A 1536 channel oligonucleotide synthesizer, the MultiSyn, was developed with the capability to si... more A 1536 channel oligonucleotide synthesizer, the MultiSyn, was developed with the capability to simultaneously synthesize 1536 oligonucleotides of 20mer length in 10 h. The instrument was designed to synthesize different sequences of various lengths in micro-wells and has synthesized oligonucleotides as long as 119 nt with reasonably good yields using CPG beads of 1000 A pore size. The instrument consists of four 384 channel synthesis modules. Phosphoramidite chemistry was employed and step yields as high as 99.3% were achieved. The enhancement of oligonucleotide synthesis throughput is accomplished by increasing the spatial density of reaction wells. We have identified several parameters that are critical in achieving a good synthesis yield and negligible failure rate in small reaction wells. The coefficient of variation (CV) of product yields in 1536 reaction wells was 20%. The quality of the product was examined by capillary electrophoresis and mass spectrometry. The instrument ha...
Organs are composed of heterotypic cells with patterned architecture that enables intercellular i... more Organs are composed of heterotypic cells with patterned architecture that enables intercellular interaction to perform specific functions. In tissue engineering, the ability to pattern heterotypic cells into desired arrangement will allow us to model complex tissues in vitro and to create tissue equivalents for regeneration. This study was aimed at developing a method for fast heterotypic cell patterning with controllable topological manipulation on a glass chip. We found that poly(vinyl alcohol)-coated glass showed a biphasic change in adhesivity to cells in vitro: low adhesivity in the first 24 h and higher adhesivity at later hours due to increased serum protein adsorption. Combining programmable CO2 laser ablation to remove poly(vinyl alcohol) and glass, we were able to create arrays of adhesive microwells of adjustable patterns. We tested whether controllable patterns of epithelial-mesenchymal interaction could be created. When skin dermal papilla cells and fibroblasts were see...
We use structured-illumination nano-profilometry with sub-diffraction-limit lateral resolution to... more We use structured-illumination nano-profilometry with sub-diffraction-limit lateral resolution to measure the filopodium dynamics of lung cancer cells under stimulation of DC electric fields. The cathode growth bias and enhanced expression of filopodia are observed.
ABSTRACT Different cellular accumulations with distinct fluorescence properties of BMVC in cancer... more ABSTRACT Different cellular accumulations with distinct fluorescence properties of BMVC in cancer cells from normal cells allow us to establish a simple and economic method for the diagnosis of cancer cells. With using a light emitting diode to excite the BMVC molecule, microarray fluorescence analysis of a cell-based glass chip provides an easy method towards the detection of a limited number of cancer cells.
ABSTRACT The spectral features of satellite holes are used to investigate 9‐aminoacridine‐DNA int... more ABSTRACT The spectral features of satellite holes are used to investigate 9‐aminoacridine‐DNA interactions. The hole depths of the outer ring vibronic modes are reduced more than that of the inner ring vibronic modes, implying that inner ring motion is less perturbed than outer ring motion. As a result, the mode coupling between the inner ring and outer ring is reduced upon binding to DNA. However, similar hole frequency and width of the satellite hole corresponding to the NH2 mode upon binding to DNA imply that the amino group of 9‐aminoacridine sits outside the DNA.
Conference on Lasers and Electro-Optics 2010, 2010
ABSTRACT We use structured-illumination nano-profilometry with sub-diffraction-limit lateral reso... more ABSTRACT We use structured-illumination nano-profilometry with sub-diffraction-limit lateral resolution to measure the filopodium dynamics of lung cancer cells under stimulation of DC electric fields. The cathode growth bias and enhanced expression of filopodia are observed.
In this work, a material new to reed making, the bamboo, was compared with the traditionally used... more In this work, a material new to reed making, the bamboo, was compared with the traditionally used Arundo donax L. (the cane). The cross-sectional anatomy, relationship between the thickness and the reed strength, the spectral cen-troid, and the effect of the water extraction on the timbre were studied. The moso-bamboo has higher density of fibre inside a vascular bundle but has lower number density of the vascular bundles. For both materials, the reed thickness alone was not a good index for the reed strength. When the reed is new, the moso-bamboo gives brighter sound at the high note. After the sugar extraction by water, the spectral centroid of both materials reduced to lower frequency, in-dicating less bright sound. The cane seems to be more durable when the high note was compared. For the low note, the two materials perform similarly after the sugar extraction..
