System for organ injection

Abstract

A system and method for enabling treatment through cell therapy. The system can enable cell injections, such as injections of beta cells / islets, chondrocytes, adipocytes, and others. The system and method ensures that the delivery rate and volume of material pumped through the tubing and into the injection needle is consistent over the course of a start-run-stop process, from start to start. The system and method can automatically stop delivery and sound an alarm if an obstruction is detected during delivery.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Provisional Patent Application No. 63 / 253,079 (Attorney Docket No. AA707), filed October 6, 2021, and entitled "SYSTEM AND METHOD FOR ORGAN INJECTION." This application also claims the benefit of U.S. Provisional Patent Application No. 63 / 364,390 (Attorney Docket No. AA831), filed May 9, 2022, and entitled "SYSTEM AND METHOD FOR ORGAN INJECTION," both of which are incorporated herein by reference in their entireties. [Background technology]

[0002] The present teachings relate generally to maintaining organ health. The devices and methods of the present teachings are not limited in their usefulness to one type of organ, as one of ordinary skill in the art will discover.

[0003] There is a need for a system to enable treatment through cell therapy. The system can enable cell injections, such as injections of beta cells / islets, chondrocytes, adipocytes, and others. Typically, cells are injected as a mixture of cells in a medical liquid or cell mixture. It would be beneficial to ensure that the delivery rate of material is consistent over the course of a start-run-stop process, from start-to-start. It would be beneficial to adjust the pump rate according to conditions during the pumping operation. It would be beneficial to include user-friendly operation, including features such as, but not limited to, rapid filling of the injection needle, delivery accuracy, and end stops and occlusion detection. Summary of the Invention [Means for solving the problem]

[0004] Devices of the present teachings solve the problems described herein, as well as other problems, by one or a combination of the features described herein.

[0005] One general aspect includes an apparatus for injecting a medical fluid. The apparatus also includes a housing, a syringe barrel with a fitting at a closed end, the syringe attached to the housing, a plunger including a lead screw, the plunger disposed within the syringe barrel, a mechanism for driving the lead screw toward the closed end of the syringe barrel, and an electric motor for driving the mechanism. The apparatus also includes the mechanism configured to selectively disengage from the lead screw to allow the plunger to move freely axially within the syringe barrel.

[0006] The implementation may include one or more of the following features. The apparatus may include a second syringe configured to engage a fitting on the syringe barrel, the second syringe may retract a plunger toward a closed end of the syringe barrel when the mechanism is selectively disengaged from the lead screw. The lead screw has at least one flat surface parallel to the lead screw axis. The lead screw cannot rotate and in the second position the lead screw rotates freely and rotation of the drive gear moves the lead screw along its axis when the anti-rotation flexure is in the first position and the lead screw can rotate and move along its axis when the drive gear is fixed and the anti-rotation flexure is in the second position. The key is configured to rotate within the housing and push the at least one arm away from the lead screw and place the anti-rotation flexure in the second position. The mechanism may include a drive gear mechanically driven by an electric motor, the drive gear having a plurality of petal elements extending generally on the axis of the lead screw, the petal elements having a threaded surface that engages the lead screw in a first position and disengages from the lead screw in a second position. The plunger further includes a tip with a distal surface that contacts the liquid and a proximal surface that is removably connected to a distal end of the lead screw, the tip being disengaged from the lead screw when negative pressure is applied to the distal surface. The plunger further includes a tip with a distal surface that contacts the liquid and a proximal surface configured to rotate relative to the lead screw. The electric motor may be displaced to disengage from the drive gear, and the lead screw may freely orbit the drive gear as it moves axially. The device may include a controller that receives input from the pressure sensor, at least one user input, and controls a speed and direction of the electric motor. The at least one user input includes a trigger and a directional switch. The device may include a battery switch. The latching relay is closed by the first full pull of the trigger. The device may include a battery connected to the controller. The device may include a status output, which may include at least one of an LCD display, a vibrating element, and one or more status lights.The status light and LCD display are controlled by the controller. The mechanism may include a reduction gear train on the motor output shaft. The device may include a rotation sensor that detects the number of rotations of an element in the mechanism. In the device, the rotation sensor measures the rotations of a magnet on the end of the output shaft of the reduction gear train. The device is disposable. The device is used only for a single treatment. The housing, drive mechanism, plunger, electric motor, and syringe barrel are disposable after a single treatment. The housing, drive mechanism, plunger, electric motor, and syringe barrel are disposable and are sterilized as a unit prior to use. The treatment kit is sterilized with ethylene oxide.

[0007] One general aspect includes an apparatus for injecting a medical fluid, the apparatus also including a housing, a syringe barrel with a fitting at a closed end, the syringe attached to the housing, a plunger including a lead screw, the plunger disposed within the syringe barrel, a mechanism for driving the lead screw toward the closed end of the syringe barrel, an electric motor for driving the mechanism, a controller for controlling an electric motor speed, and a pressure sensor mounted within the housing and configured to measure a pressure of the fluid in the syringe barrel, the controller varying the electric motor speed based on a pressure signal received from the pressure sensor.

[0008] Implementations may include one or more of the following features: In the device, a pressure sensor is mounted to sense pressure in tubing downstream of the syringe. A pressure sensor is mounted in front of the syringe barrel to sense axial force applied by the plunger on the liquid in the barrel. A controller detects an occlusion when the pressure signal exceeds a predetermined value. The controller reverses the electric motor when an occlusion is detected, and the controller continues to run the electric motor in reverse until the pressure signal drops below the predetermined value. The controller monitors parameters of the electric motor, and the controller declares an end of stroke based on the motor parameters and the pressure signal. The controller reverses the electric motor when the end of stroke is declared, and the controller continues to run the electric motor in reverse until the pressure signal drops below the predetermined value.

[0009] One general aspect includes a method for delivering a volume of a cell mixture to an in vivo organ using a disposable syringe pump, the disposable syringe pump including a syringe barrel fluidly connected to an insertion needle. The method also includes the steps of positioning a distal end of the insertion needle in the organ, receiving a user input to deliver the cell mixture, driving an electric motor at a first speed, receiving a signal from a pressure sensor, driving the electric motor at a second speed after the signal from the pressure sensor exceeds a first predetermined value, monitoring the number of revolutions of an element in the mechanism, determining a delivery volume of the cell mixture, stopping the electric motor when the delivery volume exceeds the predetermined volume, and reversing the electric motor until the pressure signal drops below a second predetermined value.

[0010] Implementations may include one or more of the following features: In the method, the user input is a signal from a switch or trigger, and the method may include monitoring the user input signal, stopping the electric motor when less than the predetermined volume is delivered and providing the user signal is terminated, and restarting the electric motor when the user signal is resumed. The user input is a signal from a switch or trigger, and the method may include terminating the user input after the predetermined volume is delivered, resuming the user input, and delivering a second predetermined volume of the cell mixture.

[0011] One general aspect includes an apparatus for injecting a medical fluid, the apparatus also including a housing, a syringe barrel with a fitting at a closed end, the syringe attached to the housing, a plunger including a lead screw, the plunger disposed within the syringe barrel, a mechanism for driving the lead screw toward the closed end of the syringe barrel, an electric motor for driving the mechanism, a pressure sensor configured to measure a pressure characteristic of a medical fluid pressure in the syringe barrel or a line fluidly connected to the syringe barrel, a rotation sensor configured to measure rotations of an element of the mechanism, and a controller that determines a volume of the injected medical fluid based on the pressure value and the number of rotations measured by the rotation sensor.

[0012] Implementations may include one or more of the following features: In the device, the controller is configured to decelerate the electric motor after the pressure signal exceeds a predetermined pressure, and the controller calculates a volume of injected fluid based on the predetermined pressure. The predetermined pressure is 800 mmHg. The controller calculates the volume of injected fluid based on an average pressure during previous injections of the predetermined volume of medical liquid. A pressure sensor is mounted to sense pressure in a tube downstream of the syringe. A pressure sensor is mounted in front of the syringe barrel to sense an axial force applied by the plunger against the liquid in the barrel.

[0013] One general aspect includes a method for injecting an aliquot of a material into an organ using a handheld injection device. The method also includes the steps of loading a delivery component with the aliquot, activating a delivery mechanism, delivering a preselected volume of the aliquot at a preselected rate by the delivery mechanism, and detecting a status of the injection device.

[0014] Implementations may include one or more of the following features: In the method, the delivery component may include an aliquot container, an organ penetrating device, and a plunger operably coupled to the aliquot container, the plunger pushing the aliquot towards the organ, through the aliquot container, and into the organ penetrating device. The delivery component may include a disposable component. The delivery component may include a durable component. The delivery mechanism may include a spring, a plunger component of the delivery component, and a lead screw that pushes the plunger component when the spring is released. The delivery mechanism may include a lead screw, a motor, and a gear train driven by the motor, the lead screw driving the lead screw, which activates the delivery component. The method may include detecting a status of the aliquot. The method may include detecting a characteristic of the aliquot. The delivery mechanism may include a mechanical component. The delivery mechanism may include an electromechanical component. The injection device may include a mechanical delivery component operably coupled to the electromechanical delivery mechanism. The injection device may include a purely mechanical delivery component operably coupled to a mechanical delivery mechanism. Activating the delivery mechanism may include winding a spring, the spring operably coupled to the delivery mechanism. Activating the delivery mechanism may include depressing a trigger, the trigger operably coupled to a motor, the motor operably coupled to the delivery mechanism. Delivering the aliquot may include driving the delivery mechanism forward to deliver the aliquot. Detecting the status of the injection device may include issuing a first alert, ceasing delivery of the aliquot, and driving the delivery mechanism in reverse if the status of the delivery mechanism meets at least one first preselected criterion. Detecting the status of the injection device may include issuing a second alert and driving the delivery mechanism in reverse if the rate of delivery of the aliquot meets at least one second preselected criterion.Detecting a status of the injection device may include issuing a third alert and stopping the delivery mechanism if the aliquot pressure meets at least one third preselected criterion. Detecting a status of the injection device may include activating an indicator light when at least one fourth preselected criterion is met.

[0015] One general aspect includes a handheld injection device for injecting an aliquot of a material into an organ. The handheld injection device also includes a delivery mechanism. The device also includes a delivery component operably coupled to the delivery mechanism, the delivery component including a container configured to hold the aliquot, the delivery mechanism activating the delivery component to deliver a preselected volume of the aliquot to the organ at a preselected rate.

[0016] Implementations may include one or more of the following features: In the handheld injection device, the material may include a cell therapy. The material may include at least one agent. The material may include at least one drug. The organ may include a kidney. The organ may include a liver. The delivery component may include an organ penetrating device and a plunger operably coupled to the container, the plunger pushing the aliquot toward the organ, through the container, and into the organ penetrating device. In the handheld injection device, the device may include at least one disposable component. In the handheld injection device, the device may include at least one durable component. The delivery mechanism may include a spring, a plunger component of the delivery component, and a lead screw that pushes the plunger component when the spring is released. The delivery mechanism may include a lead screw, a motor, and a gear train driven by the motor, driving the lead screw, which activates the delivery component. The handheld injection device may include at least one sensor configured to detect at least one characteristic of the aliquot and at least one processor configured to control the handheld injection device based on the at least one characteristic. The handheld injection device may include at least one sensor configured to detect at least one status value of the handheld injection device and at least one processor configured to control the handheld injection device based on the at least one status value. The handheld injection device may include at least one sensor configured to detect at least one status value of the handheld injection device and at least one processor configured to report the at least one status to a user. The handheld injection device may include at least one sensor configured to detect at least one status value of the handheld injection device and at least one processor configured to log the at least one status. The delivery mechanism may include electromechanical components. The delivery mechanism may include purely mechanical components.The handheld injection device may include a mechanical delivery component operably coupled to the electromechanical delivery mechanism. The handheld injection device may include a mechanical delivery component operably coupled to the mechanical delivery mechanism. The delivery mechanism may include a spring operably coupled to the delivery mechanism, the spring configured to activate the delivery mechanism. The delivery mechanism may include a motor operably coupled to the delivery mechanism and a trigger operably coupled to the motor. The delivery mechanism may include being configured to be driven forward to deliver the aliquot. The handheld injection device may include an alert system that provides a status of the handheld injection device and a first alert and drives the delivery mechanism in reverse if the status of the handheld injection device meets at least one first preselected criterion. The handheld injection device may include an alert system that provides a status of the handheld injection device and a second alert and drives the delivery mechanism in reverse if the rate of delivery of the aliquot meets at least one second preselected criterion. The handheld injection device may include an alert system that provides a third alert and stops the delivery mechanism if the status of the handheld injection device and the pressure of the aliquot meets at least one third preselected criterion. The handheld injection device may include an alert system that provides a status of the handheld injection device and activates an indicator light if at least one fourth preselected criterion is met. The handheld injection device may include at least one pressure sensor configured to detect the pressure of the aliquot. The handheld injection device may include at least one pressure sensor integrated with the delivery mechanism, the at least one pressure sensor configured to detect the pressure of the aliquot.

[0017] One general aspect includes an organ injection device for injecting a substance into an organ, the organ injection device also including a motor, an activation means configured to activate the motor, a delivery mechanism configured to deliver the substance, an energy transfer mechanism configured to transfer energy generated by the motor to the delivery mechanism, a controller configured to control the energy transfer mechanism, and at least one sensor configured to provide data about the motor and the delivery mechanism to the controller.

