Category Archives: publication

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New X-ray-induced photodynamic therapy system

19 June 2018:

Researchers from CNBP have developed an X-ray-induced photodynamic therapy (PDT) system where nanoparticles incorporating a photosensitizer, verteporfin, were triggered by X-ray radiation to generate cytotoxic singlet oxygen. This system offers the possibility of enhancing the radiation therapy commonly prescribed for the treatment of cancer by simultaneous PDT.

Lead author on the paper was Dr Sandhya Clement (pictured).

Journal: International Journal of Nanomedicine.

Publication title: X-ray radiation-induced and targeted photodynamic therapy with folic acid-conjugated biodegradable nanoconstructs.

Authors: Sandhya Clement, Wenjie Chen, Wei Deng, Ewa M Goldys.

Introduction: The depth limitation of conventional photodynamic therapy (PDT) with visible electromagnetic radiation represents a challenge for the treatment of deep-seated tumors. Materials and methods: To overcome this issue, we developed an X-ray-induced PDT system where poly(lactide-co-glycolide) (PLGA) polymeric nanoparticles (NPs) incorporating a photosensitizer (PS), verteporfin (VP), were triggered by 6 MeV X-ray radiation to generate cytotoxic singlet oxygen. The X-ray radiation used in this study allows this system to breakthrough the PDT depth barrier due to excellent penetration of 6 MeV X-ray radiation through biological tissue. In addition, the conjugation of our NPs with folic acid moieties enables specific targeting of HCT116 cancer cells that overexpress the folate receptors. We carried out physiochemical characterization of PLGA NPs, such as size distribution, zeta potential, morphology and in vitro release of VP. Cellular uptake activity and cell-killing effect of these NPs were also evaluated. Results and discussion: Our results indicate that our nanoconstructs triggered by 6 MeV X-ray radiation yield enhanced PDT efficacy compared with the radiation alone. We attributed the X-ray-induced singlet oxygen generation from the PS, VP, to photoexcitation by Cherenkov radiation and/or reactive oxygen species generation facilitated by energetic secondary electrons produced in the tissue. Conclusion: The cytotoxic effect caused by VP offers the possibility of enhancing the radiation therapy commonly prescribed for the treatment of cancer by simultaneous PDT.


Fluorescence microscopy gets the BAMM treatment!

7 June 2018:

A novel technique developed by researchers at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) will help shine new light on biological questions by improving the quality and quantity of information that can be extracted in fluorescence microscopy.

The technique, ‘bleaching-assisted multichannel microscopy’ (BAMM) takes a current long-standing weakness of fluorescence microscopy – photobleaching – and turns it into a strength that improves imaging output by up to three times, with no additional hardware required.

Reported in the journal ‘Biomedical Optics Express’ (lead author Dr Antony Orth, CNBP Research Fellow at RMIT University), BAMM will help researchers gain biological insights into the intricate processes taking place within living cells. This includes the interplay between proteins and molecules which have the potential to impact a wide range of health areas from fertility, to pain, to heart disease and more.

Publication authors: Antony Orth, Richik N. Ghosh, Emma R. Wilson, Timothy Doughney, Hannah Brown, Philipp Reineck, Jeremy G. Thompson, and Brant C. Gibson.

Read more about this innovative technique from our media release or access the publication online.

Below – This figure shows the information-rich cellular images made possible by using the newly reported BAMM technique. The ‘Original’ image shows cells containing multiple fluorescent targets, all having similar colours. This results in a monochrome image. With BAMM, photobleaching rates are colour coded red, green and blue for visualisation, so that each fluorescently labelled structure can be identified even though the fluorophore’s native colour information was never used.

Detecting glycosylated hemoglobin

Jagjit Kaur7 June 2018:

A new review paper from CNBP researchers (lead author PhD student Jagjit Kaur) outlines current research activities on developing assays including biosensors for the detection of  glycosylated hemoglobin  (HbA1c). Measurement of HbA1c is used for assessing long term glycemic control in individuals with diabetes.

Journal: Biosensors and Bioelectronics.

Publication title: Different strategies for detection of HbA1c emphasizing on biosensors and point-of-care analyzers.

Authors: Jagjit Kaur, Cheng Jiang, Guozhen Liu.

