Fluidic flow cytometry devices and particle sensing based on signal-encoding

Abstract

Microfluidic devices, systems and techniques in connection with particle sorting in liquid, including cytometry devices and techniques and applications in chemical or biological testing and diagnostic measurements.

What is claimed is: 
     
         1 . A system for flow cytometry, comprising:
 an input fluidic channel including a first port for receiving a sample fluid and a second port for outputting the received sample fluid;   a particle sorting junction coupled to the second port of the input fluidic channel;   branch fluidic channels coupled to the particle sorting junction as outlets of the sample liquid from the second port of the input fluidic channel;   an actuator coupled to the particle sorting junction to control a direction of the sample fluid in the particle sorting junction in response to a sorting control signal, the actuator structured to interact with the sample fluid to change the direction of sample fluid to be in different directions corresponding to the branch fluidic channels, respectively, in response to changes in the sorting control signal, wherein the actuator is operable to direct a target particle in the sample fluid into a selected one of the branch fluidic channels;   a particle detection module coupled to the input fluidic channel to receive light from the sample fluid in the input fluid channel, the particle detection module including an encoding structure that produces different optical signals from the received light and encodes the different optical signals with different codes;   an optical detector that receives the different optical signals to produce a detector signal that carries information of the different optical signals and the different codes; and   a particle sorter control module in communication with the particle detection module to receive the detector signal and in communication with the actuator to send the sorting control signal to the actuator, the particle sorter control module including a signal processing mechanism to extract information of the different optical signals from the detector signal based on the different codes in the different optical signals, and a control mechanism that produces the sorting control signal based on the extracted information, including timing of a particle detected at the particle detection module for arriving at the particle sorting junction.   
     
     
         2 . The system as in  claim 1 , comprising:
 a branch verification structure coupled to one of the branch fluidic channels to receive light from the one branch fluidic channel and to produce a branch verification optical signal that is encoded with a branch code that is uniquely associated with the one branch fluidic channel and is different from the different codes for the different optical signals produced by the particle detection module coupled to the input fluidic channel,   wherein the optical detector receives both the different optical signals and the branch verification optical signal and the detector signal produced by the optical detector carries information of the different optical signals with the different codes and the branch verification optical signal with the branch code, and   wherein the signal processing mechanism in the particle sorter control module extracts information of the branch verification optical signal based on the branch code to produce a verification of whether a target particle is directed by the actuator into the one branch fluidic channel.   
     
     
         3 . The system as in  claim 2 , wherein:
 the encoding structure in the particle detection module includes a first spatial pattern at a region of the input fluidic channel where the particle detection module is coupled to the input fluidic channel to provide one or more of the different codes for the different optical signals,   the branch verification structure includes a second spatial pattern at the region of the one branch fluidic channel to provide the branch code.   
     
     
         4 . The system as in  claim 3 , comprising:
 a mask that covers the input fluidic channel and the one branch fluidic channel and is patterned to provide the first and second spatial patterns.   
     
     
         5 . The system as in  claim 2 , wherein:
 different branch verification structures coupled to the branch fluidic channels, respectively, to receive light from the branch fluidic channels, respectively, and to produce branch verification optical signals that are encoded with different branch codes that are uniquely associated with the respective branch fluidic channels and are different from the different codes for the different optical signals produced by the particle detection module coupled to the input fluidic channel.   
     
     
         6 . The system as in  claim 1 , wherein:
 the encoding structure of the particle detection module includes optical apertures along the input fluidic channel to respond to light from a moving particle in the sample fluid as the moving particle sequentially passes through the optical apertures to produce optical signals at different times to be received by the optical detector to effectuate space-time codes for the optical signals.   
     
     
         7 . The system as in  claim 6 , wherein:
 the signal processing mechanism of the particle sorter control module includes a bank of digital signal filters to filter and separate different signal components at different signal frequencies that correspond to different speeds of a particle in the sample fluid measured at the particle detection module, and   the signal processing mechanism processes the different signal components that correspond to different speeds of a particle in the sample fluid to determine a speed of a particle.   
     
     
         8 . The system as in  claim 6 , wherein:
 the encoding structure of the particle detection module includes, in addition to the optical apertures, optical filters of optical transmission bands respectively centered at different center transmission frequencies that are spatially separated at different locations along the input fluidic channel to receive light from a moving particle in the sample fluid as the moving particle sequentially passes through the optical filters to produce different filtered optical transmission signals with different optical spectral bands centered at the different center transmission frequencies and at different times to be received by the optical detector to effectuate color-space-time codes for the optical signals,   the signal processing mechanism in the particle sorter control module extracts spectral information carried by the different filtered optical transmission signals to identify particles of different types that have different optical spectral responses in interacting with light, and   the control mechanism in the particle sorter control module that produces the sorting control signal based on both the optical spectral response and timing of a particle detected at the particle detection module for arriving at the particle sorting junction in the extracted information to control the actuator for directing the particle to a desired branch fluidic channel.   
     
     
         9 . The system as in  claim 8 , wherein:
 each optical filter includes an optical waveguide formed of an optical filtering material that exhibits an optical transmission in a respective optical spectral band centered at a respective center transmission frequency.   
     
     
         10 . The system as in  claim 9 , wherein:
 each optical filter includes an optical waveguide formed of an optical filtering material that exhibits an optical transmission in a respective optical spectral band centered at a respective center transmission frequency.   
     
     
         11 . The system as in  claim 10 , wherein:
 the optical filtering material for each optical filter includes a polymer material.   
     
     
         12 . The system as in  claim 11 , wherein:
 the optical filtering material for each optical filter includes a PDMS polymer material.   
     
     
         13 . The system as in  claim 8 , wherein:
 the optical filters are configured to have spectral overlaps in the optical transmission bands respectively centered at different center transmission frequencies.   
     
     
         14 . The system as in  claim 1 , comprising:
 optically opaque structures located relative to the input fluidic channel and particle detection module to block light other than optical signals from entering the optical detector.   
     
     
         15 . The system as in  claim 1 , wherein:
 each fluidic channel has an inner wall that is coated with a thin film layer having a refractive index lower than a refractive index of the sample liquid.   
     
     
         16 . The system as in  claim 1 , wherein:
 each fluidic channel has an inner wall that is coated with a thin film layer to reduce effects of porosity and permeation caused by a material of the fluidic channel.   
     
     
         17 . The system as in  claim 1 , wherein:
 the actuator includes a piezoelectric actuator that moves in response to a voltage signal as the sorting control signal to cause the sample fluid in the particle sorting junction to change a flow direction.   
     
     
         18 . The system as in  claim 1 , comprising:
 a light source that emits light that is coupled into the input fluidic channel to illuminate the sample fluid.   
     
     
         19 . The system as in  claim 1 , wherein:
 the optical detector includes a photomultiplier tube.   
     
     
         20 . The system as in  claim 1 , wherein:
 the optical detector includes an avalanche photodiode.