Hyaluronan (HA), a component of the extracellular matrix, plays an important role in cell-cell ad... more Hyaluronan (HA), a component of the extracellular matrix, plays an important role in cell-cell adhesion and cell migration. Membrane type 1-matrix metalloproteinase (MT1-MMP) is often expressed in invasive cancer cells. CD44, a transmembrane receptor for HA, is implicated in various adhesion-dependent cellular processes including cell migration, tumor cell metastasis and invasion. Previous studies have shown that CD44 is highly expressed in cancer cells and may be proteolytically cleaved at the ectodomain by MT1-MMP; this process of inducing CD44 cleavage plays a critical role in cancer cell migration. We hypothesized that HA modulates MT1-MMP expression to facilitate breast cancer cell migration. Flow cytometry, real-time PCR, western blotting and immunofluorescence staining were used to quantify HA-induced MT1-MMP expression in breast cancer cells. In order to validate the relevance of cell migration and HA-induced MT1-MMP, we analyzed the cell migration via Matrigel-coated transwell. We found that after HA oligosaccharide (6.5 kDA) stimulation, MT1-MMP expression in the membrane of breast cancer cells was increased. In response to HA oligosaccharide stimulation, significant upregulation of MT1-MMP mRNA occurred. Our data also provide evidence that HA oligosaccharide enhances MT1-MMP; the elevated expression of MT1-MMP confers enhanced CD44 cleavage and cell migration. In conclusion, we have identified a new function of HA in the induction of MT1-MMP expression in breast cancer cell lines and CD44 cleavage to increase cell migration during the invasion process. The HA oligosaccha-ride-induced MT1-MMP expression in breast cancer cells may be a critical step in the formation of metastatic colonies.
Photons are seriously scattered when entering turbid medium; thus the images of objects hidden in... more Photons are seriously scattered when entering turbid medium; thus the images of objects hidden in turbid medium can not be obtained by just collecting the transmitted photons. Early-arriving photons, which are also called ballistic or snake photons, are much less scattered when passing through turbid medium, and contains more image information than the late-arriving ones. Therefore, objects embedded in turbid medium can be imaged by gathering the ballistic and snake photons. In the present research, we try to recover images of objects in turbid medium by simultaneously "time-gate" and "polarizationgate" to obtain the snake photons. An Argon-pumped Ti-Sapphire laser with lOOfs pulses was employed as light source. A streak camera with 2ps temporal resolution was used to extract the ballistic and snake photons. Two pieces of lean swine meat, measured 4mmX3mm and 5mmX4mm, respectively, were placed in a lOcmXlOcmX3cm acrylic tank, which was full of diluted milk. A pair of a polarizer and an analyzer was used to extract the light that keeps polarization unchanged. The combination oftime gating and polarization gating resulted in good images ofobjects hidden in turbid medium.
A polarization controllable optical coherence tomography (OCT) system was built with the broadban... more A polarization controllable optical coherence tomography (OCT) system was built with the broadband source generated with femtosecond Ti:sapphire laser pulses in an ordinary fiber and a photonic crystal fiber. Spectral broadening in such fiber originated from self-phase modulation, four-wave mixing, Raman scattering, and other nonlinear-optics effects. Two different mode-locked Ti:sapphire lasers with 100 fsec and 12 fsec pulses were used. The generated spectral shape and width were compared in terms of the application to the OCT system. The relationship between the OCT resolution and the source spectrum shape was studied. Also, an algorithm was built for increasing the effective longitudinal resolution in data processing. The scheme of this algorithm meant to separate the contribution of the central portion from those of the tails in the interference fringe envelope. By removing the tail contribution to the scanning results, the effective longitudinal resolution was improved. Such a procedure is particularly important when the light source spectrum is not a well-defined shape. This procedure involved in the computation of a matrix inversion. The OCT system and the process algorithm were used for oral cancer study. Features of oral cancer were well identified. A probe was also fabricated for in vivo scan of oral tissues.
Colorectal cancer (CRC) is the third most common cancer in the world and its disease-specific mor... more Colorectal cancer (CRC) is the third most common cancer in the world and its disease-specific mortality is estimated to be approximately 33% in the developed world. KRAS mutations have been shown to predict response to anti-EGFR (epidermal growth factor receptor) targeted monoclonal antibody therapy. Therefore, KRAS mutation testing of metastatic CRC patients is mandatory in the clinical setting to aid in the choice of appropriate therapy. Currently, the most common strategy for KRAS mutation detection consists of conventional polymerase chain reaction (PCR) and direct sequencing. However, it is a time-consuming and complicated procedure, not suitable for routine clinical test. The objective of this study is to develop and evaluate a highly sensitive and rapid method using peptide nucleic acid (PNA) oligomers mediated real-time PCR clamping for detection of KRAS mutations. The PNA-mediated PCR clamping assay can real-time detect a mutation in a sample containing 1% of the mutant allele in a mixture of wild-type genomic DNA, which also enables the accurate and rapid detection of all KRAS codon 12 and 13 mutations in a single reaction. The total assay time is short as it requires only 1.5 hours after the samples preparation. Thus, the present method offers a potential alternative to be applied in clinical samples of CRC for detection of DNA carrying KRAS mutations.
