System for analysis and selection of encapsulated cellular materials

• US 7,252,987 B2
• Filed: 12/06/2002
• Issued: 08/07/2007
• 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.
• Primary Examiner(s): Beisner; William H.
• Application Number:
  US10/313,987
• Publication Number:
  US 20030232425A1
• Time in Patent Office: 1,705 Days
• Field of Search: 435/288.7, 435/288.5, 436/63, 422/73
• US Class Current: 435/286.5
• 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 capsules a minority of which contain encapsulated cellular material comprising:

a first channel through which a first fluid stream containing capsules is introduced into the system and will exit from the system if undeflected;

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, the sensor system equipped to image the minority of the capsules which contain encapsulated cellular material from among the capsules contained in the first fluid stream; and

a fluid jet system pulsed responsive to a control system coupled to the sensor system that identifies the minority of capsules which contain encapsulated materials and controls the fluid jet system for selectively deflecting the minority of the capsules which contain encapsulated cellular material from the first fluid stream across the window and into the second fluid stream such that fluid flow disturbance of the first fluid is generally created only when a capsule containing cellular material is detected by the sensor system,

wherein a majority of the capsules not containing cellular material persists flowing through the first channel through which the first fluid stream containing capsules is introduced, without creating a fluid flow disturbance of the first fluid that affects imaging of the capsules by the sensor system.

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 control 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.

4. 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.

5. 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.

6. The automated system of claim 5, wherein the radiation source includes a polarization filter before the output.

7. The automated system of claim 5, wherein the radiation source is oriented at an angle other than normal to the first channel.

8. 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.

9. 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.

10. The automated system of claim 9 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.

11. The automated system of claim 9 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.

12. 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 control system including a sensor system operably positioned along the main channel, the sensor system equipped to image a minority of the capsules containing cellular material from among the capsules contained in the fluid stream;

an outlet channel fluidically coupled to the main channel; and

a fluid jet system operably positioned along the channel downstream of the sensor system, wherein the fluid jet system comprises a plurality of impulse jet nozzles arranged for sequential pulsing under control of the control system, each jet nozzle in the plurality of impulse jet nozzles configured to generate a fluid jet characterized by a jet momentum, the jet momentum calculated so that upon sequential pulsing, paired pulsing, or pulsing in unison of the impulse jet nozzles each of the minority of capsules containing cellular material is selectively deflected from the main channel into the output channel without generally contacting the main channel or the output channel and without generally causing a fluid flow disturbance in the fluid stream flowing in the first channel that would otherwise disrupt the imaging of the capsules, such that the capsules other than the minority of capsules containing cellular material remain in the fluid stream flowing in the main channel.

13. 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 control system including a sensor system operably positioned along the main channel that images the capsules, the control system evaluating the images to determine 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 control 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 while reducing disturbance of the fluid stream with respect to the sensor system.