Chips and Tips

Anil B. Shrirao¹ and Raquel Perez-Castillejos^1,2
1 Department of Electrical and Computer Engineering, ² Department of Biomedical Engineering, New Jersey Institute of Technology, Newark NJ, USA

Why is this useful?

We present a method for fabricating PDMS microfluidic devices based on replicating a master made of Scotch tape.  Often the fabrication of microfluidic devices by soft lithography is restricted to those who have access to a cleanroom that allows the fabrication of a master with micrometric features.  Here we demonstrate that patterned Scotch tape can be used (without the need of any chemical treatment) as a master for soft lithography yielding microfluidic devices with a uniform height of ~ 60 µm.  As a difference to previous Chips & Tips on rapid and easy prototyping techniques [1, 2], in this method the Scotch tape does not remain as part of the microfluidic device after fabrication.  Here we used a handheld cutting tool (scalpel) to pattern the Scotch tape.  A laser cutting machine could be used, instead, for masters requiring higher precision.

What do I need?

• Glass slides, pre-cleaned from Manufacturer (Fisher Scientific, 75mm x 50mm x 1mm, Cat. No. 12-550-C)
• Scotch tape (3M Scotch® Transparent Tape 600[6])
• Stainless steel Scalpel or surgical blade with (Feather Safety Razor Co., LTD, Cat. No. 2976#11)
• Polystyrene Petri dish (Fisher Scientific, 100mm x 15mm, Cat. No. 08-757-12)
• Tweezers
• Oven or hot plate (to work at 65°C)
• Gloves (do not use latex gloves)
• PDMS silicone elastomer base and curing agent (Sylgard 184, Dow Corning)

What do I do?

1. Attach a strip of Scotch tape to the glass slide.  The thickness of the Scotch tape will determine the height of the microchannel.  (To increase the height of the channel, attach additional strips of Scotch tape.)
2. Print the layout of the microchannel on regular paper.  Place the printout on a flat surface.
3. Place the glass slide on the printout, with the Scotch tape facing up.  Align the glass slide to the microchannel layout.  Fix the glass slide to the printout with a piece of Scotch tape on the corner of the slide.
4. Use the scalpel to cut the tape on the glass slide according to the layout.  (For cutting, we used another glass slide as a ruler)
5. Remove the Scotch tape from all regions of the glass slide except those in the layout of the microchannel.
6. Place the glass slide with patterned Scotch tape in a heating oven at 65°C for 2-3min; this improves the adhesion of the edges of patterned Scotch tape to the glass substrate.  At this point, the Scotch-tape pattern does not need any further treatment in order to be used as a master for soft lithography [1].
7. Mix the base and curing components of PDMS as recommended by the manufacturer [2].  Place the glass slide in a Petri dish, with the patterned Scotch tape facing up.  Pour the PDMS mixture in the Petri dish until the master (i.e., glass slide and Scotch tape) is covered completely.  Degas PDMS in vacuum (if needed) and allow it to cure for 1 hour at 65°C.
8. Use the scalpel to cut the slab of PDMS containing the microchannel.  Peel off the PDMS replica.  (The Scotch-tape master can be used again by repeating step 7.)
9. Punch holes in the PDMS replica for the inlets and outlets of the microfluidic device.
10. Seal the PDMS replica to a substrate, either (i) conformally-by bringing the PDMS replica in contact with a smooth, clean substrate-or (ii) irreversibly-by bringing the PDMS replica in contact with the substrate after oxidizing both parts in an oxygen plasma [3]).

Acknowledgements

R. P.-C. acknowledges the support of the New Jersey institute of Technology through starting faculty funds.

References

[1] R. J. Holmes and N. J, Goddard, Rapid prototyping of microfluidics, Chips & Tips (Lab on a Chip), 15 February 2007.
[2] R, Kumar, R. L. Smith, and M. G. Pappas, A method for rapid fabrication of microfluidic devices, Chips & Tips (Lab on a Chip), 30 June 2009.
[3] Y. Xia and G. M. Whitesides, Annu. Rev. Sci., 1998, 28, 153-184.
[4] Dow Corning Product Information, “Information about Dow Corning® brand Silicone Encapsulants”.
[5] M. K. Chaudhury and G. M. Whitesides, Langmuir, 1991, 7, 1013-1025.
[6] Scotch tape

Jonathan Siegrist, Mary Amasia, and Marc Madou
Departments of Biomedical, Chemical, and Mechanical Engineering, University of California, Irvine, CA, 92697, USA

Why is this useful?

