ORCID Profile
0000-0003-4878-7589
Current Organisation
University of South Australia
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Publisher: Elsevier BV
Date: 2023
Publisher: American Chemical Society (ACS)
Date: 23-04-2010
DOI: 10.1021/BM1000907
Abstract: We report on the synthesis and characterization of end-tethering polypeptide monolayers based on poly(beta-benzyl-L-aspartate) (PBLA) homopolymer and PBLA-b-poly(gamma-benzyl-L-glutamate) block copolymer. The homopolypeptide and copolypeptide brushes were fabricated by the sequential, surface-initiated vapor deposition polymerization of the N-carboxyanhydride of beta-benzyl-L-aspartate or gamma-benzyl-L-glutamate, yielding 80-nm-thick, chemically grafted films after 30 min of reaction time. Both Fourier transform infrared spectrometry and circular dichroism showed that the polypeptide brushes could be reversibly and repeatedly switched between left-handed and right-handed alpha-helical structures in response to solvent vapor exposure or permanently converted to a beta-sheet structure when heated to 160 degrees C in air. The facile, in vacuo manufacturability and the robustness of the films of PBLA-based brushes could allow them to be incorporated as active components for biosensing and nanofabricated devices.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6TC03981B
Abstract: Gold nanoparticle (AuNP) molecular tags yield a significant signal enhancement in long range SPR-based biosensing.
Publisher: American Chemical Society (ACS)
Date: 04-09-2019
DOI: 10.1021/ACS.ANALCHEM.9B03559
Abstract: Potentiometric sensors based on silicon nanowire field effect transistors (SiNW FETs) typically display exquisite sensitivities, but their bioanalytical implementation is limited due to the need for stringent measurement conditions and high-precision readout units. An alternative operation principle where SiNW FETs are operated in a frequency-domain electrical impedimetric approach is promising. However, to date only limited data is available in regard to the sensing performance and translational relevance of this novel approach in comparison to the standard charge detection paradigm. We demonstrate the feasibility of conducting electrical impedimetric FET measurements with a portable unit for the ultrasensitive detection of cancer biomarkers in biospecimens. Compared to standard potentiometric measurements, electrical impedimetric FET measurements yielded significant improvements in biosensing performances, including the limit of detection, sensing resolution, and dynamic range.
Publisher: SPIE
Date: 22-12-2015
DOI: 10.1117/12.2202554
Publisher: MDPI AG
Date: 30-03-2018
DOI: 10.20944/PREPRINTS201803.0267.V1
Abstract: Despite huge effort has been devoted to the design of the initiators and reaction conditions, it remains challenging to synthesize high molecular weight polypeptides with conventional solution phase synthesis. In this work, surface-initiated vapor deposition polymerization (SI-VDP) was utilized to graft synthetic polypeptides poly (& gamma -benzyl L-glutamate) (PBLG) from polystyrene (PS) resin beads by ring-opening polymerization of N-carboxyanhydrides (NCAs). It was demonstrated for the first time that high molecular weight bulk PBLG (& 500,000) could be readily obtained within one hour via solvent-free synthetic method which paves the way for the synthesis of copolypeptides with high molecular weight.
Publisher: Wiley
Date: 28-06-2022
Abstract: Measuring tumor cell invasiveness through 3D tissues, particularly at the single‐cell level, can provide important mechanistic understanding and assist in identifying therapeutic targets of tumor invasion. However, current experimental approaches, including standard in vitro invasion assays, have limited physiological relevance and offer insufficient insight into the vast heterogeneity in tumor cell migration through tissues. To address these issues, here the concept of optical cellular micromotion is reported on, where digital holographic microscopy is used to map the optical nano‐ to submicrometer thickness fluctuations within single‐cells. These fluctuations are driven by the dynamic movement of subcellular structures including the cytoskeleton and inherently associated with the biological processes involved in cell invasion within tissues. It is experimentally demonstrated that the optical cellular micromotion correlates with tumor cells motility and invasiveness both at the population and single‐cell levels. In addition, the optical cellular micromotion significantly reduced upon treatment with migrastatic drugs that inhibit tumor cell invasion. These results demonstrate that micromotion measurements can rapidly and non‐invasively determine the invasive behavior of single tumor cells within tissues, yielding a new and powerful tool to assess the efficacy of approaches targeting tumor cell invasiveness.
