Tools for Exploring the Interface Between Semiconductors and Life

Michael IsaacsonDepartment of Electrical Engineering

Baskin School of EngineeringUC Santa Cruz

msi@soe.ucsc.edu

9/24/04

Nanodevices Require Atomic

Characterization

Scanning Transmission Electron Microscope

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20 nanometers

Uranium atoms on carbon

Scanning Transmission

Electron Microscope

Nanodevices requireAtomic

Characterization

100 10-1 10-2 10-3 10-4 10-5 10-6 10-7 10-8 10-9 10-10

Systems Cells Molecules

Characteristic Size (Meters)

Photolithography

Electron Beam Lithography

Microcontact Printing New Materials

DimensionsDimensions

Fabrication TechnologiesFabrication Technologies

Scanned Probes

1 nanometer

Size Scales Accessible to Nanofabrication Approach

1 micrometer

The NanoBiotechnology Cycle

What parameters can we use to control surfaces?

What parameters can we use to control surfaces?

Chemistry

What parameters can we use to control surfaces?

Chemistry

And

Topography

Stamp cast fromphotolith master

Stamp onto substrateusing “ink”

Peel stamp fromsurface

Surface Chemical Patterning byMicrocontact Printing

Requires no harsh solvents or basesRapid and low cost

Can be used to stamp multiple components

Location of cells in culture without manipulation -Enhances abililty to interface to signal transducers

LRM55 cells adhering preferentially to DETA pads on silicon with a background of OTS. Cells arelabeled with dilC18(3). Scanning confocal image taken 6 hours after plating.

Multielectrode array for neural recording

1. Microelectrode array

Aligned CP

2. Alignment tool

stamp feature

4. Protein pattern3. Stamp in contact with the array surface

Microcontact Stamp

a. SEM micrograph of a microcontact stampb. Optical micrograph of a stamped poly-L-lysine

pattern stamped on a gold electrode arrayScale bars are 50micrometers

proteinaxon

Fluorescent and phase contrast images of protein pattern and cultured neurons grown on the pattern (after four days growth)

In vitro patterned neuronal growth

James, Spence, Isaacson, et. al.

20m

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Control of Neuronal Growth by Microcontact Printing

unpatterned patterned

Neuronal Response to Microfabricated Pillars

50 microns

Engineered Chaperonin for Self-Assembly

• Left: Backscattered Electron Image showing filaments and some end on views, 7keV

• Right: Backscattered Electron Image, 7keV

• Sample from A, McMillan, J. Trent (NASA-Ames)

Engineered Biomolecules

Engineered Biomolecules for Nanotechnology

• Left: modified chaperonin model (17nm diameter)• Right: backscattered electron image (7keV)

• Model/sample from A.McMillan, J.Trent

10 nm

Microfabricated Electrode Arrays Used In Vivo

• Microfabricated electrode arrays record the activity of simple insect neural networks.

• Fruit flies with just 14 large motion sensitive neurons navigate their surroundings at 1 m/s, land on surfaces, avoid obstacles.

Time (s)

Geometry of the bridge array multielectrodeFor in vivo invertebrate nerve recordings

Cricket cercal system and ventral nerve cord

across a bridge electrode array

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Cybercricket response to directional airflow

posterior Neural response

Spence, Hoy and Isaacson

Ladder and tweezer electrode geometries

Neural Prosthetic Micro/Nanodevices

How do we interface with the brain?

Diagnostics

Electrical interventionOptical intervention

Pharmacological intervention

The prosthetic device is shown in grey, with fluidchannels (blue) and electrical connections (gold).Neurons (pink), microglia (blue), astrocytes (red),and vasculature (purple) are seen encapsulatingthe probe.

Schematic of neural tissue responseto a prosthetic device

Cortical Microprosthetic Device

Optical Section of Rat Cortex

Microdevice in Silicon Wafer

MRI (coronal view) demonstrating swelling (reactive response)around a deep brain stimulating electrode 4 days after device insertion.

The device track and swollen area are indicated by the white arrow.

MRI Imaging of Reactive Response

1 day 3 days 1 week 6 weeks

GFAP GLUT-1 Lam GFAP GLUT-1 Lam GFAP GLUT-1 Lam GFAP GLUT-1 Lam

Device insertion damages the brain vasculature and promotes a reactive response from endothelial cells of the brain microvasculature. Micrographs taken with different selective fluorescent stains show a sheath forming around the device after prolonged insertion.

Formation of Sheath Around Device Due to Reactive Response

A Model DeviceA Model DeviceStimulating the Neural Tissue Immune ResponseStimulating the Neural Tissue Immune Response

Development of Prostheses with Fluidic ChannelsDevelopment of Prostheses with Fluidic ChannelsLocal Drug DeliveryLocal Drug Delivery

20 m

20 m

Development of Prostheses with Fluidic ChannelsDevelopment of Prostheses with Fluidic ChannelsLocal Drug DeliveryLocal Drug Delivery

Successive Silicon Dioxide deposition and patterning

Low-Stress LPCVD Silicon Nitride Structural Layer

Sacrificial Etch – SiO2 Removal

Etch vias are sealed by upon deposition of the SiO2 hard mask

Local Drug DeliveryLocal Drug DeliveryDevice Characterization Device Characterization

500 m

Local Drug DeliveryLocal Drug DeliveryDevice Characterization Device Characterization

500 m

Local Drug DeliveryLocal Drug DeliveryDevice Characterization Device Characterization

500 m

Controlling drug release to insertion sites

100nm channels

Nanofluidic Channels

AC Electrokinetic Manipulation of Bioparticles

Characterization and Isolation of Fetal Cells in Maternal Blood

•Current methods for obtaining genetic material for prenatal diagnosis are highly invasive, posing serious risks to both mother and fetus.

•Conventional invasive techniques result in a loss of 1:100 pregnancies.

•Consequently, prenatal genetic screening is only offered to a small percentage of pregnant women.

The problem:

Progress

Fabrication and PackagingGold thin film electrode arrays with aligned fluidic networks will be used to perform preliminary experiments.

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AC Electrokinetic Manipulation of Rare Cells

– Develop AC electrokinetic device capable of characterizing and isolating rare cells found in heterogeneous biological samples.

• S. Retterer

15 micrometers

Collaborators

Keith Neeves, CornellScott Retterer, Cornell

Andrew Spence, Cornell, UCBSahar Mahmoud, Cornell

Conrad James, SandiaAndrea Turner, Cornell

Ron Hoy, CornellGary Banker, OHSU

James Turner, WadsworthWilliam Shain, WadsworthKaren Smith, Wadsworth

Chris Bjornson, WadsworthMark Saltzman,Yale

Jonathan Trent, NASA-AmesAndrew McMillan, NASA-Ames

Support: NIH, NSF, DARPA