The fabrication and bonding of rapid-prototyped polymer-based microfluidic devices is of great interest. The emphasis is not only on the ability to produce large numbers of devices rapidly, but to perform fast design and test iterations. Here, we present a method for rapidly cutting thin plastic films into complex shapes, such that sophisticated 2.5-D microfluidic chips can be created. The plastic layers are bonded together using traditional, low-pressure thermal bonding to minimize channel deformation while achieving high bond strengths capable of withstanding high-pressure & temperature operations, such as polymerase chain reaction (PCR). The authors have found this method to be particularly amenable to fast design iterations, as one can easily go from a design on the computer screen to testing of a real part within 3 hours.

The method presented here of cutting plastic films using a commercially-available knife-based cutter/plotter avoids the use of traditional CNC milling, which can leave behind burrs and rough edges. While hot-embossing and laser machining can be superior alternatives to CNC milling, they are considerably more complex and expensive than the method presented here. Also, by using a computer-controlled cutter, obvious advantages are gained in terms of possible design complexity and reproducibility as compared to previous Tips [1, 2]. Finally, this cutting method can be used for many types of plastic films (< 400 um thick, depending on the machine being used) without the need for extensive optimization of cutting speeds or feed rates.

The use of thermal bonding allows for much higher bond strengths as compared to the use of pressure-sensitive adhesives or double-sided tapes, and also provides a large dynamic range in terms of the types of plastics that can be used. For example, thin films of either high glass-transition temperature (Tg) materials such as polycarbonate or low-Tg cyclic olefin copolymers can be used with this method, as compared to lamination methods that are limited to low Tg materials only [3].

What do I need?

• Hydraulic Thermal Press, ideally with a max. temperature of at least 200ºC and a max. pressure of at least 1 MPa (the device used here was an MTP-8 from Tetrahedron Associates, Inc., CA, USA)
• Computer-Controlled Cutter/Plotter (the device used here was a CE-2000 from Graphtec America, Inc., CA, USA)
• CAD software
• Bare Si Wafers, at least single-side polish
• Plastic Films (the films used here were polycarbonate from McMaster-Carr, CA, USA)
• Double-sided Tape (3M Scotch brand was used here)
• Aluminium Foil
• Tweezers
• Alignment Pins (optional)
• Oxygen Plasma System (optional)

What do I do?

1. Design your microfluidic device using common CAD software (Fig. 1). Ensure the drawing for each layer is in a “polyline” format (i.e., each continuous line is defined as a single object) to facilitate smooth cutting. Import the CAD file into the software that controls the cutter/plotter.

2. Attach your plastic film (using double-sided tape) to a plastic sheet that will act as your support/sacrificial layer (e.g., 0.75 mm thick). Place this structure in the cutter/plotter, and cut the film (Fig. 2). Cutting force and number of cuts may need to be optimized depending on the film thickness. We found that 2x low-force cuts worked well for 127 µm-thick polycarbonate films, and 4x medium-force cuts worked well for 254 µm-thick films.

3. After all cuts are complete, carefully remove the part from the sacrificial layer and use tweezers to remove and discard the cut-out plastic features (Fig. 3). Repeat this for all layers, and then clean the plastic layers using isopropanol and water.

4. Align all of the layers, and hold together using a clip. You may include alignment pin features on your layers, and use pins to assist in alignment. For example, you could use 1 mm-diameter pins (McMaster-Carr, CA, USA – #91585A001).
5. Place the assembled microfluidic device layers on the mirror-finished side of a Si wafer, and remove the clip(s) (Fig. 4). Then place the second wafer mirror-finished side down on top of the microfluidic device, being careful not to disturb the alignment.

6.  Place the assembly in the thermal press sandwiched between two pieces of foil, and thermally bond. Approximate parameters we found to work well for our proof-of-concept, multi-layer, polycarbonate device (1-top layer with loading/venting holes: 254 µm thick, 2-film with serpentine channel: 127 µm thick, 3-film with access holes and reservoirs: 127 µm thick, 4-film with linear channel: 127 µm thick, and 5-bottom layer: 254 µm thick) are shown in Fig. 5.

