Systems, articles, and methods for flowing particles

Abstract

Systems and methods for flowing particles, such as biological entities, in a fluidic channel(s) are generally provided. In some cases, the systems described herein are designed such that a single particle may be isolated from a plurality of particles and flowed into a fluidic channel (e.g., a microfluidic channel) and/or collected e.g., on fluidically isolated surfaces. For example, the single particle may be present in a plurality of particles of relatively high density and the single particle is flowed into a fluidic channel, such that it is separated from the plurality of particles. The particles may be spaced within a fluidic channel so that individual particles may be measured/observed over time. In certain embodiments, the particle may be a biological entity. Such article and methods may be useful, for example, for isolating single cells into individual wells of multi-well cell culture dishes (e.g., for single-cell analysis).

1 - 5 . (canceled) 
     
     
         6 . A system, comprising:
 a first fluidic channel;   a second fluidic channel intersecting and in fluidic communication with the first fluidic channel;   at least one pressure source associated with the first fluidic channel; and   a detector associated with the second fluidic channel, wherein the system is configured such that, upon detection by the detector of the presence of a single particle in the second fluidic channel, at least one property of one or more of the at least one pressure source is changed.   
     
     
         7 . A system as in any  claim 6 , wherein the plurality of particles are a plurality of biological entities. 
     
     
         8 . A system as in  claim 7 , wherein the plurality of biological entities comprise virions, bacteria, protein complexes, exosomes, cells, or fungi. 
     
     
         9 . A system as in  claim 6 , wherein the first fluidic channel has an average cross-sectional dimension of greater than or equal to 5 microns and less than or equal to 2 mm. 
     
     
         10 . A system as in  claim 6 , wherein the second fluidic channel has an average cross-sectional dimension of greater than or equal to 50 microns and less than or equal to 2 mm. 
     
     
         11 . A system as in  claim 6 , wherein the of the average cross-sectional dimension of the first fluidic channel to the average cross-sectional dimension of the second fluidic channel is at least 1 and less than or equal to 10. 
     
     
         12 . A system as in  claim 6 , wherein a density of particles in the first fluidic channel is greater than or equal to 100 particles per milliliter and less than or equal to 1,000,000 particles per milliliter. 
     
     
         13 . A system as in  claim 6 , wherein a fluidic pressure at the intersection during a flushing regime is within less than or equal to 10% and greater than or equal to 0.01% of the fluidic pressure at the intersection during an active loading regime. 
     
     
         14 . A system as in  claim 6 , wherein a flow rate of the fluid in the second fluidic channel during a flushing regime is within less than or equal to 10% and greater than or equal to 0.01% of the flow rate of the fluid in the second fluidic channel during the active loading regime. 
     
     
         15 . A system as in  claim 6 , wherein particles within the second fluidic channel may be spaced at an average spacing of at least 20 microns and less than or equal to 500 mm apart along a longitudinal axis of the second fluidic channel. 
     
     
         16 . A system as in  claim 6 , wherein individual particles flowed in the second fluidic channel may be separated such that at least 90% of the spacings differ by no more than less than 10% and greater than or equal to 0.1%) of the average spacing between the particles. 
     
     
         17 . A system as in  claim 6 , wherein an average velocity of the particles along the longitudinal axis of the second fluidic channel is greater than or equal to 0.1 mm/second and less than or equal to 10 mm/second. 
     
     
         18 . A system as in  claim 6 , wherein each particle enters the second fluidic channel from the first fluidic channel at a frequency of less than or equal to 1 particle per 10 seconds and greater than or equal to 1 particle per 120 seconds. 
     
     
         19 . A system as in  claim 6 , wherein the particles are suspended in a fluid. 
     
     
         20 . A system as in  claim 6 , wherein the second fluidic channel is in fluidic communication with at least one suspended microchannel resonator. 
     
     
         21 . (canceled) 
     
     
         22 . A system as in  claim 6 , wherein the detector is selected from the group consisting of optical detectors, mass sensors, capacitive sensors, thermal sensors, resistive pulse sensors, electrical current sensors, MEMS-based pressure sensors, acoustic sensors, ultrasonic sensors and suspended microchannel resonators. 
     
     
         23 - 52 . (canceled)