UC San Diego UC San Diego Electronic Theses and Dissertations Title Magnetic flow cytometry for point-of-care applications Permalink https://escholarship.org/uc/item/45b287bv Author Sridhar, Kaushik Publication Date 2016 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California UNIVERSITY OF CALIFORNIA, SAN DIEGO Magnetic Flow Cytometry for Point-of-care Applications A Thesis submitted in partial satisfaction of the requirements for the degree Master of Science in Bioengineering by Kaushik Sridhar Committee in charge: Drew A. Hall, Chair Pedro Jo Cabrales Michael J. Heller 2016 The thesis of Kaushik Sridhar is approved, and it is acceptable in quality and form for publication on microfilm and electronically: ____________________________________ ____________________________________ ____________________________________ Chair University of California, San Diego 2016 iii EPIGRAPH “History repeats, but science reverberates” ― Siddhartha Mukherjee, “The Emperor of All Maladies: A Biography of Cancer” iv TABLE OF CONTENTS Signature Page....................................................................................................................iii Epigraph..............................................................................................................................iv Table of contents..................................................................................................................v List of Figures....................................................................................................................vii List of Tables.......................................................................................................................ix Acknowledgements..............................................................................................................x Abstract of the thesis...........................................................................................................xi Chapter 1- Introduction........................................................................................................1 1.1 Motivation........................................................................................1 1.2 Organization of the thesis.................................................................3 Chapter 2 - Background........................................................................................................4 2.1 Optical Biosensors - Gold standard.........................................................4 2.2 Electrochemical Biosensors...................................................................7 2.3 Magnetic Biosensors..............................................................................8 2.3.1 SQUID.....................................................................................8 2.3.2 Magnetoresistive (MR) sensors...............................................9 Chapter 3 - Materials and protocols....................................................................................12 3.1 GMR SV Sensors..................................................................................12 3.1.1 MR curve measurements.......................................................15 3.2 Construction of microfluidic channel...................................................17 3.2.1 PolyMethylMethAcrylate based channel...............................17 3.2.2 Poly-dimethyl siloxane based channel...................................18 Chapter 4 - System Modeling.............................................................................................21 4.1 Flow characteristics..............................................................................21 v 4.2 MR simulation for FCM chips..............................................................25 4.2.1 Resistance change over the sensor surface.............................26 4.2.2 Resistance change over distance............................................30 4.2.3 Effect of magnetic force on beads..........................................32 Chapter 5 - Results.............................................................................................................34 5.1 In-plane component measurement in GMR chip..................................34 5.2 Resistance change with dried beads......................................................36 5.3 GMR-SV platform to detect magnetic beads........................................37 Chapter 6 - Discussion........................................................................................................40 6.1 Sources of error....................................................................................40 6.2 Future directions...................................................................................41 6.3 Potential Impact....................................................................................41 References..........................................................................................................................42 vi LIST OF FIGURES Figure 2.1: Basic components of the flow cytometer..........................................................5 Figure 2.2: Cell phone integrated flow cytometer..............................................................6 Figure 2.3: Flow cell impedance biosensor........................................................................8 Figure 3.1: GMR SV sensor.............................................................................................13 Figure 3.2: GMR SV sensor stacks... ...............................................................................14 Figure 3.3: Sensor chip in a Helmholtz coil......................................................................15 Figure 3.4: Resistance across varying magnetic fields.....................................................16 Figure 3.5: PMMA-DSA assembly of microfluidic channel............................................17 Figure 3.6: PMMA-DSA assembly of Microfluidic chip setup........................................18 Figure 3.7: PDMS microfluidic chip fabrication..............................................................19 Figure 3.8: PDMS chip assembly.....................................................................................20 Figure 4.1.1: Velocity profile in a laminar regime..............................................................23 Figure 4.1.2: Velocity profile as a function of distance.......................................................24 Figure 4.2.1: GMR SV chip geometry................................................................................25 Figure 4.2.2: Sensor block dimensions...............................................................................26 Figure 4.2.3: Orientation of magnetic bead over the sensor................................................27 Figure 4.2.4: Resistance drop in single sensor strip............................................................28 Figure 4.2.5: Resistance changes due to M-450 stray fields................................................29 Figure 4.2.6: Resistance change along the axes..................................................................30 Figure 4.2.7: Resistance change over distances..................................................................31 Figure 4.2.8: Resistance changes over sensor block...........................................................31 Figure 4.2.9: Illustration of sensor-bead positioning.........................................................32 Figure 4.2.10: MATLAB simulation of magnetic force on bead........................................33 Figure 5.1: Processed resistance in sensor column..........................................................34 vii Figure 5.2: Change in resistance as a function of dH.......................................................35 Figure 5.3: Resistance change due to magnetic bead droplet...........................................36 Figure 5.4: Microfluidic assembly with GMR-SV sensor...............................................37 Figure 5.5: Sequential signal response from 8 sensors.....................................................38 Figure 6.1: Background noise signal...............................................................................40 Figure 6.2: Point-of-care diagnostic device.....................................................................41 viii LIST OF TABLES Table 2.1: Evolution of magnetic biosensors and their analytes.........................................11 Table 4.2: Magnetic bead parameters.................................................................................26 Table 4.3: Sensor parameters..............................................................................................28 Table 5.1: Color label for sensors.......................................................................................38 ix ACKNOWLEDGEMENTS I am grateful to many people who have helped me towards the completion of my Masters’ program. First and foremost, I would like to thank my advisor, Dr. Drew A. Hall, whose outstanding vision, intellect and ingenuity have guided me every step of the way. Apart from his scientific guidance, I would forever be indebted to him for encouraging me to think outside the box and inspiring me to continue working in Bioengineering. Next, I would like to thank Dr. Michael J. Heller, who kindly accepted to be part of my reading committee and introduced me to the field of point-of-care cancer diagnostics through his class. His passion towards