7.  Remove the microfluidic device from the thermal press, and test (Fig. 6).

What else should I know?

Thermal bonding parameters, such as bonding temperature, pressure, dwell times, and ramping rates, will need to be optimized to ensure complete bonding of the plastic layers. The main disadvantage of thermal bonding is possible microchannel deformation, which can affect fluidic function. Thus, the Tg of your material, the number of layers, and the required bond strength will all need to be considered. The previous Tip on prevention of chamber-sagging has obvious uses here [4].

The limitations on feature size using this method should also be noted. The thickness (z-axis) of your channels/chambers is determined by the thickness of the films. We found the feature size (x-y plane) limitations when cutting films to be ~ 200 µm, as limited by the cutter/plotter being used. Newer machines list resolutions on the order of 10s of µm.

Finally, while these plastic parts are inherently hydrophobic, they can be made hydrophilic via oxygen-plasma treatment. Common plasma-treatment parameters for our devices are 200 W for 2 mins at 200 mTorr O2-pressure to provide hydrophilicity for many weeks. This can facilitate liquid loading and also serve as a sterilization step.

Acknowledgements

We would like to thank the DARPA-MF3 center for funding, and Dr. Albert Yee of UC Irvine for generously allowing us to use his thermal press.

References

[1] R. J. Holmes and N. J, Goddard, Rapid prototyping of microfluidics, Chips & Tips, (Lab on a Chip), 15 February 2007.
[2] R, Kumar, R. L. Smith, and M. G. Pappas, A method for rapid fabrication of microfluidic devices, Chips & Tips, (Lab on a Chip), 30 June 2009.
[3] D. Olivero and Z. Fan, Lamination of plastic microfluidic devices, Chips & Tips, (Lab on a Chip), 30 July 2008.
[4] J. Xu and D. Attinger, How to prevent sagging during the bonding or lamination of chips with large aspect ratio chambers, Chips & Tips, (Lab on a Chip), 24 July 2009.

S. Ghorbanian, M. A. Qasaimeh and D. Juncker
Biomedical Engineering Department, McGill University and Genome Quebec Innovation Centre, McGill University, 740 Dr. Penfield Avenue, Montreal, QC, H3A 1A4 Canada

Why is this useful?

Polydimethylsiloxane (PDMS) is widely used for the fabrication of microfluidic systems because it can readily be molded into the desired shape, is easy to seal onto substrates, and is transparent thus permitting visualization of the sample [1]. However, the fabrication of PDMS microfluidic devices depends on a microfabricated mould that needs to be made in a clean room using photolithography and microfabrication methods, all of which are costly and time consuming and beyond the reach of many researchers. Rapid prototyping techniques that circumvent the requirement for a clean room have been proposed, such as the use of double sided scotch tapes, but lack precision and control [2,3].

Here we present a method for rapid prototyping of branched microfluidics in PDMS with control over the architecture, channel width and depth. We propose using capillaries as the mould.  They are cut to size, then arranged on a flat PDMS according to the desired architecture and covered with PDMS which is then cured. The size of each channel can be adjusted by selecting a capillary with the desired diameter, and different branch architectures can readily be produced. The capillaries are then simply removed from the PDMS replica and leave behind a network of channels.

A key challenge is the gaps formed at the intersections between abutting capillaries. We found that a small flake of paraffin can be used which is then melted to fill up this gap. The use of capillaries with a square cross-section further facilitates the moulding, and allows for making complex networks with ease and good yield. This protocol only requires materials which are commercially available and comparatively inexpensive and takes less than one hour of hands-on time, followed by three hours of curing.

What do I need?

1. A layer of flat cured PDMS, Figure 1d
2. Uncured PDMS
3. Petri dishes
4. Square capillaries (preferably) or circular capillaries [4], Figure 1a
5. Ceramic cutting stone [4], Figure 1b
6. Paraffin [5], Figure 1c
7. Oven or hot plate
8. Sharp tweezers and razor blade, Figure 1(e,f)
9. Double-sided tape [6]

Figure 1. Required materials: (a) Glass capillaries, (a1) Cross section of the square glass capillary and (a2) the round glass capillary [4]. (b) Capillary cutting stone [4]. (c) Paraffin flakes [5]. (d) Flat cured PDMS piece in a Petri dish. (e) Razor blade. (f) Tweezers

What do I do?