Journal of Colloid and Interface Science, Oct 1, 2005
A core-shell copolymer latex with thermal-responsive properties was prepared and its potential ap... more A core-shell copolymer latex with thermal-responsive properties was prepared and its potential application as a vehicle for drug targeting was investigated in this work, where the crosslinked copolymer of N -isopropylacrylamide (NIPAAm) and chitosan was prepared as the core and the copolymer of methacrylic acid (MAA) and methyl methacrylate (MMA) was prepared as the shell. By using soapless dispersion polymerization, the poly(NIPAAm-chitosan) crosslinked copolymer latex was synthesized first. Then the monomers of MAA and MMA were added to continue the reaction to obtain the core-shell copolymer latex. The weight ratio of MAA/MMA and the concentration of shell monomers (MAA and MMA) in the feed of the reaction mixture had been changed to investigate their effects on the particle size, reaction rate, zeta-potential, specific surface area, and surface functional groups of the latex particles. The swelling and thermoresponsive behavior of the film made from these core-shell latices were also studied under different pH values of buffer solution. The model drug (caffeine) could be merged inside the copolymer particles and protected from releasing through the transport process effectively. And the thermoresponsive property of these copolymer particles significantly enhances the ligand (protein) conjugation that shows the potential of the latex being applied on the targeting drug carrier.
This study reports the development of two enzyme-less biosensors by using IrO x for pH and Pt-Ir ... more This study reports the development of two enzyme-less biosensors by using IrO x for pH and Pt-Ir for glucose sensors. Nanostructures of electrodeposited IrO x and Pt-Ir were examined by SEM and XPS on the electrode surfaces. We used chronopotentiometry (CP) for pH and linear sweep voltammetry (LSV) for glucose measurement at 37 o C in 1X PBS (0.15M NaCl). In the physiological range of pH 4-10 and glucose concentration 1 mM-12 mM, these two biosensors exhibited good linearity of -68.5 mV/pH (R 2 : 0.99) and, 0.97 mA/mM-dm 2 (R 2 : 0.988), respectively. Because the linear ranges are suitable for cell culture, the presented electrochemical sensors are prospective for applying to continuous cell culture monitoring.
Osteoarthritis (OA) is characterized by degradation of the cartilage matrix, leading to pathologi... more Osteoarthritis (OA) is characterized by degradation of the cartilage matrix, leading to pathologic changes in the joints. However, the pathogenic effects of synovial tissue inflammation on OA knees are not clear. To investigate whether the inflammation caused by the medial plica is involved in the pathogenesis of osteoarthritis, we examined the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α in the medial plica and pannus-like tissue in the knees of patients with medial compartment OA who underwent either arthroscopic medial release (stage II; 15 knee joints from 15 patients) or total knee replacement (stage IV; 18 knee joints from 18 patients). MMP-2, MMP-3, MMP-9, IL-1β, and TNF-α mRNA and protein levels measured, respectively, by quantitative real-time PCR and Quantibody human MMP arrays, were highly expressed in extracts of medial plica and pannus-like tissue from stage IV knee joints. Immunohistochemical staining also demonstrated high expression of MMP-2, MMP-3, and MMP-9 in plica and pannus-like tissue of stage IV OA knees and not in normal cartilage. Some TIMP/MMP ratios decreased significantly in both medial plica and pannus-like tissue as disease progressed from stage II to stage IV. Furthermore, the migration of cells from the pannus-like tissue was enhanced by IL-1β, while plica cell migration was enhanced by TNF-α. The results suggest that medial plica and pannus-like tissue may be involved in the process of cartilage degradation in medial compartment OA of the knee.
International Journal of Molecular Sciences, May 1, 2020
In this work, hybridization chain reactions (HCRs) toward Severe Acute Respiratory Syndrome Coron... more In this work, hybridization chain reactions (HCRs) toward Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) nucleocapsid phosphoproteins gene loci and human RNase P are proposed to provide an isothermal amplification screening tool. The proposed chain reactions target the complementary DNA (cDNA) of SARS-CoV-2, with loci corresponding to gold-standard polymerase chain reaction (PCR) loci. Four hybridization chain reaction reactions are demonstrated herein, targeting N1/N2/N3 loci and human RNase P. The design of the hybridization chain reaction, herein, is assisted with an algorithm. The algorithm helps to search target sequences with low local secondary structure and high hybridization efficiency. The loop domain of the fuel hairpin molecule H1 and H2, which are the tunable segments in such reactions, are used as an optimization parameter to improve the hybridization efficiency of the chain reaction. The algorithm-derived HCR reactions were validated with gel electrophoresis. All proposed reactions exhibit a hybridization complex with a molecular mass >1.5k base pairs, which is clear evidence of chain reaction. The hybridization efficiency trend revealed by gel electrophoresis corresponds nicely to the simulated data from the algorithm. The HCR reactions and the corresponding algorithm serve as a basis to further SARS-CoV-2 sensing applications and facilitate better screening strategies for the prevention of on-going pandemics.