[0018] Implementations may include one or more of the following features: In the injection device, the device may include a stop mechanism configured to prevent the delivery mechanism from delivering the substance. In the injection device, the device may include an energy storage means configured to power the motor. In the injection device, the device may include a monitor configured to provide information to the controller. The controller may include an electromagnetic controller configured to control the speed of the motor. In the injection device, the device may include a brake configured to stop the delivery mechanism. In the organ injection device, the device may include a case configured to protect the motor, the activation means, the delivery mechanism, the energy transfer mechanism, the at least one sensor, and the controller from micro-contaminants. In the organ injection device, the device may include a case configured to protect the motor, the activation means, the delivery mechanism, the energy transfer mechanism, the at least one sensor, and the controller from macro-contaminants. In the organ injection device, the device may include a delivery mechanism case configured to protect the delivery mechanism from environmental contaminants. In the organ injection device, the device may include a directional switch configured to enable multi-directional operation of the organ injection device. In the organ injection device, the device may include at least one status indicator. The organ injection device may include a first speed of the motor, where the motor operates at the first speed when the substance begins to be dispensed, a second speed of the motor, where the motor operates at the second speed after the substance begins to be dispensed, and a third speed of the motor, where the motor operates at the third speed after at least one preselected condition is met.

[0019] One general aspect includes a mechanical injector for injecting a substance into an organ. The mechanical injector also includes a delivery mechanism, a trigger, and an activation mechanism configured to move a substance within the delivery mechanism into the organ when the trigger is engaged.

[0020] Implementations may include one or more of the following features: In a mechanical injector, the device may include a protective casing configured to enclose the injection device. The protective casing may include a plurality of interconnecting sections. The protective casing may include a single section. The protective casing may include a body lid, a body upper portion operably coupled to the body lid, a middle body operably coupled to the body upper portion, and a handle casing operably coupled to the middle body. The handle casing may include a left handle casing and a right handle casing operably coupled to the left handle casing. The activation mechanism may include a spring winding device with a timing escapement that drives the delivery mechanism, and the trigger controls when the spring winding device is released to drive the delivery mechanism. The delivery mechanism may include a syringe plunger and a lead screw operably coupled to and driving the syringe plunger. The delivery mechanism may include a lead screw, a syringe stopper operably coupled to the lead screw, and an axially stable drive nut configured to rotate in place to drive the lead screw into the syringe plunger, the lead screw being rotationally stable and configured to translate forward. The drive nut may have gear teeth on its exterior periphery, the drive nut operably coupled to a drive shaft via a gear train, the drive shaft operably coupled to a torque drum assembly, the torque drum assembly may be wound with a spring, the spring configured with a plurality of turns and including gear teeth providing a constant torque output from each of the plurality of turns, the gear train configured to be geared up or down to meet a preselected number of drive nut revolutions per volume of a stroke in the syringe plunger, and the drive shaft operably coupled to a timing mechanism that ensures the drive shaft rotates at a fixed rate. The timing mechanism may include a static rate. The timing mechanism may include a gear transmission configured to modify gears connecting to the drive shaft to allow for multiple fixed rates of delivery.The torque drum assembly may include a torque drum and a storage drum configured to hold the spring, and the activation mechanism is configured to be charged by rotating the torque drum and winding the spring onto the torque drum. The activation mechanism may include a bolt rail, a ball knob configured to slide along the bolt rail, a primary pulley and a secondary pulley, and a pulley belt operatively coupling the primary pulley and the secondary pulley, and the ball knob, the primary pulley, the secondary pulley, and the pulley belt may include a movable assembly that operates cooperatively with the storage drum to charge the activation mechanism. The activation mechanism may include a tilted beam, a rotating arm including teeth, and at least one torsion spring configured to hold the rotating arm at a center of the swing arc, and when an aliquot is completed, the teeth contact the tilted beam, which pushes the rotating arm and compresses one of the at least one torsion spring. The trigger may include a spring-loaded mechanism that, when at rest, pushes a wedge into the teeth of the drive nut to prevent rotation of the drive nut, and when pressed, the trigger pulls the wedge from the teeth without unwinding the spring-loaded mechanism. The mechanical injector may include a pivoting device configured to rewind the spring-loaded mechanism after a preselected number of aliquots of the substance have been delivered. The pivoting device may include a ratcheting lever. The pivoting device may include a linear slide with a gear rack configured to engage a bevel gear on the drive shaft. The mechanical injector may include at least one sensor associated with the delivery mechanism, the at least one sensor configured to detect a change in a characteristic of the delivery mechanism.The mechanical injector may include at least one sensor configured to monitor a characteristic of the injector as sensor data, and at least one processor configured to receive sensor data from the at least one sensor, the at least one processor configured to store a buffer of the characteristic from a preselected amount of time at a preselected sampling rate, the at least one processor configured to compare values ​​of the sensor data collected at a first time with values ​​of the sensor data collected at a second time that differs from the first time by a preselected amount of time, the at least one processor configured to monitor a change in the characteristic indicative of the delivery mechanism being mispositioned, and the at least one processor configured to issue an alert based on the change in the characteristic. The mechanical injector may include a delivery mechanism restraint configured to secure the delivery mechanism against movement when under pressure from an activation mechanism. The activation mechanism may include drawing a vacuum into the delivery mechanism, the vacuum drawing the substance into the delivery mechanism.

[0021] One general aspect includes an organ injection device, in which at least one status indicator may also include a moving pattern of lights that is activated when the activation means is enabled.

[0022] Implementations may include one or more of the following features: In the injection device, the injection device includes a charging means configured to charge the energy storage means. The at least one status indicator may include that the organ injection device includes a delivery mechanism status indicator configured to provide a status of the delivery mechanism.

[0023] The present teachings generally relate to the injection of cell therapy or other drugs and medications. Any version of the injection device can include features such as, but not limited to, a sealed enclosure, an integrated syringe with a lead screw and volumetric markings to drive the plunger, a pressure sensor that directly engages the syringe, a motor and gearbox used to drive the lead screw, a toggle switch used to select the direction of movement and reset the accumulated volume accumulator, a trigger switch used to start the movement of the motor, a display used to communicate the status of the device, a vibration motor used to non-visually indicate that the user may check the display, a power source used to power the device, a power source switch used to externally engage the power source to the system, a release mechanism to allow recovery of the injection solution in the event of a complete device failure, a circuit board, and on-board software used to control the injection device subsystem and log data, for example, but not limited to, the injection device subsystem.

[0024] The device of the present teachings can drive a bolus of potentially viscous material at a specific rate from a disposable device whose characteristics are monitored to maintain the rate of delivery and other properties. In one exemplary treatment, organ cells are stored in DMSO. The DMSO / organ cell mixture or medical liquid is stored in a frozen condition and then thawed before being injected into the body. The device can be used to extract material from a vial, and a syringe can be integrated into the device. The device includes an automated method for injecting a specific amount. The device can target a desired flow rate and flow volume, potentially increasing the flow rate at the beginning and end of the injection. The device can detect changes in delivery pressure, which can indicate the status of the injection, for example, due to blockage, unintended target in the body, or unexpected pressure in the target organ.

[0025] The first exemplary device includes a trigger that is pressed for delivery, a syringe, a spring to drive the syringe, and an electrical box for the pressure sensor circuit. This primarily mechanical device is constructed to have a minimal number of points of failure, yet be durable. Such a device can be economical to manufacture and easy to operate. The device can optionally include a means for allowing the lead screw to be easily retracted, thereby eliminating the need to rewind the spring between aliquots.

[0026] The device can also optionally include another mechanism for winding the spring and a means for automatically stopping delivery after each aliquot. A stopcock can optionally be added to the trigger, along with a mounting geometry for a pressure sensor.

[0027] A second exemplary device includes means for adjusting delivery rate / volume, providing user feedback, removing the operator from the pressure feedback loop, assisting with vial decant, and includes a digital stopcock. The second device includes means for varying the decant rate, means for adjusting the digital stopcock, means for adjusting the rate controller, and a soft stop in the actuator range area. The second exemplary device includes a processor that controls a pump, controls a motor, connected to a tube at one end of the tube and to a needle at the other end of the tube. The needle pressure is monitored by a pressure sensor. The device is powered by a power source, such as, for example, but not limited to, a battery. The power source characteristics can be monitored by the processor.

[0028] Any version of the injection device may include features such as, but not limited to, a sealed enclosure, an integrated syringe with lead screw and volumetric markings integrated into the plunger, a pressure sensor that directly meshes with the syringe, a motor and gearbox used to drive the lead screw, a toggle switch used to select the direction of movement and reset the deposition volume accumulator, a trigger switch used to initiate the movement of the motor, a display used to communicate the status of the device, a vibration motor used to non-visually indicate that the user may check the display, a power source used to power the device, a power source switch used to externally engage the power source to the system, a release mechanism to allow recovery of the injection solution in the event of a complete device failure, a circuit board, and on-board software used to control the injection device subsystems and log data, for example, but not limited to, a mechanical bellows / baffled cartridge or a diaphragm cartridge may be used instead of a syringe.

[0029] The electromechanical component of the system of the present teachings is a durable device into which a disposable pre-sterilized injection device or single-use syringe is inserted, which uses a piston to draw liquid into the syringe and then dispenses it at a controlled rate. In one aspect, the injection device includes a needle or other type of injection device, transfer tubing, and a vial adapter. The injection needle can include a high gauge non-coring (side port) needle that acts as a semi-rigid liquid pathway injection deposition positioning aid. The transfer tubing acts as a flexible liquid pathway between the injection device and the injection needle, reducing the possibility of the needle accidentally dislodging while performing the injection. The vial adapter is used to assist in filling the injection device with the injection solution. The vial adapter can puncture the vial septum and vent to prevent a vacuum from building up in the vial. The components used by the system of the present teachings that are commercially available can include consumables, including, but not limited to, injection and guide needles, transfer tubing, and vial adapters. The guide needle or trocar is configured to pierce the patient's skin to the outer surface of the kidney. The injection needle is then inserted through the guide needle and into the renal capsule. In some configurations, the injection needle can include a 25G needle with a thin wall to minimize damage to the kidney during needle insertion. The injection needle can include a non-coring (blunt, conical) tip with a side port to minimize tissue damage or clogging of the needle during insertion. The base of the injection needle can include a connector, such as, for example, but not limited to, a Luer lock socket, to allow connection to the transfer tubing. The transfer tubing can include tubing with a connector socket on one end and a plug on the other. The transfer tubing can provide a connection between the injection device and the injection needle. In some configurations, thick-walled microporous tubing with few external features can minimize dead volume and compliance in the present system. The vial adapter can include fittings that connect to the injection device through a needleless injection port on one end and to the injection storage container (vial) through a low gauge needle that pierces the septum on the other end. There is also a retaining feature to hold the vial in place and a venting filter to prevent vacuum from building up inside the vial. The controller can be configured to adjust the pump rate to reach a preselected pressure of material pumped through the tubing and into the injection needle over the course of the start-run-stop process from start to start, or the pressure can be adjusted to apply a preselected pump rate. Monitoring and adjusting the operation of the device can enable efficient filling of the injection needle, accurate delivery, end stopping, and occlusion detection.

[0030] The method of the present teachings includes the steps of filling, priming, injecting, connecting / disconnecting, monitoring the delivered volume, purging, controlling the user interface, and optionally withdrawing the injection solution. The filling step can include connecting the vial adapter to the vial and the injection device, then inverting the vial, driving the injection device plunger in reverse, and drawing the injection solution into the integrated injection volume container (syringe). The priming step can include removing any air bubbles present in the injection volume container and the air in the transfer tubing and injection needle after performing the filling step. In some configurations, removing the air bubbles can include, but is not limited to, orienting the injection device so that the tip of the injection volume container faces up with the transfer tubing and injection needle attached, and driving the injection device plunger forward until the air is pushed out of the system. The injecting step can include inserting the injection needle through the guide needle into the kidney after performing the priming step and driving the injection device plunger forward at a controlled rate until stopped by the user, a deposition volume limit is reached, or the injection device software detects a potential problem. The disconnecting step can include disconnecting the luer lock coupling from the injection needle to the transfer tubing or from the transfer tubing to the injection device at various times during therapy, for example, when moving the patient to ensure the injection needle is correctly positioned. During the disconnecting step, the flow of injection solution from the injection device or the transfer tubing (if connected to the injection device) can be interrupted. After imaging is completed, the connecting step can include connecting the disconnected luer lock coupling.

[0031] Monitoring the delivered volume may include estimating the amount of volume delivered during the current deposition during the injection step, and automatically interrupting the injection and notifying the user when a deposition volume limit is reached. The monitoring may include resetting the deposition accumulator before the next injection, which may be reset at any time when the injection device plunger is not moving to allow deposition of a partial volume.

[0032] After completing the last full injection action and sensing the presence of residual injection solution in the transfer tubing that the healthcare provider wishes to inject into the patient, the purging step can include disconnecting the injection device from the transfer tubing, performing a fill action with air or saline, reconnecting the injection device, and injecting air until the transfer tubing is empty. A manual syringe can be used to perform the purging step if the remaining injection device power is deemed insufficient to enable the fill action. Controlling the injection can include requiring the operator to maintain pressure on the trigger throughout the entire injection, such that releasing the trigger will immediately stop the injection.

[0033] Controlling the user interface may include indicating the function currently being performed by the injection device, the status of the battery, and whether any faults or alarms exist. Controlling the user interface may also include notifying the user, e.g., by haptic feedback, when there are messages that the user may access to continue to operate the injection device safely and effectively during the injection. For example, if the injection device suffers a critical failure, an optional step of recovering the injection solution may include removing the injection solution from the injection device and proceeding manually.

