Three-dimensional flow focusing and cytometry (Issadore)

Purpose: The sensitive measurement of individual cells requires that each cell pass one-by-one through a small detection volume.This module employs fluidic structures to hydrodynamically focus cells laterally into the middle of a micro-channel, and chevron patterns to push cells vertically toward the bottom of the channel.(Howell, 2008).

Method of Fabrication/Use: This device can be fabricated using conventional two-layer SU-8 based soft lithography. Only a single source of negative pressure is required at the outlet to generate the entire flow. Furthermore, this pressure source does not need to be stable because the flow focusing is sensitive only to the relative velocities between the sheath and the sample flow.

Results: The Issadore Lab has used this flow-focusing module to sensitively measure rare circulating tumor cells in blood (Issadore, 2012) and rare pathogens in complex media (Issadore, 2013). A hybrid microfluidic/semiconductor chip structure was utilized, in which the flow-focusing module was built directly on top of an array of sensors fabricated on a semiconductor substrate. For each specific application, the microfluidic structure was iteratively optimized through finite element simulations. Hydrodynamic flow focusing allows the physical micro-channel to be much larger than the size of the cells, effectively reducing the fluidic resistance and thus the risk of clogging.

 In microfluidic flow cytometry, sensors are built that are the same size as individual cells, for highly sensitive single cell detection. Away from the sensor surface, the signal strength decayed rapidly. b. To enhance the signal, a hydrodynamic focusing structure is used to bring individual cells close to the sensor. c. Iterative finite element simulations are used to design these microstructures for specific applications. d. Cells entering the chip (red) though the sample input are pushed to the bottom of the channel by the sheath flow (green) and focused towards the center of the channel by the lateral sheaths.

In microfluidic flow cytometry, sensors are built that are the same size as individual cells, for highly sensitive single cell detection. Away from the sensor surface, the signal strength decayed rapidly. b. To enhance the signal, a hydrodynamic focusing structure is used to bring individual cells close to the sensor. c. Iterative finite element simulations are used to design these microstructures for specific applications. d. Cells entering the chip (red) though the sample input are pushed to the bottom of the channel by the sheath flow (green) and focused towards the center of the channel by the lateral sheaths.

References

Howell PB, Jr., Golden JP, Hilliard LR, Erickson JS, Mott DR, Ligler FS. Two simple and rugged designs for creating microfluidic sheath flow. Lab Chip Jul 2008; 8 (7): 1097-1103.

Issadore D, Chung HJ, Chung J, Budin G, Weissleder R, Lee H. muHall Chip for Sensitive Detection of Bacteria. Adv Healthc Mater Sep 2013; 2 (9): 1224-1228.

Issadore D, Chung J, Shao H, Liong M, Ghazani AA, Castro CM, Weissleder R, Lee H. Ultrasensitive clinical enumeration of rare cells ex vivo using a micro-hall detector. Sci Transl Med Jul 4 2012; 4 (141): 141ra192.

Bookmark the permalink.

Comments are closed