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1.
J Lab Autom ; 20(1): 17-24, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25249275

ABSTRACT

Label-free measurements of the reaction kinetics of a small sample volume are essential for efficient drug discovery, requiring methods and systems that are rapid, accurate, and cost-effective. Herein, we present an integrated optofluidic system for label-free characterization of reactions in a nanoliter reagent volume. This system contains a droplet-based microfluidic sampling section and an optical fiber-based spectroscopy detection section. By manipulating droplets containing reagents at certain concentrations at different times, quantifiable measurements via absorption spectroscopy can be made in a simple, sensitive, and high-throughput manner. We have demonstrated our system's capability by performing potency (IC50) assays of an inhibitor in a TEM-1 ß-lactamase (enzyme) and nitrocefin (substrate) system. This integrated platform can potentially provide an automated, label-free, and low-cost method for many other assays of reaction kinetics.


Subject(s)
Drug Discovery/methods , Drug Evaluation, Preclinical/methods , Microfluidics/instrumentation , Microfluidics/methods , Spectrum Analysis/instrumentation , Spectrum Analysis/methods , Enzyme Inhibitors/metabolism , High-Throughput Screening Assays/instrumentation , High-Throughput Screening Assays/methods , Inhibitory Concentration 50 , Kinetics , beta-Lactamases/metabolism
2.
J Lab Autom ; 19(2): 137-43, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23592570

ABSTRACT

We report an on-chip acoustofluidic method for sequential trapping and transporting of microparticles via acoustically oscillating bubbles. The size and location of bubbles were precisely controlled by lithography. When the acoustic waves were turned off, particles followed the streamlines dictated by laminar flow. When the acoustic waves were turned on, particles were attracted to and trapped in a vortex near the surface of bubble. Therefore, particles could move across the microfluidic channel with programmed trajectories. Additionally, a theoretical model based on acoustic radiation force and drag force due to acoustic microstreaming was established to help design this particle-trapping and -transporting system.


Subject(s)
Acoustics/instrumentation , Automation, Laboratory/methods , Microfluidic Analytical Techniques/methods , Microspheres , Microfluidic Analytical Techniques/instrumentation
3.
Anal Chem ; 85(11): 5468-74, 2013 Jun 04.
Article in English | MEDLINE | ID: mdl-23647057

ABSTRACT

The emerging field of droplet microfluidics requires effective on-chip handling and sorting of droplets. In this work, we demonstrate a microfluidic device that is capable of sorting picoliter water-in-oil droplets into multiple outputs using standing surface acoustic waves (SSAW). This device integrates a single-layer microfluidic channel with interdigital transducers (IDTs) to achieve on-chip droplet generation and sorting. Within the SSAW field, water-in-oil droplets experience an acoustic radiation force and are pushed toward the acoustic pressure node. As a result, by tuning the frequency of the SSAW excitation, the position of the pressure nodes can be changed and droplets can be sorted to different outlets at rates up to 222 droplets s(-1). With its advantages in simplicity, controllability, versatility, noninvasiveness, and capability to be integrated with other on-chip components such as droplet manipulation and optical detection units, the technique presented here could be valuable for the development of droplet-based micro total analysis systems (µTAS).


Subject(s)
Hydrodynamics , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Oils/chemistry , Sound , Water/chemistry , Equipment Design , Surface Properties
5.
Lab Chip ; 13(1): 17-24, 2013 Jan 07.
Article in English | MEDLINE | ID: mdl-23138193

ABSTRACT

More than a decade of research work in optofluidics has yielded a large catalogue of optofluidic elements that can manipulate light at the micro-scale (e.g., lenses, prisms). Although these elements have proven useful for many on-chip processes (e.g., miniaturized flow cytometry, interferometry and sample spectroscopy), certain deficiencies have precluded their use in micro-scale imaging. However, recent work in optofluidic imaging has avoided optofluidic elements entirely and focused instead on image capture and composition techniques, demonstrating impressive resolution in both 2D imagery and 3D tomography. In this Focus article, we will discuss some of the recent successes in optofluidic imaging and will expound our expectations for the near future of the optofluidic imaging discipline.