[0034] Various metrics can be monitored to determine if the device is delivering injections accurately. In some configurations, average flow rate accuracy based on the inner diameter of the syringe, the pitch of the lead screw, the gear train, the motor shaft angular velocity, and pressure readings. The deposition volume limit for a given injection can be measured by monitoring the total degrees of rotation of the motor shaft as measured by the motor rotation encoder. To detect blockages, the measured in-line pressure can be monitored, the injection can be automatically interrupted, and the device can go into or begin a shutdown when the pressure exceeds a preselected threshold. To detect bad or incorrect connections, for example, pressure readings can be monitored during the fill and injection action. If the pressure drop falls below a preselected threshold, the fill / injection action can be interrupted and the system can return to an idle state. For example, if the motor angular velocity based on the voltage applied to the motor (pulse wave modulation) and the in-line pressure sensor feedback are not within a preselected range of each other because the plunger has reached either a forward or reverse end stop based on the current direction of travel, the motor will be stopped and the user will be notified. If the power source charge falls below a limit threshold, the injection device will allow the user to inject the remaining injection solution but will prevent them from performing the fill action. If the power source charge is determined to be insufficient to continue safely, the injection device can enter a disabled state and ignore commands to move the plunger in the injection direction as well. A power-on self-test (POST) can verify the functionality of the motor and motor encoder, pressure readings, display, other user information, and device memory after shipping and storage, for example, but not limited to. A watchdog can be used to monitor for potential runaway software conditions, memory corruption, hardware failure, unexpected failure modes, or unexpected user input and reconfigure the primary controller or enter a disabled state or notify the user.The Watchdog receives periodic communication from the main controller while the device is operating normally. If the software is unable to provide this input, the Watchdog will attempt to fail-safe and reconfigure the master control unit. [Brief description of the drawings]

[0035] The present teachings may be more readily understood by reference to the following description taken in conjunction with the accompanying drawings.

[0036] [Figure 1A] 1A-1B are schematic block diagrams of an exemplary system of the present teachings. [Figure 1B] 1A-1B are schematic block diagrams of an exemplary system of the present teachings.

[0037] [Figure 2A] 2A-2L are schematic perspective views of exemplary drawings of various configurations of the mechanical system of the present teachings. [Figure 2B] 2A-2L are schematic perspective views of exemplary drawings of various configurations of the mechanical system of the present teachings. [Figure 2C] 2A-2L are schematic perspective views of exemplary drawings of various configurations of the mechanical system of the present teachings. [Figure 2D] 2A-2L are schematic perspective views of exemplary drawings of various configurations of the mechanical system of the present teachings. [Figure 2E] 2A-2L are schematic perspective views of exemplary drawings of various configurations of the mechanical system of the present teachings. [Figure 2F] 2A-2L are schematic perspective views of exemplary drawings of various configurations of the mechanical system of the present teachings. [Figure 2G] 2A-2L are schematic perspective views of exemplary drawings of various configurations of the mechanical system of the present teachings. [Figure 2H] 2A-2L are schematic perspective views of exemplary drawings of various configurations of the mechanical system of the present teachings. [Figure 2I]2A-2L are schematic perspective views of exemplary drawings of various configurations of the mechanical system of the present teachings. [Figure 2J] 2A-2L are schematic perspective views of exemplary drawings of various configurations of the mechanical system of the present teachings. [Figure 2K] 2A-2L are schematic perspective views of exemplary drawings of various configurations of the mechanical system of the present teachings. [Figure 2L] 2A-2L are schematic perspective views of exemplary drawings of various configurations of the mechanical system of the present teachings.

[0038] [Figure 3A] 3A-3D are schematic perspective views of an exemplary drawing of a first configuration of an electromechanical system of the present teachings. [Figure 3B] 3A-3D are schematic perspective views of an exemplary drawing of a first configuration of an electromechanical system of the present teachings. [Figure 3C] 3A-3D are schematic perspective views of an exemplary drawing of a first configuration of an electromechanical system of the present teachings. [Figure 3D] 3A-3D are schematic perspective views of an exemplary drawing of a first configuration of an electromechanical system of the present teachings.

[0039] [Figure 4A] 4A-4N are schematic perspective views of an exemplary drawing of a second configuration of the electromechanical system of the present teachings. [Figure 4B] 4A-4N are schematic perspective views of an exemplary drawing of a second configuration of the electromechanical system of the present teachings. [Figure 4C] 4A-4N are schematic perspective views of an exemplary drawing of a second configuration of the electromechanical system of the present teachings. [Figure 4D] 4A-4N are schematic perspective views of an exemplary drawing of a second configuration of the electromechanical system of the present teachings. [Figure 4E] 4A-4N are schematic perspective views of an exemplary drawing of a second configuration of the electromechanical system of the present teachings. [Figure 4F]4A-4N are schematic perspective views of an exemplary drawing of a second configuration of the electromechanical system of the present teachings. [Figure 4G] 4A-4N are schematic perspective views of an exemplary drawing of a second configuration of the electromechanical system of the present teachings. [Figure 4H] 4A-4N are schematic perspective views of an exemplary drawing of a second configuration of the electromechanical system of the present teachings. [Figure 4I] 4A-4N are schematic perspective views of an exemplary drawing of a second configuration of the electromechanical system of the present teachings. [Figure 4J] 4A-4N are schematic perspective views of an exemplary drawing of a second configuration of the electromechanical system of the present teachings. [Figure 4K] 4A-4N are schematic perspective views of an exemplary drawing of a second configuration of the electromechanical system of the present teachings. [Figure 4L] 4A-4N are schematic perspective views of an exemplary drawing of a second configuration of the electromechanical system of the present teachings. [Figure 4M] 4A-4N are schematic perspective views of an exemplary drawing of a second configuration of the electromechanical system of the present teachings. [Figure 4N] 4A-4N are schematic perspective views of an exemplary drawing of a second configuration of the electromechanical system of the present teachings.

[0040] [Figure 5A] 5A-5B are schematic perspective views of an exemplary drawing of a third configuration of the electromechanical system of the present teachings. [Figure 5B] 5A-5B are schematic perspective views of an exemplary drawing of a third configuration of the electromechanical system of the present teachings.

[0041] [Figure 6A] 6A-6C are schematic perspective views of an exemplary drawing of a fourth configuration of the electromechanical system of the present teachings. [Figure 6B] 6A-6C are schematic perspective views of an exemplary drawing of a fourth configuration of the electromechanical system of the present teachings. [Figure 6C]6A-6C are schematic perspective views of an exemplary drawing of a fourth configuration of the electromechanical system of the present teachings.

[0042] [Figure 7A] 7A-7C are schematic perspective views of an exemplary drawing of a fifth configuration of the electromechanical system of the present teachings. [Figure 7B] 7A-7C are schematic perspective views of an exemplary drawing of a fifth configuration of the electromechanical system of the present teachings. [Figure 7C] 7A-7C are schematic perspective views of an exemplary drawing of a fifth configuration of the electromechanical system of the present teachings.

[0043] [Figure 8A] 8A-8G are schematic perspective views of exemplary drawings of various other configurations of the electromechanical system of the present teachings. [Figure 8B] 8A-8G are schematic perspective views of exemplary drawings of various other configurations of the electromechanical system of the present teachings. [Figure 8C] 8A-8G are schematic perspective views of exemplary drawings of various other configurations of the electromechanical system of the present teachings. [Figure 8D] 8A-8G are schematic perspective views of exemplary drawings of various other configurations of the electromechanical system of the present teachings. [Figure 8E] 8A-8G are schematic perspective views of exemplary drawings of various other configurations of the electromechanical system of the present teachings. [Figure 8F] 8A-8G are schematic perspective views of exemplary drawings of various other configurations of the electromechanical system of the present teachings. [Figure 8G] 8A-8G are schematic perspective views of exemplary drawings of various other configurations of the electromechanical system of the present teachings.

[0044] [Figure 9A] 9A-9E are flow charts of an exemplary method of using the present teachings. [Figure 9B] 9A-9E are flow charts of an exemplary method of using the present teachings. [Figure 9C] 9A-9E are flow charts of an exemplary method of using the present teachings. [Figure 9D] 9A-9E are flow charts of an exemplary method of using the present teachings. [Figure 9E] 9A-9E are flow charts of an exemplary method of using the present teachings.

[0045] [Figure 10] FIG. 10 is a schematic block diagram of state transitions of the system of the present teachings. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0046] Detailed Description The devices and methods of the present teachings are discussed in detail herein, however, various configurations of the devices and methods of the present teachings are contemplated by the description.

[0047] The disposable device for cell delivery to an organ of the present teachings can take several forms, some with manual aspects and some with automated aspects. The organ cells are mixed into a sterile liquid to facilitate injection and optimize therapeutic benefits in the receiving organ. The liquid containing the cells for injection is referred to herein as a medical liquid or cell mixture. In one exemplary treatment, the organ cells are stored in DMSO. The DMSO / organ cell mixture or medical liquid is stored in a frozen condition and then thawed before being injected into the body. Exemplary configurations of the injector of the present teachings include, but are not limited to, a trigger mechanism, a syringe, and a pressure sensor. Exemplary configurations include a sealed enclosure, an integrated syringe with volumetric markings, a pressure sensor that directly mates with the syringe, a motor and gearbox used to drive a lead screw that moves the syringe plunger through the syringe, and any of the other features. In one aspect, the device provides a volumetric and rate-measured injection of the cell mixture into the organ. In one aspect, the sealed enclosure protects the functional mechanism from debris / liquid ingress and holds the components in place relative to each other. The cell mixture can be drawn or pulled into the device or provided to the device by a pre-filled syringe. In one aspect, a force, possibly provided by a mechanical spring or an automated mechanism, drives a lead screw, urging the syringe plunger into the syringe and moving the cell mixture out of the syringe. Data from a pressure sensor can be used to control the liquid flow to a preselected pressure. In one aspect, in cases where the cell mixture cannot be delivered, the cell mixture can be extracted from the syringe to a holding container for storage and use in another procedure.

[0048] 1A-1B, various exemplary configurations of the system of the present teachings are shown in schematic block diagram form. In one aspect, a delivery device of the present teachings (FIG. 1A) includes a winding mechanism 205 that charges an energy storage mechanism 207 to provide force to a drive mechanism 211. The drive mechanism 211 engages a delivery mechanism 217 and delivers the cell mixture to an organ when an activation mechanism 209 is pressed or otherwise brought into communication with the drive mechanism. In one aspect, sensor data from the sensor 215 is processed by a controller 213 to adjust the characteristics of the cell delivery. In one aspect, the characteristics can include, but are not limited to, pressure. In one aspect, the activation mechanism 209 includes a trigger that releases the drive mechanism 211. For example, the activation mechanism 209 can include a device that engages and remains stationary with a drive gear and is moved to release the drive gear, initiating a chain of movements that causes the drive mechanism 211 to apply a force to, for example, a lead screw. The lead screw ultimately engages a delivery mechanism 217, e.g., a syringe plunger, which delivers the cell mixture through the syringe and into the organ. In one aspect, the winding mechanism 205 actuates a spring, such as a torsion spring, positioned within a timer gear train, and a motor mechanism, such as a storage and torque drum. Releasing the gear train engaged with the drive gear activates the motor mechanism and a timer that controls the release of energy by the motor mechanism 207.

[0049] Optionally, a delivery stop mechanism 219 may be included that locks the drive mechanism 211 in place. Such action ensures that no further transfer of the cell mixture will occur, whatever the status of the activation device. Additionally, the delivery device may optionally include a display 221, which may be built into the device. In certain aspects, the display 221 indicates, for example, but not limited to, the status of the device, the volume of cell mixture remaining to be delivered, error messages, and delivery pressure. In certain aspects, the display includes a code. In certain aspects, the code is displayed pictorially. In certain aspects, the code is depicted in color.

[0050] 1B, in one aspect, the electromechanical configuration of the present teachings includes a battery 225 and an electric motor 208 that provides power to the delivery mechanism 217 through the drive mechanism 211. In one aspect, energy can be stored in the battery 225, including but not limited to the following battery types: dry cell, lithium ion, zinc carbon, alkaline, lithium iron sulfide, nickel metal hydride, and nickel cadmium. In one aspect, the battery 225 is replaced by other forms of electrical energy storage devices, such as, for example but not limited to, a capacitor. The motor 208 is controlled by an electromechanical controller 214. The electromechanical (EM) controller 214 receives and processes sensor data from the sensor 215. In one aspect, the sensor data includes pressure data indicative of the pressure of the cell mixture as they are delivered to the organ. Other data can also be collected by sensors associated with the device. In one aspect, a cell characteristic sensor provides data to the controller 214. In one aspect, the sensor data is used by the controller 214 to adjust the volume of the cell mixture delivered and the pressure at which the mixture is delivered. Other types of control are also contemplated by the present teachings. In one aspect, the controller 214 associates the collected sensor data with a desired action through an algorithm, recipe, or dynamically varying association, and prescribes the action based on the results of the application of the method to the data. A command is issued by the controller 214 to the drive mechanism 211 based on the prescribe action. The drive mechanism 211 provides a mechanical force to the delivery mechanism 217 to cause the cell mixture to be delivered to the organ.

[0051] 1B , the delivery device may include a brake 223. The brake 223 prevents further movement of the drive mechanism 211 regardless of the status of the activation mechanism 209. In one aspect, the brake 223 includes a mechanical stop that physically blocks movement. In one aspect, the brake 223 includes an electrical signal, possibly augmented by mechanical means, that stops the motion of the drive mechanism 211 or the electric motor. Other possible brake configurations are also contemplated by the present teachings, including a signal to the controller 213 to stop the electric motor 208. Additionally, the delivery device may include a display 221. In one aspect, the display 221 can be used as described herein to inform the user of various characteristics of the device, the cells, and the cell's environment.