Abstract: Measurement of glycosylated hemoglobin (HbA1c) is a gold standard procedure for assessing long term glycemic control in individuals with diabetes mellitus as it gives the stable and reliable value of blood glucose levels for a period of 90–120 days. HbA1c is formed by the non-enzymatic glycation of terminal valine of hemoglobin. The analysis of HbA1c tends to be complicated because there are more than 300 different assay methods for measuring HbA1c which leads to variations in reported values from same samples. Therefore, standardization of detection methods is recommended. The review outlines the current research activities on developing assays including biosensors for the detection of HbA1c. The pros and cons of different techniques for measuring HbA1c are outlined. The performance of current point-of-care HbA1c analyzers available on the market are also compared and discussed. The future perspectives for HbA1c detection and diabetes management are proposed.

Detecting zearalenone (a toxin found in cereals)

1 May 2018:

CNBP PhD student at Macquarie University, Fuyuan Zhang (pictured), is first author on a new paper reporting on the development of magnetic nanobead based fluoroimmunoassays  for detection of zearalenone (a toxin found in cereals).

Journal: Sensors and Actuators B: Chemical.

Publication title: Novel magnetic nanobeads-based fluoroimmunoassays for zearalenone detection in cereals using protein G as the recognition linker.

Authors: Fuyuan Zhang, Bing Liu, Guozhen Liu, Wei Sheng, Yan Zhang, Qi Liu, Shuo Wang.

Abstract: Zearalenone (ZEN) is a type of estrogenic mycotoxin commonly found in cereals. In order to satisfy the need for ultrasensitive detection of ZEN, we developed two novel magnetic nanobeads (MNBs)-based fluoroimmunoassays using protein G (PG) as recognition binder on the sensing interface. One proposed facile strategy is based on a first capture last react (FCLR) procedure while the other is a first react last capture (FRLC) format. Specifically, CdTe/CdS/ZnS quantum dots were synthesized and modified to antigen (OVA-ZEN) as the signal probes. The PG modified MNBs specifically captured the fragment crystallizable region of immunoglobulin G (IgG) with a level of orientation while avoiding the destruction of antibody’s binding sites caused by chemical coupling. Under the optimized conditions, the detection limits of 0.019 ng mL−1 and 0.049 ng mL−1 in the extract solution were obtained for the FCLR and FRLC, respectively. Furthermore, the established methods proved to be successful in detecting ZEN in real cereal samples with the detection limits being 0.6 μg kg−1 and 1.5 μg kg−1 in the FCLR and FRLC, respectively. The performance of the proposed assays was evaluated utilizing commercial ELISA kits with satisfactory results.

A novel, high sensitivity Sagnac-interferometer biosensor

30 April 2018:

A new publication featuring CNBP co-authors (Dr Stephen Warren-Smith pictured left and Prof Heike Ebendorff-Heidepriem) reports on the design and implementation of a novel, high sensitivity Sagnac-interferometer biosensor based on an exposed core microstructured optical fiber (ECF).

Journal: Sensors and Actuators B: Chemical.

Publication title: High-sensitivity Sagnac-interferometer biosensor based on exposed core microstructured optical fiber.

Authors: Xuegang Li, Linh V. Nguyen, Yong Zhao, Heike Ebendorff-Heidepriem, Stephen C. Warren-Smith.

Abstract: A novel, high sensitivity Sagnac-interferometer biosensor based on exposed core microstructured optical fiber (ECF) has been designed and implemented in this paper. The exposed core fiber has noncircular symmetry and thus exhibits birefringence and can form a sensing element within a Sagnac loop interferometer. The exposed-core fiber design provides direct access to the evanescent field, allowing the measurement of bulk refractive index (RI) with a sensitivity of up to −3137 nm/RIU while maintaining the fiber’s robustness. The sensor can also detect the localized refractive index changes at the fiber core’s surface as the result of a biological binding event. We demonstrate the use of this sensor for label-free sensing of biological molecules by immobilizing biotin onto the fiber core as the probe to capture the target molecule streptavidin.

New CNBP review paper on SERS

23 April 2018:

CNBP researchers have  published a new review paper on surface enhanced Raman scattering (SERS), reporting on recent developments and applications, and in particular examining SERS nanotags in biosensing and bioimaging, describing case studies in which differing types of biomarkers have been investigated. Lead author on the paper was Wei Zhang from Macquarie University.

Journal: Journal of Analysis and Testing.

Publication title: SERS Nanotags and Their Applications in Biosensing and Bioimaging.