Subject(s)
Optical Imaging/methods , Optical Imaging/trends , Animals , Fluorescent Dyes/chemistry , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Microfluidic Analytical Techniques/trends , Microscopy/methods , Nematoda , Optical Imaging/instrumentation , Tomography/methods
6.
Adv Funct Mater ; 23(6): 720-730, 2013 Feb 11.
Article in English | MEDLINE | ID: mdl-31588203

ABSTRACT

A new strategy to achieve large-scale, three-dimensional (3D) micro- and nanostructured surface patterns through selective electrochemical growth on monolayer colloidal crystal (MCC) templates is reported. This method can effectively create large-area (>1 cm2), 3D surface patterns with well-defined structures in a cost-effective and time-saving manner (<30 min). A variety of 3D surface patterns, including semishells, Janus particles, microcups, and mushroom-like clusters, is generated. Most importantly, our method can be used to prepare surface patterns with prescribed compositions, such as metals, metal oxides, organic materials, or composites (e.g., metal/metal oxide, metal/polymer). The 3D surface patterns produced by our method can be valuable in a wide range of applications, such as biosensing, data storage, and plasmonics. In a proof-of-concept study, we investigated, both experimentally and theoretically, the surface-enhanced Raman scattering (SERS) performance of the fabricated silver 3D semishell arrays.

7.
Anal Chem ; 84(24): 10745-9, 2012 Dec 18.
Article in English | MEDLINE | ID: mdl-23140515

ABSTRACT

Analysis of chemical or biomolecular contents in a tiny amount of specimen presents a significant challenge in many biochemical studies and diagnostic applications. In this work, we present a single-layer, optofluidic device for real-time, high-throughput, quantitative analysis of droplet contents. Our device integrates an optical fiber-based, on-chip detection unit with a droplet-based microfluidic unit. It can quantitatively analyze the contents of individual droplets in real-time. It also achieves a detection throughput of 2000 droplets per second, a detection limit of 20 nM, and an excellent reproducibility in its detection results. In a proof-of-concept study, we demonstrate that our device can be used to perform detection of DNA and its mutations by monitoring the fluorescent signal changes of the target DNA/molecular beacon complex in single droplets. Our approach can be immediately extended to a real-time, high-throughput detection of other biomolecules (such as proteins and viruses) in droplets. With its advantages in throughput, functionality, cost, size, and reliability, the droplet-based optofluidic device presented here can be a valuable tool for many medical diagnostic applications.


Subject(s)
Microfluidic Analytical Techniques/methods , Optical Fibers , Evaluation Studies as Topic , Sequence Analysis, DNA/methods
8.
Lab Chip ; 12(21): 4228-31, 2012 Nov 07.
Article in English | MEDLINE | ID: mdl-22992833

ABSTRACT

We introduce a novel microfluidic device for cell sorting in continuous flow using tunable standing surface acoustic waves. This method allows individual cells to be precisely directed into five different outlet channels in a single step. It is versatile, simple, label-free, non-invasive, and highly controllable.


Subject(s)
Acoustics , Flow Cytometry , Microfluidic Analytical Techniques , Flow Cytometry/instrumentation , Microfluidic Analytical Techniques/instrumentation , Surface Properties
9.
Anal Chem ; 84(17): 7495-501, 2012 Sep 04.
Article in English | MEDLINE | ID: mdl-22880882

ABSTRACT

In this work we present an acoustofluidic approach for rapid, single-shot characterization of enzymatic reaction constants K(m) and k(cat). The acoustofluidic design involves a bubble anchored in a horseshoe structure which can be stimulated by a piezoelectric transducer to generate vortices in the fluid. The enzyme and substrate can thus be mixed rapidly, within 100 ms, by the vortices to yield the product. Enzymatic reaction constants K(m) and k(cat) can then be obtained from the reaction rate curves for different concentrations of substrate while holding the enzyme concentration constant. We studied the enzymatic reaction for ß-galactosidase and its substrate (resorufin-ß-D-galactopyranoside) and found K(m) and k(cat) to be 333 ± 130 µM and 64 ± 8 s(-1), respectively, which are in agreement with published data. Our approach is valuable for studying the kinetics of high-speed enzymatic reactions and other chemical reactions.