Background: The occurrence and prevalence of integrons in clinical microorganisms and their role ... more Background: The occurrence and prevalence of integrons in clinical microorganisms and their role played in antimicrobial resistance have been well studied recently. As screening and detection of integrons are concerned, current diagnostic methodologies are restricted by significant drawbacks and novel methods are required for integrons detection. Results: In this study, three loop-mediated isothermal amplification (LAMP) assays targeting on class 1, 2 and 3 integrons were implemented and evaluated. Optimization of these detection assays were performed, including studing on the reaction temperature, volume, time, sensitivity and specificity (both primers and targets). Application of the established LAMP assays were further verified on a total of 1082 isolates (previously identified to be 397 integron-positive and 685 integron-negative strains). According to the results, the indispensability of each primer had been confirmed and the optimal reaction temperature, volume and time were found to be 65°C, 45 min and 25 μL, respectively. As application was concerned, 361, 28 and 8 isolates carrying intI1, intI2 and intI3 yielded positive amplicons, respectively. Other 685 integron-negative bacteria were negative for the integron-screening LAMP assays, totaling the detection rate and specificity to be 100%. The intI1-, intI2-and intI3-LAMP assays established in this study were demonstrated to be the valid and rapid detection methodologies for the screening of bacterial integrons.
An antenna-based sensor with novel combinational design of metamaterial and transmission line are... more An antenna-based sensor with novel combinational design of metamaterial and transmission line are proposed for the applications of biosensors. Working at 1.6 GHz resonant frequency, our design aims to reduce the size of antenna biosensor by applying metamaterial structure. The active sensing area of antenna was optimized based on the distribution of electrical field to measure the permittivity and loss tangent of sample by the scattering parameters. The resonant frequency shifts from 1.69 GHz to 1.63 GHz under different concentrations of water-ethanol solutions (3% to 100%) with equivalent permittivity of 79 to 14. According to our results, this antenna biosensor has advantages of small size, lower resonant frequency, real time, label free, sensitive, low profile and easy to integrated with printed circuit boards (PCB) for practical applications.
In this work, the synthesis, properties of a thermal/pH-sensitive core-shell copolymer latex were... more In this work, the synthesis, properties of a thermal/pH-sensitive core-shell copolymer latex were studied and its potential application as a targeting drug carrier was also investigated, where the crosslinked copolymer of N-isopropylacrylamide (NIPAAm) and chitosan was synthesized by soapless dispersion polymerization as the core, and the copolymer of methacrylic acid (MAA) and methyl methacrylate (MMA) was prepared as the shell. The weight ratio of chitosan/NIPAAm and the concentration of crosslinking agent in feed had been changed to investigate their effects on the particle size, reaction rate, zeta potential, surface functional groups, and specific surface area of latex particles. The swelling and thermo-sensitive behavior of the film made from these core-shell latexes were also studied under different pH values of buffer solution. The model drug (caffeine) could be loaded inside the copolymer particles and protected from releasing through the transport process effectively. And the thermo-responsive property of these copolymer particles significantly enhanced the protein conjugation that showed the potential of the latex being applied on the targeting drug carrier.
Gold nanoparticles are popularly used in biological and chemical sensors and their applications o... more Gold nanoparticles are popularly used in biological and chemical sensors and their applications owing to their fascinating chemical, optical, and catalytic properties. Particularly, the use of gold nanoparticles is widespread in colorimetric assays because of their simple, cost-effective fabrication, and ease of use. More importantly, the gold nanoparticle sensor response is a visual change in color, which allows easy interpretation of results. Therefore, many studies of gold nanoparticle-based colorimetric methods have been reported, and some review articles published over the past years. Most reviews focus exclusively on a single gold nanoparticle-based colorimetric technique for one analyte of interest. In this review, we focus on the current developments in different colorimetric assay designs for the sensing of various chemical and biological samples. We summarize and classify the sensing strategies and mechanism analyses of gold nanoparticle-based detection. Additionally, typical examples of recently developed gold nanoparticle-based colorimetric methods and their applications in the detection of various analytes are presented and discussed comprehensively.
Phase-sensitive surface plasmon resonance biosensors are known for their high sensitivity. One of... more Phase-sensitive surface plasmon resonance biosensors are known for their high sensitivity. One of the technology bottle-necks of such sensors is that the phase sensorgram, when measured at fixed angle set-up, can lead to low reproducibility as the signal conveys multiple data. Leveraging the sensitivity, while securing satisfying reproducibility, is therefore is an underdiscussed key issue. One potential solution is to map the phase sensorgram into refractive index unit by the use of sensor calibration data, via a simple non-linear fit. However, basic fitting functions poorly portray the asymmetric phase curve. On the other hand, multi-layer reflectivity calculation based on the Fresnel coefficient can be employed for a precise mapping function. This numerical approach however lacks the explicit mathematical formulation to be used in an optimization process. To this end, we aim to provide a first methodology for the issue, where mapping functions are constructed from Bayesian optimi...