Authors: Wei Zhang, Lianmei Jiang, James A. Piper, Yuling Wang.

Abstract: Owing to the unique advantages of surface enhanced Raman scattering (SERS) in high sensitivity, specifcity, multiplexing capability and photostability, it has been widely used in many applications, among which SERS biosensing and bioimaging are the focus in recent years. The successful applications of SERS for non-invasive biomarker detection and bioimaging under in vitro, in vivo and ex vivo conditions, ofer signifcant clinical  information to improve diagnostic and prognostic outcomes. This review provides recent developments and applications of SERS, in particular SERS nanotags in biosensing
and bioimaging, describing case studies in which diferent types of biomarkers have been investigated, as well as outlining future challenges that need to be addressed before SERS sees both pathological and clinical use.

Advanced sensor to unlock the secrets of the brain

17 April 2018:

CNBP researchers have announced the development of a state-of-the-art sensor that can for the first time detect signalling molecules, called cytokines, which operate in the living brain. Cytokines in the brain are secreted by glia cells that make up nearly 90% of all brain cells. Cytokines play a central role in controlling mood and cognition and may also contribute to a number of mental health disorders.

“What we’ve developed is the first sensor capable of monitoring the release of these cytokines in the brain,” says lead researcher Kaixin Zhang, a PhD candidate at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) at Macquarie University.

“Critically, there is mounting evidence that these glial-released cytokines play a central role in regulating a range of brain functions. In particular they are responsible for affecting mood, cognition and behaviour.”

“Our innovative new sensor has the potential to increase our knowledge not only of how the brain works, but may be able to shed light on conditions such as depression, stress, anxiety and even schizophrenia,” he says.

The sensor consists of a modified optical fibre which has had its surface treated with a capture protein. The protein reacts to the presence of cytokine molecules and is capable of monitoring local cytokine release in discrete and targeted parts of the brain.

Professor Ewa Goldys, CNBP Deputy Director, and a senior researcher on the project, notes that brain functionality is an extremely complex area where scientific knowledge is still limited.

“Our research in understanding cytokine secretion, neural circuits and how these two work together is essential to improving our understanding of the brain, in health and disease. Our sensor has opened a new window to the brain, but we still have far more to discover,” she says.

“The key benefit of our new sensor is that it enables the detection of cytokine release precisely as it happens, in living, naturally behaving animals, which is the key step on this discovery journey. To date, suitable tools have not been available to do this as the living brain is an incredibly difficult part of the body to access, and these cytokines are very difficult to measure.”

Published in the leading scientific journal ‘Brain, Behavior, and Immunity’, the cytokine sensor research was undertaken by an international team of scientists at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University, University of Colorado Boulder, Central China Normal University and The University of Adelaide.

“This is a really fantastic example of the work which we do at the CNBP, which is all about creating state-of-the-art sensing tools that can measure the inner workings of the living organism,” says Prof Goldys.

“It may be early days in this research but it will be fascinating to see where this cytokine detection takes us. It may prove to be a pivotal point in the understanding, and eventual diagnostic and clinical treatment, of a whole range of health conditions.”

A novel platform for in vivo detection of cytokine release within discrete brain regions.

AUTHORS: Kaixin Zhang, Michael V. Baratta, Guozhen Liu, Matthew G. Frank, Nathan R. Leslie, Linda R. Watkins, Steven F. Maier, Mark R. Hutchinson, Ewa M. Goldys.

Below – CNBP PhD Candidate – Kaixin Zhang.

Sensing magnesium

17 April 2018:

A new publication from CNBP researchers (lead author Georgina Sylvia pictured), presents the rational design and photophysical characterisation of spiropyran-based chemosensors for magnesium.

Journal: Chemosensors.

Publication title: A Rationally Designed, Spiropyran-Based Chemosensor for Magnesium.

Authors: Georgina M. Sylvia, Adrian M. Mak, Sabrina Heng, Akash Bachhuka, Heike Ebendorff-Heidepriem, and Andrew D. Abell.