[0052] mechanical syringe Referring now to FIG. 2A, a first exemplary configuration 100 (FIG. 2A) of a mechanical cell injector of the present teachings is shown. The disposable mechanical system 100 (FIG. 2A) includes a protective casing, a delivery mechanism, a trigger, and an activation mechanism that moves the cells in the delivery mechanism into a receiving organ. The protective casing can be formed in multiple interconnecting sections or can be formed as a single section. In one aspect, the protective casing includes a body cover 121 (FIG. 2A), a body upper portion 139 (FIG. 2A), a mid-body 141 (FIG. 2A), and a handle casing. In one aspect, the handle casing includes a right handle casing 149 (FIG. 2A) and a left handle casing 147 (FIG. 2D). Other casing configurations are also contemplated by the present teachings. Operationally, the device is spring wound with a timing escapement that drives a syringe plunger at a fixed rate. The device has a trigger that controls when the spring is released to drive the plunger. A pressure sensor is aligned with the nozzle of the syringe to detect a preselected change in pressure at the needle tip. The benefit of the device is that it is human driven. The delivery energy input into the device is done by the operator, but unlike manually pushing the syringe, the device drives the delivery of the liquid in the syringe at a fixed rate across a range of viscosities. The delivery system is purely mechanical and is rechargeable by winding a spring mechanism. In one aspect, the syringe plunger is pushed by a lead screw. In one aspect, component 135 (FIG. 2A) attaches component 136 (FIG. 2A) to the end of lead screw 113 (FIG. 2A) that interfaces with the syringe plunger. In FIGS. 2J-2L, the syringe plunger is replaced by a plunger seal that is attached to the end of the lead screw. An axially stable drive nut pivots in place to drive the lead screw into the syringe plunger. The lead screw is held rotationally stable so that it does not translate forward and rotate with the nut. The drive nut has gear teeth on its exterior periphery and is connected to the drive shaft through a short gear train.The drive shaft has a torque drum around which the spring is wound. The selected spring is designed to have multiple turns with a constant torque output from each turn. The gear train connecting the drive shaft to the drive nut can be geared up or down to meet a preselected number of drive nut revolutions per volume of stroke in the syringe. This is a function of the syringe geometry and the pitch of the lead screw. The drive shaft is also connected to a mechanical timing mechanism (similar to a spring wound egg timer). This mechanism ensures that the drive shaft rotates at a fixed rate and limits the rate of delivery. The rate of this timing mechanism can be either static or can be varied between multiple fixed rates using a drive train with a "gear transmission" that modifies the gears that connect to the drive shaft. In one aspect, the trigger is a spring loaded mechanism that, when stationary, pushes a wedge into the teeth of the drive nut, preventing its rotation and thus blocking delivery of the drug. In one aspect, the start / stop mechanism includes a friction brake. In one aspect, the start / stop mechanism includes an axial mechanism. In response to the user pulling the trigger, the wedge is pulled out of the path of the drive nut teeth and the device is freed to continue delivery. The safety mechanism allows the operator to release the trigger in an emergency and the spring will push the wedge back into the gear teeth, causing the device to stop delivery. Releasing the trigger will not unwind the spring and pulling the trigger will restore motion. The spring must be rewound after the preselected number of aliquots has been delivered. There are several options for accomplishing this including a crank or knob on the rear of the drive shaft, a ratcheting lever on the side of the device, or a linear slide with a gear rack that engages with a bevel gear on the drive shaft. In one aspect, when the operator winds the spring, the drive nut cannot be rotated back as this would retract the syringe plunger. An intermediate gear in the gear train is therefore introduced which is pushed out of contact with the drive nut during the winding action, thereby breaking the gear train. The gear is forced back into contact with the drive nut as the spring unwinds.A pressure sensor is attached to a luer lock connector at the tip of the syringe. This is connected to a microprocessor, stored in an electrical box on the side of the device. A rocker switch connects battery power to the microcontroller and the pressure sensor. The microcontroller monitors the pressure at the sensor, sampling at 10 Hz to store a rolling buffer of pressure from the last 3 seconds. The processor compares the new reading with the reading from the previous 3 seconds and looks for a drop (e.g., >50 mmHg) over the interval that may indicate the needle tip is moving into a blood vessel or other unintended tissue area. The drop threshold and time frame can be variably adjusted. An LED on the electrical box may change, for example, from green to red, to indicate to the user that such a drop in pressure is present. In response to seeing a red light, the user may release the trigger and then adjust the location of the insertion needle before resuming injection of the aliquot by pulling the trigger again.

[0053] 2B-2, the main portions of the delivery mechanism and activation mechanism in an exemplary configuration are shown within the environmental case. In one aspect, the delivery mechanism includes a syringe 125 coupled with a plunger 123. In one aspect, the syringe 125 is held in place by a syringe restraint 127, which secures the syringe 125 against movement when under pressure by a lead screw 113. Other delivery mechanisms are also contemplated by the present teachings. The activation mechanism provides a desired amount of pressure to push the cells from the delivery mechanism into the organ. The amount of pressure applied is based on at least avoiding cell hemolysis, the resistance of the organ, which is influenced by the delivery mechanism, and possibly the environment surrounding the organ. In one aspect, the applied pressure is automatically monitored to allow for adjustment of the applied pressure. In one aspect, a pressure sensor / needle / administration kit can be attached to the device and the pressure sensor can be enabled. A rocker switch, among other types of switches, can be used to enable the sensor. 2B-2C and 2D, in one aspect, the delivery device includes a timing mechanism 119, a torque drum assembly 112, and a drive nut assembly 191. In one aspect, use of a device of the present teachings is initiated by charging the torque drum assembly 112, also referred to as the torsion spring or main spring mechanism. With respect to charging, in one aspect, the torque drum assembly 112 includes a torque drum 137 (FIG. 2D), a storage drum 177 (FIG. 2D), and a torsion spring (not shown). In one aspect, the storage drum 177 (FIG. 2D) and the torque drum 137 (FIG. 2D) are arranged such that a strip of spring sheet metal has two ends, the ends being attached to one of the drums. The strip of spring sheet metal is wound onto the storage drum 177 (FIG. 2D) in a relaxed state.The motor mechanism can be charged by rotating the torque drum 137 (FIG. 2D), thereby winding the strip of spring sheet metal onto the torque drum 137 (FIG. 2D), causing the torsion spring or strip of spring sheet metal to bend in the opposite direction to that in the relaxed state, thus causing the strip of spring sheet metal to tend to rewind onto the storage drum 177 (FIG. 2D), thereby generating torque, to reach a charged state. In one aspect, a torque generation method is selected that results in a constant torque, thereby allowing for a constant delivery rate and force. Once charging is complete, the device can be operationally used.

[0054] 2D, to operatively use the device, the trigger 105, when at rest, slides a wedge between the teeth of the drive gear 111, preventing its rotation and thus blocking the delivery of cells in the syringe 125. In response to a user pulling the trigger 105, the wedge 107 is pulled out of the path of the teeth of the drive gear 111, and the device is freed to continue delivery. In one aspect, if the trigger 105 is spring loaded, the operator can "pull" or release the trigger 105 in an emergency, and the spring will push the wedge 107 back into the gear teeth, causing the device to stop delivery. In this way, the trigger 105 is released and re-pressed after aliquoting. This can prevent unintentional over-delivery of drug. This also gives the device a sort of memory; i.e., if the trigger 105 is depressed partway through an aliquot and then the trigger 105 is pressed again, the device will complete the remainder of that aliquot instead of starting a new one. In some aspects, a pressure sensor (not shown) can be attached to a connector at the tip of the syringe to detect the pressure within the syringe 125 (FIG. 2B). In some aspects, the pressure sensor is connected to a processor, which monitors the pressure at the sensor. In some aspects, the processor samples at a preselected rate and stores a rolling buffer of pressure from a preselected amount of time. The processor compares new measurements to measurements from the stored rolling buffer, looking for a drop (e.g., >50 mmHg) over a preselected interval that may indicate the needle tip is moving into a blood vessel or other unintended tissue area. In some aspects, the drop threshold and time frame can be adjusted. In some aspects, the device is single use. In some aspects, the device or portions of the device are durable.

[0055] 2C, the timing mechanism 119 can moderate the release of energy stored within the torque drum assembly 112. When the gear nut assembly 191 is released to move, the torque shaft 129 (FIG. 2E) is free to move as well, allowing the timing mechanism 119 to initiate a moderated release of energy from the torque drum assembly 112 and rotation of the gear train within the gear drive assembly 191, thus driving the lead screw 113, which pushes the plunger 123 into the syringe 125.

[0056] 2E, 2F, the timing mechanism 119 (FIG. 2E) includes a timer gear mount 159 and a timer shaft 163 that is permitted to rotate by the release of a torsion spring in the torque drum assembly 112 (FIG. 2E), which allows a timer spring gear 167 to rotate. The timer spring gear 167 also rotates timer gears 179 / 181 / 183 / 185. The timer gear 185 interfaces with an escapement 166, which periodically releases the gear train to move, thus metering the flow of the cell mixture into the organ.

[0057] 2G-2I, in another exemplary configuration, the activation mechanism includes a movable device that charges the device. When the ball knob 175 (FIG. 2H) slides along the bolt rail 104 (FIG. 2H) under the body lid 122 (FIG. 2I), the primary pulley 227 (FIG. 2I), the secondary pulley 229 (FIG. 2I), the pulley belt 102 (FIG. 2I), and the bolt pivot 103 (FIG. 2H) cooperatively operate to transmit a rotational force to the torque shaft 129 (FIG. 2H). The force rotates the torque drum 137 (FIG. 2H) in cooperation with the storage drum 177 (FIG. 2H), charging the torque drum mechanism 112 (FIG. 2C). Other charging mechanisms are also contemplated by the present teachings.

[0058] 2J-2, in yet another exemplary configuration, a syringe stopper is attached to the end of the lead screw, eliminating the syringe plunger from the design and saving length. An axially stable drive nut 249 (FIG. 2K) drives the lead screw / plunger 247 (FIG. 2K) into the syringe 233 (FIG. 2K) by pivoting in place. The lead screw / plunger 247 (FIG. 2K) is held rotationally stable so that it does not translate forward and rotate with the drive nut 249 (FIG. 2K). The drive nut 249 (FIG. 2K) has gear teeth on its exterior periphery that mesh directly with the drive gear 243 (FIG. 2K). The drive shaft 245 (FIG. 2K) has a torque drum 241 (FIG. 2K) around which a spring (not shown) is wound. The housing 231 (FIG. 2O) allows for a relatively large spring, allowing for a relatively large torque. The spring selected is designed to have multiple turns with a constant torque output from the turns. The drive gear 243 (FIG. 2K) includes a spring 261 (FIG. 2L) that is sized so that one full rotation of the drive gear 243 (FIG. 2K) results in one complete aliquot of liquid delivery. In one aspect, one full rotation of the drive gear equals one aliquot, and the device includes a feature that forces the operator to release the trigger after each aliquot before beginning the next aliquot as a safety mechanism to prevent over-delivery. A timer assembly 251 (FIG. 2K) ensures that the drive shaft 245 (FIG. 2K) rotates at a fixed rate, limiting the rate of cell delivery.

[0059] 2J-2L, in one aspect, the device includes a stopcock 235 (FIG. 2K) that can ensure that cells are delivered at a preselected rate and that the cell aliquot is delivered completely in synchrony with the mechanical delivery. The stopcock 235 (FIG. 2K) is operably coupled to a stopcock pivot 239 (FIG. 2K) that engages a trigger 237 (FIG. 2K) to activate cell delivery. In one aspect, a force is applied to the lead screw / plunger 247 (FIG. 2K), for example, by rotating a crank 193 (FIG. 2O). The drive shaft 245 (FIG. 2K) can be rotated a number of times, for example, four times, to move the lead screw / plunger 247 (FIG. 2K) a desired amount. Cell delivery is initiated when the trigger 237 (FIG. 2K) is pressed and the drive nut 249 (FIG. 2K) is released. The drive shaft 245 (FIG. 2K) is rewound at a preselected interval. When present, a display (not shown) may alert the user if the pressure drops by a preselected amount over a preselected time frame, for example, but not limited to, 50 mmHg over 3 seconds.

[0060] Limited liquid delivery per trigger pull In one aspect, the device includes a mechanism that limits the amount of cell mixture delivered per pull of the trigger. The delivery limiting mechanism allows the user to deliver a quantified volume of cell mixture to a given site. With continued reference to FIGS. 2J-2L, while the trigger 237 (FIG. 2K) is pressed, an activation mechanism including a tilted beam 242 (FIG. 2K) is brought into close proximity to the front face of the drive gear 243 (FIG. 2K). Within the activation mechanism is a rotating arm 203 that is held in the center of the swing arc 202A (FIG. 2K) by a preloaded torsion spring 261 (FIG. 2L). The end of the arm 203 includes a tooth 204 (FIG. 2K) that protrudes outward from the front face of the gear 243 (FIG. 2K). When the aliquot is completed, the tooth 204 (FIG. 2K) contacts the tilted beam 242 (FIG. 2K) of the trigger mechanism. The tilted nature of the beam pushes the arm rotationally, further compressing one of the torsion springs 261 (FIG. 2L). The tooth 204 swings to the end of the advancement slot 202A (FIG. 2K), while the arm swings to the surface of the cutout 243A. The tilted beam 242 stops the rotation of the pin 204 and therefore the rotation of the drive gear 243 (FIG. 2K), and therefore the delivery of liquid. When the trigger is released, the tilted beam 242 (FIG. 2K) is moved out of the path of the tooth 204 (FIG. 2K), which allows the drive gear 243 to rotate and resume the delivery of liquid. Once the pin 204 is no longer blocked by the tilted beam 242, the arm 203 returns to its neutral position due to the two torsion springs 261 balancing their forces applied to the arm 203. In the neutral position of the arm, the tines 204 (FIG. 2K) are centered in the slot 202A and can be rotationally passed through the angled beam 242 (FIG. 2K) such that when the trigger 237 (FIG. 2K) is re-pressed, the beam no longer blocks the tines 204 (FIG. 2K) until the drive gear 243 completes another rotation and, in some cases, delivers another aliquot.

[0061] This approach can be expanded beyond one rotation of the drive gear per trigger pull. In another embodiment, there are two, three, or more assemblies of arms 203, each with a tooth 204 and centering spring 261. The drive gear 243 and liquid delivery will stop when each tooth 204 is engaged by the angled beam 242. The drive gear and liquid delivery will then resume when the trigger is released, allowing the arm 203 to a neutral position and then repulsed. In this way, smaller aliquots of liquid can be dispensed per rotation of the drive gear 243 by adding additional arms 203 to the drive gear 243. The mechanism including portions 202, 203, 204, 242, 243, and 261 described herein and referenced in Figures K and L may also be applied to any of the exemplary configurations shown in Figures 2A-2J.

