#7 Microfluidic Systems: Sheng-Shian Li

#7 Microfluidic Systems
Sheng-Shian Li ()
Professor
Institute of NanoEngineering and MicroSystems
National Tsing Hua University, Hsinchu, Taiwan
INEMS at NTHU, Taiwan Copyright: NTHU INEMS, proprietary Information, do not distribute or copy 1
Example Application
Traditional Chemical Analysis (DNA Assay)
INEMS at NTHU, Taiwan Copyright: NTHU INEMS, proprietary Information, do not distribute or copy Source: Michigan 2
The Need for Integration
Sample-to-sequence device is highly desirable (eliminates all manual
transfers and interactions)
Integrated DNA Analysis
Microfluidic Transducers
A fluid is a material (gas or liquid) that deforms continually under shear
stress, i.e., the material can flow and has no rigid three-dimensional
structure.
Micromachining applications in fluidics have become more important
as people strive to create complete fluidic systems in miniaturized
formats. Many of the key building blocks (flow channels, flow
restrictors, mixers, pumps, valves, sensors, etc.) are either fairly
mature or are already under development. A broad variety of materials
are available for fabricating the systems or their components, including
glass, plastics/polymers, metals, ceramics, and semiconductors.
Applications of micromachined fluidic systems include chemical
analysis, biological and chemical sensing, drug delivery, molecular
separation, amplification, sequencing or synthesis of nucleic acids,
environmental monitoring; and many others.
Issues in Microfluidic Systems

To take full advantage of micromachining technologies for
microfluidics, one must deal with significant additional
issues, such as packaging, interfaces between
components (often made from different materials), and
testing.
In the early development of electronic systems, similar
issues were present and were dealt with by standardized
packaging, interconnects like printed circuit board and with
modern electronic test components.
Unfortunately, the analog between electronic and fluidic
systems is not perfect, since electronic components do not
generally require consideration of flowing materials,
chemical compatibilities, high pressures, packaging with
openings for fluidic access, etc. It is likely, however, that as
high-volume markets are identified, mass production
issues will drive the development of solutions to these
problems.
Difference Between Macroscopic and
Micromachined Fluidic Devices
Microfluidic Components and Systems

Components
Flow channels
Pumps
Valves
Integrated microfluidic systems
Microarrays
Microreactors (gas and liquid), synthesis
Chemical Analysis (DNA, blood, etc.)
Drug delivery
Miniature combustion systems
Flow Channels
Flow channels for fluids and gases are fundamental building blocks of microfluidic
systems, analogous to wire or thin-film electrical interconnects in conventional ICs.
It is readily possible to fabricate flow channels in silicon using various etching
techniques. Similarly, flow channels can be fabricated in glass and other materials,
but generally, only isotropic etches are readily available.
A wide variety of fluidic channels have been fabricated using micromachining
approaches from one of three categories: bulk micromachined, surface
micromachined (additive), and others (such as molding, etch pit replication, etc.).
The most important factors for selecting suitable fabrication technologies are
generally:
1) available channel cross-sectional areas and other geometric constraints (note
that most surface micromachined fluidic channels have significant channel height
constraints, leading to surface areas that scale directly with the channel cross
section).
2) channel interior surface materials (key issues are typically whether or not all
surfaces are of one material type, and the compatibility of the material(s) with any
biological or chemical fluids they may encounter).
3) complexity of fabrication (hence yield and cost).
Other factors to be considered are mostly application-specific and include whether
or not the channels are optically accessible, interior wall roughness, hermeticity,
burst pressure, etc.
Flow Channels In Glass, Silica, Quartz,
Flow Channels in Silicon
Bulk Micromachined Channels

The realization of this buried flow
channel array in silicon depends on the
anisotropy of the silicon etch rate in
EDP. For example, the (100) plane in
silicon has an etch rate which is about
fifty times faster than that of the (111)
plane. In addition, highly-boron-doped
single crystal silicon with a doping
concentration higher than 7e19 cm-3 is
not significantly attacked in EDP.
Based on these characteristics, if
highly boron doped silicon is used as
an etch mask and an opening
perpendicular to the 100 direction is
cut through this layer to expose the
(100) plane, a subsequent wet etch in
EDP will undercut the mask to form a
continuous flow channel as shown in
the figure.
Bulk Micromachined Channels (Cont.)
Fig. 3(a) shows the cross section of a
flow channel formed after
undercutting the highly-boron doped
rib array using EDP etch, while Fig.
3(b) shows the channel structure
after sealing the ceiling with thermal
oxide and LPCVD dielectrics. This
approach results in a planar upper
surface on which to accommodate
the heaters and interconnect leads.
Multichannel arrays with channel-to-
channel separations as small as 4m
can be achieved because of the high
lateral dimensional control achieved
by the anisotropic etch. Where
convex corners are used in routing
the microchannels, no corner
compensation was used.
Bulk Micromachined Channels (Cont.)