1. Cure a layer of PDMS in a Petri dish. Remove the PDMS, and cut it to the desired size. Flip this piece to obtain the flat surface on top and place it inside another Petri dish as shown in Figure 2.

2. Cut two pieces of capillary, Figure 1a (or as many needed to make the branched channels) using a ceramic cutting stone. The capillaries should be cut to a length that facilitates handling, typically three or more times the length of the final channels of interest and shorter than the diameter of the Petri dish. Also see “What else should I know I”. After cutting the capillaries, dip their tip at each side in melted paraffin or liquid glue and let it solidify. This helps prevent air trapped in the capillaries from exiting while degassing the PDMS, which can lead to bubbles and displacement of the capillaries.

3. Under the stereomicroscope grind the tip of the capillaries (which will be making the connections between capillaries) to remove the bumps seen in Figure 3a using a polishing stone, such as the side surface of a cutting stone, with horizontal movements, Figure 3b and flatten the tip completely, Figure 3c, which can be done at angles other than 90 degress as well, Figure 3d.

4. Stick double-sided tape at the outer extremities (preferably not at the connection sites) where the capillaries will be placed on the flat PDMS in the Petri dish, Figure 4a. Under a stereomicroscope place the capillaries according to the desired architecture. Figure 4b illustrates the placement of capillaries for fabricating T-shaped microchannels.

5. Examine the gaps and connections between the capillaries to ensure good contact. A T-shaped connection and 45 degree connections are shown in Figure 5 below.

6. Carefully place a small piece of paraffin using sharp tweezers on each of the capillary connections, Figure 6a. Heat the tip of the tweezers on a hot plate for a minute, and then carefully approach the tip to melt the paraffin, which fills the gaps between the capillaries due to capillary effects and joins them to one another, Figure 6b. The excess melted paraffin can be removed carefully wiht the tip of a razor or sharp tweezers.

7. Pour a layer of uncured PDMS over the connected capillaries as shown in Figure 7 and degas the PDMS by placing the Petri dish in a vacuum desiccator to remove all air bubbles, for alternative methods see “What else should I know II”. Then, place the Petri dish in the oven at 65°C for 3 hours or more. For shorter curing time see “What else should I know III”.

8. Remove the whole piece of cured PDMS from the Petri dish. Cut the sides of the cured PDMS using a razor blade, leaving a significant amount of the capillary exposed outside as shown below. Then carefully pull out the capillaries from the sides of the PDMS using pliers as shown in Figure 8. To make this process easier, the network can be immersed into or washed with acetone which will swell the PDMS and expand the channels prior to pulling out the capillaries.

If residues of paraffin are left inside the microchannels these can be dissolved and washed by flushing the microchannels with acetone.

9. Trim the microfluidic device to the desired shape using a razor blade or a cutter, Figure 9.

What else should I know?

Several alternative fabrication tips are listed below:

I) To fabricate an open channel microfluidic network replace the flat cured PDMS layer (in step 1) with a clean glass slide. Once the PDMS is cured it can be separated from the glass slide. In this process smaller capillaries can be used to make the channels which can be removed using tweezers after detaching the PDMS from the substrate. This open network can also be bonded to another PDMS layer after the capillaries are removed.
II) If no vacuum desiccator is available to degas PDMS, the sample can be left to be degassed and cured at room temperature overnight followed by post-curing in an oven at 65°.
III) To increase the speed of PDMS curing in step 8, the Petri dish may be replaced by an aluminum foil or a glass plate and allow to use much higher temperatures inside an oven or on a hot plate to cure the PDMS within a few minutes.
IV) It is preferable to use square capillaries because there are no gaps formed at the connection sites due to the square shapes of the capillaries as opposed to the round capillaries which will have a small gap formed at the connection sites due to the rounded shape of the capillary walls, Figure 1(a1). These gaps can, however, get filled with melted paraffin.