[0062] 2K-2L, the arm 203 can also swing in the other direction. This, combined with the fact that the spring can store enough energy for a syringeful of aliquots, means that the device can assist with vial decant. To accomplish this, the trigger 237 (FIG. 2K) is pressed and held, and the crank 193 (FIG. 2K) is rotated, rotating the torque shaft 245 (FIG. 2K) in the opposite direction to the direction during aliquot delivery for a preselected number of full turns. As the drive gear rotates in the opposite direction, the tooth 204 (FIG. 2K) strikes the diagonally inclined side of the inclined beam 242 (FIG. 2K), which pushes the tooth upwards and over the top of the beam 242 (FIG. 2K), resulting in the torsion spring 261 (FIG. 2L) resetting the arm back to its neutral position. Rotation of drive gear 243 (FIG. 2K) jerk the drive nut 249 (FIG. 2K) back, pulling the stopper back and drawing a vacuum in the syringe, which allows drug to be drawn therein. In addition, reverse rotation of the drive gear winds the torsion spring back onto the torsion drum 239. Because energy has been cranked into the device during vial decant, crank 193 (FIG. 2K) can be removed and no further energy needs to be input into the device during the remainder of the drug delivery process.

[0063] Electromechanical Syringe 3A-3D, a first exemplary configuration of an electromechanical injection device of the present teachings is shown. The disposable device includes an environmental casing, power, a delivery mechanism, an activation mechanism, a motor mechanism, an optional status display, and a charging option. The charging option can be used in devices with field-deployed syringes, where the electromechanical actuator portion of the device contains a durable and rechargeable or replaceable battery. With reference to FIG. 3A, the exemplary device 20001 includes a syringe cover 30006. In one aspect, the syringe cover 30006 is hinged to the device case 30001. In one aspect, the syringe cover 30006 is removable / replaceable. In one aspect, the syringe cover 30006 is molded to allow placement of the syringe 503 within the case 30001. In certain aspects, the syringe cover 30006 may latch onto the device case 30001, thereby securing the syringe within the case. In certain aspects, the components of the exemplary device 20001 are protected from environmental contaminants by the case 30001. In certain aspects, the case 30001 ensures that the internal components of the device 20001 are protected from liquid contaminants. In certain aspects, the case 30001 ensures that the components of the device 20001 are protected from micro-contaminants. In certain aspects, the case 30001 ensures that the components of the device 20001 are protected from macro-contaminants. In certain aspects, the case 30001 includes internal features that hold the components in place when the device 20001 is in use.

[0064] Referring now to FIG. 3A, depicted is an electromechanical configuration of an injection device. Use of the device can include loading an empty syringe into the device and closing the lid. In some configurations, an indication to the user that the syringe is properly loaded can be provided. For example, an LED can switch from blue to green when the syringe is properly loaded. A direction selector can be toggled to reverse the device. LED light signal

[0065] In some configurations, the LED array can display a reverse pattern. To extract liquid from the vial, the trigger can be pressed and released once the liquid is extracted. In some configurations, the LED array can display a movement pattern, for example, while the trigger is pressed. The vial can be replaced with a pressure sensor and needle set, and a cable for the pressure sensor can be connected to the device. The direction selector can again be toggled to place the device in dispense mode. In some configurations, the LED array can display a forward pattern. The trigger is then pressed and held to begin dispensing the liquid. At this point, the motor will rotate up to reach the appropriate pressure to dispense the liquid and then slow down to the delivery speed. In some configurations, the LED array can display a forward movement pattern. The motor can be automatically stopped when a preselected condition occurs. For example, the motor can be stopped when a preselected amount of liquid is dispensed. This condition can be indicated by a pattern on the LED array. The motor can be automatically stopped when a pressure drop is detected. In some configurations, the LED array can flash a preselected color and release of the trigger can clear out a malfunction. The motor can be automatically stopped when the trigger is released. At this point, the motor can retract the plunger, equalizing pressure and preventing further dispensing of liquid. Manual retraction of the plunger is also a possibility, to activate a manual withdrawal mechanism.

[0066] Continuing with reference to FIG. 3A, the pressure sensor 501 senses the pressure in the syringe, allowing the user to observe, among other things, whether the tip of the needle or any part of the liquid path is blocked. The syringe can be held in the device case 30001 using a bayonet assembly. Alternatively, or in addition, the syringe cover 30006 may latch onto the device case 30001, thereby securing the syringe within the device case 30001. The device cover 30001 does not necessarily seal to the syringe. When the lead screw is driven forward, the gears are rotating around the lead screw. Continuing with reference to FIG. 3A, there are multiple ways that the user can interact with the device. The direction the plunger moves can be selected and the trigger can be pressed. In some configurations, a photointerrupter can indicate the status of the trigger. When the trigger is pulled back, it contacts a steeply angled surface and a haptic click activates the trigger. Changing the orientation can trigger haptic feedback to the user. The system can be sealed. A tunnel can be formed from one side of the device to the other to protect the printed circuit board (PCB) from moisture. The device can include a power supply button for interacting with a terminal of the power supply. In some configurations, the button can include a plastic tab between the power supply terminal and a spring contact. When a user presses on the dome formed by the button, the button flips, allowing the spring contact to interact with the power supply terminal.

[0067] Continuing with reference to FIG. 3B, the motor can have multiple speeds. A relatively fast speed can be used to accomplish rapid priming of the needle. During fast fill, liquid can be pumped at a rate of, for example, but not limited to, 5-6 ml / min. Back pressure from the cells can build up at the intersection of the tubing and the needle. The processor can slow down the motor when the pressure as detected by the pressure sensor reaches a pressure threshold that can be in the range of 300-1,000 mmHg. In one aspect, the pressure threshold is 800 mgHg. The motor 5013 can drive the pump at its relatively slower speed to deliver liquid at a rate consistent with the uptake rate of the organ. During operation, liquid can be pumped at a rate of, for example, but not limited to, 1 ml / min. Pressure can be monitored during operation to check for delivery rate. The user can stop the operation by releasing the trigger 509. The orientation of the switch 30002 can instruct the processor to start the motor in reverse. The pump may stop when the pressure measured by the pressure sensor 501 drops below a second threshold, such as below 40 mmHg, or when the lead screw 30003 reaches a limit, or when the user releases the trigger. During operation, the processor can issue an alert if the power supply voltage drops below a preselected threshold. The user can command the remaining aliquot to be delivered with the trigger 509. When the plunger reaches the end of the stroke in the syringe barrel, the processor can detect when the plunger reaches the end of the stroke in the syringe barrel by comparing the change in pressure at the sensor 501 and the rotational speed of the motor 513. The end of the stroke may be declared if the motor speed is not consistent with the measured pressure. Two examples, though not the only examples, where the end of the stroke is not consistent are the motor shaft not rotating or the measured pressure is dropping but the rotor is still rotating. The controller will place the pump in an idle state until the user changes the input.The microprocessor will reject any attempt to move forward until the user changes direction. Raising the alarm can include, but is not limited to, providing tactile feedback such as vibration.

[0068] 3B-3D, in one aspect, the components of device 20001 include battery 511, which powers motor 513. In one aspect, battery 511 is sized to provide the desired power while allowing for a relatively small footprint of device 20001. In one aspect, battery 511 is a spring mounted within case 30001 with leaf spring battery contacts 523. In one aspect, power is provided by a light and / or motion energy conversion device. In one aspect, power is provided by a rechargeable battery. In one aspect, power is provided by an electrical grid. Trigger 509 activates motor 513, which rotates gear 30011 (FIG. 3C) and gear 515. In one aspect, trigger 509, when pressed, signals a controller to jerk the motor in a direction and at a speed based, in part, on the pressure and syringe position measured by sensor 501. The controller provides power transfer from the battery 511 to the motor 513. In one aspect, the directional switch 30002 establishes the direction in which the lead screw 30003 is driven. In a first orientation of the directional switch 30002, the lead screw 30003 is driven in a first direction, and in a second orientation of the directional switch 30002, the lead screw 30003 is driven in a second direction that is opposite to the first direction. When the lead screw 30003 is driven in a first direction, e.g., counterclockwise, the coupler 30008, which is operatively coupled to the syringe plunger 516, moves the syringe plunger 516 into the syringe 503, thus displacing the contents within the syringe 503. The gear 515 rotates when the pinion 30011 is driven by the motor. Gear 515 has matching ACME threads within a bore through which it draws lead screw 30003 which in turn draws coupler 30008 and actuates the syringe plunger. Coupler 30008 is fixedly attached to lead screw 30003 and prevents the lead screw from rotating about its longitudinal axis. Syringe presence detect switch actuator 30009 includes a clearance pocket or opening 30009A to accommodate lead screw 30003.In one aspect, as the coupler 30008 progresses linearly along the lead screw 30003, an end stop detector 521 mounted on the bar 30010 detects when the coupler 30008 reaches a preselected travel point, and the end stop detector 521 signals the controller to reverse the motor 513, which reverses the direction of the lead screw 30003. In one aspect, the status of the device is displayed by at least a pattern of LEDs on the status display 505. In one aspect, when the coupler 30008 is pushing the syringe plunger 516 into the syringe 503, the status is displayed in a first color pattern. A second color pattern can be displayed when the coupler 30008 is moving away from the syringe 503. When the device 20001 is experiencing a problem, the status is displayed in a third color pattern. Several states can be represented, for example, by color combinations or numeric status indicators. In some aspects, the status is provided through audio, numerical / color, video, tactile (such as a vibrator in the handle), and / or olfactory means. In some aspects, the pressure exerted on the cells as they move out of the syringe 503 and into the organ is measured by a pressure sensor 501. In some aspects, the pressure sensor 501 provides sensor data to an on-board controller (not shown), which adjusts the delivery force to maintain the desired pressure. In some aspects, adjusting the delivery force includes adjusting the rate at which the lead screw 30003 is progressing laterally through adjusting the rotational speed of the motor 513. In some aspects, the pressure sensor 501 is located relative to the syringe 503. In some aspects, the pressure sensor 501 is hardwired to the battery 523 and controller, or communicates data wirelessly. In some aspects, other properties of the cells besides pressure are also measured by other sensors appropriately positioned on the device and in close proximity to the cells. In some aspects, heat, pH, and dissolved oxygen data are collected and stored. In one aspect, the data storage is remote to the device 20001 and the data is transmitted wirelessly to the remote (relative to the device 20001) storage location.

[0069] 4A-4L, another exemplary configuration of an electromechanical injection device of the present teachings is shown. In one aspect, the device 20016 includes a two-part case 30097 having a right side 30097-2 and a left side 30097-1 operably coupled to enclose the components of the device 20016. In one aspect, the case 30097 includes a mounting cavity 567 (FIG. 4B) for a syringe 30054. The case 30097 can be formed to accommodate syringes of various sizes and can include an adapter (not shown) that allows the cavity to accommodate a syringe that is smaller than the cavity. In one aspect, the case can include more than two sections. For example, the case 30060 (FIG. 4E) includes a rear section 30060-1, a middle section 30060-2, and a syringe section 30060-3. Other cases are also contemplated by the present teachings. The primary function of the case is to protect the components from environmental contaminants. In some aspects, the case provides a sturdy grip for the user to steadily deliver cells to the organ until delivery is complete or otherwise terminated. In some aspects, the case provides access to charging and data ports. In some aspects, the case provides access to a power source and a switch associated with the power source. In some aspects, the case provides access to an activation means that enables the injection process. In some aspects, the activation means is a trigger. In some aspects, the case provides, among other things, a way for the user to monitor the status of the device and potentially the status of cell delivery.

[0070] In the event the device fails, unused or remaining cell mixture can be retrieved using the retrieve knob 30093 and one of the disclosed anti-rotation flexures 300094, 30114. A cam can allow the lead screw to be driven to allow liquid to be withdrawn by another syringe. Allowing the tip or plunger seal to rotate on the end of the lead screw reduces friction during retrieval of the cell mixture.

[0071] 4E-4H, the configuration shown includes a syringe / lead screw system coupled with an override actuator cam that can allow the lead screw to be driven to allow liquid to be drawn by another syringe. The configuration includes a PCB into which the trigger mechanism, user display, trigger button / snap action / flex snap, directional selection button, and power supply are coupled. The PCB can include mounting and connections between the master processor and devices providing data to the master processor. A communication interface can also be included on the PCB.

[0072] 4E-4H, an exemplary set of components that enables electromechanical organ injection is shown. The general categories of components include a battery 40011, an activation mechanism 30087, a motor 40001, drive mechanisms 30057, 30087, 30094, and delivery mechanisms 30098, 30054. In one aspect, the battery 40011 is mounted to the PCB 50018 using a mounting spring 565. Other forms of power are also contemplated by the present teachings, such as, for example, grid power, capacitors, supercapacitors, rechargeable batteries, single use batteries, and various types of batteries including lithium, alkaline, carbon zinc, silver oxide, and zinc air batteries. In one aspect, a power switch 30089 / battery button pressure plate 30088 activates / deactivates the battery power source or places the battery in a low power mode to conserve battery life during use, for example, during long procedures. In one aspect, power is provided by a 9V battery. In one aspect, the activation mechanism is a trigger 30087.

