System for analysis and selection of encapsulated cellular materials

• US 20030232425A1
• Filed: 12/06/2002
• Published: 12/18/2003
• Est. Priority Date: 12/06/2001
• Status: Active Grant

• Current Assignee: William D. Bachalo
• Original Assignee: Islet Technology, Inc.
• Inventors: Bachalo, William D., Fidrich, Michael J.
• Granted Patent: US 7,252,987 B2
• Time in Patent Office: Days
• US Class Current: 435/283.1
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream

Abstract

Capsules, entrained in a fluid medium, are directed into a channel deflection system designed to enable evaluation and separation of successfully encapsulated cellular material from the blanks and other debris. Preferably, the fluid media with the capsule is introduced into a first or main channel and the capsules first pass one or more windows in the main channel for evaluation that is conducted by electromagnetic and/or optical means. Preferably, the evaluation results in the selection of acceptable capsules and subsequent removal of the blank capsules from the medium through the use of multiple jets that gently redirect the acceptable capsules into an alternate channel. Preferably, fluid is also introduced into the alternate .channel and the main channel and the alternate channel are arranged such that there is a window defined between the two channels where the fluid flow between the two channel is directly adjacent and the jet deflection system can selectively deflect capsules across this window between the two channels with a minimum amount of force and a minimum of turbulence created in either channel.

Claims

1. An automated system for evaluation and selection of encapsulated cellular material comprising:

a first channel through which a first fluid stream containing capsules is introduced;

a second channel through which a second fluid stream is introduced;

a window defined between the first channel and the second channel across which the first fluid stream is directly adjacent the second fluid stream;

a sensor system operably positioned along the first channel upstream of the window; and

a fluid jet system responsive to the sensor system for selectively deflecting capsules from the first fluid stream across the window and into the second fluid stream.

2. The automated system of claim 1, wherein the fluid jet system comprises a plurality of impulse jet nozzles which are sequentially fired to deflect capsules from the first fluid stream across the window and into the second fluid stream.

3. The automated system of claim 1, wherein the sensor system includes at least two detectors spaced apart along the first channel such that the sensor system determines a speed of a capsule from the at least two detectors and utilizes the speed to determine when to activate the fluid jet system.

4. The automated system of claim 1, wherein the capsules to be selectively deflected are a minority of the capsules containing cellular material and a majority of the capsules not containing cellular material are not deflected, such that fluid flow disturbance of the first fluid is created only when a capsule containing cellular material is detected by the sensor system.

5. The automated system of claim 1, wherein the sensor system comprises a radiation source emitting a known beam profile and a detector for detecting an amount of the known beam profile that is obscured by a capsule passing through the beam profile from which the sensor system determines a size of cellular material within the capsule in at least one dimension.

6. The automated system of claim 5, wherein the sensor system includes at least two radiation sources emitting beam profiles in different directions and at least two corresponding detectors from which the sensor system determines a size of cellular material within the capsule in at least two dimensions.

7. The automated system of claim 1, wherein the sensor system includes a radiation scattering interferometer from which the sensor system determines a wall thickness of the capsule.

8. The automated system of claim 1, wherein the sensor system determines whether any portion of the cellular material is outside the capsule as part of a determination of whether to selectively deflects the capsule.

9. The automated system of claim 1, wherein the first fluid and the second fluid are cell culture liquid media that are oxygenated and temperature regulated to accommodate the cellular material.

10. The automated system of claim 1, wherein the sensor system includes at least one radiation source having an output which is oriented to decrease back reflection.

11. The automated system of claim 10, wherein the radiation source includes a polarization filter before the output.

12. The automated system of claim 10, wherein the radiation source is oriented at an angle other than normal to the first channel.

13. The automated system of claim 1, wherein the encapsulated cellular material are islets and the sensor system determines a number of islets contained by the capsule and selectively deflects capsules containing one and only one islet.

14. The automated system of claim 1, wherein the encapsulated cellular material is contained within capsule having a radius of between 10 to 500 microns and the first channel has cross-sectional dimensions that are four to eight time the radius of the capsules.

15. The automated system of claim 1, further comprising a first supply vessel fluidically coupled to an input of the first channel, a second supply vessel fluidically coupled to an input of the second channel and a first collection vessel fluidically coupled to an output of the first channel and a second collection vessel fluidically coupled to an output of the second channel and a flow rate of the first fluid stream and the second fluid stream is established by creating a pressure differential between the first and second supply vessels and the first and second collection vessels.

16. The automated system of claim 15 wherein the first and second supply vessel are connected to a first air pressure system and wherein the first and second collection vessels are connected to second air pressure system and wherein the pressure differential between the first air pressure system and the second air pressure system is used to establish the flow rate.

