Ferrohydrodynamics Ferrohydrodynamic Separation of Circulating Tumour Cells Nneoma Okonkwo 1,2 , Wujun Zhao 3 , Carsten Schroeder 1,4 and Leidong Mao 1,3* 1 Nanotechnology and Biomedicine REU, 2 Massachusetts Institute of Technology 3 University of Georgia, 4 Georgia Regents University http://magnet.engr.uga.edu Circulating Tumour Cells (CTCs) Microfluidic Devices Background & Motivation Results Results Conclusions & Future Work Advantages Over Other Devices Our microfluidic chip addresses the limitations of other separation techniques with its low cost of production (~$2 per device), high throughput (86 ± 3.4%) and high efficiency. Future Work Future work will include adjusting the device dimensions and magnetic field gradients for even more efficient separation and higher throughputs, lower costs, and ease of use by physicians. We also plan on testing the device on human cancer specimens. • A higher throughput, which entails shorter processing time, could be achieved with multiple channels and more magnetic field gradients. • Low cost and ease of use are needed to make the device available in low resource settings. The magnet could be embedded in the device to eliminate the need for a microscope, and a pressure difference applied in place of a syringe pump. Acknowledgements: This material is based upon work supported by a National Science Foundation Research Experiences for Undergraduates (REU) site program under Grant No. 1359095. • CTCs are cancer cells that are shed from primary tumours and travel through the bloodstream to other organs. • About 1-100 CTCs are found in 1mL of peripheral blood. • Separation of CTCs is essential as they serve as a liquid biopsy target for cancer diagnosis (eliminating the need for painful biopsies), genotyping and prognosis, as well as a key factor in making therapeutic decisions. • Simple and inexpensive means of separating CTCs. • Provides high throughput and high separation efficiency. Calibration • Inlet A: 55 uL/min • Inlet B: 205 uL/min • Recovery rate: 86 ±3.4% • 1 mL blood can be processed in 18 min CTC Separation Experiment Magnetic Field OFF Magnetic Field ON • Inlet A: 50 uL/min • Inlet B: 160 uL/min • 1 mL blood can be processed in 20 min Existing Works CellSearch by Veridex Fluorescence Activated Cell Sorter (FACS) Acoustophoresis CTC-iChip • Only FDA approved device. • CTC capture is based on EpCAM expression. • Expensive antibodies needed. • Separation takes several hours. • Antibody staining kills cells. • CTC separation using acoustic radiation force. • Blood lysis required. • Low throughput. • CTC separation using magnetophoresis. • Expensive magnetic beads for tagging cells needed. • Low purity of negative depletion (0.1%). • Flow cytometry using fluorescent lights. • Large and expensive system. Source: Ozkumur, Sci. Transl. Med. Source: Invitrogen Source: Lenshof, Anal. Chem. Source: www.ctc-lab.info Simulation Experimental Schematic of the separation device with the permanent magnet and a microfluidic channel. Ferrofluids • Colloidal suspensions of magnetic (iron oxide) nanoparticles. • The nanoparticles are covered by either electrostatic or steric surfactants to keep them apart. Source: Ferrotec Corp. • Ferrofluids have high initial magnetic susceptibility and high magnetization allowing for fast manipulation of non-magnetic objects in them leading to high separation throughputs. Ferrohydrodynamic Separation • Negative magnetophoresis • Magnetic buoyancy force • Hydrodynamic viscous drag force • Size-based separation • Label free, low cost With a residual flux density of 1.48T, the minimum sample velocity for optimum purity lies between 0.3733m/s and 0.3850m/s
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Ferrohydrodynamics
Ferrohydrodynamic Separation of Circulating Tumour Cells Nneoma Okonkwo1,2, Wujun Zhao3, Carsten Schroeder1,4 and Leidong Mao1,3*
1Nanotechnology and Biomedicine REU, 2Massachusetts Institute of Technology 3University of Georgia, 4Georgia Regents University
http://magnet.engr.uga.edu
Circulating Tumour Cells (CTCs)
Microfluidic Devices
Background & Motivation
Results
Results
Conclusions & Future Work Advantages Over Other Devices Our microfluidic chip addresses the limitations of other separation techniques with its low cost of production (~$2 per device), high throughput (86 ± 3.4%) and high efficiency. Future Work Future work will include adjusting the device dimensions and magnetic field gradients for even more efficient separation and higher throughputs, lower costs, and ease of use by physicians. We also plan on testing the device on human cancer specimens.
• A higher throughput, which entails shorter processing time, could be achieved with multiple channels and more magnetic field gradients.
• Low cost and ease of use are needed to make the device available in low resource settings. The magnet could be embedded in the device to eliminate the need for a microscope, and a pressure difference applied in place of a syringe pump.
Acknowledgements:
This material is based upon work supported by a National Science Foundation Research Experiences for Undergraduates (REU) site program under Grant No. 1359095.
• CTCs are cancer cells that are shed from primary tumours and travel through the bloodstream to other organs.
• About 1-100 CTCs are found in 1mL of peripheral blood. • Separation of CTCs is essential as they serve as a liquid
biopsy target for cancer diagnosis (eliminating the need for painful biopsies), genotyping and prognosis, as well as a key factor in making therapeutic decisions.
• Simple and inexpensive means of separating CTCs. • Provides high throughput and high separation efficiency.
Calibration
• Inlet A: 55 uL/min • Inlet B: 205 uL/min • Recovery rate: 86 ±3.4% • 1 mL blood can be
processed in 18 min
CTC Separation Experiment
Magnetic Field OFF Magnetic Field ON
• Inlet A: 50 uL/min • Inlet B: 160 uL/min • 1 mL blood can be
processed in 20 min
Existing Works
CellSearch by Veridex Fluorescence Activated Cell Sorter (FACS)
Acoustophoresis CTC-iChip • Only FDA approved device. • CTC capture is based on
EpCAM expression. • Expensive antibodies needed. • Separation takes several hours. • Antibody staining kills cells.
• CTC separation using acoustic radiation force.
• Blood lysis required. • Low throughput.
• CTC separation using magnetophoresis.
• Expensive magnetic beads for tagging cells needed.
• Low purity of negative depletion (0.1%).
• Flow cytometry using fluorescent lights.
• Large and expensive system.
Source: Ozkumur, Sci. Transl. Med. Source: Invitrogen Source: Lenshof, Anal. Chem. Source: www.ctc-lab.info
Simulation
Experimental
Schematic of the separation device with the permanent magnet and a microfluidic channel.
Ferrofluids • Colloidal suspensions of magnetic (iron
oxide) nanoparticles. • The nanoparticles are covered by either
electrostatic or steric surfactants to keep them apart. Source: Ferrotec Corp.
• Ferrofluids have high initial magnetic susceptibility and high magnetization allowing for fast manipulation of non-magnetic objects in them leading to high separation throughputs.
Ferrohydrodynamic Separation • Negative magnetophoresis
• Magnetic buoyancy force • Hydrodynamic viscous drag force
• Size-based separation • Label free, low cost
With a residual flux density of 1.48T, the minimum sample velocity for optimum purity lies between 0.3733m/s and 0.3850m/s
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