[0073] In another aspect, the battery switch 30089 feeds a low power circuit that feeds the latching relay. Initially, the trigger 30087 is pulled fully towards the handle, and the latching relay is closed, connecting the battery power to the controller located on the PCB 50018. Continued and subsequent pulls on the trigger 30087 command the controller to drive the motor. The speed and direction of the motor depend on the measured pressure from the pressure sensor 50019 and the control logic described below and with reference to Figures 9A-9E. In one aspect, the trigger 30087 is operatively coupled to the spring 40004, allowing the trigger 30087 to return to its pre-pressed position. Other forms of activation are also contemplated by the present teachings. The device 20016 can include, for example, a switch or push button that can activate the motor 40001. In one aspect, the device 20016 includes a communication means (not shown) that allows remote activation / deactivation. In one aspect, the remote activation message is communicated through wireless or wired means.

[0074] 4E-4H, the motor orbits the drive mechanism and applies a force to the delivery mechanism, including the lead screw / plunger 30098 and the syringe barrel 30054. In one aspect, the motor 40001 rotates the pinion 30057, which in turn rotates the gear 30084, which includes a medium-sized spiral slot gear. The spiral slot gear of the gear 30084 rotates around the lead screw 30098, which translates forward or backward depending on the direction of rotation of the gear 30084. The anti-rotation flexure 30094 prevents the lead screw 30098 from rotating, thereby causing the slot gear 30084 to rotate and translate the lead screw forward or backward along the longitudinal axis of the lead screw. The lead screw 30098 is crowned on its forward end by a flexure tip 30095 (FIG. 2H) and a plunger seal 40000. The plunger seal 40000 (FIG. 4K) communicates directly with the cell mixture in the syringe barrel 30054 and pushes the mixture forward and out of the syringe 30054 as the lead screw 30098 moves forward. O-rings 40007 / 40008 (FIG. 4G) seal the housings 30060-2, 30060-3 (FIG. 4B) to the syringe 30054, thereby protecting the components inside the housings 30060-1, 2, 4 from the environment. Pressure measurements from the sensor 50019 are transmitted to a controller on the circuit board 50018. In one aspect, the controller can use the pressure information to create an indicator for the display 20023. In one aspect, the controller can use the pressure information to, for example, adjust the speed of the lead screw 30098. In one aspect, the syringe 30054, motor 40001, and lead screw 30098 are operatively coupled by the combination of a gearbox front plate 30055 and a gearbox rear plate 30074. The gearbox rear plate 30055 includes a coupling cavity 569 that also acts as a bearing surface for a hub on the gear 30084, allowing a plunger seal 40000, disposed within the syringe 30054 during assembly, to move as the drive gear 30084 rotates and the lead screw 30098 moves linearly.The gearbox plate 30055 provides the motor shaft termination cavity 571 (FIG. 4H) and the surface against which the pinion 30057 rotates. In one aspect, to limit the rotation to the lead screw 30098 and gear translation, the syringe gearbox backplate 30074 operatively couples to the gearbox plate 30055 by coupling the connection tabs 573 (FIG. 4H) with the tab slots 575 (FIG. 4H) and the pins 577 (FIG. 4H) with the cavities 579 (FIG. 4P). In one aspect, the backplate 30074 includes tabs and hooks 30072 that guide and secure the motor 40001 to the backplate 30074. In one aspect, various designs of the backplate 30074 can accommodate various gearbox sizes. Other geometries of the backplate 30074 and the gearbox plate 30055 are also contemplated by the present teachings. In one aspect, the back plate 30074 includes a guide 30055 for routing the flat cable 40014 with the drive gear 30084. The back plate 30074 includes a pincher 30072 that holds the syringe / gearbox assembly in place within the case during assembly.

[0075] 4F, the pressure applied to the cell mixture in the syringe 30054 may be measured in a number of ways. In one aspect, the cell mixture pressure in the syringe may be approximately measured by the force exerted by the syringe barrel 30054 against the pressure sensor 50019. The syringe barrel 30054 includes a nozzle and luer fitting 40008 that is located off the centerline of the barrel to provide a larger contact area for the pressure sensor 50019. This design is advantageous because the barrel directly contacts the sensor plate or sensor element on the pressure sensor 50019 with no sliding or rotating elements in between that would add friction and reduce both the accuracy and responsiveness of the signal to changes in mixture pressure inside the syringe barrel 30054.

[0076] In another aspect, the mixture pressure may be measured using a pressure sensor 501 (FIG. 3C) that contacts a flexible section of tubing downstream of the syringe 503. In another aspect, the mixture pressure may be measured using a force or pressure sensor mounted between a drive mechanism element, such as the back plate 30074, and the housings 30060-1, 30060-2. In one aspect, the mixture pressure can be assessed by measuring the voltage and / or current supplied to the electric motor 40001.

[0077] A flexure to allow collection of cell mixtures

[0078] 4F-4G, in a first position shown in FIG. 4F, the anti-rotation flexure 30094 prevents the lead screw 30094 from rotating axially about its longitudinal axis. The lead screw 30094 includes one or more flat surfaces 30102 that are parallel to the longitudinal axis. The flexure 30094 has a matching flat surface 30108 that prevents the lead screw 30098 from rotating. Additionally or alternatively, the lead screw 30098 may have one or more axial notches 30104 and the flexure 30094 may have a matching insert 30106 that prevents the lead screw from rotating. The combined action of the rotating gear 30084 and the anti-rotation flexure 30094 results in the lead screw 30098 translating along its axis without rotation.

[0079] In normal operation, the remaining cell mixture is retrieved by injecting fluid so that the delivery device returns into the vial for storage. In some cases, the delivery device is unable to deliver the remaining cell mixture due to pump failure, low battery, etc. In these cases, the remaining cell mixture can be retrieved by manually driving the lead screw forward and pushing the cell mixture out of the syringe barrel 30054. In the delivery configuration, manually pushing the lead screw forward would require significant force to backdrive the gear 30084, pinion gear 30057, and electric motor 40001.

[0080] In one alternative, the anti-rotation flexure 30094 is spread open by rotating the retrieval knob 30093. The retrieval knob 30093 includes protrusions that interface with elements 30110 at the top of the anti-rotation flexure 30094 on each side of the split. Rotating the retrieval knob 30093 applies a force against the flexure protrusions 30110 which spreads the two halves of the anti-rotation flexure 30094. The spread open flexure 30094 moves the surfaces 30106, 30108 away from the lead screw 30098, which allows the lead screw 30098 to rotate. Once the lead screw 30098 is free to rotate, the lead screw 30098 can be manually translated forward without turning the gear 30084, thus reducing the force required to push the lead screw 30098 forward and push the remaining cell mixture out of the syringe barrel 30054. The retrieval knob 30112 may include a one-way drive slot 30112, allowing the retrieval knob 30093 to be used only once. After use, the retrieval knob with the one-way slot 30112 cannot be easily returned to a delivery configuration, which would allow the anti-rotation flexure 30094 to re-engage the flat surface of the lead screw 30098. The one-way drive slot 30112 on the retrieval knob 30093 prevents the user from using the device after failure.

[0081] 4K, an exemplary configuration of a syringe / lead screw device 20015 is shown. The device 20015 includes a manual override system to retrieve the cell mixture when the device is electrically or programmatically disabled. Specifically, rather than a rigid thread within the pore of the gear 30058 to convert the rotational motion of the motor 50005 to the linear motion of the lead screw 30098, the internal thread of the gear 30058 can be moved into / out of engagement with the lead screw 30098. In one aspect, multiple flexible petals are used that form both the pores and the hub on the gear 30058. The natural unconstrained shape of the petals is in an outwardly flexed position where the lead screw 30098 can slide freely through the pore of the gear 30058. When the petals are radially constrained, the threads cut into the inner surface of the petals engage the lead screw 30098. An exemplary configuration includes a removable rigid ring (not shown) that radially constrains the petals so that they engage the threads on the lead screw. In another configuration, an O-ring (not shown) constrains the petals. In yet another configuration, a U-piece (not shown) slides through the housing and constrains the top and sides of the petals. In all these configurations, the user would remove the constraint before manually pushing the lead screw forward to retrieve the cell mixture.

[0082] 4M, 4N, an exemplary configuration of a system for enabling manual recovery of a cell mixture includes a rounded anti-rotation flexure 30114 that rotates between two positions, 30120, where a flat surface of the lead screw 30098 is engaged, and 30122, where an inner surface of the flexure 30114 allows the lead screw 30098 to rotate. In the delivery position 30120, the rounded anti-rotation flexure 30114 engages with at least one of a flat surface on the side of the lead screw and a longitudinal notch on the lead screw, thus preventing the lead screw 30098 from rotating. In the second position 30122, the rounded anti-rotation flexure 30114 allows the lead screw 30098 to rotate freely. The rounded flexure 30114 rotates between the delivery position 30120 and the second position 30122 about an axis perpendicular to the longitudinal axis of the lead screw. The rounded flexure 30114 has a rounded exterior so that it can rotate while remaining in a fixed location relative to the plate 30074. The rounded anti-rotation flexure 30114 may include a recess 30116 that allows for engagement with the retrieval knob 30093 and allows the user to change the position of the rounded flexure 30114 by rotating the retrieval knob 30093.

[0083] In some aspects, the device 20015 can include a removable tip plunger that can allow the tip 30066 to be removed from the lead screw 30067 (FIG. 4T) and move independently. In some aspects, a wire clip 30068 (FIG. 4U) is used to remove the tip 30066. In some aspects, a quick release pin-type design (not shown) is used to remove the tip 30066. In some configurations, a backdrivable lead screw with a relatively high pitch lead screw can be backdriven by applying an axial force. In some configurations, the gear train can be decoupled, which can move the motor axially, moving the gear out of engagement and allowing free rotation of the driven gear. In some configurations, for example, in the injection device 20016 (FIG. 4H), the anti-rotation can be removed. The torque applied to the screw opposes the frictional component of the conversion of the motor torque to a linear plunger force. The elimination of this reaction torque allows for rotational motion (and therefore linear motion) independent of gear motion.

[0084] Direction Switch 4C-4E, in one aspect, the lead screw 30098 can be advanced linearly forward and backward by reversing the rotation of the motor 40001 and thus the gear train. In one aspect, the direction of advancement of the lead screw 30098 can be selected. In one aspect, the selection is accomplished by use of the direction selector buttons 30077 / 30078. The buttons cooperate through an operable coupling between the geometry of the buttons 30077 / 30078 and the selector tunnel 30092. The two buttons 30077 and 30078 are interconnected and have sliding surfaces that ride on guide tabs 711 in the selector tunnel 30092. The button / tunnel assembly is configured as a bistable switch such that the button combination is in one of two extreme positions. The position of the buttons is optically determined by emitters and sensors mounted on the PCB 50018 (FIG. 4F). A window in the selector tunnel 30092 allows light from at least one IR emitter on the PCB to reach a matched IR sensor on the PCB by passing through a window / light pipe / lens 717 in the selector tunnel 30092. At least one IR emitter or IR sensor will be blocked by the buttons 30077, 30078 in one of the bistable positions. At least one IR emitter or IR sensor will be unblocked by the buttons 30077, 30078 in one of the bistable positions.

[0085] In certain aspects, other selector button configurations are also contemplated by the present teachings. With reference to FIG. 4D, four external tabs 711 provide guidance to the button. Center tab 713 provides spring alignment during assembly. Misalignment size 715 ensures proper orientation during assembly. Spring arms 719 provide a preload against the PCB to ensure proper seating. O-ring 40009 seals the tunnel to the case halves. In certain aspects, other selector button configurations are also contemplated by the present teachings. With reference to FIG. 4D, four external tabs 711 provide guidance to the button. Center tab 713 provides spring alignment during assembly. Misalignment size 715 ensures proper orientation during assembly. Spring arms 719 provide a preload against the PCB to ensure proper seating. O-ring 40009 seals the tunnel to the case halves.

[0086] Pump in tray 4J, in one aspect, the carrying case 581 includes a cavity sized to fit the injection device 20016 (FIG. 4A) in an exemplary configuration. In one aspect, the carrying case 581 includes syringe storage 587, needle storage 585, and transfer tubing storage 583, in addition to storage for the device 20016. The carrying tray 581 provides for convenient assembly of parts to be sterilized and then sealed. In one aspect, the tray and components within the tray may be sterilized with ethylene oxide. Other configurations of the carrying case are also contemplated by the present teachings. For example, the case can include storage locations for spare batteries, spare sensors, spare displays, and other items.

[0087] display screen 4I, an exemplary monitoring screen is shown. In one aspect, a power button 30089 and a trigger button 30087 receive user input. Other user input features are also contemplated by the present teachings. For example, an arrow button (not shown) can allow the user to adjust the pressure of the cells entering the organ. In one aspect, when the power button 30089 is pressed, identifying information about the device, such as the manufacturer and version number of the device, is displayed on the display assembly 20023 (FIG. 4H), which is powered through the connector 563 (FIG. 4H). In an aspect for training, for example, a first operating screen is displayed, through which the screens can be stepped by repeatedly pressing the trigger button 30087 (FIG. 4H) or by pressing and holding the trigger button 30087 (FIG. 4H). In one aspect, at the top of the screen, as shown in FIG. 4F, there is a battery level indicator. Once the user steps through the screens, the user is returned to the first operating screen and the battery indicator is updated. In one aspect, the first operating screen, power-on self-test screen 601, is displayed after power-up and after the identification screen is shown. A possibly animated arrow on the power-on screen 601 indicates syringe movement as the device prepares for the first "fill" operation. A forward end stop indicator display 603 indicates that the syringe is in a fully forward position and therefore empty. An idle display 605 indicates that the device is idle and waiting for a directional (fill or inject) operation to be selected. In one aspect, the screen toggles between a forward pointing arrow and a backward pointing arrow. A pre-fill screen 607 indicates that a "fill" direction has been selected. In one aspect, pressing the trigger button 30087 (FIG. 4H) initiates the "fill" operation. In one aspect, the arrow toggles between two preselected colors. A fill screen 609 indicates that a "fill" operation is in progress. A possibly animated arrow indicates the direction of syringe movement as it fills. An occlusion during fill indicator 611 indicates that the "fill" action has been interrupted by an occlusion.A geometric shape, such as a triangle, can toggle between visible and hidden in the display. A rear end stop indicator display 613 indicates that the syringe is in the full rear position and is therefore full. A pre-injection display 615 indicates that an "inject" direction has been selected. In one aspect, a trigger button 30087 (FIG. 4H) initiates the "inject" action. An arrow can toggle between two preselected colors in the display. An injection display 617 indicates that an "inject" action is in progress. An arrow, possibly animated, indicates the direction of syringe movement when it is empty. An occlusion during injection display 619 indicates that the "inject" action has been interrupted by an occlusion. A geometric shape, such as a triangle, can toggle between visible and hidden in the display.