17. The automated system of claim 15 wherein the first supply vessel includes a means for stirring a first fluid containing the capsules to disperse the capsules within the first fluid stream.

18. The automated system of claim 1 further comprising at least a second sensor system positioned downstream of the window to detect at least one quality of a capsule having cellular material.

19. The automated system of claim 18 wherein the second sensor system uses interferometry to determine a surface quality of the capsule.

20. The automated system of claim 18 wherein the second sensor system uses two orthogonal beams to determine a size of the capsule.

21. An automated system for evaluation and selection of encapsulated cellular material comprising:

a main channel through which a fluid stream containing capsules is introduced;

a sensor system operably positioned along the main channel;

an outlet channel fluidically coupled to the main channel; and

a fluid jet system operably positioned along the channel downstream of the sensor system and pulsed in response to the sensor system for selectively deflecting capsules from the main channel to the output channel such that capsule remain in the main channel unless the fluid jet system is pulsed.

22. The automated system of claim 21, wherein the fluid jet system comprises a plurality of impulse jet nozzles which are sequentially pulsed to deflect capsules from the main channel into the output channel.

23. The automated system of claim 21 further including;

a capsule evaluation system operably positioned along the outlet channel;

an examination channel fluidically coupled to the outlet channel; and

a secondary fluid jet system operably positioned along the outlet channel downstream of the capsule evaluation system and pulsed in response to the capsule evaluation system for selectively deflecting capsules from the outlet channel to the examination channel such that capsule remain in the outlet channel unless the secondary fluid jet system is pulsed.

24. An automated system for evaluation and selection of encapsulated cellular material comprising:

a main channel through which a fluid stream containing capsules is introduced;

a sensor system operably positioned along the main channel, the sensor system including at least two detectors. spaced apart such that the sensor system determines a speed of a capsule from the at least two detectors;

an outlet channel fluidically coupled to the main channel; and

a fluid jet system operably positioned along the channel downstream of the sensor system and pulsed in response to the sensor system based on the speed of the capsule to move the capsule from the main channel to the outlet channel.

25. An automated system for evaluation and selection of encapsulated cellular material comprising:

a main channel through which a fluid stream containing capsules is introduced;

a sensor system operably positioned along the main channel, the sensor system including at least two radiation sources emitting beam profiles in different directions and at least two corresponding detectors from which the sensor system determines a size of cellular material within the capsule in at least two dimensions;

an outlet channel fluidically coupled to the main channel; and

a fluid jet system operably positioned along the channel downstream of the sensor system and pulsed in response to the sensor system based on the size of the cellular material within the capsule to move the capsule from the main channel to the outlet channel.

26. An automated system for evaluation and selection of encapsulated cellular material comprising:

a main channel through which a fluid stream containing capsules is introduced;

a sensor system operably positioned along the main channel, the sensor system including a radiation scattering interferometer from which the sensor system that determines a wall thickness of the capsule;

an outlet channel fluidically coupled to the main channel; and

a fluid jet system operably positioned along the channel downstream of the sensor system and pulsed in response to the sensor system based on the wall thickness of the capsule to move the capsule from the main channel to the outlet channel.

27. An automated system for evaluation and selection of encapsulated cellular material comprising:

a main channel through which a fluid stream containing capsules is introduced;

a sensor system operably positioned along the main channel that makes a determination as to whether any portion of the cellular material is outside the capsule;

an outlet channel fluidically coupled to the main channel; and

a fluid jet system operably positioned along the channel downstream of the sensor system and pulsed in response to the sensor system based on the determination as to whether any portion of the cellular material is outside the capsule in order to. move the capsule from the main channel to the outlet channel.

28. An automated system for evaluation and selection of encapsulated islets comprising:

main channel through which a fluid stream containing capsules is introduced;

a sensor system operably positioned along the main channel that determines a number of islets contained by the capsule;

an outlet channel fluidically coupled to the main channel; and

a fluid jet system operably positioned along the channel downstream of the sensor system and is pulsed based on the number of islets in a capsule to move the capsule from the main channel to the outlet channel.

29. An automated system for evaluation and selection of encapsulated cellular material comprising:

a first channel through which a fluid stream containing capsules is introduced;

a first sensor system operably positioned along the first channel;

a second channel fluidically coupled to the first channel;

a first fluid jet system operably positioned along the channel downstream of the first sensor system and pulsed in response to the first sensor system for selectively deflecting capsules from the first channel to the second channel;

a second sensor system operably positioned along the second channel downstream of the first fluid jet system;

a third channel fluidically coupled to the second channel; and

a secondary fluid jet system operably positioned along the second channel downstream of the second sensor system and pulsed in response to the second sensor system for selectively deflecting capsules from the second channel to the third channel.