Sensing for automated biological cell injection

Abstract

A method of controlling a needle actuator to interact with a cell is provided, the method comprising: providing an actuator comprising a tower, a stage and a needle, wherein the needle is mounted on the stage; applying an electrostatic potential between the tower and the stage to retract the needle; moving the actuator towards the cell; reducing the potential so as to allow the stage and needle to move towards the cell; applying calibration data to detect when the needle has pierced the cell; and reducing the potential further once it has been detected that the needle has pierced the cell. The cell can be a biological cell. The needle can be a micro-needle and the stage can be a micro-stage.

What is claimed: 
     
         1 . A method of generating calibration data for target voltage potentials associated with cell-type data, the method comprising:
 providing a calibration apparatus comprising a manipulator and a cell trap, the manipulator comprising a tower, a stage, and a needle, wherein the needle is mounted perpendicularly on a surface of the stage;   identifying a cell type to be calibrated;   applying a voltage so as to pull the stage towards the tower in a retracted position;   moving the manipulator to within a defined range of the cell trap configured to house a cell type;   changing the voltage to allow the stage and mounted needle to be forced away from the tower and the retracted position while measuring a displacement of the stage;   determining when the needle has reached a target region; and   recording actuation data for use in cell injection for the identified cell type.   
     
     
         2 . The method of  claim 1 , further comprising:
 receiving a user input of the cell type to a controller provided on the calibration apparatus.   
     
     
         3 . The method of  claim 1 , further comprising:
 applying a voltage to an actuator provided on the calibration apparatus, so as to pull the stage towards the tower in a retracted position.   
     
     
         4 . The method of  claim 1 , further comprising:
 moving the manipulator to within the defined range of the cell trap, wherein a camera provided on the calibration apparatus is programmed to determine if the manipulator is within the defined range.   
     
     
         5 . The method of  claim 4 , wherein the camera on the calibration apparatus is programmed to determine if the manipulator is within the defined range of a periphery of the cell trap. 
     
     
         6 . The method of  claim 1 , further comprising:
 reducing the voltage to allow the stage and mounted needle to be forced away from the tower and the retracted position while measuring the displacement of the stage.   
     
     
         7 . The method of  claim 6 , wherein measuring the displacement of the stage is performed by a laser interferometer provided in the calibration apparatus. 
     
     
         8 . The method of  claim 1 , wherein the actuation data is selected from a group consisting of a record target voltage, a target vertical actuation displacement, a point of penetration, a point of poking, a Voltage-Displacement characteristic curve distortion, and combinations thereof. 
     
     
         9 . A computer-readable medium in which a program is stored for causing a computer to perform a method for generating calibration data for target voltage potentials associated with cell-type data, the method comprising:
 providing a calibration apparatus comprising a manipulator and a cell trap, the manipulator comprising a tower, a stage, and a needle, wherein the needle is mounted perpendicularly on a surface of the stage;   identifying a cell type to be calibrated;   applying a voltage so as to pull the stage towards the tower in a retracted position;   moving the manipulator to within a defined range of the cell trap configured to house a cell type;   changing the voltage to allow the stage and mounted needle to be forced away from the tower and the retracted position while measuring a displacement of the stage;   determining when the needle has reached a target region; and   recording actuation data for use in cell injection for the identified cell type.   
     
     
         10 . The computer-readable medium of  claim 9 , the method further comprising:
 receiving a user input of the cell type to a controller provided on the calibration apparatus.   
     
     
         11 . The computer-readable medium of  claim 9 , the method further comprising:
 applying a voltage to an actuator provided on the calibration apparatus, so as to pull the stage towards the tower in a retracted position.   
     
     
         12 . The computer-readable medium of  claim 9 , the method further comprising moving the manipulator to within the defined range of the cell trap, wherein a camera provided on the calibration apparatus is programmed to determine if the manipulator is within the defined range. 
     
     
         13 . The computer-readable medium of  claim 12 , wherein the camera on the calibration apparatus is programmed to determine if the manipulator is within the defined range of a periphery of the cell trap. 
     
     
         14 . The computer-readable medium of  claim 9 , the method further comprising reducing the voltage to allow the stage and mounted needle to be forced away from the tower and the retracted position while measuring the displacement of the stage. 
     
     
         15 . The computer-readable medium of  claim 14 , wherein measuring the displacement of the stage is performed by a laser interferometer provided in the calibration apparatus. 
     
     
         16 . The computer-readable medium of  claim 9 , wherein the actuation data is selected from a group consisting of a record target voltage, a target vertical actuation displacement, a point of penetration, a point of poking, a Voltage-Displacement characteristic curve distortion, and combinations thereof. 
     
     
         17 . A system for controlling a needle actuation to interact with an object or a cell, the system comprising:
 an injection device comprising a tower, stage, needle and actuator, the needle mounted perpendicularly on a surface of the stage, and the actuator arranged and configured to apply a voltage potential to the stage to move the needle toward and away from the tower;   a cell trap configured to house a cell to be penetrated by the needle of the injection device;   a first camera configured and arranged to monitor a proximity of the injection device to the cell trap; and   a controller configured to control the movement of the injection device.   
     
     
         18 . The system of  claim 17 , wherein the first camera is configured and arranged to monitor movement on a Z-axis. 
     
     
         19 . The system of  claim 17 , wherein the injection device further comprises a plurality of actuators. 
     
     
         20 . The system of  claim 17 , wherein the system further comprises:
 a second camera configured and arranged to monitor the alignment between the injection device and the cell trap.   
     
     
         21 . The system of  claim 20 , wherein the first camera is configured and arranged to monitor movement on a Z-axis, and wherein the second camera is configured and arranged to monitor movement on the X-axis and Y-axis. 
     
     
         22 . The system of  claim 17 , wherein the system further comprises:
 a microscope comprising a second camera, the microscope configured and arranged to monitor the alignment between the injection device and the cell trap.   
     
     
         23 . The system of  claim 22 , wherein the first camera is configured and arranged to monitor movement on a Z-axis, and wherein the microscope is configured and arranged to monitor movement on the X-axis and Y-axis. 
     
     
         24 . The system of  claim 22 , wherein the microscope is an inverted microscope. 
     
     
         25 . The system of  claim 17 , the system further comprises:
 a macro-stage configured and arranged to control movement of the injection device.