Publisher: Elsevier BV
Date: 2020
Publisher: MDPI AG
Date: 15-01-2019
DOI: 10.3390/S19020323
Abstract: Surface plasmon enhanced light scattering (SP-LS) is a powerful new sensing SPR modality that yields excellent sensitivity in sandwich immunoassay using spherical gold nanoparticle (AuNP) tags. Towards further improving the performance of SP-LS, we systematically investigated the AuNP size effect. Simulation results indicated an AuNP size-dependent scattered power, and predicted the optimized AuNPs sizes (i.e., 100 and 130 nm) that afford extremely high signal enhancement in SP-LS. The maximum scattered power from a 130 nm AuNP is about 1700-fold higher than that obtained from a 17 nm AuNP. Experimentally, a bio-conjugation protocol was developed by coating the AuNPs with mixture of low and high molecular weight PEG molecules. Optimal IgG antibody bioconjugation conditions were identified using physicochemical characterization and a model dot-blot assay. Aggregation prevented the use of the larger AuNPs in SP-LS experiments. As predicted by simulation, AuNPs with diameters of 50 and 64 nm yielded significantly higher SP-LS signal enhancement in comparison to the smaller particles. Finally, we demonstrated the feasibility of a two-step SP-LS protocol based on a gold enhancement step, aimed at enlarging 36 nm AuNPs tags. This study provides a blue-print for the further development of SP-LS biosensing and its translation in the bioanalytical field.
Publisher: Elsevier BV
Date: 10-2023
Publisher: American Chemical Society (ACS)
Date: 23-09-2018
DOI: 10.1021/ACSSENSORS.8B00785
Abstract: Cryptosporidium parvum ( C. parvum) is a highly potent zoonotic pathogen, which can do significant harm to both human beings and livestock. However, existing technologies or methods are deficient for rapid on-site detection of water contaminated with C. parvum. Better detection approaches are needed to allow water management agencies to stop major breakouts of the pathogen. Herein, we present a novel detection method for cryptosporidium in a tiny drop of s le using a magnetic nanoparticle (MNP) probe combined with dark-field microscopy in 30 min. The designed MNP probes bind with high affinity to C. parvum, resulting in the formation of a golden garland-like structure under dark-field microscopy. This MNP-based dark-field counting strategy yields an amazing PCR-like sensitivity of 8 attomolar (aM) (5 pathogens in 1 μL). Importantly, the assay is very rapid (∼30 min) and is very simple to perform as it involves only one step of mixing and magnetic separation, followed by dropping on a slide for counting under dark-field microscope. By combining the advantages of the specific light-scattering characteristic of MNP probe under dark field and the selective magnetic separation ability of functionalized MNP, the proposed MNP-based dark-field enumeration method offers low cost and significant translational potential.
Publisher: American Chemical Society (ACS)
Date: 13-01-2015
DOI: 10.1021/AC5031978
Abstract: Long-range surface plasmon resonance (LRSPR) is a powerful biosensing technology due to a substantially larger probing depth into the medium and sensitivity, compared with conventional SPR. We demonstrate here that LRSPR can provide sensitive noninvasive measurement of the dynamic fluctuation of adherent cells, often referred to as the cellular micromotion. Proof of concept was achieved using confluent layers of 3T3 fibroblast cells and MDA-MB-231 cancer cells. The slope of the power spectral density (PSD) of the optical fluctuations was calculated to determine the micromotion index, and significant differences were measured between live and fixed cell layers. Furthermore, the performances of LRSPR and conventional surface plasmon resonance (cSPR) were compared with respect to micromotion monitoring. Our study showed that the micromotion index of cells measured by LRSPR sensors was higher than when measured with cSPR, suggesting a higher sensitivity of LRSPR to the micromotion of cells. To investigate further this finding, simulations were conducted to establish the relative sensitivities of LRSPR and cSPR to membrane fluctuations. Increased signal intensity was predicted for LRSPR in comparison to cSPR, suggesting that membrane fluctuations play a significant role in the optical micromotion measured in LRSPR. Analogous to cellular micromotion measured using impedance techniques, LRSPR micromotion has the potential to provide important biological information on the metabolic activity and viability of adherent cells.