Rapid detection for infectious diseases is highly demanded in diagnosis and infection prevention.... more Rapid detection for infectious diseases is highly demanded in diagnosis and infection prevention. In this work, we introduced a plasmonic enhanced digitizing biosensor for the rapid detection of nucleic acids. The sensor successfully achieved the detection of loop-mediated isothermal amplification for the hepatitis virus in this work. The sensor comprised a nanodisc array and Bst polymerases conjugated on the rough surface of a nanodisc. The rough surface of the nanodisc provided plasmonic hot spots to enhance the fluorescence signal. The virus DNA was detected by conducting a modified loop-mediated isothermal amplification with fluorescence resonance energy transfer reporter conjugated primers on the sensor. The modified isothermal amplification improved the signal contrast and detection time compared to the original assay. By integrating the modified amplification assay and plasmonic enhancement sensor, we achieved rapid detection of the hepatitis virus. Nucleic acid with a concen...
Superparamagnetic magnetite nanoparticles (MNPs), Fe3O4, were synthesized via the modified coprec... more Superparamagnetic magnetite nanoparticles (MNPs), Fe3O4, were synthesized via the modified coprecipitation method. The morphology of these MNPs is polyhedral. The particle size of MNPs ranged from 20 to 100 nm. For combined hyperthermia and thermoresponsive drug delivery applications, the heating element, MNPs, in the core of drug carriers should increase the temperature of the target up to 43 °C under AC magnetic field. Therefore, the heating effect of these MNPs under AC magnetic field produced by a high frequency induction heater was examined. From the results, one can see that as the weight of these MNPs increased, the higher the increase in temperature was observed. Besides, the temperature increase has reached 8.7 °C in 15 min, when 20 mg MNPs were added to 2 ml water. The preliminary temperature rise suggests that it is applicable for hyperthermia and thermoresponsive drug delivery.
This paper mainly studies the optical property of gold nanoparticle films and its variations unde... more This paper mainly studies the optical property of gold nanoparticle films and its variations under different surface coverages. Au nanoparticle monolayers with different surface densities are prepared and its optical constants are decided by variable-angle ellipsometry at 530nm and 643nm, respectively. The extinction coefficient shows a linear correlation with the surface coverage, nonetheless the refractive index n presents a more complex behavior. This measured optical constants are compared to the theoretical estimations of effective medium theory(EMT); both Maxwell-Garnett and Bruggeman models are employed. Neither of these two theoretical predictions fit in with the experimental results. When the surface coverage is nearly full, the optical constant does not approaches to the bulk values as predicted by EMT, which implies the Au nanoparticle film has distinct optical property from the bulk gold and calls for a deeper understanding in its electronic structure.
Electrical impedance tomography (EIT), a noninvasive and radiation-free medical imaging technique... more Electrical impedance tomography (EIT), a noninvasive and radiation-free medical imaging technique, has been used for continuous real-time regional lung aeration. However, adhesive electrodes could cause discomfort and increase the risk of skin injury during prolonged measurement. Additionally, the conductive gel between the electrodes and skin could evaporate in long-term usage and deteriorate the signal quality. To address these issues, in this work, textile electrodes integrated with a clothing belt are proposed to achieve EIT lung imaging along with a custom portable EIT system. The simulation and experimental results have verified the validity of the proposed portable EIT system. Furthermore, the imaging results of using the proposed textile electrodes were compared with commercial electrocardiogram electrodes to evaluate their performance.
Pandemic and epidemic outbreaks of influenza A virus (IAV) infection pose severe challenges to hu... more Pandemic and epidemic outbreaks of influenza A virus (IAV) infection pose severe challenges to human society. Passive immunotherapy with recombinant neutralizing antibodies can potentially mitigate the threats of IAV infection. With a high throughput neutralizing antibody discovery platform, we produced artificial anti-hemagglutinin (HA) IAV-neutralizing IgGs from phage-displayed synthetic scFv libraries without necessitating prior memory of antibody-antigen interactions or relying on affinity maturation essential for in vivo immune systems to generate highly specific neutralizing antibodies. At least two thirds of the epitope groups of the artificial anti-HA antibodies resemble those of natural protective anti-HA antibodies, providing alternatives to neutralizing antibodies from natural antibody repertoires. With continuing advancement in designing and constructing synthetic scFv libraries, this technological platform is useful in mitigating not only the threats of IAV pandemics bu...
The work presented a simple way to prepare a meso-tetra(4-pyridyl)porphyrin (MTPyP) film for opti... more The work presented a simple way to prepare a meso-tetra(4-pyridyl)porphyrin (MTPyP) film for optical gas sensor. The dip-dry coating method that was developed by our reaserch shows a strong absorption band at 418 nm. We also proposed a simple method, peak ratio, to do the semiquantitative analysis of hydrochloric acid (HCl) and ammonia (NH 3 ) molecules adsorbed on the dipdry coating MTPyP film by their absorption bands. The MTPyP film was prepared on glass substrate and spectrometer was used to obtain the spectra as sensing the vapor molecules. The ratio of peaks values at 418 nm and 450 nm was used to identify the vapor types and to determine the concentrations. The results show that the peak ratio of HCl is approaching less than one and the peak ratio of NH 3 is always larger than one for two-hour measurment.
