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what functions were intergrates into the microfluidic chip project
what functions were intergrates into the microfluidic chip project
Solution
Fabrication of Microfluidic Chips via Hot Embossing
Cost is a prime factor that dictates the level of success of a product or technology is capable of
achieving. In the world of microfluidics, polymer replication is the most promising technology
for Fluidic Interconnects Electronic Interconnects Alignment Verification features 1”3”854 mass
production of microfluidics chips. Molding technologies used for fabricating macro scale
polymer components such as injection molding and hot embossing have been adapted with
considerable success for fabrication of polymer microfluidics chips. We use hot embossing to
fabricate a variety of microfluidics chips (Fig 1) since the mold design and fabrication process
for an embossing process is easier compared to injection molding, thus making hot embossing an
ideal manufacturing process for rapid prototyping and small scale production. Hot embossing has
been used to fabricate both single sided and double-sided partsThe Jenoptik HEX02 embossing
machine used for embossing is capable of precise alignment for double sided embossing. Parts
fabricated by hot embossing exhibit good overall dimensional control and low internal stresses.
Molded parts were measured to evaluate the dimensional variation due to the hot embossing
process. On average, a dimensional variation of 353 microns was observed over a distance of
70.4 mm on the interconnect layer chip.Hot embossing typically results in a thin residual layer of
polymer at the bottom of the part. This layer had to be removed in order to open the ports for
fluidic interconnections. Flycutting was used to remove this residual layer. Interconnection and
sealing between the layers of the chip was achieved by a combination of methods that included
spin coated layers of PDMS, adhesive backed clear tape and transfer adhesive
Stack Alignment Methodology
As multiple layers are stacked to form the complete microfluidics chip, precise alignment of the
layers
is necessary to ensure that all the fluidic interconnects align as they are supposed to. Keeping
with the
spirit of versatility of the design philosophy, different layers of the chip with various designs
should
align with sufficient accuracy to form a working device. Post molding, some dimensional
variation of
the geometry is always observed. These variations have a strong dependence on design
geometry,
hence the different layers of the modular chip stack exhibit different dimensional changes with
respect
to the original design. In order to account for this, an unconventional alignment method called
elastic
averaging11 was chosen.
Elastic averaging is an alignment technique in which a solid body is aligned to another by
over-constraining them using a large number of fairly compliant members. The elastic properties
of
the material and the constraint structure cause deformations in each individual contact feature to
average out over the sum of contact features throughout the solid body11. The repeatability and
accuracy of an elastically averaged system can be as good as that of a kinematically constrained
system. This method also has the advantage that the resultant assembly has higher stiffness and
lower
localized contact stresses. The repeatability of alignment is inversely proportional to square root
of the
number of contact points12. The accuracy of an elastically averaged interface is on the order
square
root of n better than the accuracy of the contacting elements where n is simultaneously engaged
contactors13.855
As discussed previously, molded polymer parts have dimensional variation from their original
design. The total variation is the combination of errors accumulated from the mold insert
fabrication
by micromilling process and the embossing process. The alignment members are five
V-grooves on the walls of the molded chips. 1mm diameter steel dowel pins attached to a plastic
fixture act as the secondary alignment feature. The dowel pins align into the crevices of the V-
grooves
As the dowel pins are fixed into holes in a plastic fixture, there exists some natural compliance
in them. Pressure was applied to the opposite edge of the chip stack using an elastic band.
The efficiency of passive alignment using this method was verified to be better than 50 microns
by
repeating the assembly process three times. Fig 3 illustrates the accuracy on one of the
alignment
attempts. As it was not possible to simultaneously focus on both layers of the chip stack, this
image
was generated by taking two separate pictures while keeping the setup stationary and only
changing
the focal plane of the microscope. The images were later overlaid using image processing
software.
Fluid Supply and Control
Keeping with the design philosophy, the Supplies & Instrument platform (SIP) consists of an
independent fluid delivery and control module. Maintaining an independent fluid delivery and
control
system that can easily plug and play with the rest of the system via a standard interface provides
the
most flexibility for design changes. Modifications can be made to the module with minimal
concerns
regarding integration. The fluidic supply and control module interfaces with the rest of the
system
through standard commercial connectors. A simple vacuum driven system with a push-button
user
interface has been designed to allow an easy control of fluid flowing through the microfluidic
chip.
Single use syringes are used as reservoirs and connected with standard Luer-lock connectors to
silicone tubing. This unit allows us to test the design of various microfluidic chip configurations
at a
very low cost. When more precise control or better automation is desired, this module can be
swapped
out with a more complex, expensive unit.
Biological Protocol
The demonstrated biological experiment is based on an ongoing project that involves the
integration of giant
magneto-resistive (GMR) sensors fabricated in silicon, with a microfluidic circuit. The goal of
the project is to attach
appropriate biology to the silicon surface in order to bind molecules with paramagnetic beads.
