This work was funded by Startup funding from the University of Illinois at Urbana-Champaign, DARPA ORCHID program through a grant from AFOSR, the National Science Foundation through grant CMMI-1265164, and the National Science Foundation Graduate Research Fellowship program. We acknowledge enlightening discussions with Prof. Jack Harris, Prof. Pierre Meystre, Dr. Matt Eichenfield, Prof. Taher Saif, and Prof. Rashid Bashir.

1. Fabrication of Ultra-high-Q Microfluidic Resonators
<ol>
	<li>Preparation of capillary manufacturing setup
	<ol>
		<li>Fabricate the microfluidic optomechanical resonator in the following way &#8211; Heat a glass capillary preform with approximately 10 W of CO2 laser radiation at 10.6 microns wavelength, and draw out the heated capillary linearly using motorized translation stages. Figure 1 shows the arrangement of the linear translation stages, the lasers, and the location of the capillary preform before the pulling process.</li>
		<li>Program suitable automation software to simultaneously control the two CO2 lasers (for heating) and the two linear stages. The two linear stages perform the drawing process for the laser-heated capillary.</li>
		<li>One of the linear stages must be fast (e.g. 5 mm/sec) for the linear drawing process. Feed in more material to the heating zone with the second, slower linear stage (e.g. 0.5 mm/sec) since the capillary preform material gets depleted during the pulling process.</li>
		<li>Align the sample holders on the linear stages along both vertical and horizontal axes.</li>
		<li>Carefully align both CO2 laser beams such that they target the same spot in space (between the sample holders). A piece of card paper or heat sensitive paper is useful for this process. Do not forget to use eye protection for laser safety. Do not lower eyes to table level. Use suitable beam blocks, fume exhaust, and fire protection.</li>
		<li>Select reasonable parameters for the drawing process. For example, the following parameters reliably produce a good capillary size &#8212; 10 mm/sec pulling speed, 0.5 mm/sec feed-in speed, 3 sec preheating time, 4.5 W preheating powers for both lasers, and 5 W heating powers for both lasers.</li>
		<li>Modulation of the laser power during pulling can be used to control the capillary radius lengthwise during the drawing process to form the &#8216;bottle&#8217; resonators. An example is shown in Figure 2d. Select the proper modulation parameters: 3 Hz frequency, 6 W and 3 W for laser powers, and 50% duty cycle.</li>
	</ol>
	</li>
	<li>Fabrication of microfluidic optomechanical resonators
	<ol>
		<li>Cut a sufficiently long segment (about 2-4 cm) of fused silica capillary such that it can reach the two holders attached to the linear translation stages.</li>
		<li>Mount the capillary sample on the sample holders such that the laser target zone is roughly in the middle of the capillary. Readjust CO2 laser alignment if needed.</li>
		<li>Pull the capillary using the parameters as stated in 1.1.6. First preheat the capillary for a few seconds (Figure 2a), and then pull it with or without laser modulation (parameters in 1.1.7) as needed.</li>
		<li>Remove the drawn capillary (Figure 2b) from the sample holder. Handle the sample with gloves at the two thick ends only, in order not to contaminate the clean resonator surface.</li>
		<li>Vary the pulling parameters to fabricate capillaries with different diameters. Typically outer diameter varies from 30 &#181;m to 200 &#181;m depending on pulling conditions.</li>
	</ol>
	</li>
	<li>Mounting the fabricated device for testing
	<ol>
		<li>Prepare an E shape glass holder (Figure 2c). Cut three 1 cm x 0.5 cm and one 3 cm x 0.5 cm glass pieces from glass slides. Assemble them into an E shape using glass adhesive or superglue.</li>
		<li>Cut a length of microfluidic capillary out of the drawn sample. This length should be longer than the distance between two adjacent glass branches on the E shape holder.</li>
		<li>Glue the microcapillary device onto the holder using optical adhesive while making sure to keep a portion hanging uncontaminated between two branches of the E shape holder. Cure the optical adhesive with a LED UV curing light source for 10 sec. Figures 2c and 2d show the finished product.</li>
		<li>Carefully insert both ends of the mounted resonator into two slightly larger plastic tubes (e.g. 200 &#181;m in inner diameter). Glue and UV cure both ends to the plastic tubes with optical adhesive.</li>
		<li>Clamp the E shape structure from the third (free) glass branch to a clamped mounting device for testing. The optical quality factor of the final microfluidic resonator depends on how well the fabrication lasers were aligned and how stable their power levels were.</li>
	</ol>
	</li>
</ol>
2. Experimental Setup for Optomechanical Testing
<ol>
	<li>Fabrication of tapered optical fiber
	<ol>
		<li>Prepare a single mode telecom-band optical fiber of desired length (e.g. a few feet). Fiber segment should be long enough to be both mounted in the tapering area and connected to the setup (Figure 4). The tapering method explained here is similar to what is suggested and demonstrated in 22.</li>
		<li>Connect the prepared fiber segment to the rest of the experimental setup using any convenient fiber-splicing method.</li>
		<li>Mount the spliced fiber segment onto two linear pullers that face each other.</li>
		<li>Strip off the fiber jacket in the center of the mounted fiber fragment to expose cladding area. This is where taper will be fabricated. Clean the stripped area with methanol.</li>
		<li>Turn on the tunable laser to see real-time transmission on an oscilloscope. Make sure to set attenuators so that photodetectors are not damaged.</li>
		<li>Place a narrow nozzle hydrogen gas burner immediately underneath the unjacketed portion of the fiber. Follow all recommended safety procedures when working with pressurized flammable gases such as hydrogen. Other &#8220;clean burning&#8221; sources of flame or ceramic heaters could also be used.</li>