Label-free detection of rare cells in biological samples is an important and highly demanded task... more Label-free detection of rare cells in biological samples is an important and highly demanded task for clinical applications and various fields of research, such as detection of circulating tumor cells for cancer therapy and stem cells studies. Surface Plasmon Resonance (SPR) as a label-free method is a promising technology for detection of rare cells for diagnosis or research applications. Short detection depth of SPR (400 nm) provides a sensitive method with minimum interference of non-targets in the biological samples. In this work, we developed a novel microfluidic chip integrated with gold nanoslit SPR platform for highly efficient immunomagnetic capturing and detection of rare cells in human blood. Our method offers simple yet efficient detection of target cells with high purity. The approach for detection consists of two steps. Target cells are firs captured on functionalized magnetic nanoparticles (MNPs) with specific antibody I. The suspension containing the captured cells (...
In this work, electrokinetic acceleration of DNA hybridization was investigated by different comb... more In this work, electrokinetic acceleration of DNA hybridization was investigated by different combinations of frequencies and amplitudes of actuating electric signals. Because the frequencies from low to high can induce different kinds of electrokinetic forces, i.e., electroosmotic to electrothermal forces, this work provides an in-depth investigation of electrokinetic enhanced hybridization. Concentric circular Cr/Au microelectrodes of 350µm in diameter were fabricated on a glass substrate and probe DNA was immobilized on the electrode surface. Target DNA labeled with fluorescent dyes suspending in solution was then applied to the electrode. Different electrokinetic forces were induced by the application of different electric signals to the circular microelectrodes. Local microfluidic vortexes were generated to increase the collision efficiency between the target DNA suspending in solution and probe DNA immobilized on the electrode surface. DNA hybridization on the electrode surface could be accelerated by the electrokinetic forces. The level of hybridization was represented by the fluorescent signal intensity ratio. Results revealed that such 5-min dynamic hybridization increased 4.5 fold of signal intensity ratio as compared to a 1-h static hybridization. Moreover, dynamic hybridization was found to have better differentiation ability between specific and non-specific target DNA. This study provides a strategy to accelerate DNA hybridization in microsystems.
2013 Conference on Lasers and Electro-Optics Pacific Rim (CLEOPR), 2013
ABSTRACT We measured the membrane roughness of neuroblastoma cells by non-interferometric wide-fi... more ABSTRACT We measured the membrane roughness of neuroblastoma cells by non-interferometric wide-field optical profilometry. We found that the peptide related to Alzheimer's disease, Amyloid-beta 42, reduces membrane roughness, but direct-current electrical fields recover this effect.
Journal of the Chemical Society, Faraday Transactions, 1997
Page 1. Satellite hole investigations of the hole-burning mechanism and vibrational mode coupling... more Page 1. Satellite hole investigations of the hole-burning mechanism and vibrational mode coupling of 9-aminoacridine doped in glycerol–water glasses at di†erent pH values Chien-Chih Chiang,a,b Bor-Chyuan Hwang,a,§ Jenwei ...
ABSTRACT We present a flexible microfluidic channel fabrication platform that can be used to deve... more ABSTRACT We present a flexible microfluidic channel fabrication platform that can be used to develop microfluidic chips. A DPSS (diode pumped solid state) frequency quadrupled (lambda = 266 nm, the UV system) Nd:YAG laser and a CO2 laser (lambda = 10.6 mum, the IR system) are compared for their ablation capability on quartz and glass. We have also compared their performance in developing microfluidic chips. The resultant surface quality, including microcracking, debris, and distortion, is examined by SEM and a surface profiler. In these systems, users design microfluidic patterns by commercial software. The pattern is then transferred to a CNC stage for trenching. The microfabrication process can be completed in several minutes. Without the need to fabricate photomask for patterning, the development time can be reduced from weeks to hours. In addition, the substrate size is not limited by the dimension of the photomask. Asymmetric trenches demonstrating the machining capability of these systems have been fabricated by these systems. The minimal feature for the IR system and the UV system is 140 mum and 5 mum, respectively. These systems are very powerful for rapid glass microfluidic chip development.