Hyaluronan (HA), a component of the extracellular matrix, plays an important role in cell-cell ad... more Hyaluronan (HA), a component of the extracellular matrix, plays an important role in cell-cell adhesion and cell migration. Membrane type 1-matrix metalloproteinase (MT1-MMP) is often expressed in invasive cancer cells. CD44, a transmembrane receptor for HA, is implicated in various adhesion-dependent cellular processes including cell migration, tumor cell metastasis and invasion. Previous studies have shown that CD44 is highly expressed in cancer cells and may be proteolytically cleaved at the ectodomain by MT1-MMP; this process of inducing CD44 cleavage plays a critical role in cancer cell migration. We hypothesized that HA modulates MT1-MMP expression to facilitate breast cancer cell migration. Flow cytometry, real-time PCR, western blotting and immunofluorescence staining were used to quantify HA-induced MT1-MMP expression in breast cancer cells. In order to validate the relevance of cell migration and HA-induced MT1-MMP, we analyzed the cell migration via Matrigel-coated transwell. We found that after HA oligosaccharide (6.5 kDA) stimulation, MT1-MMP expression in the membrane of breast cancer cells was increased. In response to HA oligosaccharide stimulation, significant upregulation of MT1-MMP mRNA occurred. Our data also provide evidence that HA oligosaccharide enhances MT1-MMP; the elevated expression of MT1-MMP confers enhanced CD44 cleavage and cell migration. In conclusion, we have identified a new function of HA in the induction of MT1-MMP expression in breast cancer cell lines and CD44 cleavage to increase cell migration during the invasion process. The HA oligosaccha-ride-induced MT1-MMP expression in breast cancer cells may be a critical step in the formation of metastatic colonies.
Photons are seriously scattered when entering turbid medium; thus the images of objects hidden in... more Photons are seriously scattered when entering turbid medium; thus the images of objects hidden in turbid medium can not be obtained by just collecting the transmitted photons. Early-arriving photons, which are also called ballistic or snake photons, are much less scattered when passing through turbid medium, and contains more image information than the late-arriving ones. Therefore, objects embedded in turbid medium can be imaged by gathering the ballistic and snake photons. In the present research, we try to recover images of objects in turbid medium by simultaneously "time-gate" and "polarizationgate" to obtain the snake photons. An Argon-pumped Ti-Sapphire laser with lOOfs pulses was employed as light source. A streak camera with 2ps temporal resolution was used to extract the ballistic and snake photons. Two pieces of lean swine meat, measured 4mmX3mm and 5mmX4mm, respectively, were placed in a lOcmXlOcmX3cm acrylic tank, which was full of diluted milk. A pair of a polarizer and an analyzer was used to extract the light that keeps polarization unchanged. The combination oftime gating and polarization gating resulted in good images ofobjects hidden in turbid medium.
A polarization controllable optical coherence tomography (OCT) system was built with the broadban... more A polarization controllable optical coherence tomography (OCT) system was built with the broadband source generated with femtosecond Ti:sapphire laser pulses in an ordinary fiber and a photonic crystal fiber. Spectral broadening in such fiber originated from self-phase modulation, four-wave mixing, Raman scattering, and other nonlinear-optics effects. Two different mode-locked Ti:sapphire lasers with 100 fsec and 12 fsec pulses were used. The generated spectral shape and width were compared in terms of the application to the OCT system. The relationship between the OCT resolution and the source spectrum shape was studied. Also, an algorithm was built for increasing the effective longitudinal resolution in data processing. The scheme of this algorithm meant to separate the contribution of the central portion from those of the tails in the interference fringe envelope. By removing the tail contribution to the scanning results, the effective longitudinal resolution was improved. Such a procedure is particularly important when the light source spectrum is not a well-defined shape. This procedure involved in the computation of a matrix inversion. The OCT system and the process algorithm were used for oral cancer study. Features of oral cancer were well identified. A probe was also fabricated for in vivo scan of oral tissues.
Colorectal cancer (CRC) is the third most common cancer in the world and its disease-specific mor... more Colorectal cancer (CRC) is the third most common cancer in the world and its disease-specific mortality is estimated to be approximately 33% in the developed world. KRAS mutations have been shown to predict response to anti-EGFR (epidermal growth factor receptor) targeted monoclonal antibody therapy. Therefore, KRAS mutation testing of metastatic CRC patients is mandatory in the clinical setting to aid in the choice of appropriate therapy. Currently, the most common strategy for KRAS mutation detection consists of conventional polymerase chain reaction (PCR) and direct sequencing. However, it is a time-consuming and complicated procedure, not suitable for routine clinical test. The objective of this study is to develop and evaluate a highly sensitive and rapid method using peptide nucleic acid (PNA) oligomers mediated real-time PCR clamping for detection of KRAS mutations. The PNA-mediated PCR clamping assay can real-time detect a mutation in a sample containing 1% of the mutant allele in a mixture of wild-type genomic DNA, which also enables the accurate and rapid detection of all KRAS codon 12 and 13 mutations in a single reaction. The total assay time is short as it requires only 1.5 hours after the samples preparation. Thus, the present method offers a potential alternative to be applied in clinical samples of CRC for detection of DNA carrying KRAS mutations.