		<li>Before lighting up the gas, check the flow rate so that flame will not be too large (a 1-2 cm tall flame is adequate). Note that the flame is mostly invisible but may be seen as a faint orange glow in a dark room. The hydrogen flow rate should be set to a point where lighted flame will adequately soften the glass fiber.</li>
		<li>Light up the flame. As soon as flame is on, start pulling the fiber using motorized stages. Appropriate pulling speed depends on flow rate of hydrogen gas and vicinity of the flame. NOTE: Transmission through the fiber will begin to show temporal oscillation behavior as pulling continues. This indicates multimode operation.</li>
		<li>When oscillatory behavior stops and shows an unchanging signal over time, stop pulling and turn-off the flame immediately. This is when single-mode taper is obtained. Check the transmission. If transmission is too low, repeat the procedure from 2.1.1. with modified gas flow rate, flame size, and flame location. On occasion, low transmission could be due to bad alignment at step 2.1.3. or due to contamination of the exposed cladding.</li>
		<li>If resultant transmission through the taper is satisfactory, wait a few minutes to cool down the taper.</li>
		<li>Inspect the taper under a microscope. For 1,550 nm operational wavelength, typical diameter of the single-mode taper is in the order of 1-2 &#181;m.</li>
	</ol>
	</li>
	<li>Taper-coupling to WGR and searching for electronic signals indicating vibration
	<ol>
		<li>Set up the experiment in the configuration shown in Figure 3. Mechanical vibrations can be generated through both SBS and RP by the same experimental configuration. In order to clearly detect back-scattered signals as in the case of backward-SBS4,21, use a circulator between taper and tunable laser.</li>
		<li>Before turning on the tunable IR laser, make sure to set attenuators in place so that photodetectors are not damaged.</li>
		<li>Turn on and stabilize the tunable IR laser. A function generator is used to sweep the frequency of the input IR laser.</li>
		<li>Mount the resonator holder on a nanopositioning stage. Carefully bring the resonator close to the tapered fiber in order to obtain evanescent coupling. As the laser frequency is swept, optical resonances will appear as dips in transmission in the oscilloscope, as in Figure 2b of 22.</li>
		<li>Connect the photodetector output to an electrical spectrum analyzer (ESA), where the temporal interference (i.e. beat note) between the input laser light and the scattered light can be observed. This temporal interference occurs at the mechanical oscillation frequency. The &#8220;peak hold&#8221; function on the spectrum analyzer is often useful in the initial search for mechanical vibrations.</li>
		<li>Use higher input power while performing the initial search for mechanical vibration, especially when liquids are present inside the device. NOTE: Typically, input power in the order of 100 &#181;W to the device is sufficient to excite mechanical vibration.</li>
		<li>If mechanical oscillation is observed, attempt to lock to the relevant optical mode by turning off the laser frequency scan and controlling the laser wavelength in CW mode. Here, both oscilloscope and spectrum analyzer are useful in tandem. Periodic signals appear on the oscilloscope when a mechanical mode is present, as seen in Figure 5 and 1,6.</li>
	</ol>
	</li>
</ol>
3. Measuring Optomechanical Vibrations
<ol>
	<li>Optical and electronic signature of radiation pressure (RP) modes
	<ol>
		<li>As described in 2.2, mechanical oscillations will be observed when the taper and device are correctly coupled, the device optical and mechanical modes have sufficient Q-factors, and sufficient input optical power is provided. If oscillations in the range of 10 MHz - 1 GHz are not observed, attempt to change polarization to investigate different resonances, or increase the input power from tunable laser in order to overcome the minimum threshold for oscillation. When increasing the input power, always be careful not to saturate the photodetectors. Also, as described in 8, coupling distance is a key factor for exciting different RP modes.</li>
		<li>If mechanical modes are still not observed, try measuring optical quality factor. For microfluidic optomechanical resonators, results show that optical quality factor of 106 is sufficient to excite parametric oscillations13. 
		NOTE: Usually, RP modes will manifest as electronic oscillations on the spectrum analyzer accompanied by their harmonics, as seen in Figure 5. Representative results will be discussed in section 4.</li>
		<li>Use a scanning Fabry-Perot interferometer or high-resolution optical spectrum analyzer to detect the optical side bands that are generated due to amplitude and phase modulation, which is in turn induced by the periodic cavity deformation. An example measurement may be seen in Figure 3h of 1.</li>
	</ol>
	</li>
	<li>Optical and electronic signature of whispering-gallery acoustic modes
	<ol>
		<li>The acoustic frequency of backward-SBS for silica glass is approximately 11 GHz when a 1.5 micron pump laser is used4,23. Use a circulator that monitors the back-scattered light and some small amount of Rayleigh-scattered pump, to observe electronic signals for these vibrational modes. Use a high-resolution optical spectrum analyzer to resolve the scattered light. An example measurement is shown in Figure 2 of 4.</li>
		<li>Use the beat note between forward scattered light and the pump laser to observe lower frequency (sub-1 GHz) whispering-gallery acoustic modes.</li>
		<li>Due to the lower mechanical rigidity in the breathing direction, the signal from SBS is sometimes weaker than the signal from the RP modes. Again, sweep the laser at slow speed, and use &#8220;peak hold&#8221; on the spectrum analyzer to help in finding the SBS signal.</li>
		<li>Note that unlike RP-excited breathing modes, SBS-excited whispering-gallery acoustic modes do not exhibit harmonics in the optical and electronic spectra (unless cascaded excitation takes place4,24). Instead only one Stokes sideband appears for SBS modes.</li>
	</ol>
	</li>
</ol>