Environmental contamination has become a serious problem to human and environmental health, as ex... more Environmental contamination has become a serious problem to human and environmental health, as exposure to a wide range of possible contaminants continuously increases due to industrial and agricultural activities. Whole cell sensors have been proposed as a powerful tool to detect class-specific toxicants based upon their biological activity and bioavailability. We demonstrated a robust toxicant detection platform based on a bioluminescence whole cell sensor array biochip (LumiChip). LumiChip harbors an integrated temperature control and a 16-member sensor array, as well as a simple but highly efficient luminescence collection setup. On LumiChip, samples were infused in an oxygen-permeable microfluidic flow channel to reach the sensor array. Time-lapse changes in bioluminescence emitted by the array members were measured on a single window-removed linear charge-coupled device (CCD) commonly used in commercial industrial process control or in barcode readers. Removal of the protective window on the linear CCD allowed lens-free direct interfacing of LumiChip to the CCD surface for measurement with high light collection efficiency. Bioluminescence induced by simulated contamination events was detected within 15 to 45 minutes. The portable LumiSense system utilizing the linear CCD in combination with the miniaturized LumiChip is a promising potential platform for on-site environmental monitoring of toxicant contamination.
This work describes a novel and simple modification of the current microarray format. It reduces ... more This work describes a novel and simple modification of the current microarray format. It reduces the sample/reagent volume to 1 ml and the hybridization time to 500 s. Both 20mer and 80mer oligonucleotide probes and singly labeled 20mer and 80mer targets, representative of the T-cell acute lymphocytic leuk- emia 1 (TAL1) gene, have been used to elucidate the performance of this hybridization approach. In this format, called shuttle hybridization, a conventional flat glass DNA microarray is integrated with a PMMA microfluidic chip to reduce the sample and reagent consumption to 1/100 of that associated with the conventional format. A serpentine microtrench is designed and fabricated on a PMMA chip using a widely available CO2 laser scriber. The trench spacing is compatible with the inter-spot distance in standard microarrays. The microtrench chip and microarray chip are easily aligned and assembled manually so that the microarray is integrated with a microfluidic channel. Discrete sa...
A 1536 channel oligonucleotide synthesizer, the MultiSyn, was developed with the capability to si... more A 1536 channel oligonucleotide synthesizer, the MultiSyn, was developed with the capability to simultaneously synthesize 1536 oligonucleotides of 20mer length in 10 h. The instrument was designed to synthesize different sequences of various lengths in micro-wells and has synthesized oligonucleotides as long as 119 nt with reasonably good yields using CPG beads of 1000 A pore size. The instrument consists of four 384 channel synthesis modules. Phosphoramidite chemistry was employed and step yields as high as 99.3% were achieved. The enhancement of oligonucleotide synthesis throughput is accomplished by increasing the spatial density of reaction wells. We have identified several parameters that are critical in achieving a good synthesis yield and negligible failure rate in small reaction wells. The coefficient of variation (CV) of product yields in 1536 reaction wells was 20%. The quality of the product was examined by capillary electrophoresis and mass spectrometry. The instrument ha...
Organs are composed of heterotypic cells with patterned architecture that enables intercellular i... more Organs are composed of heterotypic cells with patterned architecture that enables intercellular interaction to perform specific functions. In tissue engineering, the ability to pattern heterotypic cells into desired arrangement will allow us to model complex tissues in vitro and to create tissue equivalents for regeneration. This study was aimed at developing a method for fast heterotypic cell patterning with controllable topological manipulation on a glass chip. We found that poly(vinyl alcohol)-coated glass showed a biphasic change in adhesivity to cells in vitro: low adhesivity in the first 24 h and higher adhesivity at later hours due to increased serum protein adsorption. Combining programmable CO2 laser ablation to remove poly(vinyl alcohol) and glass, we were able to create arrays of adhesive microwells of adjustable patterns. We tested whether controllable patterns of epithelial-mesenchymal interaction could be created. When skin dermal papilla cells and fibroblasts were see...
We use structured-illumination nano-profilometry with sub-diffraction-limit lateral resolution to... more We use structured-illumination nano-profilometry with sub-diffraction-limit lateral resolution to measure the filopodium dynamics of lung cancer cells under stimulation of DC electric fields. The cathode growth bias and enhanced expression of filopodia are observed.
