Download IC / Microfluidic Hybrid Microsystem for 2D Magnetic Manipulation of

IC / Microfluidic Hybrid Microsystem for
2D Magnetic Manipulation of
Individual Biological Cells
Negin Nematollahi
Winter 2006
Advanced VLSI Course
Tehran university
Based on the paper by
Hakho Lee, Yong Liu,
E. Alsberg, D. Ingber,
R. M. Westervelt, & Donhee Ham
From ISSCC 2005_4.3
Harvard University
& Harvard Medical School
Outline
1. IC / Microfluidic Hybrid System
2. First Prototype:
SiGe IC / Microfluidic Hybrid
3. Second Prototype:
CMOS IC / Microfluidic Hybrid
4. Tissue Assembly in Progress
IC / Microfluidic Hybrid
IC / Microfluidic Hybrid
Magnetic Manipulation
Magnetic bead
Bead-bound cell
Hybrid System - Summary
Ultimate Goal : Tissue Assembly
• Assemble cells in a controlled way
Outline
1. IC / Microfluidic Hybrid System
2. First Prototype:
SiGe IC / Microfluidic Hybrid
3. Second Prototype:
CMOS IC / Microfluidic Hybrid
4. Tissue Assembly in Progress
SiGe IC Micrograph
Microcoil arrays
Control electronics
Control electronics
Chip size 1 mm  4 mm
Microcoil array [4]
Control electronics
Microcoil Array Design
Microcoil Array Design
Microcoil Array Design
• Single magnetic field peak generation
Cross section of a microcoil
with contours of magnetic field magnitude[4]
Microcoil Array Design
Magnetic field magnitude on the surface
Microfluidic Channel Fabrication
• Dicing silicon wafer
Microcoil arrays
Silicon chip
Microfluidic Channel Fabrication
• Dicing silicon wafer
• Patterning microfluidic channel
Polyimide
Microfluidic Channel Fabrication
• Dicing silicon wafer
• Patterning microfluidic channel
• Sealing with coverslip
Resist coating
Coverslip
Microfluidic Channel Fabrication
• Dicing silicon wafer
• Patterning microfluidic channel
• Sealing with coverslip
Coverslip
Microfluidic Channel Fabrication
• Dicing silicon wafer
• Patterning microfluidic channel
• Sealing with coverslip
• Tubing[1]
Tube fitting
st
1
Hybrid Prototype
Tube fitting
Coverslip
Microcoils
Polyimide
Silicon chip
Fluidic flow
Fluidic channel
Magnetic Bead Manipulation
• Individual magnetic beads control[2]
10 mm
Magnetic Beads
10 mm
Biological Cell Manipulation
• Cell preparation
Cells with engulfed
magnetic beads
Outline
1. IC / Microfluidic Hybrid System
2. First Prototype:
SiGe IC / Microfluidic Hybrid
3. Second Prototype:
CMOS IC / Microfluidic Hybrid
4. Tissue Assembly in Progress
CMOS IC Micrograph
TSMC
0.18 mm
2 mm  5 mm
Large array of coils
Logic/timing circuits
Temperature sensors
Large Array of Microcoils
• Problem
– Current consumption
Ex) Turning on 64 microcoils
Current : 64 x 15 mA ~ 1 A
Solution: Time-division of a dc current[3]
Time Division of a DC Current
Sequential distribution of a dc current
Resolution Enhancement
• Magnetic field peak between coils
– Controlling the direction of currents
Current
Current
Resolution Enhancement
• Moving magnetic field peak
– Controlling the direction and magnitude of currents
Overall Architecture
Outline
1. IC / Microfluidic Hybrid System
2. First Prototype:
SiGe IC / Microfluidic Hybrid
3. Second Prototype:
CMOS IC / Microfluidic Hybrid
4. Tissue Assembly in Progress
Microscale Tissue Engineering
• Multi-cellular network assembly
• Protein patterning for cell adhesion
Microscale Tissue Engineering
• Multi-cellular network assembly
• Protein patterning for cell adhesion
• Spontaneous tissue formation
Microscale Tissue Engineering
• Multi-cellular network assembly
• Protein patterning for cell adhesion
• Spontaneous tissue formation
Microscale Tissue Engineering
• Multi-cellular network assembly
• Protein patterning for cell adhesion
• Spontaneous tissue formation
• Bringing in another type of cells[4]
Microfluidics
Integrated Circuits
Programmable Microfluidic System
• Simultaneous manipulation of individual cells.
• Accurate spatial control.
• Miniaturized and low cost.
• Single-use, disposable unit.
• New tool for tissue engineering
REFRENCES
[1] D. Meldrum et al., “Microfluidics: Microscale Bioanalytical Systems,”
Science, vol. 297, pp. 1197-1198, 2002.
[2] T. Thorsen et al., “Microfluidic Large-Scale Integration,” Science, vol.
298, pp. 580-584, 2002.
[3] N. Manaresi et al., “A CMOS Chip for Individual Cell Manipulation
and Detection,” IEEE J. Solid-State Circuits, vol. 38, no. 12, pp. 2297
-2305, 2003.
[4] H. Lee, A.M. Purdon, and R.M. Westervelt, “Manipulation of Biologica
l Cells Using a Microelectromagnet Matrix,” Applied Physics Letters,
vol. 85, pp. 1063-1065, 2004.