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We have nothing to disclose.

We have fabricated and tested a new device that bridges between cavity optomechanics and microfluidics by employing high-Q optical resonances to excite (and interrogate) mechanical vibration. It is surprising that multiple excitation mechanisms are available in the very same device, which generate a variety of mechanical vibrational modes at rates spanning 2 MHz to 11,300 MHz. Centrifugal radiation pressure supports both wineglass modes and breathing modes in the 2-200 MHz span, Forward stimulated Brillouin scattering al...

Cavity optomechanics studies the parametric coupling between phonon modes and photon modes in microresonators by means of radiation pressure (RP)1-3 and stimulated Brillouin scattering (SBS)4-6. SBS and RP mechanisms have been demonstrated in many different optical systems, such as fibers7, microspheres4,6,8, toroids1,9, and crystalline resonators5,10. Through this photon-phonon coupling, both cooling11 and excitation6,10 of mechanical modes have been demonstrated. However, almost all reported optomechanics experiments are with solid phases of matter. This is because direct liquid immersion of the optomechanical devices results in greatly increased radiative acoustic loss because of the higher impedance of liquids compared against air. In addition, in some situations dissipative loss mechanisms in liquids may exceed the radiative acoustic losses.
Recently, a new type of hollow optomechanical oscillator with a microcapillary geometry was introduced12-15, and which by design is equipped for microfluidic experiments. The diameter of this capillary is modulated along its length to form multiple &#8216;bottle resonators&#8217; that simultaneously confine optical whispering-gallery resonances16 as well as mechanical resonant modes17. Multiple families of mechanical resonant modes participate, including breathing modes, wine-glass modes, and whispering-gallery acoustic modes. The wine-glass (standing-wave) and whispering-gallery acoustic (traveling-wave) resonances are formed when a vibration with integer multiple of acoustic wavelengths occurs around the device circumference. Light is evanescently coupled into the optical whispering-gallery modes of these &#8216;bottles&#8217; by means of a tapered optical fiber18. Confinement of the liquid inside19,20 the capillary resonator, as opposed to outside it, enables high mechanical- and optical- quality factors simultaneously, which allows the optical excitation of mechanical modes by means of both RP and SBS. As has been shown, these mechanical excitations are able to penetrate into the fluid within the device12,13, forming a shared solid-liquid resonant mode, thus enabling an opto-mechanical interface to the fluidic environment within.
In this paper we describe fabrication, RP and SBS actuation, and representative measurement results for this novel optomechanical system. Specific material and tool lists are also provided.