Journal of Colloid and Interface Science, Oct 1, 2005
A core-shell copolymer latex with thermal-responsive properties was prepared and its potential ap... more A core-shell copolymer latex with thermal-responsive properties was prepared and its potential application as a vehicle for drug targeting was investigated in this work, where the crosslinked copolymer of N -isopropylacrylamide (NIPAAm) and chitosan was prepared as the core and the copolymer of methacrylic acid (MAA) and methyl methacrylate (MMA) was prepared as the shell. By using soapless dispersion polymerization, the poly(NIPAAm-chitosan) crosslinked copolymer latex was synthesized first. Then the monomers of MAA and MMA were added to continue the reaction to obtain the core-shell copolymer latex. The weight ratio of MAA/MMA and the concentration of shell monomers (MAA and MMA) in the feed of the reaction mixture had been changed to investigate their effects on the particle size, reaction rate, zeta-potential, specific surface area, and surface functional groups of the latex particles. The swelling and thermoresponsive behavior of the film made from these core-shell latices were also studied under different pH values of buffer solution. The model drug (caffeine) could be merged inside the copolymer particles and protected from releasing through the transport process effectively. And the thermoresponsive property of these copolymer particles significantly enhances the ligand (protein) conjugation that shows the potential of the latex being applied on the targeting drug carrier.
This study reports the development of two enzyme-less biosensors by using IrO x for pH and Pt-Ir ... more This study reports the development of two enzyme-less biosensors by using IrO x for pH and Pt-Ir for glucose sensors. Nanostructures of electrodeposited IrO x and Pt-Ir were examined by SEM and XPS on the electrode surfaces. We used chronopotentiometry (CP) for pH and linear sweep voltammetry (LSV) for glucose measurement at 37 o C in 1X PBS (0.15M NaCl). In the physiological range of pH 4-10 and glucose concentration 1 mM-12 mM, these two biosensors exhibited good linearity of -68.5 mV/pH (R 2 : 0.99) and, 0.97 mA/mM-dm 2 (R 2 : 0.988), respectively. Because the linear ranges are suitable for cell culture, the presented electrochemical sensors are prospective for applying to continuous cell culture monitoring.
Osteoarthritis (OA) is characterized by degradation of the cartilage matrix, leading to pathologi... more Osteoarthritis (OA) is characterized by degradation of the cartilage matrix, leading to pathologic changes in the joints. However, the pathogenic effects of synovial tissue inflammation on OA knees are not clear. To investigate whether the inflammation caused by the medial plica is involved in the pathogenesis of osteoarthritis, we examined the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α in the medial plica and pannus-like tissue in the knees of patients with medial compartment OA who underwent either arthroscopic medial release (stage II; 15 knee joints from 15 patients) or total knee replacement (stage IV; 18 knee joints from 18 patients). MMP-2, MMP-3, MMP-9, IL-1β, and TNF-α mRNA and protein levels measured, respectively, by quantitative real-time PCR and Quantibody human MMP arrays, were highly expressed in extracts of medial plica and pannus-like tissue from stage IV knee joints. Immunohistochemical staining also demonstrated high expression of MMP-2, MMP-3, and MMP-9 in plica and pannus-like tissue of stage IV OA knees and not in normal cartilage. Some TIMP/MMP ratios decreased significantly in both medial plica and pannus-like tissue as disease progressed from stage II to stage IV. Furthermore, the migration of cells from the pannus-like tissue was enhanced by IL-1β, while plica cell migration was enhanced by TNF-α. The results suggest that medial plica and pannus-like tissue may be involved in the process of cartilage degradation in medial compartment OA of the knee.
International Journal of Molecular Sciences, May 1, 2020
In this work, hybridization chain reactions (HCRs) toward Severe Acute Respiratory Syndrome Coron... more In this work, hybridization chain reactions (HCRs) toward Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) nucleocapsid phosphoproteins gene loci and human RNase P are proposed to provide an isothermal amplification screening tool. The proposed chain reactions target the complementary DNA (cDNA) of SARS-CoV-2, with loci corresponding to gold-standard polymerase chain reaction (PCR) loci. Four hybridization chain reaction reactions are demonstrated herein, targeting N1/N2/N3 loci and human RNase P. The design of the hybridization chain reaction, herein, is assisted with an algorithm. The algorithm helps to search target sequences with low local secondary structure and high hybridization efficiency. The loop domain of the fuel hairpin molecule H1 and H2, which are the tunable segments in such reactions, are used as an optimization parameter to improve the hybridization efficiency of the chain reaction. The algorithm-derived HCR reactions were validated with gel electrophoresis. All proposed reactions exhibit a hybridization complex with a molecular mass >1.5k base pairs, which is clear evidence of chain reaction. The hybridization efficiency trend revealed by gel electrophoresis corresponds nicely to the simulated data from the algorithm. The HCR reactions and the corresponding algorithm serve as a basis to further SARS-CoV-2 sensing applications and facilitate better screening strategies for the prevention of on-going pandemics.