The GMR sensor
generates a signal when bead are bound directly to its surface. In order to optimize the binding
chemistry, numerous screening experiments are being run on dummy silicon dies with a surface
identical to that of the GMR sensor. One such screening experiment was carried out using the
microfluidic stack and dummy silicon dies. The surface of the silicon dies were covalently
coated with protein conjugate using a well defined sequence of
aminoproplytriethoxysilane, gluteraldehyde, and strepavidin – horse radish peroxidase (S-HRP)
treatment. The dies were then placed within the chambers of the microfluidic stack . A
chemiluminiscent material (Pico Supersignal, Pierce Biotechnology, Inc.) was flowed through
the
microfluidic channels to interact with the silicon die surfaces. Light was generated by the
interaction
between S-HRP and Supersignal. X-ray film was placed directly on top of the stack and exposed
for
less than 10 seconds. The film was developed and scanned into digital format .Then the mean
was calculated for relevant regions with SCION software (public domain from NIH) and results

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what functions were intergrates into the microfluidic chip projec.pdf

  • 1. what functions were intergrates into the microfluidic chip project what functions were intergrates into the microfluidic chip project Solution Fabrication of Microfluidic Chips via Hot Embossing Cost is a prime factor that dictates the level of success of a product or technology is capable of achieving. In the world of microfluidics, polymer replication is the most promising technology for Fluidic Interconnects Electronic Interconnects Alignment Verification features 1”3”854 mass production of microfluidics chips. Molding technologies used for fabricating macro scale polymer components such as injection molding and hot embossing have been adapted with considerable success for fabrication of polymer microfluidics chips. We use hot embossing to fabricate a variety of microfluidics chips (Fig 1) since the mold design and fabrication process for an embossing process is easier compared to injection molding, thus making hot embossing an ideal manufacturing process for rapid prototyping and small scale production. Hot embossing has been used to fabricate both single sided and double-sided partsThe Jenoptik HEX02 embossing machine used for embossing is capable of precise alignment for double sided embossing. Parts fabricated by hot embossing exhibit good overall dimensional control and low internal stresses. Molded parts were measured to evaluate the dimensional variation due to the hot embossing process. On average, a dimensional variation of 353 microns was observed over a distance of 70.4 mm on the interconnect layer chip.Hot embossing typically results in a thin residual layer of polymer at the bottom of the part. This layer had to be removed in order to open the ports for fluidic interconnections. Flycutting was used to remove this residual layer. Interconnection and sealing between the layers of the chip was achieved by a combination of methods that included spin coated layers of PDMS, adhesive backed clear tape and transfer adhesive Stack Alignment Methodology As multiple layers are stacked to form the complete microfluidics chip, precise alignment of the layers is necessary to ensure that all the fluidic interconnects align as they are supposed to. Keeping with the spirit of versatility of the design philosophy, different layers of the chip with various designs should align with sufficient accuracy to form a working device. Post molding, some dimensional variation of
  • 2. the geometry is always observed. These variations have a strong dependence on design geometry, hence the different layers of the modular chip stack exhibit different dimensional changes with respect to the original design. In order to account for this, an unconventional alignment method called elastic averaging11 was chosen. Elastic averaging is an alignment technique in which a solid body is aligned to another by over-constraining them using a large number of fairly compliant members. The elastic properties of the material and the constraint structure cause deformations in each individual contact feature to average out over the sum of contact features throughout the solid body11. The repeatability and accuracy of an elastically averaged system can be as good as that of a kinematically constrained system. This method also has the advantage that the resultant assembly has higher stiffness and lower localized contact stresses. The repeatability of alignment is inversely proportional to square root of the number of contact points12. The accuracy of an elastically averaged interface is on the order square root of n better than the accuracy of the contacting elements where n is simultaneously engaged contactors13.855 As discussed previously, molded polymer parts have dimensional variation from their original design. The total variation is the combination of errors accumulated from the mold insert fabrication by micromilling process and the embossing process. The alignment members are five V-grooves on the walls of the molded chips. 1mm diameter steel dowel pins attached to a plastic fixture act as the secondary alignment feature. The dowel pins align into the crevices of the V- grooves As the dowel pins are fixed into holes in a plastic fixture, there exists some natural compliance in them. Pressure was applied to the opposite edge of the chip stack using an elastic band. The efficiency of passive alignment using this method was verified to be better than 50 microns by repeating the assembly process three times. Fig 3 illustrates the accuracy on one of the alignment attempts. As it was not possible to simultaneously focus on both layers of the chip stack, this image
  • 3. was generated by taking two separate pictures while keeping the setup stationary and only changing the focal plane of the microscope. The images were later overlaid using image processing software. Fluid Supply and Control Keeping with the design philosophy, the Supplies & Instrument platform (SIP) consists of an independent fluid delivery and control module. Maintaining an independent fluid delivery and control system that can easily plug and play with the rest of the system via a standard interface provides the most flexibility for design changes. Modifications can be made to the module with minimal concerns regarding integration. The fluidic supply and control module interfaces with the rest of the system through standard commercial connectors. A simple vacuum driven system with a push-button user interface has been designed to allow an easy control of fluid flowing through the microfluidic chip. Single use syringes are used as reservoirs and connected with standard Luer-lock connectors to silicone tubing. This unit allows us to test the design of various microfluidic chip configurations at a very low cost. When more precise control or better automation is desired, this module can be swapped out with a more complex, expensive unit. Biological Protocol The demonstrated biological experiment is based on an ongoing project that involves the integration of giant magneto-resistive (GMR) sensors fabricated in silicon, with a microfluidic circuit. The goal of the project is to attach appropriate biology to the silicon surface in order to bind molecules with paramagnetic beads. The GMR sensor generates a signal when bead are bound directly to its surface. In order to optimize the binding chemistry, numerous screening experiments are being run on dummy silicon dies with a surface identical to that of the GMR sensor. One such screening experiment was carried out using the microfluidic stack and dummy silicon dies. The surface of the silicon dies were covalently coated with protein conjugate using a well defined sequence of
  • 4. aminoproplytriethoxysilane, gluteraldehyde, and strepavidin – horse radish peroxidase (S-HRP) treatment. The dies were then placed within the chambers of the microfluidic stack . A chemiluminiscent material (Pico Supersignal, Pierce Biotechnology, Inc.) was flowed through the microfluidic channels to interact with the silicon die surfaces. Light was generated by the interaction between S-HRP and Supersignal. X-ray film was placed directly on top of the stack and exposed for less than 10 seconds. The film was developed and scanned into digital format .Then the mean was calculated for relevant regions with SCION software (public domain from NIH) and results