<table><tbody><tr><td>Tunable IR laser</td><td>Newfocus</td><td>TLB-6328</td><td></td></tr><tr><td>Photodetectors</td><td>Newfocus</td><td>1811-FC (Low speed 125MHz) / 1611-FC-AC (High speed 1GHz)</td><td></td></tr><tr><td>Optical fiber</td><td>Corning</td><td>SMF28</td><td></td></tr><tr><td>Silica capillary</td><td>PolyMicro</td><td>TSP700850</td><td></td></tr><tr><td>10.6 um wavelength CO&lt;sub&gt;2&lt;/sub&gt; laser</td><td>Synrad</td><td>48-1KWM and 48-2KWM</td><td></td></tr><tr><td>UV-curing optical adhesive</td><td>Thorlabs</td><td>NOA81</td><td></td></tr><tr><td>Tubing</td><td>Tygon</td><td>EW-06418-01</td><td></td></tr><tr><td>Syringes</td><td>B-D</td><td>YO-07940-12</td><td></td></tr><tr><td>Needles</td><td>Weller</td><td>KDS201P</td><td></td></tr><tr><td>Electrical spectrum analyzer</td><td>Agilent Technologies</td><td>N9010A (EXA Signal Analyzer)</td><td></td></tr><tr><td>Electrical spectrum analyzer</td><td>Tektronix</td><td>6114A (RSA, Real-time spectrum analyzer)</td><td></td></tr><tr><td>Optical spectrum analyzer</td><td>Advantest</td><td>Q8384</td><td></td></tr><tr><td>Oscilloscope</td><td>Tektronix</td><td>DPO 4104B-L</td><td></td></tr><tr><td>Gold mirrors</td><td>II-VI Infrared</td><td>836627</td><td></td></tr><tr><td>Linear stage (slow)</td><td>DryLin</td><td>H1W1150</td><td></td></tr><tr><td>Linear stage (fast)</td><td>PBC Linear</td><td>MTB055D-0902-14F12</td><td></td></tr><tr><td>Fabry Perot optical spectrum analyser</td><td>Thorlabs</td><td>SA 200-14A (FSR: 1.5 GHz)</td><td></td></tr></tbody></table>

fabrication and testing of microfluidic optomechanical oscillators

Cavity optomechanics experiments that parametrically couple the phonon modes and photon modes have been investigated in various optical systems including microresonators. However, because of the increased acoustic radiative losses during direct liquid immersion of optomechanical devices, almost all published optomechanical experiments have been performed in solid phase. This paper discusses a recently introduced hollow microfluidic optomechanical resonator. Detailed methodology is provided to fabricate these ultra-high-Q microfluidic resonators, perform optomechanical testing, and measure radiation pressure-driven breathing mode and SBS-driven whispering gallery mode parametric vibrations. By confining liquids inside the capillary resonator, high mechanical- and optical- quality factors are simultaneously maintained.

The capillaries produced by this method are thin (between 30 &#181;m and 200 &#181;m), clear, and very flexible, but are sufficiently robust for direct handling. It is important to protect the outer surface of the capillary device against dust and water (moisture) in order to maintain a high optical quality factor (Q). By dipping one end of the capillary in water and blowing air through the capillary by means of a syringe, it can be verified whether the capillary is through or whether was sealed off during fabrication du...

Watch this Scientific Journal Video about Fabrication and Testing of Microfluidic Optomechanical Oscillators at JoVE.com

Fabrication and Testing of Microfluidic Optomechanical Oscillators

Parametric optomechanical excitations have recently been experimentally demonstrated in microfluidic optomechanical resonators by means of optical radiation pressure and stimulated Brillouin scattering. This paper describes the fabrication of these microfluidic resonators along with methodologies for generating and verifying optomechanical oscillations.