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5RA15839G
Abstract: Surface-tethered chemoresponsive polypeptides prepared by surface-initiated vapor deposition polymerization were used to investigate conversion efficiency between α-helical and β-sheet conformations.
Publisher: Wiley
Date: 07-03-2019
Publisher: Elsevier BV
Date: 04-2021
Publisher: American Chemical Society (ACS)
Date: 20-04-2017
DOI: 10.1021/ACSSENSORS.6B00776
Abstract: The development of simple yet ultrasensitive biosensing approaches for the detection of cancer prognostic microRNA is an important step toward their successful clinical implementation. We demonstrate the relevance for the detection of circulating miRNA of a novel signal lification scheme based on surface plasmon resonance enhanced light scattering (SP-LS). In addition to experimental optimization carried out using gold nanoparticle (AuNP) tags conjugated with a monoclonal antibody with high affinity for RNA*DNA hybrid duplexes, simulation modeling was conducted to obtain insights about SP-LS biosensing. SP-LS enabled the detection of miRNA-122 at subpicomolar concentrations within 30 min, and a limit of detection of 2 attomoles (60 fM, 50 μL) was determined. MiRNA-122 could also be reliably detected in a high concentration background of nontarget miRNA. The proposed SP-LS miRNA detection approach could be readily applied to other miRNA targets of diagnostic importance and further developed to allow for multiplex measurements of miRNA panels. The promising results obtained in this study and advantageous features of SP-LS warrant further development and its application to clinical s les.
Publisher: MDPI AG
Date: 08-02-2023
DOI: 10.3390/NANO13040665
Abstract: Malignant tumor is one of the leading causes of death in human beings. In recent years, bacteriophages (phages), a natural bacterial virus, have been genetically engineered for use as a probe for the detection of antigens that are highly expressed in tumor cells and as an anti-tumor reagent. Furthermore, phages can also be chemically modified and assembled with a variety of nanoparticles to form a new organic/inorganic composite, thus extending the application of phages in biological detection and tumor therapeutic. This review summarizes the studies on genetically engineered and chemically modified phages in the diagnosis and targeting therapy of tumors in recent years. We discuss the advantages and limitations of modified phages in practical applications and propose suitable application scenarios based on these modified phages.
Publisher: American Chemical Society (ACS)
Date: 24-03-2020
Publisher: American Chemical Society (ACS)
Date: 22-11-2016
DOI: 10.1021/ACS.ANALCHEM.6B03798
Abstract: Development of new detection methodologies and lification schemes is indispensable for plasmonic biosensors to improve the sensitivity for the detection of trace amounts of analytes. Herein, an ultrasensitive scheme for signal enhancement based on the concept of surface-plasmon-resonance-enhanced light scattering (SP-LS) was validated experimentally and theoretically. The SP-LS of gold nanoparticles' (AuNPs) tags was employed in a sandwich assay for the detection of cardiac troponin I and provided up to 2 orders of magnitude improved sensitivity over conventional AuNPs-enhanced refractometric measurements and 3 orders of magnitude improvement over label-free SPR. Simulations were also performed to provide insights into the physical mechanisms.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Elsevier BV
Date: 12-2021
Publisher: American Chemical Society (ACS)
Date: 03-12-2008
DOI: 10.1021/BM8007956
Abstract: End-tethered cationic polypeptide brushes of poly(L-lysine) (t-PLL) were combined with three anionic polymers, poly(acrylic acid) (PAA), poly(L-glutamic acid) (PLGA), and poly(L-aspartic acid) (PLAA), to form reversible polyelectrolyte complex films at surfaces at neutral pH. The polyelectrolyte complex formation was confirmed by an in situ zeta-potential study and by positive fluorescent images after adding prelabeled anionic polymers. The secondary conformations of the t-PLL complex films depend upon the specific polyelectrolyte with which t-PLL was coupled as studied by circular dichroism and FTIR. Specifically, the random coil chain configuration of the t-PLL film was converted to an alpha-helical, beta-sheet, or random coil structure after forming complexes with PAA, PLGA, or PLAA, respectively. Each of these complexes could be returned to the original random coil t-PLL structure by a dilute acid rinse. Additional thickness and morphological studies from ellipsometry and atomic force microscopy have further shown that the corresponding film thicknesses of the in idual solvated films were affected more by the secondary structures in films than by the adsorbed mass or surface net charges. The solvated thickness was reduced significantly after the random coil t-PLL film was coupled with polyanions in forming compact regulated structures in films. This biomimetic approach provides a new opportunity for controlling the molecular organization in surface macromolecular assemblies and may provide a model for structural study of protein complexes on a chip.