Subject(s)
Acoustics , Microfluidic Analytical Techniques , Dimethylpolysiloxanes/chemistry , Escherichia coli/enzymology , Galactosides/metabolism , Kinetics , Oxazines/metabolism , beta-Galactosidase/metabolism
10.
Biomicrofluidics ; 6(2): 24113-241139, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22567082

ABSTRACT

In this work, we demonstrate an integrated, single-layer, miniature flow cytometry device that is capable of multi-parametric particle analysis. The device integrates both particle focusing and detection components on-chip, including a "microfluidic drifting" based three-dimensional (3D) hydrodynamic focusing component and a series of optical fibers integrated into the microfluidic architecture to facilitate on-chip detection. With this design, multiple optical signals (i.e., forward scatter, side scatter, and fluorescence) from individual particles can be simultaneously detected. Experimental results indicate that the performance of our flow cytometry chip is comparable to its bulky, expensive desktop counterpart. The integration of on-chip 3D particle focusing with on-chip multi-parametric optical detection in a single-layer, mass-producible microfluidic device presents a major step towards low-cost flow cytometry chips for point-of-care clinical diagnostics.

11.
Lab Chip ; 11(10): 1795-800, 2011 May 21.
Article in English | MEDLINE | ID: mdl-21479332

ABSTRACT

We have developed a planar, optofluidic Mach-Zehnder interferometer for the label-free detection of liquid samples. In contrast to most on-chip interferometers which require complex fabrication, our design was realized via a simple, single-layer soft lithography fabrication process. In addition, a single-wavelength laser source and a silicon photodetector were the only optical equipment used for data collection. The device was calibrated using published data for the refractive index of calcium chloride (CaCl(2)) in solution, and the biosensing capabilities of the device were tested by detecting bovine serum albumin (BSA). Our design enables a refractometer with a low limit of detection (1.24 × 10(-4) refractive index units (RIU)), low variability (1 × 10(-4) RIU), and high sensitivity (927.88 oscillations per RIU). This performance is comparable to state-of-the-art optofluidic refractometers that involve complex fabrication processes and/or expensive, bulky optics. The advantages of our device (i.e. simple fabrication process, straightforward optical equipment, low cost, and high detection sensitivity) make it a promising candidate for future mass-producible, inexpensive, highly sensitive, label-free optical detection systems.


Subject(s)
Interferometry/instrumentation , Animals , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , Calcium Chloride/chemistry , Cattle , Interferometry/methods , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Serum Albumin, Bovine/chemistry
12.
Lab Chip ; 9(14): 2050-8, 2009 Jul 21.
Article in English | MEDLINE | ID: mdl-19568674

ABSTRACT

We report a tunable optofluidic microlens configuration named the Liquid Gradient Refractive Index (L-GRIN) lens for focusing light within a microfluidic device. The focusing of light was achieved through the gradient refractive index (GRIN) within the liquid medium, rather than via curved refractive lens surfaces. The diffusion of solute (CaCl(2)) between side-by-side co-injected microfluidic laminar flows was utilized to establish a hyperbolic secant (HS) refractive index profile to focus light. Tailoring the refractive index profile by adjusting the flow conditions enables not only tuning of the focal distance (translation mode), but also shifting of the output light direction (swing mode), a second degree of freedom that to our knowledge has yet to be accomplished for in-plane tunable microlenses. Advantages of the L-GRIN lens also include a low fluid consumption rate, competitive focusing performance, and high compatibility with existing microfluidic devices. This work provides a new strategy for developing integrative tunable microlenses for a variety of lab-on-a-chip applications.


Subject(s)
Lenses , Microfluidic Analytical Techniques/instrumentation , Motion , Diffusion , Light
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