Systems and Methods for Automated Single Cell Cytological Classification in Flow

Abstract

Systems and methods in accordance with various embodiments of the invention are capable of rapid analysis and classification of cellular samples based on cytomorphological properties. In several embodiments, cells suspended in a fluid medium are passed through a microfluidic channel, where they are focused to a single stream line and imaged continuously. In a number of embodiments, the microfluidic channel establishes flow that enables individual cells to each be imaged at multiple angles in a short amount of time. A pattern recognition system can analyze the data captured from high-speed images of cells flowing through this system and classify target cells. In this way, the automated platform creates new possibilities for a wide range of research and clinical applications such as (but not limited to) point of care services.

1 .- 20 . (canceled) 
     
     
         21 . A cell classification system comprising:
 a flow channel configured to transport a cell through the flow channel, wherein the flow channel comprises an inlet, an outlet, and an imaging region between the inlet and the outlet;   an imaging device operatively coupled to the imaging region and configured to capture (i) a first image of the cell at a location within the imaging region and (ii) a second image of the cell at a different location within the imaging region, wherein the first image and the second image are captured by a same imaging mode; and   a processor configured to determine a classification of the cell based on analysis of both the first image and the second image.   
     
     
         22 . The system of  claim 21 , wherein the location is upstream of the different location within the imaging region. 
     
     
         23 . The system of  claim 21 , wherein the cell is oriented at different angles in the first image and the second image. 
     
     
         24 . The system of  claim 21 , wherein the flow channel is configured to subject the cell to rotation while transporting the cell through the imaging region. 
     
     
         25 . The system of  claim 24 , wherein the flow channel is configured to rotate the cell by applying a velocity gradient to the cell. 
     
     
         26 . The system of  claim 25 , wherein the cell is suspended in a fluid within the flow channel, and wherein the flow channel is configured to apply the velocity gradient to the cell by applying co-flow of an additional fluid to the flow channel. 
     
     
         27 . The system of  claim 25 , wherein the flow channel is configured to apply the velocity gradient to the cell by subjecting the cell to flow across a cell rotation region within the flow channel, wherein the cell rotation region comprises a plurality of cross-sectional dimensions along a longitudinal axis of the cell rotation region. 
     
     
         28 . The system of  claim 21 , wherein the classification of the cell is determined by one or more morphological features of the cell. 
     
     
         29 . The system of  claim 21 , wherein the cell is derived from a biological sample. 
     
     
         30 . The system of  claim 29 , wherein the biological sample is blood. 
     
     
         31 . A method for classifying a cell, comprising:
 (a) transporting a cell through a flow channel, wherein the flow channel comprises an inlet, an outlet, and an imaging region between the inlet and the outlet;   (b) while the cell is flowing through the imaging region, capturing (i) a first image of the cell at a location within the imaging region and (ii) a second image of the cell at a different location within the imaging region, wherein the first image and the second image are captured by a same imaging mode; and   (c) determining a classification of the cell based on analysis of both the first image and the second image.   
     
     
         32 . The method of  claim 31 , wherein the location is upstream of the different location within the imaging region. 
     
     
         33 . The method of  claim 31 , wherein the cell is oriented at different angles in the first image and the second image. 
     
     
         34 . The method of  claim 31 , further comprising rotating the cell while transporting the cell through the imaging region. 
     
     
         35 . The method of  claim 34 , further comprising applying a velocity gradient to the cell, to rotate the cell. 
     
     
         36 . The method of  claim 35 , wherein the cell is suspended in a fluid within the flow channel, and wherein the method further comprises applying co-flow of an additional fluid to the flow channel, to apply the velocity gradient. 
     
     
         37 . The method of  claim 35 , further comprising flowing the cell across a cell rotation region within the flow channel to apply the velocity gradient, wherein the cell rotation region comprises a plurality of cross-sectional dimensions along a longitudinal axis of the cell rotation region. 
     
     
         38 . The method of  claim 31 , wherein the classification of the cell is determined by one or more morphological features of the cell. 
     
     
         39 . The method of  claim 31 , wherein the cell is derived from a biological sample. 
     
     
         40 . The method of  claim 39 , wherein the biological sample is blood.