ABSTRACT Different cellular accumulations with distinct fluorescence properties of BMVC in cancer... more ABSTRACT Different cellular accumulations with distinct fluorescence properties of BMVC in cancer cells from normal cells allow us to establish a simple and economic method for the diagnosis of cancer cells. With using a light emitting diode to excite the BMVC molecule, microarray fluorescence analysis of a cell-based glass chip provides an easy method towards the detection of a limited number of cancer cells.
ABSTRACT The spectral features of satellite holes are used to investigate 9‐aminoacridine‐DNA int... more ABSTRACT The spectral features of satellite holes are used to investigate 9‐aminoacridine‐DNA interactions. The hole depths of the outer ring vibronic modes are reduced more than that of the inner ring vibronic modes, implying that inner ring motion is less perturbed than outer ring motion. As a result, the mode coupling between the inner ring and outer ring is reduced upon binding to DNA. However, similar hole frequency and width of the satellite hole corresponding to the NH2 mode upon binding to DNA imply that the amino group of 9‐aminoacridine sits outside the DNA.
Conference on Lasers and Electro-Optics 2010, 2010
ABSTRACT We use structured-illumination nano-profilometry with sub-diffraction-limit lateral reso... more ABSTRACT We use structured-illumination nano-profilometry with sub-diffraction-limit lateral resolution to measure the filopodium dynamics of lung cancer cells under stimulation of DC electric fields. The cathode growth bias and enhanced expression of filopodia are observed.
In this work, a material new to reed making, the bamboo, was compared with the traditionally used... more In this work, a material new to reed making, the bamboo, was compared with the traditionally used Arundo donax L. (the cane). The cross-sectional anatomy, relationship between the thickness and the reed strength, the spectral cen-troid, and the effect of the water extraction on the timbre were studied. The moso-bamboo has higher density of fibre inside a vascular bundle but has lower number density of the vascular bundles. For both materials, the reed thickness alone was not a good index for the reed strength. When the reed is new, the moso-bamboo gives brighter sound at the high note. After the sugar extraction by water, the spectral centroid of both materials reduced to lower frequency, in-dicating less bright sound. The cane seems to be more durable when the high note was compared. For the low note, the two materials perform similarly after the sugar extraction..
Label-free detection of rare cells in biological samples is an important and highly demanded task... more Label-free detection of rare cells in biological samples is an important and highly demanded task for clinical applications and various fields of research, such as detection of circulating tumor cells for cancer therapy and stem cells studies. Surface Plasmon Resonance (SPR) as a label-free method is a promising technology for detection of rare cells for diagnosis or research applications. Short detection depth of SPR (400 nm) provides a sensitive method with minimum interference of non-targets in the biological samples. In this work, we developed a novel microfluidic chip integrated with gold nanoslit SPR platform for highly efficient immunomagnetic capturing and detection of rare cells in human blood. Our method offers simple yet efficient detection of target cells with high purity. The approach for detection consists of two steps. Target cells are firs captured on functionalized magnetic nanoparticles (MNPs) with specific antibody I. The suspension containing the captured cells (...
In this work, electrokinetic acceleration of DNA hybridization was investigated by different comb... more In this work, electrokinetic acceleration of DNA hybridization was investigated by different combinations of frequencies and amplitudes of actuating electric signals. Because the frequencies from low to high can induce different kinds of electrokinetic forces, i.e., electroosmotic to electrothermal forces, this work provides an in-depth investigation of electrokinetic enhanced hybridization. Concentric circular Cr/Au microelectrodes of 350µm in diameter were fabricated on a glass substrate and probe DNA was immobilized on the electrode surface. Target DNA labeled with fluorescent dyes suspending in solution was then applied to the electrode. Different electrokinetic forces were induced by the application of different electric signals to the circular microelectrodes. Local microfluidic vortexes were generated to increase the collision efficiency between the target DNA suspending in solution and probe DNA immobilized on the electrode surface. DNA hybridization on the electrode surface could be accelerated by the electrokinetic forces. The level of hybridization was represented by the fluorescent signal intensity ratio. Results revealed that such 5-min dynamic hybridization increased 4.5 fold of signal intensity ratio as compared to a 1-h static hybridization. Moreover, dynamic hybridization was found to have better differentiation ability between specific and non-specific target DNA. This study provides a strategy to accelerate DNA hybridization in microsystems.
