 defining a port 406 and a passage 408 fluidly coupled to the flow path 133. The fluid line 204 is coupled to the upstream valve 122 and the side fitting 404. When the cartridge 130 has a smaller diameter and the non-contact dispenser 400 is used to dispense smaller volumes, the fluid line 204 may be coupled to the side fitting 404 rather than directly to the hollow plunger 132.

[0086] The pressure source 226 is shown coupled to the reagent reservoir 106 and is used to pressurize one or more wells of the reagent reservoir 106 and / or the reagents 135, 137 and / or wash buffer 136 contained therein. The fluids 135, 136, 137 may be pushed toward the valve 158 and the non-contact dispenser 400 under pressure from the pressure source 226. The valve 158 may be used to select which fluid 135, 136, 137 flows into the non-contact dispenser 400. The regulator 228 is positioned between the pressure source 226 and the reagent reservoir 106 and regulates the gas pressure provided to the reagent reservoir 106.

[0087] Figure 7 A flowchart describing a process of using the contactless dispenser 118, 200, 300, 400, or any of the other implementations disclosed herein is shown. The order of execution of the blocks may be changed, and / or some of the blocks described may be changed, eliminated, combined, and / or subdivided into multiple blocks.

[0088] Figure 7 The process of the present invention begins by positioning the upstream valve 122 of the non-contact dispenser 118, 200, 300, 400 in an open position (frame 702) and positioning the downstream valve 126 of the non-contact dispenser 118, 200, 300, 400 in a closed position (frame 704). The reagent 108 is caused to flow into the inlet 120 of the non-contact dispenser 118, 200, 300, 400 and flow through the upstream valve 122 and the hollow plunger 132 of the syringe pump 124 (frame 706). The reagent 108 may be a first reagent 135 and / or a second reagent 137. The reagent 108 is caused to flow into the inlet 120 of the non-contact dispenser 118, 200, 300, 400 and flow through the upstream valve 122 and the hollow plunger 132 of the syringe pump 124 includes filling the barrel 130 of the syringe pump 124 with the reagent 108. While the barrel 130 of the syringe pump 124 is filled with the reagent 108, the hollow plunger 132 is moved away from the outlet 128 of the non-contact dispenser 118, 200, 300, 400 (block 710). The force of the reagent 108 may be used to move the hollow plunger 132 away from the outlet 128 of the non-contact dispenser 118, 200, 300, 400, and / or the actuator 134 may be used to move the hollow plunger 132 away from the outlet 128 of the non-contact dispenser 118, 200, 300, 400.

[0089] The upstream valve 122 of the non-contact dispenser 118, 200, 300, 400 is positioned in a closed position (block 712), and the downstream valve 126 of the non-contact dispenser 118, 200, 300, 400 is positioned in an open position (block 714). The hollow plunger 132 is moved toward the outlet 128 of the non-contact dispenser 118, 200, 300, 400 to dispense the reagent 108 from the outlet 128 (block 716). When dispensing a smaller volume of the reagent 108, the hollow plunger 132 may be moved relative to the outlet 128 of the non-contact dispenser 118, 200, 300, 400.

[0090] The upstream valve 122 of the non-contact dispenser 118, 200, 300, 400 is positioned in an open position (frame 718), and the downstream valve 126 of the non-contact dispenser 118, 200, 300, 400 is positioned in an open position (frame 720). The reagent 108 is dispensed from the outlet 128 of the non-contact dispenser 118, 200, 300, 400 (frame 722). When dispensing a larger volume of reagent 108, both the upstream valve 122 and the downstream valve 126 can be positioned in an open position, and the hollow plunger 132 can be maintained in a fixed position or a relatively fixed position, and therefore, when dispensing a larger volume of reagent 108, the hollow plunger may not move. Alternatively, the hollow plunger 132 may move when dispensing a larger volume of reagent 108. The wash buffer 136 is flowed through the non-contact dispenser 118, 200, 300, 400 (frame 724). The process determines whether to dispense another reagent 108 (block 726). Another reagent 108 may be a first reagent 135, a second reagent 137, etc. The second reagent 137 may flow through the contactless dispenser 112 by opening the downstream valve 126, opening the upstream valve 122, and dispensing the second reagent 137 from the outlet 128 of the contactless dispenser 118. Therefore, by having the downstream valve 126 and the upstream valve 122 in the open position, the second reagent 137 may flow through the contactless dispenser 118.

[0091] The above description is provided to enable those skilled in the art to practice the various configurations described herein. Although the subject technology has been described in detail with reference to various drawings and configurations, it should be understood that these drawings and configurations are only for illustrative purposes and should not be considered to limit the scope of the subject technology.