References

[1] D. Duffy, J. McDonald, O. Schueller, G. Whitesides, Rapid prototyping of microfluidic systems in poly (dimethylsiloxane), Anal. Chem., 1998, 70, 4974-4984.
[2] R. J. Holmes and N. J, Goddard, Rapid prototyping of microfluidics, Chips & Tips, (Lab on a Chip), 15 February 2007.
[3] R, Kumar, R. L. Smith, and M. G. Pappas, A method for rapid fabrication of microfluidic devices, Chips & Tips, (Lab on a Chip), 30 June 2009.
[4] Polymicro technologies
[5] Fisher Scientific
[6] Scotch Tape

Gang Li*, Qiang Chen and Jianlong Zhao

Shanghai Institute of Microsystem and Information Technology, Chinese academic of Sciences, Shanghai, China

Why is this useful?

To fabricate PDMS chips, one usually pours an un-cured PDMS mixture into a Petri dish or an aluminum foil tray containing the patterned master, and then cures for 2 h at 85°C. However, these casting dishes or trays present some cost problems. Often a relatively high consumption of PDMS is demanded for these casting holders because quite a part of PDMS will seep into the gap between the wafer and trays due to capillary forces during PDMS pouring. On the other hand, the seepage of PDMS under the master wafer may tilt the master causing the thickness of the PDMS mold to vary from one side to the other. Furthermore these casting dishes or trays are generally throw-away holders for casting PDMS chips, which also increases the fabrication cost of PDMS chips.

This tip presents a new casting holder, made of a hollow plate whose bottom is enveloped by an adhesive tape. This casting holder can simplify the operation of releasing the cured PDMS casting, and minimize the consumption of PDMS. In addition, this holder can be used to fabricate double-side flat PDMS chips by placing a flat substrate on its top.

What do I need?

• Circular hollow plate (home-made of PMMA)
• Adhesive tape (Nitto Denko Corp., SPV-224)
• PDMS (Dow Corning Sylgard 184)
• Hotplate (Chemat Technilogy Inc., KW-4AH hotplate)
• PET (Polyethylene terephthalate) film and flat glass slide (for optional double-side flat PDMS chips)  
  

What do I do?

1. Seal the bottom opening of the hollow plate with adhesive tape to form a casting holder (Figure 1), whose diameter is a little bigger than that of master wafer.

2. Place the master in the holder, and carefully apply a pressure to attach it to the tape, preventing any gaps from forming at the interface (Figure 2).

3. Mix the PDMS according to the manufacturer’s procedure [1].

4. Pour the PDMS mixture in the casting holder, and then place the holder on a hotplate at 85ºC for 2 hours.

5. Once the PDMS is cured, remove the holder from the hotplate and allow it to cool to room temperature.

6. Gently peel off tape from the bottom of holder (Figure 3).

7. Carefully cut around the edge of the PDMS mold using a sharp scalpel, and separate the PDMS from the holder (Figure 4).

8. Finally, peel the PDMS mold from the master wafer (Figure 5).

9. (Optional, for double-side flat PDMS chips) Prepare the casting holder as described above,  pour the PDMS mixture in the casting holder until the level of PDMS is a little higher than the top of holder, and then carefully drop a PET film onto the prepolymer mixture (Figure 6), which provides an easy way to remove the cover plates from the PDMS molds after curing.

10. Apply a pressure on the top of the film with a stack of glass slides and steel block to planarize the surface of the PDMS chips, and then cure the PDMS by placing the holder on a hotplate (Figure 7).

11. After curing, remove the glass slide and steel block from the top of holder, and then gently peel off the tape and PET film from the PDMS block (Figure 8).

12. Finally, separate the PDMS block from the holder and peel the PDMS mold from the master.

Acknowledgements

This material is based upon work supported by the Major State Basic Research Development Program of China (No. 2005CB724305), and the National High Technology Research and Development Program of China (No.2006AA02Z136).

References

[1] Dow Corning Product Information, “Information about Dow Corning® brand Silicone Encapsulants,” 2005.

Koesdjojo, M.T., Mandrell, D.T., Tennico, Y.H., Remcho, V.T.*
Department of Chemistry, Oregon State University, Corvallis, Oregon, USA

Why is this useful?

