Pens for Biological Micro-Objects

Abstract

Individual biological micro-objects can be deterministically selected and moved into holding pens in a micro-fluidic device. A flow of a first liquid medium can be provided to the pens. Physical pens can be structured to impede a direct flow of the first medium into a second medium in the pens while allowing diffusive mixing of the first medium and the second medium. Virtual pens can allow a common flow of medium to multiple ones of the pens.

1 - 41 . (canceled) 
     
     
         42 . A system for processing biological micro-objects, comprising:
 a camera configured to capture an image of a biological micro-object within a first liquid medium in a channel of a microfluidic device, the image depicting the channel interfacing with a holding pen having:
 (i) an interior space structured to hold biological micro-objects in a second liquid medium, and 
 (ii) a single opening to the channel and oriented such that a direct flow of the first liquid medium into the said second liquid medium in the interior space is impeded while diffusive mixing of the first liquid medium with the second liquid medium in the interior space is allowed; 
   a light source configured to project light onto the microfluidic device; and   a controller configured to process the image captured by the camera and, in response to the processing of the image, use the light source to project a pattern of light onto the microfluidic device, thereby generating a force within the microfluidic device to move the biological micro-object from the channel into the interior space of the holding pen.   
     
     
         43 . The system of  claim 42 , further comprising:
 a sensor configured to determine a condition of the first liquid medium or the second liquid medium, wherein the controller is configured to adjust the first liquid medium or the second liquid medium in response to the condition determined by the sensor.   
     
     
         44 . The system of  claim 43 , wherein the condition is one or more of: a property of the first liquid medium or the second liquid medium, or composition of the first liquid medium or the second liquid medium. 
     
     
         45 . The system of  claim 44 , wherein the property of the first liquid medium or the second liquid medium is temperature, pH, osmolarity, or a combination thereof. 
     
     
         46 . The system of  claim 44 , wherein the composition of the first liquid medium or the second liquid medium is a level of dissolved oxygen or carbon dioxide. 
     
     
         47 . The system of  claim 43 , wherein adjusting the first liquid medium or the second liquid medium in response to the condition determined by the sensor includes adjusting that condition. 
     
     
         48 . The system of  claim 43 , wherein adjusting the first liquid medium or the second liquid medium in response to the condition determined by the sensor includes adjusting an input of the first liquid medium to the channel. 
     
     
         49 . The system of  claim 42 , wherein the camera further monitors a characteristic of the biological micro-object while in the holding pen. 
     
     
         50 . The system of  claim 49 , wherein the characteristic is a biological activity or biological state of the biological micro-object in the holding pen. 
     
     
         51 . The system of  claim 42 , wherein the pattern of light activates an electrode mechanism that generates the force to move the biological micro-object. 
     
     
         52 . A system for processing biological micro-objects, comprising:
 an imaging device configured to capture an image of a biological micro-object within a first liquid medium in a channel of a microfluidic device, the image depicting the channel interfacing with a holding pen having:
 (i) an interior space structured to hold biological micro-objects in a second liquid medium, and 
 (ii) a single opening to the channel and oriented such that a direct flow of the first liquid medium into the said second liquid medium in the interior space is impeded while diffusive mixing of the first liquid medium with the second liquid medium in the interior space is allowed; 
   a light source configured to project light onto the microfluidic device; and   a controller configured to process the image captured by the imaging device and, in response to the processing of the image, use the light source to project a pattern of light onto the microfluidic device, thereby generating a force within the microfluidic device to move the biological micro-object.   
     
     
         53 . The system of  claim 52 , further comprising:
 a sensor configured to determine a condition of the first liquid medium or the second liquid medium, wherein the controller is configured to adjust the first liquid medium or the second liquid medium in response to the condition determined by the sensor.   
     
     
         54 . The system of  claim 53 , wherein the condition is one or more of: a property of the first liquid medium or the second liquid medium, or composition of the first liquid medium or the second liquid medium. 
     
     
         55 . The system of  claim 54 , wherein the property of the first liquid medium or the second liquid medium is temperature, pH, osmolarity, or a combination thereof. 
     
     
         56 . The system of  claim 54 , wherein the composition of the first liquid medium or the second liquid medium is a level of dissolved oxygen or carbon dioxide. 
     
     
         57 . The system of  claim 53 , wherein adjusting the first liquid medium or the second liquid medium in response to the condition determined by the sensor includes adjusting that condition. 
     
     
         58 . The system of  claim 53 , wherein adjusting the first liquid medium or the second liquid medium in response to the condition determined by the sensor includes adjusting an input of the first liquid medium to the channel. 
     
     
         59 . The system of  claim 52 , wherein the imaging device further monitors a characteristic of the biological micro-object while in the holding pen. 
     
     
         60 . The system of  claim 59 , wherein the characteristic is a biological activity or biological state of the biological micro-object in the holding pen. 
     
     
         61 . The system of  claim 52 , wherein the pattern of light activates an electrode mechanism that generates the force to move the biological micro-object.