[0092] As used herein, an element or step recited in the singular and preceded by the word "one" or "a kind of" should be understood not to exclude a plurality of said elements or steps, unless such exclusion is expressly indicated. In addition, reference to "a specific implementation" is not intended to be interpreted as excluding the existence of additional specific implementations that also include the described features. In addition, unless expressly stated to the contrary, a specific implementation that "includes" or "has" one or more elements having a particular property may include additional elements, whether or not they have that property. In addition, the terms "includes," "has," etc. are used interchangeably herein.

[0093] The terms "substantially", "approximately" and "about" used throughout this specification are used to describe and illustrate small fluctuations, such as small fluctuations caused by changes in processing. For example, they can refer to less than or equal to ±5%, such as less than or equal to ±2%, such as less than or equal to ±1%, such as less than or equal to ±0.5%, such as less than or equal to ±0.2%, such as less than or equal to ±0.1%, such as less than or equal to ±0.05%. In one example, these terms include the absence of a variation of -0%.

[0094] There may be many other ways to realize the subject technology. Without departing from the scope of the subject technology, the various functions and elements described herein may be divided differently from those shown and elements. Various modifications to these specific implementations may be apparent to those skilled in the art, and the general principles defined herein may be applied to other specific implementations. Therefore, without departing from the scope of the subject technology, those of ordinary skill in the art may make many changes and modifications to the subject technology. For example, different numbers of given modules or units may be adopted, one or more different types of given modules or units may be adopted, given modules or units may be added or given modules or units may be omitted.

[0095] Underlined and / or italicized headings and subheadings are used for convenience only, do not limit the subject technology, and are not referenced in conjunction with the explanation of the description of the subject technology. All structural and functional equivalents of the elements of each specific implementation described throughout the present disclosure that are known or will later be known to those of ordinary skill in the art are expressly incorporated herein by reference and are intended to be covered by the subject technology. In addition, nothing disclosed herein is intended to be dedicated to the public, regardless of whether such disclosure is explicitly recited in the above description.

[0096] It should be understood that all combinations of the foregoing concepts and the additional concepts discussed in more detail below (assuming such concepts are not mutually inconsistent) are contemplated as being part of the subject matter disclosed herein. In particular, all combinations of the claimed subject matter appearing at the end of this disclosure are contemplated as being part of the subject matter disclosed herein.

Claims

1. A device, comprising: Board receptacle; a reagent reservoir receptacle, the reagent reservoir receptacle being used to receive a reagent reservoir, the reagent reservoir containing a reagent; A contactless dispenser, comprising: Entrance; Upstream valve; a syringe pump having a barrel and a hollow plunger movably disposed within the barrel; Downstream valve; and exit; wherein a flow path is defined between the inlet and the outlet and passes through the upstream valve, the cartridge, the hollow plunger, and the downstream valve, the cartridge being fluidly disposed between the upstream valve and the downstream valve, The plate receptacle is used to receive a well plate having wells, and the non-contact dispenser is used to dispense the reagent from the reagent reservoir into the wells of the plate.

2. The apparatus of claim 1 further comprising an actuator for actuating the hollow plunger.

3. Apparatus according to any one of the preceding claims, wherein the contactless dispenser comprises a nozzle comprising the outlet.

4. The apparatus of any one of the preceding claims, further comprising a fluid line coupled to the upstream valve and the hollow plunger.

5. The apparatus of claim 4, wherein the hollow plunger includes an upstream facing fitting, and the fluid line is coupled to the upstream facing fitting.

6. Apparatus according to any one of the preceding claims, wherein the upstream valve and the downstream valve each comprise a diaphragm valve having a diaphragm.

7. The apparatus of claim 6, wherein each of the diaphragm valves has a valve seat and an inner curved surface defining a space therebetween to allow the diaphragm of the corresponding diaphragm valve to move.

8. An apparatus according to any one of the preceding claims, wherein the upstream valve includes a first opening to allow pressure to be applied to the diaphragm of the upstream valve, thereby actuating the upstream valve, and the downstream valve defines a second opening to allow pressure to be applied to the diaphragm of the downstream valve, thereby actuating the downstream valve.

9. The apparatus of claim 8, further comprising a pressure source coupled to the actuation port of the upstream valve and the actuation port of the downstream valve.

10. Apparatus according to any preceding claim, wherein the hollow plunger carries a seal and the barrel comprises an inner surface sealingly engaging the seal.

11. The apparatus of claim 10, wherein the seal comprises Teflon.

12. Apparatus according to any preceding claim, wherein the hollow plunger carries a pair of spaced apart seals and the barrel comprises an inner surface sealingly engaged with the seals.

13. The apparatus of any preceding claim, further comprising a shaft coupled to the hollow plunger and having an end.

14. The apparatus of claim 13, further comprising an actuator connected to the end portion to actuate the hollow plunger.