Publisher: Wiley
Date: 19-10-2021
Abstract: Detection of infectious viruses relies on quantitative polymerase chain reaction (qPCR). However, qPCR requires costly equipment, a clean operating environment and experienced technicians, limiting its wide applicability. On the other hand, enzyme‐linked immunosorbent assay (ELISA) is widely used in biological laboratories due to its relatively high sensitivity and ease of operation. However, ELISA‐based detection of the virus is h ered because it is lower sensitive than qPCR. Herein, a nanoprobe ELISA (NP‐ELISA) based on a mesoporous silica nanoprobe, which is constructed by first being loaded with peroxidase and further coated with positively charged polymer polyethyleneimine, and finally functionalized with antivirus antibodies, is designed. Results show that each NP probe is encapsulating 170 peroxidase molecules and presents 200 antibody molecules on the surface. The limit of detection (LOD) of NP‐ELISA (LOD = 1450 PFU mL −1 ) for the detection of real virus s les is tenfold sensitive than that of standard ELISA (LOD = 14, 414 PFU mL −1 ) and the assay time for NP‐ELISA is reduced by 1 h as compared with standard one. Therefore, the NP‐ELISA provides a rapid and sensitive immunoassay platform that can readily be implemented for biological laboratory research as well as for on‐site clinical diagnostics.
Publisher: American Chemical Society (ACS)
Date: 24-01-2019
Abstract: Currently, it remains challenging to count protein-biomarker molecules present in a small droplet of biological s les. Herein, we propose a gold nanoparticle (GNP) probe-assisted sandwich-counting strategy that relies on a GNP probe, an antibody-functionalized chip to "count" antigen molecules using a scanning electron microscope. Both standard carcinoembryonic antigen (CEA) and two real CEA-related tumor s les (tumor tissues and serum) were assayed to demonstrate the proof-of-concept of the counting strategy. Results show that our method is excellently correlative with enzyme-linked immuno-sorbent assay (ELISA) that is widely used in clinics for antigen or antibody detection and the limit of detection of our enumeration strategy reaches down to 0.045 ng/mL, which is ∼40 times more sensitive than the conventional ELISA. Therefore, our GNP probe-assisted sandwich-counting strategy has the potential to be used for quantification of protein biomarkers at ultralow concentrations in early tumor specimens and detection of target proteins in much diluted concentrations.
Publisher: Cold Spring Harbor Laboratory
Date: 27-08-2021
DOI: 10.1101/2021.08.26.457857
Abstract: Measuring tumour cell invasiveness through three-dimensional (3D) tissues, particularly at the single cell level, can provide important mechanistic understanding and assist in identifying therapeutic targets of tumour invasion. However, current experimental approaches, including standard in vitro invasion assays, have limited physiological relevance and offer insufficient insight about the vast heterogeneity in tumour cell migration through tissues. To address these issues, here we report on the concept of optical cellular micromotion, where digital holographic microscopy (DHM) is used to map the optical thickness fluctuations at sub-micron scale within single cells. These fluctuations are driven by the dynamic movement of subcellular structures including the cytoskeleton and inherently associated with the biological processes involved in cell invasion within tissues. We experimentally demonstrate that the optical cellular micromotion correlates with tumour cells motility and invasiveness both at the population and single cell levels. In addition, the optical cellular micromotion significantly reduced upon treatment with migrastatic drugs that inhibit tumour cell invasion. These results demonstrate that micromotion measurements can rapidly and non-invasively determine the invasive behaviour of single tumour cells within tissues, yielding a new and powerful tool to assess the efficacy of approaches targeting tumour cell invasiveness. Tumour cells invasion through tissues is a key hallmark of malignant tumour progression and its measurement is essential to unraveling biological processes and screening for new approaches targeting cell motility. To address the limitations of current approaches, we demonstrate that sub-micron scale mapping of the dynamic optical thickness fluctuations within single cells, referred to as optical cellular micromotion, correlates with their motility in ECM mimicking gel, both at the population and single cell levels. We anticipate that 3D optical micromotion measurement will provide a powerful new tool to address important biological questions and screen for new approaches targeting tumour cell invasiveness.