Abstract: Magnesium ions (Mg2+) play an important role in mammalian cell function; however, relatively little is known about the mechanisms of Mg2+ regulation in disease states. An advance in this field would come from the development of selective, reversible fluorescent chemosensors, capable of repeated measurements. To this end, the rational design and fluorescence-based photophysical characterisation of two spiropyran-based chemosensors for Mg2+ are presented. The most promising analogue, chemosensor 1, exhibits 2-fold fluorescence enhancement factor and 3-fold higher binding affinity for Mg2+ (Kd 6.0 µM) over Ca2+ (Kd 18.7 µM). Incorporation of spiropyran-based sensors into optical fibre sensing platforms has been shown to yield significant signal-to-background changes with minimal sample volumes, a real advance in biological sensing that enables measurement on subcellular-scale samples. In order to demonstrate chemosensor compatibility within the light intense microenvironment of an optical fibre, photoswitching and photostability of 1 within a suspended core optical fibre (SCF) was subsequently explored, revealing reversible Mg2+ binding with improved photostability compared to the non-photoswitchable Rhodamine B fluorophore. The spiropyran-based chemosensors reported here highlight untapped opportunities for a new class of photoswitchable Mg2+ probe and present a first step in the development of a light-controlled, reversible dip-sensor for Mg2+.

Fibre-needle probe for imaging and sensing in deep tissue

6 April 2018:

A world-first tiny fibre-optic probe that can simultaneously measure temperature and sense deep inside the body has been reported by CNBP/IPAS researchers. According to lead author of the research, Dr Jiawen Li at the University of Adelaide, the probe may help researchers find better treatments to prevent drug-induced overheating of the brain, and potentially refine thermal treatment for cancers. Read the media release or click on the publication title below!

Journal: Optics Letters.

Publication title: Miniaturized single-fiber-based needle probe for combined imaging and sensing in deep tissue.

Authors: Jiawen Li, Erik Schartner, Stefan Musolino, Bryden C. Quirk, Rodney W. Kirk, Heike Ebendorff-Heidepriem, and Robert A. McLaughlin.

Abstract: The ability to visualize structure while simultaneously measuring chemical or physical properties of a biological tissue has the potential to improve our understanding of complex biological processes. We report the first miniaturized single-fiber-based imaging+sensing probe capable of simultaneous optical coherence tomography (OCT) imaging and temperature sensing. An OCT lens is fabricated at the distal end of a double-clad fiber, including a thin layer of rare-earth-doped tellurite glass to enable temperature measurements. The high refractive index of the tellurite glass enables a common-path interferometer configuration for OCT, allowing easy exchange of probes for biomedical applications. The simultaneous imaging+sensing capability is demonstrated on rat brains.

Below – Dr Jiawen Li.

Understanding the role that sugars play

30 March 2018:

CNBP scientists Chris Ashwood (pictured) and Prof Nicki Packer at Macquarie University have shown that sugars with exactly the same chemical composition but slightly different structure break apart differently in their latest publication in the area of mass spectrometry. This work is their first step in automating sugar analysis, to understand the role sugars play in human disease.

Journal: Journal of The American Society for Mass Spectrometry.

Publication title: Discrimination of Isomers of Released N- and O-Glycans Using Diagnostic Product Ions in Negative Ion PGC-LC-ESI-MS/MS.

Authors: Christopher Ashwood, Chi-Hung Lin, Morten Thaysen-Andersen, Nicolle H. Packer.

Profiling cellular protein glycosylation is challenging due to the presence of highly similar glycan structures that play diverse roles in cellular physiology. As the anomericity and the exact linkage type of a single glycosidic bond can influence glycan function, there is a demand for improved and automated methods to confirm detailed structural features and to discriminate between structurally similar isomers, overcoming a significant bottleneck in the analysis of data generated by glycomics experiments. We used porous graphitized carbon-LC-ESI-MS/MS to separate and detect released N- and O-glycan isomers from mammalian model glycoproteins using negative mode resonance activation CID-MS/MS. By interrogating similar fragment spectra from closely related glycan isomers that differ only in arm position and sialyl linkage, product fragment ions for discrimination between these features were discovered. Using the Skyline software, at least two diagnostic fragment ions of high specificity were validated for automated discrimination of sialylation and arm position in N-glycan structures, and sialylation in O-glycan structures, complementing existing structural diagnostic ions. These diagnostic ions were shown to be useful for isomer discrimination using both linear and 3D ion trap mass spectrometers when analyzing complex glycan mixtures from cell lysates. Skyline was found to serve as a useful tool for automated assessment of glycan isomer discrimination. This platform-independent workflow can potentially be extended to automate the characterization and quantitation of other challenging glycan isomers.