15. The apparatus of claim 14 wherein the shaft has the end defining a groove and the actuator has a grabber assembly having an arm movable between a closed position and an open position, the arm being received within the groove of the shaft to couple the actuator to the shaft.

16. The apparatus of claim 15, wherein the end of the shaft including the groove forms a knob.

17. Apparatus according to any one of claims 15 to 16, wherein the gripper assembly comprises a spring positioned between the arms to bias the arms towards the closed position.

18. A device, comprising: Entrance; Upstream valve; a syringe pump having a barrel and a hollow plunger movably disposed within the barrel; Downstream valve; and exit; A flow path is defined between the inlet and the outlet and passes through the upstream valve, the cartridge, the hollow plunger, and the downstream valve, the cartridge being located in fluid communication between the upstream valve and the downstream valve.

19. The apparatus of claim 18, further comprising a shaft coupled to the hollow plunger and extending from the barrel.

20. The apparatus of claim 19, wherein the shaft defines a side opening, the apparatus further comprising a fluid line coupled to the upstream valve, passing through the side opening and coupled to the hollow plunger.

21. The apparatus of claim 19, wherein the shaft includes a side fitting defining a port and a passage, the flow path being defined through the side fitting and the passage, the apparatus further comprising a fluid line coupled to the upstream valve and the side fitting.

22. Apparatus according to any one of claims 18 to 21 wherein the hollow plunger is self-sealing.

23. An apparatus according to any one of claims 18 to 22, wherein the hollow plunger comprises an outwardly tapering inner surface.

24. A method comprising: positioning an upstream valve of the touchless dispenser in an open position; positioning a downstream valve of the touchless dispenser in a closed position; as well as Reagent is caused to flow into the inlet of the touchless dispenser and through the upstream valve and the hollow plunger of the syringe pump.

25. The method of claim 24, wherein flowing the reagent into the inlet of the touchless dispenser and through the upstream valve and the hollow plunger of the syringe pump comprises filling a barrel of the syringe pump with the reagent.

26. The method of any one of claims 24 to 25, further comprising moving the hollow plunger away from an outlet of the touchless dispenser while filling the barrel of the syringe pump with the reagent.

27. The method of claim 26, wherein moving the hollow plunger away from the outlet of the touch-free dispenser comprises using a force exerted by the reagent to move the hollow plunger.

28. The method of claim 26, wherein moving the hollow plunger away from the outlet of the touch-free dispenser comprises moving the hollow plunger using an actuator.

29. The method according to any one of claims 24 to 28, further comprising: The upstream valve is positioned in a closed position, the downstream valve is positioned in an open position, and the hollow plunger is moved toward an outlet of the touchless dispenser to dispense the reagent from the outlet.

30. The method of any one of claims 24 to 29, further comprising positioning the upstream valve in an open position and dispensing the reagent from an outlet of the touch-free dispenser.

31. The method of any one of claims 24 to 30, further comprising flowing a wash buffer through the contactless dispenser.

32. The method of claim 31 further comprising flowing a second reagent through the touch-free dispenser.

33. The method of claim 32, wherein flowing the second reagent through the touchless dispenser comprises: The downstream valve is opened, the upstream valve is opened, and the second reagent is dispensed from the outlet of the non-contact dispenser.

34. The method of claim 32, wherein flowing the second reagent through the touchless dispenser comprises placing the downstream valve and the upstream valve in an open position.

35. The method of claim 32, wherein flowing the second reagent through the touchless dispenser comprises: positioning the upstream valve of the touchless dispenser in the open position; positioning the downstream valve of the touchless dispenser in the closed position; as well as The second reagent is caused to flow into the inlet of the touchless dispenser and through the upstream valve and the hollow plunger of the syringe pump.

36. A device, comprising: A contactless dispenser, comprising: A syringe pump has a barrel and a hollow plunger movably disposed within the barrel.

37. The apparatus of claim 1 further comprising a fluid line coupled to the upstream valve and the hollow plunger.

38. The apparatus of claim 4, wherein the hollow plunger includes an upstream facing fitting and the fluid line is coupled to the upstream facing fitting.

39. The apparatus of claim 1, wherein the upstream valve and the downstream valve each comprise a diaphragm valve having a diaphragm.

40. The apparatus of claim 6, wherein each of the diaphragm valves has a valve seat and an inner curved surface defining a space therebetween to allow movement of the diaphragm of the corresponding diaphragm valve.

41. An apparatus according to claim 1, wherein the upstream valve includes a first opening to allow pressure to be applied to the diaphragm of the upstream valve to actuate the upstream valve, and the downstream valve defines a second opening to allow pressure to be applied to the diaphragm of the downstream valve to actuate the downstream valve.

42. The apparatus of claim 8, further comprising a pressure source coupled to an actuation port of the upstream valve and an actuation port of the downstream valve.

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