Publisher: American Chemical Society (ACS)
Date: 26-06-2014
DOI: 10.1021/AM501390V
Abstract: A robust and flexible approach is described for the straightforward preparation of multicellular tumor spheroids of controllable dimensions. The approach is based on a one-step plasma polymerization of the monomer allylamine carried out through conformal micropatterning physical masks that is used to deposit amine-rich (PolyAA) micrometer-scale features that promote cellular attachment and initiate the formation of multicellular spheroids. A simple backfilling step of the nonpolymerized poly(dimethylsiloxane) background with Pluronic F127 significantly reduced background cellular adhesion on the untreated substrate and, in turn, improved the quality of the spheroid formed. Tumor cells grown on the PolyAA/F127 patterned surfaces reliably formed multicellular spheroids within 24-48 h depending on the cell type. The dimension of the spheroids could be readily controlled by the dimension of the amine-rich micropatterns. This simple approach is compatible with the long-term culture of multicellular spheroids and their characterization with high-resolution optical microscopy. These features facilitate the development of on-chip assays, as demonstrated here for the study of the binding of transferrin-functionalized gold nanoparticles to multicellular tumor spheroids.
Publisher: MDPI AG
Date: 08-12-2022
DOI: 10.3390/BIOS12121146
Abstract: Porcine epidemic diarrhea virus (PEDV), a coronavirus that causes highly infectious intestinal diarrhea in piglets, has led to severe economic losses worldwide. Rapid diagnosis and timely supervision are significant in the prophylaxis of PEDV. Herein, we proposed a gold-nanorod (GNR) probe-assisted counting method using dark field microscopy (DFM). The antibody-functionalized silicon chips were prepared to capture PEDV to form sandwich structures with GNR probes for imaging under DFM. Results show that our DFM-based assay for PEDV has a sensitivity of 23.80 copies/μL for simulated real s les, which is very close to that of qPCR in this study. This method of GNR probes combined with DFM for quantitative detection of PEDV not only has strong specificity, good repeatability, and a low detection limit, but it also can be implemented for rapid on-site detection of the pathogens.
Publisher: Public Library of Science (PLoS)
Date: 03-03-2016
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.ACA.2017.04.015
Abstract: A simplified approach for the fabrication of localised surface plasmon resonance (LSPR) sensors based on gold nanorods (GNRs) is described and validated in a model immunoassay for the activated leukocyte cell adhesion molecule (ALCAM) cancer biomarker. Towards improving on standard bottom-up LSPR sensor fabrication methodologies, we demonstrate that GNRs bioconjugated with monoclonal antibodies can be readily covalently immobilized onto silanized glass substrates to yield highly sensitive LSPR sensors. To maximise the performance of the proposed sensors, mixed polyethylene glycol adlayers were optimized in regards to the bioconjugation of monoclonal antibodies using the standard carbodiimide chemistry. In the optimal condition, the ALCAM GNR LSPR sensors yielded a sensitivity of 330 nm per refractive index and allowed the detection of the ALCAM antigen concentration down to 15 pM. This simple fabrication method could foster the implementation of LSPR sensors in the immunoassay field.
Publisher: American Chemical Society (ACS)
Date: 11-02-2016
Abstract: Within an hour, as little as one disseminated tumor cell (DTC) per lymph node can be quantitatively detected using an intraoperative biosensing platform based on silicon nanowire field-effect transistors (SiNW FET). It is also demonstrated that the integrated biosensing platform is able to detect the presence of circulating tumor cells (CTCs) in the blood of colorectal cancer patients. The presence of DTCs in lymph nodes and CTCs in peripheral blood is highly significant as it is strongly associated with poor patient prognosis. The SiNW FET sensing platform out-performed in both sensitivity and rapidity not only the current standard method based on pathological examination of tissue sections but also the emerging clinical gold standard based on molecular assays. The possibility to achieve accurate and highly sensitive analysis of the presence of DTCs in the lymphatics within the surgery time frame has the potential to spare cancer patients from an unnecessary secondary surgery, leading to reduced patient morbidity, improving their psychological wellbeing and reducing time spent in hospital. This study demonstrates the potential of nanoscale field-effect technology in clinical cancer diagnostics.
No related grants have been discovered for Chih-Tsung Yang.