Archive for May, 2010

Simple fabrication of microfluidic devices by replicating Scotch-tape masters

Anil B. Shrirao1 and Raquel Perez-Castillejos1,2
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

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Simple, low-cost, low-temperature cured adhesive rings for microfluidic ports

Johnny J. Perez and Jonathan G. Shackman
Department of Chemistry, Temple University, Philadelphia, PA, USA 19122

Why is this useful?


A critical step in fabrication of microfluidic devices is coupling with the macroscopic world.  Reservoirs or pressure fittings are frequently adhered to devices by liquid epoxies or heat cured adhesive rings, such as supplied with commercial Upchurch Scientific (Oak Harbor, WA, USA) NanoPorts.  Liquid methods can potentially enter the device and clog channels.  Non-tacky resin rings make alignment of critical fittings and O-rings difficult, as they are inert until heat cured.  As an alternative to PDMS-based interfacing [1,2,], we describe a simplified method for forming customized, tacky adhesive rings using 3MT VHBT pressure-sensitive tape (Fig 1).  The rings are similar to the now discontinued NanoPort rings formed from 3MT 583 tape [3], but can cure at room temperature.  We have tested NanoPorts using these rings underwater on both polycarbonate and glass substrates in excess of 40 psi with no failures.  The cost per ring (assuming a 1 cm diameter) is a few US pennies.  Rings can easily be peeled from the ports and substrate after applying sufficient torque or sheer forces without leaving residues, facilitating aggressive cleaning (such as in piranha solution) of clogged microchannels.

Figure 1

What do I need?


The materials needed are shown in Figure 2 and include:

  • 3MT VHBT tape.  We use 0.5″ wide VHBT 4926, but a variety of tapes (including 3MT 583 tape) could be used, with selectable adhesion qualities and solvent resistances.
  • Gasket Punch or Cork Borers.  Cork borers (commonly used in chemistry labs) require two cuts while dual cutting punches, such as available from McMaster-Carr (Elmhurst, IL, USA), cut both inner and outer rings simultaneously.  We use 3/16″ inner and 7/16″ outer diameter punches for NanoPort rings.
  • Hammer and pad.  A piece of scrap wood can be used for a cutting pad.
  • Forceps.  Fine tips aid in ring manipulation and removing the adhesive backing.
  • Ports and microchip.  Homemade or commercial ports and chips can be used with the method.  The glass device used for demonstration was made using previous protocols [4].
  • Binder clip.  The tape requires at least 10 psi for strong bonds and pressure should be maintained during curing.  Mini-vises or C-clamps can also be used for hard to reach ports [3].
  • Oven (optional).  VHBT tape can cure overnight at room temperature or in 1 hr at 60 to 90 °C.

Figure 2

What do I do?


The sequence is shown in Figure 3.  The following specifics can easily be modified for a given application.

Figure 3

1. Clean ports / O-rings in DI water followed by methanol or isopropanol.  It is assumed the microdevice is clean after fabrication but can also be carefully cleaned.
2. Cut a 1 cm length of tape and place the sticky side on the punch.
3. Place the end of the punch/tape on a pad or wood block and hit the opposite end of the punch with a hammer (Fig 3A).
4. The ring will likely remain in the punch, with the backing side facing out (Fig 3B).  Use forceps to remove the newly formed ring and attach the exposed tacky side to the port.  Pressing the port (prior to removing the backing) against a flat surface can help adhesion.
5. Remove the backing with forceps to expose the other tacky side (Fig 3C) and align the assembly with the microchip access hole.
6. Clamp the port and microfluidic device using a binder clip or clamps (Fig 3D).
7. Cure either overnight or for 1 hr in an oven at 60 to 90 °C.
8. Adhered ports can be removed by either twisting and tilting or tightening a nut longer than the port to lift the port off the substrate.  The remaining ring can be removed using forceps to lift an edge and peeling (Fig 4).

Figure 4

What else should I know?


Rings should be made as needed to prolong shelf life (VHBT on the roll lists a 2 yr life when stored at room temperature and 50% relative humidity) [5].  While suitable for aqueous solutions, prolonged use of organic solvents is not recommended with VHBT tape [6], and an alternative adhesive or method, such as described by Watson and Wheeler [1], is suggested.  Application of high torque will cause the rings to fail, as can occur when over-tightening pressure fittings.

References


[1] M. W. L. Watson, A. R. Wheeler, Organic solvent compatible reservoirs for glass microfluidic chips, Chips & Tips, (Lab on a Chip), 12 December 2007
[2] J. Greener, W. Li, D. Voicu, E. Kumacheva, Reusable, robust NanoPort connections to PDMS chips, Chips & Tips, (Lab on a Chip), 24 October 2008
[3] C. Koch, J. Ingle, V. Remcho, Bonding Upchurch® NanoPorts to PDMS, Chips & Tips, (Lab on a Chip), 15 February 2008
[4] N.I. Davis, M. Mamunooru, C.A. Vyas, J.G. Shackman, Anal. Chem., 2009, 81, 5452-5459.
[5] 3MT VHBT Double Coated Acrylic Foam Tapes – June 2009 Data Sheet
[6] 3MT VHBT Durability – March 2001 Bulletin

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Fast-iteration prototyping and bonding of complex plastic microfluidic devices

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.

A proof-of-concept microfluidic device laid out using CAD software, with different layers defined for each plastic part to be used.

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.

The plastic film to be cut is mounted on a support base using double-sided tape, and then placed in the cutter/plotter.

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.

A single layer of polycarbonate cut out using the cutter/plotter, after removal of the cut features (for reference, the small loading and venting holes are 1 mm diameter).

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.

All layers of the microfluidic device are aligned and held together using clips (left) and the part is then carefully placed on a Si wafer in preparation for thermal bonding (right).

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.

The thermal bonding parameters used for the proof-of-concept microfluidic device.

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

The thermal press used (left) and the completed microfluidic device (right) loaded with contrast agents for visualization.

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.

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Rapid prototyping of branched microfluidics in PDMS using capillaries

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.

Figure 2. Flat piece of a cured PDMS

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.

Figure 3. A square capillary before (a) and after grinding with the ceramic stone (b) and flattening its tip into a right angle (c) and other angles (d)

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.

Figure 4. Placing the capillaries on the flat PDMS held by double side tape

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.

Figure 5. Different connections between capillaries: (a) Capillary connection in T-shape with a right angle and (b) connections with acute angles

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.

Figure 6. Filling the interconnection gaps with melted paraffin. (a) Piece of paraffin placed on the connection site. (b) The connection site with melted paraffin after cleaning

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”.

Figure 7. Pouring uncured PDMS over the capillaries network

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.

Figure 8. Pulling off the capillaries after the PDMS is fully cured

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.

Figure 9. Fabricated branched microfluidics (a). Microchannels filled with red and blue dye (b).

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

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