Background: The occurrence and prevalence of integrons in clinical microorganisms and their role ... more Background: The occurrence and prevalence of integrons in clinical microorganisms and their role played in antimicrobial resistance have been well studied recently. As screening and detection of integrons are concerned, current diagnostic methodologies are restricted by significant drawbacks and novel methods are required for integrons detection. Results: In this study, three loop-mediated isothermal amplification (LAMP) assays targeting on class 1, 2 and 3 integrons were implemented and evaluated. Optimization of these detection assays were performed, including studing on the reaction temperature, volume, time, sensitivity and specificity (both primers and targets). Application of the established LAMP assays were further verified on a total of 1082 isolates (previously identified to be 397 integron-positive and 685 integron-negative strains). According to the results, the indispensability of each primer had been confirmed and the optimal reaction temperature, volume and time were found to be 65°C, 45 min and 25 μL, respectively. As application was concerned, 361, 28 and 8 isolates carrying intI1, intI2 and intI3 yielded positive amplicons, respectively. Other 685 integron-negative bacteria were negative for the integron-screening LAMP assays, totaling the detection rate and specificity to be 100%. The intI1-, intI2-and intI3-LAMP assays established in this study were demonstrated to be the valid and rapid detection methodologies for the screening of bacterial integrons.
An antenna-based sensor with novel combinational design of metamaterial and transmission line are... more An antenna-based sensor with novel combinational design of metamaterial and transmission line are proposed for the applications of biosensors. Working at 1.6 GHz resonant frequency, our design aims to reduce the size of antenna biosensor by applying metamaterial structure. The active sensing area of antenna was optimized based on the distribution of electrical field to measure the permittivity and loss tangent of sample by the scattering parameters. The resonant frequency shifts from 1.69 GHz to 1.63 GHz under different concentrations of water-ethanol solutions (3% to 100%) with equivalent permittivity of 79 to 14. According to our results, this antenna biosensor has advantages of small size, lower resonant frequency, real time, label free, sensitive, low profile and easy to integrated with printed circuit boards (PCB) for practical applications.
In this work, the synthesis, properties of a thermal/pH-sensitive core-shell copolymer latex were... more In this work, the synthesis, properties of a thermal/pH-sensitive core-shell copolymer latex were studied and its potential application as a targeting drug carrier was also investigated, where the crosslinked copolymer of N-isopropylacrylamide (NIPAAm) and chitosan was synthesized by soapless dispersion polymerization as the core, and the copolymer of methacrylic acid (MAA) and methyl methacrylate (MMA) was prepared as the shell. The weight ratio of chitosan/NIPAAm and the concentration of crosslinking agent in feed had been changed to investigate their effects on the particle size, reaction rate, zeta potential, surface functional groups, and specific surface area of latex particles. The swelling and thermo-sensitive behavior of the film made from these core-shell latexes were also studied under different pH values of buffer solution. The model drug (caffeine) could be loaded inside the copolymer particles and protected from releasing through the transport process effectively. And the thermo-responsive property of these copolymer particles significantly enhanced the protein conjugation that showed the potential of the latex being applied on the targeting drug carrier.
Gold nanoparticles are popularly used in biological and chemical sensors and their applications o... more Gold nanoparticles are popularly used in biological and chemical sensors and their applications owing to their fascinating chemical, optical, and catalytic properties. Particularly, the use of gold nanoparticles is widespread in colorimetric assays because of their simple, cost-effective fabrication, and ease of use. More importantly, the gold nanoparticle sensor response is a visual change in color, which allows easy interpretation of results. Therefore, many studies of gold nanoparticle-based colorimetric methods have been reported, and some review articles published over the past years. Most reviews focus exclusively on a single gold nanoparticle-based colorimetric technique for one analyte of interest. In this review, we focus on the current developments in different colorimetric assay designs for the sensing of various chemical and biological samples. We summarize and classify the sensing strategies and mechanism analyses of gold nanoparticle-based detection. Additionally, typical examples of recently developed gold nanoparticle-based colorimetric methods and their applications in the detection of various analytes are presented and discussed comprehensively.
Phase-sensitive surface plasmon resonance biosensors are known for their high sensitivity. One of... more Phase-sensitive surface plasmon resonance biosensors are known for their high sensitivity. One of the technology bottle-necks of such sensors is that the phase sensorgram, when measured at fixed angle set-up, can lead to low reproducibility as the signal conveys multiple data. Leveraging the sensitivity, while securing satisfying reproducibility, is therefore is an underdiscussed key issue. One potential solution is to map the phase sensorgram into refractive index unit by the use of sensor calibration data, via a simple non-linear fit. However, basic fitting functions poorly portray the asymmetric phase curve. On the other hand, multi-layer reflectivity calculation based on the Fresnel coefficient can be employed for a precise mapping function. This numerical approach however lacks the explicit mathematical formulation to be used in an optimization process. To this end, we aim to provide a first methodology for the issue, where mapping functions are constructed from Bayesian optimi...