The fabrication of the nozzle head begins with
the thermal oxidation of a (100) silicon wafer to a
thickness of 1m as shown in Fig. 6. The device
area is then defined by a shallow boron diffusion
on the front side of the wafer. This boron diffused
layer is used as a mask for forming the
microtubes and reservoir and is targeted to be
2m thick after the undercut etch. Next, chevron-
shaped openings are cut through this shallow-
boron-doped layer using reactive ion etching to
define the nozzles and the front-end ink reservoir
area. These trench openings are typically 1m
wide and 4m deep, leaving 2.5-m wide
chevron ribs between them. This layer is
undercut by EDP to form the front-end reservoir
and flow tubes aligned with the 110 direction.
The ceiling of the undercut area is then sealed
using thermal oxidation and LPCVD deposited
dielectrics. The lateral growth of the thermal
oxide on the sidewalls of the openings reduces
the gap width in the ceiling, while the subsequent
LPCVD oxide totally blocks these openings.
Typically, 0.5 m of thermal oxide and 0.6 m of
LPCVD oxide are required for this sealing
process.
Surface Micromachined Channels
A sketch of a silicon-processed
microneedle is shown in Fig. 1. The cross
section A-A of the microneedle shows the
interior of the fully enclosed flow channel
that runs along its length. The micro
hypodermic channels are surface
micromachined onto a silicon substrate that
is mostly etched away in the final fabrication
step. A thinned (about 50m) layer from the
original substrate is retained by using a
timed etch process. The flow channel runs
the length of the microneedle (from 16
mm) and has openings near the distal and
shank ends. In order to form the enclosed
channel, it is necessary to remove a
sacrificial layer of phosphorus-doped glass
(PSG) from within the channel region during
processing. Access holes for the etch
(which are filled in subsequent processing)
are therefore provided at regular intervals
along the channel length (each 25m),
making the duration of the sacrificial-layer
etching step independent of the channel
length.
Surface Micromachined Channels (Cont.)
Surface Micromachined Channels (Cont.)
Fig. 10 is an SEM cross section of a microneedle which has been

cleaved near the tip. The microchannel has a slightly smaller width
than the standard ones and its dimensions are 9*30m2 as seen in the
micrograph. This cross section was taken from the front portion of the
microneedle and the surface of single crystal silicon with heavily doped
boron can be clearly identified.
Parylene Surface Micromachined Channels
Slide from Senol Mutlu

INEMS at NTHU, Taiwan Copyright: NTHU INEMS, proprietary Information, do not distribute or EECS,
copy Univ. of Michigan18
Micropumps
One of the very important, and badly needed, microfluidic devices is a
micropump. Several different principles have been used for the
pumping mechanism, and different actuation mechanisms have been
employed:
Micro-displacement pumps
Electric-field assisted pumps
Magneto-hydrodynamic pumps
Acoustic streaming (ultrasonic) pumps
Pumping based on interfacial tension
Other pumps.
Actuation mechanisms utilized include:
Electrostatic
Thermal
Electromagnetic
Piezoelectric
Pneumatic
Hydrogel
Phase-change
Bubble actuation
Micropumps
Slide from Senol Mutlu

EECS, Univ. of Michigan
INEMS at NTHU, Taiwan Copyright: NTHU INEMS, proprietary Information, do not distribute or copy 20
Rectification With Check Valves
Zengerle, et al. (1995) demonstrated an electrostatically actuated bidirectional

membrane pump. A four-wafer stack of bulk micromachined wafers was
combined to form the pump.
Pulses of 150 - 200 V were used to drive the pump at frequencies from 0.1 Hz
- 10 kHz.
At frequencies < 800Hz, the pump operates in the forward mode, and at
frequencies from 2 - 8 kHz, it reverses (due to phase shift between response of
valves and pressure pulses.
Flow rates were 250 - 850 l/min (forward) and 200 - 350 l/min (reverse).
Rectification With Diffuser Nozzle

Configuration
Kinetic energy (flow
velocity) of the fluid is
transformed into potential
energy (pressure) in the
pump (pressure
recovery), but the
efficiency of this process is
greater in the diffuser
direction than in the nozzle
direction.
Ports conduct more fluid in
the diffuser direction than
the nozzle direction,
resulting in a net pumping
action .
Peristaltic Motion
Pumping is achieved in stages. Multiple pump chambers are
used, with each chamber pumping the fluid along by a little bit,
much like a bucket brigade.
C. Grosjean, Y.C. Tai, Transducer 99.

