CMOS Magnetic Particle Flow Cytometer

Pramod Murali

EECS Department
University of California, Berkeley
Technical Report No. UCB/EECS-2017-175
December 1, 2017

http://www2.eecs.berkeley.edu/Pubs/TechRpts/2017/EECS-2017-175.pdf

Neutrophils, a class of white blood cells, are our body’s first line of defense against invading pathogens. When the number of neutrophils in blood drops to 200cells/$\mu$L, it leads to a critical clinical condition called neutropenia. Currently, optical flow cytometry is the most common and powerful technique used to diagnose neutropenia, but the centralized nature of the test, time-consuming sample preparation and high cost prevent real-time modification of treatment regimens.

In this thesis, we propose an approach of using magnetic labels to tag and detect cells that allows us to design a low cost point-of-care flow cytometer to diagnose neutropenia. The cytometer cartridge integrates a gravity driven microfluidic channel with a CMOS sensor chip that detects magnetically labeled cells as they flow over it.

The sensor combines an on-chip excitation coil that magnetizes the labels and a pick-up coil that detects them. The high frequency RF signal from the sensor is down-converted and amplified by on-chip receiver circuitry, which has been optimized to maximize the signal to noise ratio. The functionality of the cytometer is demonstrated with SKBR3 cancer cells labeled with 1$\mu$m magnetic labels using streptavidin-biotin chemistry. The SKBR3 cells are used in lieu of neutrophils as they can be cultured in a laboratory setting and pose minimal bio-hazard. Furthermore, the high frequency operation of the sensor enables classification of two types of magnetic labels, which is necessary to obtain absolute cell-counts.

Advisor: Bernhard Boser and Ali Niknejad


BibTeX citation:

@phdthesis{Murali:EECS-2017-175,
    Author = {Murali, Pramod},
    Title = {CMOS Magnetic Particle Flow Cytometer},
    School = {EECS Department, University of California, Berkeley},
    Year = {2017},
    Month = {Dec},
    URL = {http://www2.eecs.berkeley.edu/Pubs/TechRpts/2017/EECS-2017-175.html},
    Number = {UCB/EECS-2017-175},
    Abstract = {Neutrophils, a class of white blood cells, are our body’s first line of defense against invading pathogens. When the number of neutrophils in blood drops to 200cells/$\mu$L, it leads to a critical clinical condition called neutropenia. Currently, optical flow cytometry is the most common and powerful technique used to diagnose neutropenia, but the centralized nature of the test, time-consuming sample preparation and high cost prevent real-time modification of treatment regimens. 

In this thesis, we  propose an  approach of using  magnetic  labels to tag and detect cells that allows us to design a low cost point-of-care flow cytometer to diagnose neutropenia. The cytometer cartridge integrates a gravity driven microfluidic channel with a CMOS sensor chip that detects magnetically labeled cells as they flow over it. 

The sensor combines an on-chip excitation coil that magnetizes the labels and a pick-up coil that detects them. The high frequency RF signal from the sensor is down-converted and amplified by on-chip receiver circuitry, which has been optimized to maximize the signal to noise ratio. The functionality of the cytometer is demonstrated with SKBR3 cancer cells labeled with 1$\mu$m magnetic labels using streptavidin-biotin chemistry. The SKBR3 cells are used in lieu of neutrophils as they can be cultured in a laboratory setting and pose minimal bio-hazard.  Furthermore, the high frequency operation of the sensor enables classification of two types of magnetic labels, which is necessary to obtain absolute cell-counts.}
}

EndNote citation:

%0 Thesis
%A Murali, Pramod
%T CMOS Magnetic Particle Flow Cytometer
%I EECS Department, University of California, Berkeley
%D 2017
%8 December 1
%@ UCB/EECS-2017-175
%U http://www2.eecs.berkeley.edu/Pubs/TechRpts/2017/EECS-2017-175.html
%F Murali:EECS-2017-175