Cavity optomechanics experiments that parametrically couple the phonon modes and photon modes have been investigated in various optical systems including ...

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12.1K Views.  University of Illinois at Urbana-Champaign. Parametric optomechanical excitations have recently been experimentally demonstrated in microfluidic optomechanical resonators by means of optical radiation pressure and stimulated Brillouin scattering. This paper describes the fabrication of these microfluidic resonators along with methodologies for generating and verifying optomechanical oscillations. 

Video: Fabrication and Testing of Microfluidic Optomechanical Oscillators

Fabrication, Operation and Flow Visualization in Surface-acoustic-wave-driven Acoustic-counterflow Microfluidics

Surface acoustic waves (SAWs) can be used to drive liquids in portable microfluidic chips via the acoustic counterflow phenomenon. In this video we present the fabrication protocol for a multilayered SAW acoustic counterflow device. The device is fabricated starting from a lithium niobate (LN) substrate onto which two interdigital transducers (IDTs) and appropriate markers are patterned. A polydimethylsiloxane (PDMS) channel cast on an SU8 master mold is finally bonded on the patterned substrate. Following the fabrication procedure, we show the techniques that allow the characterization and operation of the acoustic counterflow device in order to pump fluids through the PDMS channel grid. We finally present the procedure to visualize liquid flow in the channels. The protocol is used to show on-chip fluid pumping under different flow regimes such as laminar flow and more complicated dynamics characterized by vortices and particle accumulation domains.

In this video we first describe fabrication and operation procedures of a surface acoustic wave (SAW) acoustic counterflow device. We then demonstrate an experimental setup that allows for both qualitative flow visualization and quantitative analysis of complex flows within the SAW pumping device.

Surface acoustic waves (SAWs) can be used to drive liquids in portable microfluidic chips via the acoustic counterflow phenomenon. In this video we ...

Microfluidic Chips Controlled with Elastomeric Microvalve Arrays

Miniaturized microfluidic systems provide simple and effective solutions for low-cost point-of-care diagnostics and high-throughput biomedical assays. Robust flow control and precise fluidic volumes are two critical requirements for these applications. We have developed microfluidic chips featuring elastomeric polydimethylsiloxane (PDMS) microvalve arrays that: 1) need no extra energy source to close the fluidic path, hence the loaded device is highly portable; and 2) allow for microfabricating deep (up to 1 mm) channels with vertical sidewalls and resulting in very precise features.

The PDMS microvalves-based devices consist of three layers: a fluidic layer containing fluidic paths and microchambers of various sizes, a control layer containing the microchannels necessary to actuate the fluidic path with microvalves, and a middle thin PDMS membrane that is bound to the control layer. Fluidic layer and control layers are made by replica molding of PDMS from SU-8 photoresist masters, and the thin PDMS membrane is made by spinning PDMS at specified heights. The control layer is bonded to the thin PDMS membrane after oxygen activation of both, and then assembled with the fluidic layer. The microvalves are closed at rest and can be opened by applying negative pressure (e.g., house vacuum). Microvalve closure and opening are automated via solenoid valves controlled by computer software.

Here, we demonstrate two microvalve-based microfluidic chips for two different applications. The first chip allows for storing and mixing precise sub-nanoliter volumes of aqueous solutions at various mixing ratios. The second chip allows for computer-controlled perfusion of microfluidic cell cultures.

The devices are easy to fabricate and simple to control. Due to the biocompatibility of PDMS, these microchips could have broad applications in miniaturized diagnostic assays as well as basic cell biology studies.

We demonstrate protocols for manufacturing and automating elastomeric polydimethylsiloxane (PDMS)-based microvalve arrays that need no extra energy to close and feature photolithographically defined precise volumes. A parallel subnanoliter-volume mixer and an integrated microfluidic perfusion system are presented.

Miniaturized microfluidic systems provide simple and effective solutions for low-cost point-of-care diagnostics and high-throughput biomedical assays.  ...