[0088] 5A-5B, an exemplary configuration of an electromechanical injection device 20010 of the present teachings is shown. The device 20010 includes a syringe assembly 20009, a directional switch button 30043, a bidirectional switch 541, an environmental case top 30030-4, a case left side 30030-1, and a case right side 30030-2. The device 20010 is activated by a trigger 30039. The trigger 30039 is operably coupled to a trigger paddle 30032. The trigger paddle 30032 activates a motor 50005 through interaction between a base snap action switch 534 and a battery (not shown) when the trigger 30039 is pulled. When power is provided, the motor 50005 rotates a motor drive pinion 30036, which in turn drives a gear 30019. The threads in the gear 30019 interact with the threads of the lead screw 30016, driving the lead screw 30016 as it moves laterally backwards or forwards. The switch 30043, when pressed, reverses the current direction of the lead screw 30025. The gear 30019 and pinion 30036 are operatively coupled to the syringe 30052 and motor 50005 by cooperating mounts on the syringe gear box plate 30042 and syringe gear box back plate 30031. Features on the syringe gear box back plate 30031 allow for mounting of the motor 50005. Features on the syringe gear box plate 30042 couple the encoder board 50008 to the motor 50005. The flex board 50001 provides directional status, pressure status, and device status, for example, through visual indicators. Other ways in which the status may be indicated are through tactile feedback, audible status, and plain language messages, among other ways. In operation, as the lead screw 30016 is driven, cells are moved from the syringe 30052, past the pressure sensor 552, and into the organ.In one aspect, the back plate 30031 and gear plate 30042 provide mounting for a gear and lead screw assembly including, but not limited to, a pinion 30048, a J-sleeve bearing 556, and a magnet 550 that is coupled to the motor 50005, and a sleeve bearing 552A that surrounds the gear 30019, thrust washer 554, and lead screw 30016. The device 20010 uses an encoder 30036 based on a magnetic sensor that reads the position of a magnet attached to the shaft of the motor 50005 or the output shaft of the reduction gear at the end of the motor.

[0089] 6A-6C, an exemplary configuration of an electromechanical injection device 20013 of the present teachings is shown. The device 20013 uses a radially magnetized magnet 528 with a preselected number of poles and rotated around an axis parallel to the plane of the sensor die, thus requiring no additional PCB. The sensor integrated circuit is shown seated on the PCB 50014. The device 20013 includes separate forward and reverse direction buttons / switches 538 / 540 / 548, a directionality status indicator 542, a pressure status indicator 544, a system status indicator 546, and a power button 536. The environmental case of the device 20013 includes a case top 30044-2 and a case bottom 30044-1. The case top 30044-2 includes a mounting cavity for the syringe 30052. Operationally, the device 20013 is powered on by pressing a button 536(), which is operably coupled to a battery contact lever 30050 (FIG. 6E). Power is thus provided to a motor controller on the PCB 50014. The motor controller controls the speed and direction of the motor 50005(). As discussed herein, when a trigger paddle 30047 is pressed, the motor 50005 is activated and rotates a pinion 30048(). In one aspect, the trigger 30045 is spring loaded, causing it to automatically return to its original position. The motor 50005() rotates the pinion 30048, which rotates a gear 30019. The gear 30019 drives a lead screw 30016, which moves laterally and pushes the cells from the syringe 30052, past the pressure sensor 530, and into the organ. An alternative configuration of the encoder of device 20013 uses a set of inductive coils to sense the position of a metal screw. As the screw is driven, the effective position of the inductive target appears to change.

[0090] 7A-7C, various exemplary case configurations are shown. These cases can be combined with the drive mechanisms, sensors, and internal features shown in FIGS. 4A-L, 5A-B, and 6A-C. In the example shown in FIGS. 7A and 7B, push buttons 572 on the side of the case opposite the syringe cavity can be used for various types of control. In one aspect, one button 572 is used to enable power to the device, and the other button 572 is used to disable power to the device. In one aspect, one button 572 is used to set the forward direction of the lead screw (towards the syringe), and the other button 572 is used to set the reverse direction of the lead screw (away from the syringe). In one aspect, one button 572 is used to increase the delivery pressure for the cell mixture, and one button 572 is used to decrease the delivery pressure for the cell mixture. In some aspects, one button 572 is used as a trigger and one button 572 is used to deactivate the trigger function. In some aspects, cutouts 564 as shown in FIGS. 7A and 7B are for a snap feature as an interface option. In some aspects, the status indicators are similar in structure and use to the status indicators described with respect to device 20002. The status indicators can be associated with functionality of the buttons 572 or can report status about some other aspect of the system. In some aspects, cavity 561 allows for mounting of forward and reverse directional buttons. In some aspects, cavity 561 allows for mounting of status indicators. The case of FIGS. 7A and 7C has an ergonomic design in which the syringe carrying section 568 is at an angle from the handle section 568A. This feature reduces fatigue in the user's hand by allowing a more upright grip of the handle while the syringe is angled downward. 7C, there is shown a toggle switch 573 and an activation pad 573. In one aspect, the toggle switch 573 changes the direction of the lead screw when toggled.In an aspect, when toggle switch 573 is toggled, power to the device is either enabled or disabled. Toggle switch 573 can allow other actions as well. The present teachings are not limited to the possibilities described. The configuration of FIG. 7C includes an activation pad 576. In an aspect, activation pad 576 is used to power the device. In an aspect, activation pad 576 is used to trigger actions of the device. In an aspect, activation pad 576 is used to change the direction of the lead screw. In an aspect, activation pad 576 is used to power the device, trigger actions, and change the direction of the lead screw, the function of which is determined by the current state of the device. The syringe plunger / lead screw interface in the configuration shown in FIGS. 7A-7C is similar to the interface depicted for device 20013 (FIGS. 6A-6C). The paddle trigger flexure is an overmolded / elastomer component to complete the housing while allowing the trigger to be actuated. In operation, the trigger functions as follows: The paddle trigger 30022 pivots and activates a microswitch on the PCB. The snap / tactile nature of the trigger is provided by a piece of spring steel that spans between the case halves. In one aspect, the plastic version uses a thin plastic web rather than the spring steel used in the device shown in FIG. 8E.

[0091] 8A-C, an exemplary configuration of an electromechanical injection device 20002 of the present teachings is shown. The device 20002 includes a case top 30020-8, a case right side 30020-5, a case left side 30020-6, a syringe mount 30020-3, and a paddle trigger flexure 30023, which together protect the internal components of the device 20002. The syringe 705 encloses the lead screw 30025, the syringe plunger tip 30018, and the plunger seal 30041. The electronics portion is connected to a PCB 50003, which includes a processor that sequences commands that cause the device 20002 to deliver the cell mixture in the syringe 705 to an organ. The flexure board 50001 includes sensors, and an LED board (not shown) includes status indicators that report information collected by the sensors. When the paddle trigger flexure 30023 engages the paddle trigger 30022, the battery 701 begins to provide power to the motor 50005. When the direction selector 30021 is pressed, the pinion 30028 (FIG. 8B) begins to rotate, rotating the gear 30019 and moving the lead screw 30025 laterally. In one aspect, a press-fit pinion shaft adapter 30013A engages the pinion 30028 and couples the pinion 30028 to the encoder board 50002, the pair of which surrounds and rotates with the shaft of the motor 50005. In one aspect, the syringe assembly 20014 includes a lead screw 30025 coupled with the gear 30019 and a mating portion including a thrust washer 30027 / 709 and a sleeve 707. As the lead screw 30025 moves laterally forward, the cell mixture within the syringe 705 is displaced out of the syringe 705 .

[0092] 8D-8E, a configuration is shown in which a device of the present teachings uses a commercially available field-deployed syringe. In certain aspects, the devices shown in FIGS. 8D-8E include additional features relative to the devices shown in FIGS. 3A-3C. For example, device T20001 includes a short nose, device T20002 includes an internally threaded plunger, device T20003 includes a fully axial actuator, and device T20004 includes a variation of the signal transmission interface described herein. Specifically, device T20001 includes a syringe plunger actuator nut 30013 that encounters and presses against the syringe plunger as the plunger screw is driven toward the syringe 125. A motor / encoder / magnet 513 / 528 / 550 drives the plunger screw 30014. Battery leads / springs 524 / 523 maintain the position of the battery 701, and PCB 50001 provides mounting for the electronics. Device T20002 includes a long nose case T30019 with a status indicator. Device T20002 (FIG. 8J) includes an internally threaded plunger 30017 that rotates as a broached plunger screw 30020 is driven by a motor 513 and drives a syringe plunger. A plunger sleeve T30018 protects the internally threaded plunger and plunger screw 30020 from contaminants. Device T20003 includes a pressure sensor 501 that detects its pressure against the syringe 125 and the long nose case 30021. Other parts shown in exploded form in FIG. 8M are similar to those of device T20002. Device T20004 includes indicator light 731, pressure sensor 501, pressure sensor mount device 30000, and activation switch 733. Case T30022, which is coupled to a syringe plunger cover with a Hall magnet 30024, protects the electronics within device T20004. Direction switch 30027 provides a way to control the direction of plunger screw 30014. Pressure sensor 501 is supported by mount 30000, which is coupled to case T30022.In one aspect, a bias magnet located in the rear housing component ensures a preselected output state of a Hall effect sensor mounted on a PCB in both door open and door closed conditions. The device T20004 includes a snap action plunger trigger T30025 that activates the motor 513 and thus the plunger screw 30014. A vibration motor 743 provides tactile feedback, and the trigger slides a tab 741 that interrupts the IR signal, signaling that the operator has actuated the trigger.

[0093] operation 9A-9E, in one aspect, the device shown and described herein is used according to the following process. An exemplary method of use of the system of the present teachings is shown in flow chart form. The flow chart shows a combination of user actions, primarily related to patient treatment, and actions automatically initiated by the device, for example, in pressure fault monitoring and system health monitoring. A syringe is filled to a preselected volume, for example, but not limited to, based on the requirements of the therapy. For example, the therapy may call for 10 mL of liquid delivery. The syringe can be filled with cells manually or possibly automatically at a station along the manufacturing line. The cells are ready for the injection process, for example, when they reach a desired level of confluence. Possibly, other characteristics of the cells or organ-dependent cells can also be used to determine their readiness for insertion into an organ. Once the syringe is filled to the desired volume, it is inserted and anchored into the device of the present teachings. The insertion / anchor process can be manual or automatic. The automated process can be enabled by the manufacturing line used to build the device. At a station along the line, a filled syringe can be inserted into the device by a manufacturing line robot, which can secure the syringe to the device. The securing means can include, but is not limited to, a syringe restraint. In some aspects, the syringe restraint is held in place by a turn latch. In some aspects, the syringe restraint has a latch or has a mutual attachment mechanism such as a VELCRO® strip. Operationally, use of the device can include the process of using a directional selector, placing the device in reverse, pressing a trigger, extracting the cell mixture from a vial, and releasing the trigger when complete. The process can include the steps of replacing a vial with a pressure sensor and needle set, connecting a pressure sensor cable, using a directional selector, and placing the device in dispense (forward) mode. The process can further include pressing and holding the trigger to begin dispensing.The motor will spin up to reach a preselected dispense pressure and then slow down to a preselected delivery rate. The motor will automatically stop when a preselected amount of eluate (cells) is dispensed, or a pressure drop is detected (in which case the trigger is released and the fault cleared), or the trigger is manually released. The motor will retract the plunger, equalizing pressure and preventing further dispensing of eluate.

[0094] The flow chart of Figures 9A-9E includes steps for starting the electromechanical device, preparing the device for delivery, delivering cells from the device, and shutting down delivery. In one aspect, the user starts by thawing the injection solution and removing the device from its packaging. With reference to Figure 9A, in one aspect, the user can remove the battery pull tab or other means (305), indicate to the device to perform a start-up sequence (310), and connect the injection device to a thawed injection storage container. In one aspect, the start-up sequence includes steps 320 of starting logging of device and user actions, step 322 of verifying that a clock the device may have is operating correctly, step 322 of verifying that a communication means providing pressure 324 and encoder data 325 is operating correctly, and step 330 of determining the status of the battery. Under a set of preselected conditions, an alarm can be issued (335) and the device is disabled (340). Pressure values ​​are checked for excessive low values ​​318 and high conditions. If the startup routine executes successfully, a status indicator, if present, is activated (312).

[0095] With reference to FIG. 9B, in one aspect, the device includes an idle state 400 to which processing returns when the motor is stopped. The device exits the idle state when a user takes an action, for example, to fill the device (405) or to start an injection sequence (420). In one aspect, the filling process includes the user setting the device to a fill position and the user activating a trigger of the device (407). In one aspect, the system drives the motor in reverse (409) at a preselected speed until the trigger is released (410), stopping the motor (412) and moving the device to the idle state 400. At this point, the user can remove the injection device from the injection storage container and connect the injection device to the transfer tubing and the transfer tubing to the injection needle. The injection device is set to an injection position (420) and the trigger is pulled (422) to begin priming at a preselected forward priming rate (424). The preselected forward priming rate is different from the preselected reverse rate of 409. Priming is complete when either pressure rises to a predetermined minimum value. Once priming is complete, the user stops the priming action by releasing the trigger and inserts the needle into the patient.