The lack of an efficient interface, or interconnect, between microfluidic devices and the macroscale world is a major impediment to the broader application of micro total analysis system (µTAS). There are a number of current products and solutions available that seek to address this issue. An example of a simple approach is the direct integration of tubing or a syringe needle into the microchip inlet using epoxy glue.[1] However, direct connection to the inlet reservoir using an epoxy often leads to clogging of the microchannels. Commercially available connections to microfluidic chips and devices, such as the NanoPort from Upchurch Scientific (Oak Harbor, WA, 98277, USA), accommodate these needs by use of a threaded nut and ferrule system. These fittings can be integrated onto chip reservoirs by means of adhesive rings or epoxy glue.[2] The drawback to this method is that NanoPorts require the use of an epoxy glue that takes time to cure and is non-removable, or an adhesive ring that is not compatible with many solvents. Another drawback is that the epoxy requires high temperatures for complete curing, making it incompatible with low glass transition (Tg) polymers.[3] Commercial edge connectors provide efficient interfacing and allow rapid connections and reusability.[4] However, they are designed to be interfaced to a standard microchip format; which limits the compatibility of other chips with different geometries layout or sizes.

This tip presents an alternative approach to making simple, cost-effective universal interconnects. The device was developed to allow for standard compression tubing connectors, such as those available from Upchurch, to be interfaced with microfluidic chips. A standard breadboard fixture was used to compress the ports against the chip to apply sealing pressure, preventing leaks at the interface.  This method allowed for connections to be made without glue, epoxy, or any form of bonding, enabling the components to be easily and quickly reused or reconfigured without the need to machine new fixtures or re-bond ports. The working pressure of these ports was tested with a syringe pump, and withstood pressures in excess of 1000 psi without any signs of leakage or failure.

What do I need?

• 0.25 and 0.5 inch thick plastic substrates such as polycarbonate (PC)
• #21, #9 drill bits
• 10-32 bottoming tap
• 1mm drill bit
• 1/16 inch PEEK or Teflon tubing
• stainless steel 10-32 socket head cap screws
• 1/32 inch Silicon o-rings
• Upchurch 10-32 ferruled fittings (F-333)

What do I do?

1. The first component was a port which allowed a standard ferruled connector to be attached perpendicular to the microfluidic device.  It contained a threaded portion for the fitting and a fluid path with small port on the bottom for the interface (Figure 2). The port was manufactured using 0.25 inch PC, but can be made of any material thick enough to allow room for the ferruled connector between the compression plates.  It was machined to size using a knee mill.  The threaded port was drilled with a #21 drill bit, then tapped with a 10-32 bottoming tap.  The fluid paths were drilled using a 1mm drill bit (substitute any drill to achieve the desired internal volume).  An o-ring was then placed in the threaded hole to ensure a tight seal against the ferruled fitting.

2. The second component was a breadboard clamp which applied pressure between the microfluidic device and interconnects (Figure 3). This breadboard approach was particularly useful for prototyping devices having different dimensions and port locations, as interconnects could easily be relocated. A wide variety of bolt locations in the clamping plates allowed for a wide variety of component sizes and configurations. The breadboard clamp assembly was manufactured by cutting 0.5 inch thick PC into two five inch squares.  Using the knee mill, a one inch grid of holes was drilled and taped on one plate with the #21 drill and 10-32 tap.  Clearance holes were drilled on the same grid, using a #9 drill bit, in the second clamping plate.

3. The 90° interconnect ports were placed on each of the reservoir holes of a microchip. The ferrules were connected to their respective tubing.  The top plate of the breadboard clamp was installed and using the holes closest to the sides of the chip, 10-32 stainless steel screws were inserted to apply even pressure by clamping the entire fixture.  Figure 4 shows the setup used to pressure-test the manufactured ports.

References

[1] T. Das, Interfacing of microfluidic devices, Chips & Tips (Lab on a Chip), 27 February 2009.
[2] http://www.upchurch.com/
[3] J. Greener, W. Li, D. Voicu, E. Kumacheva,  Reusable, robust NanoPort connections to PDMS chips, Chips & Tips (Lab on a Chip), 8 October 2008.
[4] http://www.dolomite-microfluidics.com/