Biology

Fabrication and Operation of Acoustofluidic Devices Supporting Bulk Acoustic Standing Waves for Sheathless Focusing of Particles

Acoustophoresis refers to the displacement of suspended objects in response to directional forces from sound energy. Given that the suspended objects must be smaller than the incident wavelength of sound and the width of the fluidic channels are typically tens to hundreds of micrometers across, acoustofluidic devices typically use ultrasonic waves generated from a piezoelectric transducer pulsating at high frequencies (in the megahertz range). At characteristic frequencies that depend on the geometry of the device, it is possible to induce the formation of standing waves that can focus particles along desired fluidic streamlines within a bulk flow. Here, we describe a method for the fabrication of acoustophoretic devices from common materials and clean room equipment. We show representative results for the focusing of particles with positive or negative acoustic contrast factors, which move towards the pressure nodes or antinodes of the standing waves, respectively. These devices offer enormous practical utility for precisely positioning large numbers of microscopic entities (e.g., cells) in stationary or flowing fluids for applications ranging from cytometry to assembly.

Acoustofluidic devices use ultrasonic waves within microfluidic channels to manipulate, concentrate and isolate suspended micro and nanoscopic entities. This protocol describes the fabrication and operation of such a device supporting bulk acoustic standing waves to focus particles in a central streamline without the aid of sheath fluids.

Acoustophoresis refers to the displacement of suspended objects in response to directional forces from sound energy. Given that the suspended objects must ...

Fabrication and Testing of Photonic Thermometers

In recent years, a push for developing novel silicon photonic devices for telecommunications has generated a vast knowledge base that is now being leveraged for developing sophisticated photonic sensors. Silicon photonic sensors seek to exploit the strong confinement of light in nano-waveguides to transduce changes in physical state to changes in resonance frequency. In the case of thermometry, the thermo-optic coefficient, i.e., changes in refractive index due to temperature, causes the resonant frequency of the photonic device such as a Bragg grating to drift with temperature. We are developing a suite of photonic devices that leverage recent advances in telecom compatible light sources to fabricate cost-effective photonic temperature sensors, which can be deployed in a wide variety of settings ranging from controlled laboratory conditions, to the noisy environment of a factory floor or a residence. In this manuscript, we detail our protocol for the fabrication and testing of photonic thermometers.

We describe the process of fabrication and testing of photonic thermometers.

In recent years, a push for developing novel silicon photonic devices for telecommunications has generated a vast knowledge base that is now being ...

Chemistry

Fabrication of Polymer Microspheres for Optical Resonator and Laser Applications

This paper describes three methods of preparing fluorescent microspheres comprising &#960;-conjugated or non-conjugated polymers: vapor diffusion, interface precipitation, and mini-emulsion. In all methods, well-defined, micrometer-sized spheres are obtained from a self-assembling process in solution. The vapor diffusion method can result in spheres with the highest sphericity and surface smoothness, yet the types of the polymers able to form these spheres are limited. On the other hand, in the mini-emulsion method, microspheres can be made from various types of polymers, even from highly crystalline polymers with coplanar, &#960;-conjugated backbones. The photoluminescent (PL) properties from single isolated microspheres are unusual: the PL is confined inside the spheres, propagates at the circumference of the spheres via the total internal reflection at the polymer/air interface, and self-interferes to show sharp and periodic resonant PL lines. These resonating modes are so-called "whispering gallery modes" (WGMs). This work demonstrates how to measure WGM PL from single isolated spheres using the micro-photoluminescence (&#181;-PL) technique. In this technique, a focused laser beam irradiates a single microsphere, and the luminescence is detected by a spectrometer. A micromanipulation technique is then used to connect the microspheres one by one and to demonstrate the intersphere PL propagation and color conversion from coupled microspheres upon excitation at the perimeter of one sphere and detection of PL from the other microsphere. These techniques, &#181;-PL and micromanipulation, are useful for experiments on micro-optic application using polymer materials.

Protocols for the synthesis of microspheres from polymers, the manipulation of microspheres, and micro-photoluminescence measurements are presented.

This paper describes three methods of preparing fluorescent microspheres comprising &#960;-conjugated or non-conjugated polymers: vapor diffusion, ...