[0096] After priming, the user sets the device to the injection position and begins the injection action. The user waits until a preselected amount of solution is injected into the patient while monitoring the pressure. The user stops the injection action or the system reaches a deposition limit. The user repeats the injection step if needed and then moves the needle to the next injection site if needed. The device disables itself when it reaches the injection limit. At that point, the user removes the needle from the patient and disposes of the device, transfer tubing, injection needle, and remaining solution (ensuring that a reverse division exists).

[0097] 9C-9D, during injection, several conditions are continually checked, including if the trigger is released (430), if the pressure measured by the pressure sensor exceeds another preselected amount (432), or if the injection duration exceeds a preselected time period, such as 3 seconds (438), or if the motor current exceeds a preselected amount (434), or if there is a speed / estimated speed mismatch (436), an alarm 335 is issued and the motor is stopped (412) (FIG. 9A). If not, the system calculates (440) the rate of change of pressure and tests that value against various thresholds 442-446 for purposes of illuminating or otherwise activating status indicators 450-458 or any form of reporting to the user. For example, if the rate of pressure change exceeds a preselected percentage and the pressure exceeds a preselected value, some form of indication that the pressure is very high is presented to the user. Otherwise, the pressure is indicated as high. Table I provides a list of exemplary thresholds. The device continues to operate in reverse until the trigger is released, at which time a status indicator is provided to the user. [Table 1]

[0098] 9C-9D, if the motor current exceeds a preselected amount (434) or there is a speed / estimated speed mismatch (436), an alarm is issued. If there is no mismatch, and if the trigger is not released, and if the pressure is less than or equal to the preselected amount (432), and if the elapsed time exceeds the preselected amount (438), in one aspect the system drives the motor forward at a preselected rate (462) (FIG. 9E). If the pressure is less than or equal to the preselected amount and the elapsed time is less than or equal to the preselected amount, the injection loop continues. 9E, if the bolus limit is not reached (460) and if the measured pressure is above a preselected amount (316) or if the measured pressure is below another preselected amount (318), an alarm is generated (335) (FIG. 9D) and the system enters a loop that drives the motor in reverse at a preselected rate (409) (FIG. 9B) until the trigger is released, or the pressure falls below a fourth preselected value, such as 40 mmHg (464), or the elapsed time of the reverse motion exceeds a preselected time, such as 3 seconds (438). When any of these conditions occur, the motor is stopped (412) and the pump returns to idle 400.

[0099] 10, an exemplary configuration of states of the device is shown, with legal transitions indicated by connecting lines. Transitions such as between the spin up state and the inject state, between the inject state and the spin down state, and between the fill state and the inject state, among others, can be automatically initiated. Transitions such as between the pre-fill state and the fill state can also be initiated by pressing a trigger switch. Toggling a switch can also initiate transitions such as between the idle state and the pre-inject state, and others.

[0100] The present configuration also covers software / firmware / hardware for performing the methods discussed herein, and computer-readable media storing software for performing these methods. The various modules described herein can be performed on the same CPU or on different CPUs. In accordance with the statute, the present configuration has been described in more or less specific language with respect to structural and method features. However, it should be understood that the present configuration is not limited to the specific features shown and described, since the means disclosed herein comprise the form of performing the present configuration.

[0101] The method can be implemented, in whole or in part, electronically. Signals representing actions taken by elements of the system and other disclosed configurations can travel via at least one live communication network. Control and data information can be executed and stored electronically on at least one computer readable medium. The system can be implemented to execute on at least one computer node in at least one live communication network. General forms of the at least one computer readable medium can include, for example, but are not limited to, a floppy disk, a flexible disk, a hard disk, a magnetic tape, or any other magnetic medium, a compact disk read-only memory or any other optical medium, a punch card, a paper tape, or any other physical medium with a pattern of holes, a random access memory, a programmable read-only memory, and an erasable programmable read-only memory (EPROM), a flash EPROM, or any other memory chip or cartridge, or any other medium from which a computer can read. Additionally, at least one computer-readable medium may contain graphs in any format, including, but not limited to, Graphics Interchange Format (GIF), Joint Photographic Experts Group (JPEG), Portable Network Graphics (PNG), Scalable Vector Graphics (SVG), and Tagged Image File Format (TIFF), with appropriate licensing as required.

[0102] Although the present teachings have been described above in terms of specific configurations, it should be understood that they are not limited to these disclosed configurations. Numerous modifications and other configurations will occur to those skilled in the art to which this pertains, which are intended to be and will be covered by both this disclosure and the appended claims. It is intended that the scope of the present teachings should be determined by the proper interpretation and construction of the appended claims and their legal equivalents, as understood by those skilled in the art relying on the disclosures in this specification and the accompanying drawings.

[0103] Although the present teachings have been described in terms of specific configurations, it should be understood that they are not limited to these disclosed configurations. Numerous modifications and other configurations will occur to those skilled in the art to which this pertains, which are intended to be and will be covered by both this disclosure and the appended claims. It is intended that the scope of the present teachings should be determined by the proper interpretation and construction of the appended claims and their legal equivalents, as understood by those skilled in the art relying on the disclosures in this specification and the accompanying drawings.

Claims

1. 1. A device for injecting a medical fluid, comprising: The housing and a syringe barrel with a fitting at a closed end, the syringe being attached to the housing; a plunger including a lead screw, the plunger being disposed within the syringe barrel; and a mechanism for driving the lead screw toward the closed end of the syringe barrel; an electric motor for driving said mechanism; Equipped with The mechanism is configured to selectively engage and disengage from the lead screw to allow the plunger to move freely axially within the syringe barrel.

2. 10. The device of claim 1, further comprising a second syringe configured to engage the fitting on the syringe barrel, the second syringe capable of retracting the plunger toward the closed end of the syringe barrel when the mechanism is selectively disengaged from the lead screw.

3. The apparatus of claim 1 , wherein the lead screw has at least one flat surface parallel to the lead screw axis.

4. The mechanism comprises: a drive gear mechanically driven by the electric motor, the drive gear including internal threads that engage the threads of the lead screw; an anti-rotation flexure, the anti-rotation flexure having a first position in which the lead screw cannot rotate and a second position in which the lead screw is free to rotate; Equipped with 4. The apparatus of claim 3, wherein rotation of the drive gear moves the lead screw along its axis when the anti-rotation flexure is in the first position, and the lead screw can rotate and move along its axis when the drive gear is fixed and the anti-rotation flexure is in the second position.

5. Further comprising a key mounted within the housing; the anti-rotation flexure comprises at least one arm that engages the at least one flat surface on the lead screw in the first position, the at least one arm extending to the key, the key configured to rotate within the housing and push the at least one arm away from the lead screw to place the anti-rotation flexure in the second position.

5. The apparatus of claim 4.

6. 5. The apparatus of claim 4, wherein the anti-rotation flexure is configured to rotate about an axis perpendicular to the lead screw, and wherein in the first position, the anti-rotation flexure engages the at least one flat surface on the lead screw and is configured to rotate to a second position where the anti-rotation flexure does not touch the at least one flat surface of the lead screw.

7. The mechanism comprises: a drive gear mechanically driven by the electric motor, the drive gear including a plurality of petal elements extending generally on the axis of the lead screw, the petal elements having thread surfaces that engage the lead screw in a first position and disengage from the lead screw in a second position; The apparatus of claim 3 , comprising:

8. 10. The device of claim 1, wherein the plunger further includes a tip with a distal surface that contacts the liquid and a proximal surface that is removably connected to the distal end of the lead screw, the tip being detached from the lead screw when negative pressure is applied to the distal surface.

9. The device of claim 1 , wherein the plunger further includes a tip with a distal surface that contacts the liquid and a proximal surface configured to rotate relative to the lead screw.

10. 10. The apparatus of claim 1, wherein the mechanism includes a drive gear mechanically driven by the electric motor, the electric motor being displaceable into disengagement from the drive gear, whereby the lead screw is free to orbit the drive gear as it moves axially.

11. The apparatus of claim 1 further comprising a controller that receives input from a pressure sensor and at least one user input and controls the speed and direction of the electric motor.

12. The device of claim 11 , wherein the at least one user input includes a trigger and a directional switch.

13. The apparatus of claim 11 , further comprising a battery connected to the controller.

14. The device of claim 12 further comprising a battery switch.

15. a first circuit configured to be energized by the battery switch, the first circuit including a latching relay; a circuit connecting the battery to the controller through the latching relay, the latching relay being closed by a first full pull of the trigger; The apparatus of claim 14 further comprising:

16. The device of claim 1 , further comprising a status output comprising at least one of an LCD display, a vibrating element, and one or more status lights.

17. 10. The device of claim 1, further comprising a status output comprising an LCD display and a status light, said status light and LCD display controlled by said controller.

18. The apparatus of claim 1 , wherein the mechanism comprises a reduction gear train on the motor output shaft.

19. 20. The apparatus of claim 18, further comprising a rotation sensor that detects the number of rotations of an element in the mechanism.

20. 20. The apparatus of claim 18, wherein the rotation sensor measures rotation of a magnet on an end of an output shaft of the reduction gear train.

21. The device of claim 1 , wherein the device is disposable.

22. The device of claim 1 , wherein the device is used for only a single treatment.

23. 10. The device of claim 1, wherein the housing, the drive mechanism, the plunger, the electric motor, and the syringe barrel are disposable after a single treatment.

24. 10. The device of claim 1, wherein the housing, the drive mechanism, the plunger, the electric motor, and the syringe barrel are disposable and are sterilized as a unit before use.

25. 10. The device of claim 1, wherein the housing, the drive mechanism, the plunger, the electric motor, and the syringe barrel are disposable and sterilized with ethylene oxide.

26. 10. A treatment kit comprising the device of claim 1, tubing, an insertion needle, transfer tubing, and a tray for holding the components, said treatment kit being sterilized with ethylene oxide.

27. 1. A device for injecting a medical fluid, comprising: The housing and a syringe barrel with a fitting at a closed end, the syringe being attached to the housing; a plunger including a lead screw, the plunger being disposed within the syringe barrel; and a mechanism for driving the lead screw toward the closed end of the syringe barrel; an electric motor for driving the mechanism; a controller for controlling the electric motor speed; a pressure sensor mounted within the housing and configured to measure a pressure of liquid within the syringe barrel, the controller varying the electric motor speed based on a pressure signal received from the pressure sensor; and An apparatus comprising:

28. 28. The device of claim 27, wherein the pressure sensor is mounted to sense pressure in a line downstream of the syringe.

29. 28. The device of claim 27, wherein the pressure sensor is mounted to a front of the syringe barrel to sense an axial force applied by a plunger to the liquid in the barrel.

30. 30. The device of claim 29, wherein the controller detects an occlusion when the pressure signal exceeds a predetermined value.

31. 30. The apparatus of claim 29, wherein the controller monitors parameters of the electric motor, and the controller declares an end of stroke based on the motor parameters and the pressure signal.

32. 32. The apparatus of claim 31, wherein the controller reverses the electric motor when an end of stroke is declared, and the controller continues to run the electric motor in reverse until the pressure signal drops below a predetermined value.

33. 31. The apparatus of claim 30, wherein the controller reverses the electric motor when an occlusion is detected, and the controller continues to run the electric motor in reverse until the pressure signal drops below a predetermined value.

34. 1. A method for delivering a volume of a cell mixture to an in vivo organ using a disposable syringe pump, the disposable syringe pump including a syringe barrel fluidly connected to an insertion needle, a plunger including a lead screw, a mechanism for driving the lead screw, an electric motor for driving the mechanism, a controller, and a pressure sensor, the method comprising: positioning the distal end of the insertion needle within the organ; receiving a user input to deliver the cell mixture; driving the electric motor at a first speed; receiving a signal from the pressure sensor; driving the electric motor at a second speed after the signal from the pressure sensor exceeds a first predetermined value; monitoring the number of rotations of an element within the mechanism; determining a delivery volume of the cell mixture; stopping the electric motor when the delivery volume exceeds a predetermined volume; reversing the electric motor until the pressure signal drops below a second predetermined value; A method comprising:

35. The user input is a signal from a switch or a trigger, and the method further comprises: monitoring the user input signal; stopping the electric motor when less than the predetermined volume has been delivered and the user signal has ceased to be provided; restarting the electric motor when the user signal resumes; 35. The method of claim 34, comprising:

36. The user input is a signal from a switch or a trigger, and the method further comprises: terminating the user input after the predetermined volume has been delivered; resuming said user input; delivering a second predetermined volume of the cell mixture; 35. The method of claim 34, comprising:

37. 1. A device for injecting a medical fluid, comprising: The housing and a syringe barrel with a fitting at a closed end, the syringe being attached to the housing; a plunger including a lead screw, the plunger being disposed within the syringe barrel; and a mechanism for driving the lead screw toward the closed end of the syringe barrel; an electric motor for driving the mechanism; a pressure sensor configured to measure a pressure characteristic of a medical fluid pressure in the syringe barrel or a line fluidly connected to the syringe barrel; a rotation sensor configured to measure the rotation of an element of the mechanism; a controller that determines a volume of injected medical fluid based on the pressure value and the number of rotations measured by the rotation sensor; An apparatus comprising:

38. 38. The device of claim 37, wherein the controller is configured to decelerate the electric motor after the pressure signal exceeds a predetermined pressure, and the controller calculates the volume of the injected fluid based on the predetermined pressure.

39. 38. The device of claim 37, wherein the controller calculates the volume of injected fluid based on an average pressure during previous injections of a predetermined volume of medical fluid.

40. 39. The apparatus of claim 38, wherein the predetermined pressure is 800 mmHg.

41. 38. The device of claim 37, wherein the pressure sensor is mounted to sense pressure in a line downstream of the syringe.

42. 38. The apparatus of claim 37, wherein the pressure sensor is mounted to a front of the syringe barrel to sense an axial force applied by a plunger to the liquid in the barrel.

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