2013 Conference on Lasers and Electro-Optics Pacific Rim (CLEOPR), 2013
ABSTRACT We measured the membrane roughness of neuroblastoma cells by non-interferometric wide-fi... more ABSTRACT We measured the membrane roughness of neuroblastoma cells by non-interferometric wide-field optical profilometry. We found that the peptide related to Alzheimer's disease, Amyloid-beta 42, reduces membrane roughness, but direct-current electrical fields recover this effect.
Journal of the Chemical Society, Faraday Transactions, 1997
Page 1. Satellite hole investigations of the hole-burning mechanism and vibrational mode coupling... more Page 1. Satellite hole investigations of the hole-burning mechanism and vibrational mode coupling of 9-aminoacridine doped in glycerol–water glasses at di†erent pH values Chien-Chih Chiang,a,b Bor-Chyuan Hwang,a,§ Jenwei ...
ABSTRACT We present a flexible microfluidic channel fabrication platform that can be used to deve... more ABSTRACT We present a flexible microfluidic channel fabrication platform that can be used to develop microfluidic chips. A DPSS (diode pumped solid state) frequency quadrupled (lambda = 266 nm, the UV system) Nd:YAG laser and a CO2 laser (lambda = 10.6 mum, the IR system) are compared for their ablation capability on quartz and glass. We have also compared their performance in developing microfluidic chips. The resultant surface quality, including microcracking, debris, and distortion, is examined by SEM and a surface profiler. In these systems, users design microfluidic patterns by commercial software. The pattern is then transferred to a CNC stage for trenching. The microfabrication process can be completed in several minutes. Without the need to fabricate photomask for patterning, the development time can be reduced from weeks to hours. In addition, the substrate size is not limited by the dimension of the photomask. Asymmetric trenches demonstrating the machining capability of these systems have been fabricated by these systems. The minimal feature for the IR system and the UV system is 140 mum and 5 mum, respectively. These systems are very powerful for rapid glass microfluidic chip development.
Environmental contamination has become a serious problem to human and environmental health, as ex... more Environmental contamination has become a serious problem to human and environmental health, as exposure to a wide range of possible contaminants continuously increases due to industrial and agricultural activities. Whole cell sensors have been proposed as a powerful tool to detect class-specific toxicants based upon their biological activity and bioavailability. We demonstrated a robust toxicant detection platform based on a bioluminescence whole cell sensor array biochip (LumiChip). LumiChip harbors an integrated temperature control and a 16-member sensor array, as well as a simple but highly efficient luminescence collection setup. On LumiChip, samples were infused in an oxygen-permeable microfluidic flow channel to reach the sensor array. Time-lapse changes in bioluminescence emitted by the array members were measured on a single window-removed linear charge-coupled device (CCD) commonly used in commercial industrial process control or in barcode readers. Removal of the protective window on the linear CCD allowed lens-free direct interfacing of LumiChip to the CCD surface for measurement with high light collection efficiency. Bioluminescence induced by simulated contamination events was detected within 15 to 45 minutes. The portable LumiSense system utilizing the linear CCD in combination with the miniaturized LumiChip is a promising potential platform for on-site environmental monitoring of toxicant contamination.
This work describes a novel and simple modification of the current microarray format. It reduces ... more This work describes a novel and simple modification of the current microarray format. It reduces the sample/reagent volume to 1 ml and the hybridization time to 500 s. Both 20mer and 80mer oligonucleotide probes and singly labeled 20mer and 80mer targets, representative of the T-cell acute lymphocytic leuk- emia 1 (TAL1) gene, have been used to elucidate the performance of this hybridization approach. In this format, called shuttle hybridization, a conventional flat glass DNA microarray is integrated with a PMMA microfluidic chip to reduce the sample and reagent consumption to 1/100 of that associated with the conventional format. A serpentine microtrench is designed and fabricated on a PMMA chip using a widely available CO2 laser scriber. The trench spacing is compatible with the inter-spot distance in standard microarrays. The microtrench chip and microarray chip are easily aligned and assembled manually so that the microarray is integrated with a microfluidic channel. Discrete sa...
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Papers by Ji-yen Cheng