Fabrication of Refractive-index-matched Devices for Biomedical Microfluidics

The use of microfluidic devices has emerged as a defining tool for biomedical applications. When combined with modern microscopy techniques, these devices can be implemented as part of a robust platform capable of making simultaneous complementary measurements. The primary challenge created by the combination of these two techniques is the mismatch in refractive index between the materials traditionally used to make microfluidic devices and the aqueous solutions typically used in biomedicine. This mismatch can create optical artifacts near the channel or device edges. One solution is to reduce the refractive index of the material used to fabricate the device by using a fluorinated polymer such as MY133-V2000 whose refractive index is similar to that of water (n = 1.33). Here, the construction of a microfluidic device made out of MY133-V2000 using soft lithography techniques is demonstrated, using O2 plasma in conjunction with an acrylic holder to increase the adhesion between the MY133-V2000 fabricated device and the polydimethylsiloxane (PDMS) substrate. The device is then tested by incubating it filled with cell culture media for 24 h to demonstrate the ability of the device to maintain cell culture conditions during the course of a typical imaging experiment. Finally, quantitative phase microscopy (QPM) is used to measure the distribution of mass within the live adherent cells in the microchannel. This way, the increased precision, enabled by fabricating the device from a low index of refraction polymer such as MY133-V2000 in lieu of traditional soft lithography materials such as PDMS, is demonstrated. Overall, this approach for fabricating microfluidic devices can be readily integrated into existing soft lithography workflows in order to reduce optical artifacts and increase measurement precision.

This protocol describes the fabrication of microfluidic devices from MY133-V2000 to eliminate artifacts that often arise in microchannels due to the mismatching refractive indices between microchannel structures and an aqueous solution. This protocol uses an acrylic holder to compress the encapsulated device, improving adhesion both chemically and mechanically.

The use of microfluidic devices has emerged as a defining tool for biomedical applications. When combined with modern microscopy techniques, these devices ...

Label-free Single Molecule Detection Using Microtoroid Optical Resonators

Detecting small concentrations of molecules down to the single molecule limit has impact on areas such as early detection of disease, and fundamental studies on the behavior of molecules. Single molecule detection techniques commonly utilize labels such as fluorescent tags or quantum dots, however, labels are not always available, increase cost and complexity, and can perturb the events being studied. Optical resonators have emerged as a promising means to detect single molecules without the use of labels. Currently the smallest particle detected by a non-plasmonically-enhanced bare optical resonator system in solution is a 25 nm polystyrene sphere1. We have developed a technique known as Frequency Locking Optical Whispering Evanescent Resonator (FLOWER) that can surpass this limit and achieve label-free single molecule detection in aqueous solution2. As signal strength scales with particle volume, our work represents a &#62; 100x improvement in the signal to noise ratio (SNR) over the current state of the art. Here the procedures behind FLOWER are presented in an effort to increase its usage in the field.

We have developed a label-free biosensing system based on optical resonator technology known as Frequency Locking Optical Whispering Evanescent Resonator (FLOWER) that is capable of detecting single molecules in solution. Here the procedures behind this work are described and presented.

Detecting small concentrations of molecules down to the single molecule limit has impact on areas such as early detection of disease, and fundamental ...

Bioengineering

Microfluidic Fabrication Techniques for High-Pressure Testing of Microscale Supercritical CO2 Foam Transport in Fractured Unconventional Reservoirs

Pressure limitations of many microfluidic platforms have been a significant challenge in microfluidic experimental studies of fractured media. As a result, these platforms have not been fully exploited for direct observation of high-pressure transport in fractures. This work introduces microfluidic platforms that enable direct observation of multiphase flow in devices featuring surrogate permeable media and fractured systems. Such platforms provide a pathway to address important and timely questions such as those related to CO2 capture, utilization and storage. This work provides a detailed description of the fabrication techniques and an experimental setup that may serve to analyze the behavior of supercritical CO2 (scCO2) foam, its structure and stability. Such studies provide important insights regarding enhanced oil recovery processes and the role of hydraulic fractures in resource recovery from unconventional reservoirs. This work presents a comparative study of microfluidic devices developed using two different techniques: photolithography/wet-etching/thermal-bonding versus Selective Laser-induced Etching. Both techniques result in devices that are chemically and physically resistant and tolerant of high pressure and temperature conditions that correspond to subsurface systems of interest. Both techniques provide pathways to high-precision etched microchannels and capable lab-on-chip devices. Photolithography/wet-etching, however, enables fabrication of complex channel networks with complex geometries, which would be a challenging task for laser etching techniques. This work summarizes a step-by-step photolithography, wet-etching and glass thermal-bonding protocol and, presents representative observations of foam transport with relevance to oil recovery from unconventional tight and shale formations. Finally, this work describes the use of a high-resolution monochromatic sensor to observe scCO2 foam behavior where the entirety of the permeable medium is observed simultaneously while preserving the resolution needed to resolve features as small as 10 &#181;m.