Viscosity Change With Temperature

This rectification scheme takes
advantage of the change of the
viscosity of the liquid with
temperature. Liquid viscosity
decreases with the increase in
temperature. With low viscosity,
more liquid volume can be
displaced. When the diaphragm
moves up, it pumps the liquid in
the chamber into the inlet and the
outlet. Only the heater in the outlet
is on. Therefore liquid viscosity in
the outlet channel is low and more
liquid will be displaced through the
outlet than the inlet. When the
diaphragm moves down, it sucks
liquid from inlet and the outlet.
Now only the inlet heater is on.
Therefore flow from the inlet into
the chamber is more than the one
from the outlet. This way flow
rectification can be achieved
S. Matsumoto, A. Klein, R. Maeda, MEMS99. depending on which heater is on.
Rotary Pumps
Photosensitive polyimide template plating of permalloy (81% Ni,

19% Fe) was used to fabricated the rotor and stator poles, with
multi-level plating used to fabricate monolithic stator coils.
At 0.6 - 1.5W, flows of 24 l/min were demonstrated at 5000 rpm
with an achievable differential pressure of 100 hPa.
Valves
Ideal valve characteristics:
zero leakage
zero power consumption
zero dead volume
infinite differential pressure capability
insensitivity to particulate contamination
zero response time (infinitely fast state change)
potential for linear operation
ability to operate with liquids and gases of any
density/viscosity/chemistry
others?
In practice, one is faced with a trade-off.
Valves are categorized as passive , active depending upon
whether or not they use external power to actuate and
hydrogel valves.
Passive Valves
Passive valves are usually used as check valves. These are flow
control components that allow flow only in one direction. This way they
can rectify the bidirectional flow generated by micropumps. In that
respect it is analogous to a diode in electrical circuits.
Two-wafer stack design for passive valve (after Tiren, et al., (1989)).
Passive Valves
Active Valves
Many valves actuate diaphragms based on piezoelectric, shape
memory alloy, thermo-pneumatic and electrostatic principle. For good
sealing, it needs two capillary level construction. This complicates
fabrication process (unfavorable for large-scale integration).
An electrostatically actuated valve with two level capillary construction. Fabricated

using parylene process. A voltage of around 200 volts must be applied to the
electrodes in order to close the valve [J. Xie, Y.C. Tai et al, MEMS 2003]. Charging of
the insulating layer and stiction happen after repeated actuations.
Active Valves
This valve features a surface micromachined paraffin integrated into parylene

microchannels with embedded microheaters. It takes advantage of the large
volumetric thermal expansion (10-30 %) of paraffin with the microheater power
to deflect a parylene membrane and close the channel. (P. Selvaganapathy,
E.T. Carlen, C.H. Mastrangelo, Sensors & Actuators A, 2003.)
Piezoelectric Valve With Organic Membrane
(Shoji, et al. (1991))
Figures after Shoji, et al., (1991).

Thermally-Driven Valves
Normally closed gas valve of Jerman (1991), showing two-wafer construction and
thermal bimorph actuation scheme (note that the valve is shown partly open).
On/off flow ratios (defining leakage) of 5000:1 were achieved, with gas flows of 0 - 150
cc/min possible at inlet pressures of 1 - 50 PSIG, with an input power of 150 mW
required for any appreciable flow and more power required for higher flow rates (on
the order of 500 mW for full flow).
Bimorph Actuated Valve
The design of Barth, et al. (1994) used electroplated Ni (30

m) on Si bimorphs for actuation.
Approximately 1W was required for full flow (normally
closed valve).
The valve operates over a pressure range of 0 - 200 psi
and flow rates of 0 - 600 sccm.
Thermopneumatic Valves
Liquid trapped in a sealed cavity is pressurized (and/or partly vaporized) by
dissipation of power by a thin-film heater. The expanding working fluid in the
chamber forces a thin membrane against a valve seal. Fabricated by bonding
wafers together, filled cavities with a fluid (pentane in this case with a micro
syringe) and sealed afterwards with epoxy.

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#7 Microfluidic Systems

Integrated DNA Analysis

Issues in Microfluidic Systems

Microfluidic Components and Systems

Flow Channels In Glass, Silica, Quartz,

Bulk Micromachined Channels

Bulk Micromachined Channels (Cont.)

Surface Micromachined Channels (Cont.)

Fig. 10 is an SEM cross section of a microneedle which has been

Parylene Surface Micromachined Channels

Slide from Senol Mutlu

Slide from Senol Mutlu

Zengerle, et al. (1995) demonstrated an electrostatically actuated bidirectional

Rectification With Diffuser Nozzle

C. Grosjean, Y.C. Tai, Transducer 99.

Viscosity Change With Temperature

Photosensitive polyimide template plating of permalloy (81% Ni,

An electrostatically actuated valve with two level capillary construction. Fabricated

This valve features a surface micromachined paraffin integrated into parylene

Figures after Shoji, et al., (1991).

The design of Barth, et al. (1994) used electroplated Ni (30

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