Rapid detection for infectious diseases is highly demanded in diagnosis and infection prevention.... more Rapid detection for infectious diseases is highly demanded in diagnosis and infection prevention. In this work, we introduced a plasmonic enhanced digitizing biosensor for the rapid detection of nucleic acids. The sensor successfully achieved the detection of loop-mediated isothermal amplification for the hepatitis virus in this work. The sensor comprised a nanodisc array and Bst polymerases conjugated on the rough surface of a nanodisc. The rough surface of the nanodisc provided plasmonic hot spots to enhance the fluorescence signal. The virus DNA was detected by conducting a modified loop-mediated isothermal amplification with fluorescence resonance energy transfer reporter conjugated primers on the sensor. The modified isothermal amplification improved the signal contrast and detection time compared to the original assay. By integrating the modified amplification assay and plasmonic enhancement sensor, we achieved rapid detection of the hepatitis virus. Nucleic acid with a concen...
Superparamagnetic magnetite nanoparticles (MNPs), Fe3O4, were synthesized via the modified coprec... more Superparamagnetic magnetite nanoparticles (MNPs), Fe3O4, were synthesized via the modified coprecipitation method. The morphology of these MNPs is polyhedral. The particle size of MNPs ranged from 20 to 100 nm. For combined hyperthermia and thermoresponsive drug delivery applications, the heating element, MNPs, in the core of drug carriers should increase the temperature of the target up to 43 °C under AC magnetic field. Therefore, the heating effect of these MNPs under AC magnetic field produced by a high frequency induction heater was examined. From the results, one can see that as the weight of these MNPs increased, the higher the increase in temperature was observed. Besides, the temperature increase has reached 8.7 °C in 15 min, when 20 mg MNPs were added to 2 ml water. The preliminary temperature rise suggests that it is applicable for hyperthermia and thermoresponsive drug delivery.
This paper mainly studies the optical property of gold nanoparticle films and its variations unde... more This paper mainly studies the optical property of gold nanoparticle films and its variations under different surface coverages. Au nanoparticle monolayers with different surface densities are prepared and its optical constants are decided by variable-angle ellipsometry at 530nm and 643nm, respectively. The extinction coefficient shows a linear correlation with the surface coverage, nonetheless the refractive index n presents a more complex behavior. This measured optical constants are compared to the theoretical estimations of effective medium theory(EMT); both Maxwell-Garnett and Bruggeman models are employed. Neither of these two theoretical predictions fit in with the experimental results. When the surface coverage is nearly full, the optical constant does not approaches to the bulk values as predicted by EMT, which implies the Au nanoparticle film has distinct optical property from the bulk gold and calls for a deeper understanding in its electronic structure.
Electrical impedance tomography (EIT), a noninvasive and radiation-free medical imaging technique... more Electrical impedance tomography (EIT), a noninvasive and radiation-free medical imaging technique, has been used for continuous real-time regional lung aeration. However, adhesive electrodes could cause discomfort and increase the risk of skin injury during prolonged measurement. Additionally, the conductive gel between the electrodes and skin could evaporate in long-term usage and deteriorate the signal quality. To address these issues, in this work, textile electrodes integrated with a clothing belt are proposed to achieve EIT lung imaging along with a custom portable EIT system. The simulation and experimental results have verified the validity of the proposed portable EIT system. Furthermore, the imaging results of using the proposed textile electrodes were compared with commercial electrocardiogram electrodes to evaluate their performance.
Pandemic and epidemic outbreaks of influenza A virus (IAV) infection pose severe challenges to hu... more Pandemic and epidemic outbreaks of influenza A virus (IAV) infection pose severe challenges to human society. Passive immunotherapy with recombinant neutralizing antibodies can potentially mitigate the threats of IAV infection. With a high throughput neutralizing antibody discovery platform, we produced artificial anti-hemagglutinin (HA) IAV-neutralizing IgGs from phage-displayed synthetic scFv libraries without necessitating prior memory of antibody-antigen interactions or relying on affinity maturation essential for in vivo immune systems to generate highly specific neutralizing antibodies. At least two thirds of the epitope groups of the artificial anti-HA antibodies resemble those of natural protective anti-HA antibodies, providing alternatives to neutralizing antibodies from natural antibody repertoires. With continuing advancement in designing and constructing synthetic scFv libraries, this technological platform is useful in mitigating not only the threats of IAV pandemics bu...
The work presented a simple way to prepare a meso-tetra(4-pyridyl)porphyrin (MTPyP) film for opti... more The work presented a simple way to prepare a meso-tetra(4-pyridyl)porphyrin (MTPyP) film for optical gas sensor. The dip-dry coating method that was developed by our reaserch shows a strong absorption band at 418 nm. We also proposed a simple method, peak ratio, to do the semiquantitative analysis of hydrochloric acid (HCl) and ammonia (NH 3 ) molecules adsorbed on the dipdry coating MTPyP film by their absorption bands. The MTPyP film was prepared on glass substrate and spectrometer was used to obtain the spectra as sensing the vapor molecules. The ratio of peaks values at 418 nm and 450 nm was used to identify the vapor types and to determine the concentrations. The results show that the peak ratio of HCl is approaching less than one and the peak ratio of NH 3 is always larger than one for two-hour measurment.
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Papers by Chii-Wann Lin