Microfluidic Fabrication Techniques for High-Pressure Testing of Microscale Supercritical CO2 Foam Transport in Fractured Unconventional Reservoirs

This paper describes a protocol along with a comparative study of two microfluidic fabrication techniques, namely photolithography/wet-etching/thermal-bonding and Selective Laser-induced Etching (SLE), that are suitable for high-pressure conditions. These techniques constitute enabling platforms for direct observation of fluid flow in surrogate permeable media and fractured systems under reservoir conditions.

Pressure limitations of many microfluidic platforms have been a significant challenge in microfluidic experimental studies of fractured media. As a ...

Assembly and Characterization of an External Driver for the Generation of Sub-Kilohertz Oscillatory Flow in Microchannels

Microfluidic technology has become a standard tool in chemical and biological laboratories for both analysis and synthesis. The injection of liquid samples, such as chemical reagents and cell cultures, is predominantly accomplished through steady flows that are typically driven by syringe pumps, gravity, or capillary forces. The use of complementary oscillatory flows is seldom considered in applications despite its numerous advantages as recently demonstrated in the literature. The significant technical barrier to the implementation of oscillatory flows in microchannels is likely responsible for the lack of its widespread adoption. Advanced commercial syringe pumps that can produce oscillatory flow, are often more expensive and only work for frequencies less than 1 Hz. Here, the assembly and operation of a low-cost, plug-and-play type speaker-based apparatus that generates oscillatory flow in microchannels is demonstrated. High-fidelity harmonic oscillatory flows with frequencies ranging from 10-1000 Hz can be achieved along with independent amplitude control. Amplitudes ranging from 10-600 &#181;m can be achieved throughout the entire range of operation, including amplitudes &#62; 1 mm at the resonant frequency, in a typical microchannel. Although the oscillation frequency is determined by the speaker, we illustrate that the oscillation amplitude is sensitive to fluid properties and channel geometry. Specifically, the oscillation amplitude decreases with increasing channel circuit length and liquid viscosity, and in contrast, the amplitude increases with increasing speaker tube thickness and length. Additionally, the apparatus requires no prior features to be designed on the microchannel and is easily detachable. It can be used simultaneously with a steady flow created by a syringe pump to generate pulsatile flows.

The protocol demonstrates a convenient method to produce harmonic oscillatory flow from 10-1000 Hz in microchannels. This is performed by interfacing a computer-controlled speaker diaphragm to the microchannel in a modular manner.

Microfluidic technology has become a standard tool in chemical and biological laboratories for both analysis and synthesis. The injection of liquid ...

A Microfluidics Approach for the Functional Investigation of Signaling Oscillations Governing Somitogenesis

Periodic segmentation of the presomitic mesoderm of a developing mouse embryo is controlled by a network of signaling pathways. Signaling oscillations and gradients are thought to control the timing and spacing of segment formation, respectively. While the involved signaling pathways have been studied extensively over the last decades, direct evidence for the function of signaling oscillations in controlling somitogenesis has been lacking. To enable the functional investigation of signaling dynamics, microfluidics is a previously established tool for the subtle modulation of these dynamics. With this microfluidics-based entrainment approach endogenous signaling oscillations are synchronized by pulses of pathway modulators. This enables modulation of, for instance, the oscillation period or the phase-relationship between two oscillating pathways. Furthermore, spatial gradients of pathway modulators can be established along the tissue to study how specific changes in the signaling gradients affect somitogenesis.
The present protocol is meant to help establish microfluidic approaches for the first-time users of microfluidics. The basic principles and equipment needed to set up a microfluidic system are described, and a chip design is provided, with which a mold for chip generation can conveniently be prepared using a 3D printer. Finally, how to culture primary mouse tissue on a microfluidic chip and how to entrain signaling oscillations to external pulses of pathway modulators are discussed.
This microfluidic system can also be adapted to harbor other in vivo and in vitro model systems such as gastruloids and organoids for functional investigation of signaling dynamics and morphogen gradients in other contexts.

A protocol for the culture and manipulation of mouse embryonic tissue on a microfluidic chip is provided. By applying pulses of pathway modulators, this system can be used to externally control signaling oscillations for the functional investigation of mouse somitogenesis.

Periodic segmentation of the presomitic mesoderm of a developing mouse embryo is controlled by a network of signaling pathways. Signaling oscillations and ...

Fabrication and Testing of Microfluidic Optomechanical Oscillators

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