Publications (30) View all
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Article: Simultaneous detection of duplex DNA oligonucleotides using a SERS-based micro-network gradient chip.
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ABSTRACT: We report the development of a programmable surface-enhanced Raman scattering (SERS)-based micro-network gradient platform to simultaneously detect two different types of DNA oligomer mixtures. The utility of this platform was demonstrated by quantitative analysis of two breast cancer-related (BRCA1) DNA oligomer mixtures. To generate on-demand concentration gradients, the microfluidic circuit was designed using an electric-hydraulic analogy. Then a multi-gradient microfluidic channel was fabricated based on the theoretical design of the concentration control module. These micro-network structures automatically produce a series of different concentration gradients by continuously mixing Cy3-labeled DNA oligomers (BRAC1-Mutation) with TAMRA-labeled DNA oligomer (BRAC1-Wild). The SERS signals for different ratios of duplex DNA oligomer mixtures, adsorbed on the surface of silver nanoparticles, were measured under flowing conditions. Total analysis time from serial mixing to SERS detection takes less than 10 min because all experimental conditions are automatically controlled inside the exquisitely designed microfluidic channel. This novel SERS-based DNA sensing technology in a micro-network gradient channel is expected to be a powerful analytical tool to simultaneously detect multiple DNA oligomer mixtures.Lab on a Chip 10/2012; · 5.67 Impact Factor -
Article: Fusion and sorting of two parallel trains of droplets using a railroad-like channel network and guiding tracks.
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ABSTRACT: We propose a robust droplet fusion and sorting method for two parallel trains of droplets that is relatively insensitive to frequency and phase mismatch. Conventional methods of droplet fusion require an extremely precise control of aqueous/oil flows for perfect frequency matching between two trains of droplets. In this work, by combining our previous two methods (i.e., droplet synchronization using railroad-like channels and manipulation of shape-dependent droplets using guiding tracks), we realized an error-free droplet fusion/sorting device for the two parallel trains of droplets. If droplet pairs are synchronized through a railroad-like channel, they are electrically fused and the fused droplets transit to a middle guiding track to flow in a middle channel; otherwise non-synchronized non-fused droplets will be discarded into the side waste channels by flowing through their own guiding tracks. The simple droplet synchronization, fusion, and sorting technology will have widespread application in droplet-based chemical or biological experiments, where two trains of the chemically or biologically treated or pre-formed droplets yield a train of 100% one-to-one fused droplets at the desired outlet channel by sorting all the non-synchronized non-fused droplets into waste outlets.Lab on a Chip 07/2012; 12(20):3936-42. · 5.67 Impact Factor -
Article: SERS-based immunoassay using a gold array-embedded gradient microfluidic chip.
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ABSTRACT: Here we report the development of a programmable and fully automatic gold array-embedded gradient microfluidic chip that integrates a gradient microfluidic device with gold-patterned microarray wells. This device provides a convenient and reproducible surface-enhanced Raman scattering (SERS)-based immunoassay platform for cancer biomarkers. We used hollow gold nanospheres (HGNs) as SERS agents because of their highly sensitive and reproducible characteristics. The utility of this platform was demonstrated by the quantitative immunoassay of alpha-fetoprotein (AFP) model protein marker. Our proposed SERS-based immunoassay platform has many advantages over other previously reported SERS immunoassay methods. The tedious manual dilution process of repetitive pipetting and inaccurate dilution is eliminated with this process because various concentrations of biomarker are automatically generated by microfluidic gradient generators with N cascade-mixing stages. The total assay time from serial dilution to SERS detection takes less than 60 min because all of the experimental conditions for the formation and detection of immunocomplexes can be automatically controlled inside the exquisitely designed microfluidic channel. Thus, this novel SERS-based microfluidic assay technique is expected to be a powerful clinical tool for fast and sensitive cancer marker detection.Lab on a Chip 07/2012; 12(19):3720-7. · 5.67 Impact Factor -
Article: Microfluidic concentration-on-demand combinatorial dilutions
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ABSTRACT: We present a microfluidic network-based combinatorial dilution device to generate on-demand combinatorial dilutions of all input samples in the range of a 3D simplex-centroid. The device consists of an initial concentration control module and a combinatorial dilution module. In the initial concentration control module, the concept of using a single common channel has been incorporated to generate desirable concentrations of each sample, diluted independently in response to variable input flow. Then, the diluted samples flow into the combinatorial dilution module to generate a full set of seven combinations from the three samples. First, we investigated the performance of the initial concentration controller by computational simulation (CFD-ACE+). The simulated output concentrations are extremely close to the expected theoretical values. Further, a PDMS-based initial concentration controller was fabricated, and its linearity and independency were tested with fluorescent dye. Then, we designed, simulated, and tested a combinatorial dilution device integrated with the initial concentration controller. Finally, as proof-of-concept, we performed a simple combinatorial cytotoxicity test with three drugs (Mitomycin C, Doxorubicin, and 5-FU) for MCF-7 cancer cells. KeywordsCombinatorial device–Design of experiment–Dilution–Microfluidic network–Cytotoxicity testMicrofluidics and Nanofluidics 04/2012; 11(1):75-86. · 3.37 Impact Factor -
Article: Microfluidic network-based combinatorial dilution device for high throughput screening and optimization
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ABSTRACT: We present a combinatorial dilution device using a three-layer microfluidic network that can produce systematic variations of buffer and additive solutions in a combinatorial fashion for high throughput screening and optimization. A proof-of-concept device providing seven combinations (ABC/D, AB/D, BC/D, AC/D, A/D, B/D, and C/D) of three additive samples (A, B, and C) into a buffer solution (D) has been demonstrated. Such combinations are often used in simplex-centroid mixture DOE (design of experiments), useful techniques to minimize the experimental efforts at maximal information output with systematic variations of large-scale components. Based on mathematical and electrical modeling and computational fluid dynamic simulation, the device has been designed, fabricated, and characterized. KeywordsCombinatorial device-Microfluidic network-High throughput screening-Design of experimentsMicrofluidics and Nanofluidics 04/2012; 8(5):677-685. · 3.37 Impact Factor
