Category Archives: publication

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Sensors for calcium ion

15 June 2017:

Researchers from CNBP (lead author Dr Sabrina Heng pictured), have just had a paper published, reporting on three new spiropyran-based reversible sensors for calcium ion.

Journal: Sensors and Actuators B: Chemical.

Publication title: Photoswitchable calcium sensor: ‘On’–‘Off’ sensing in cells or with microstructured optical fibers.

Authors: Sabrina Heng, Adrian M. Mak, Roman Kostecki, Xiaozhou Zhang, Jinxin Peia, Daniel B. Stubing, Heike Ebendorff-Heidepriema, Andrew D. Abell.

Abstract: Calcium is a ubiquitous intracellular signaling ion that plays a critical role in the modulation of fundamental cellular processes. A detailed study of these processes requires selective and reversible sensing of Ca2+ and an ability to quantify and monitor concentration changes in a biological setting. Three new, rationally designed, synthesized and photoswitchable spiropyran-based reversible sensors for Ca2+ are reported. Sensor 1a is highly selective for Ca2+ with an improved profile relative to the other two analogues, 1b and 1c. Formation of the merocyanine–Ca2+ complex is proportional to an increase in Ca2+ released from HEK293 cells on stimulation with ionomycin. The photophysical processes surrounding the binding of Ca2+ to compound 1a were further explored using computational methods based on density functional theory (DFT). The ability of sensor 1a to bind Ca2+ and photoswitch reversibly was also characterized using silica suspended-core microstructured optical fiber (SCF). These SCF experiments (with 100 nM Ca2+) represent a first step toward developing photoswitchable, minimally invasive and highly sensitive Ca2+ sensing platforms for use in a biological setting.

The paper is accessible online.

Maximizing particle concentration

28 April 2017:

A new paper from CNBP researchers reports on an improvement to deterministic lateral displacement arrays, which allows for higher particle concentration enhancement. The work has just been published in the journal ‘Biomicrofluidics’ and is accessible online.

Journal: Biomicrofluidics.

Title: Maximizing particle concentration in deterministic lateral displacement arrays.

Authors: Shilun Feng, Alison M. Skelley, Ayad G. Anwer (pictured top left), Guozhen Liu and David W. Inglis.

Abstract: We present an improvement to deterministic lateral displacement arrays, which allows higher particle concentration enhancement. We correct and extend previous equations to a mirror-symmetric boundary. This approach allows particles to be concentrated into a central channel, no wider than the surrounding gaps, thereby maximizing the particle enrichment. The resulting flow patterns were, for the first time, experimentally measured. The performance of the device with hard micro-spheres and cells was investigated. The observed flow patterns show important differences from our model and from an ideal pattern. The 18 μm gap device showed 11-fold enrichment of 7 μm particles and nearly perfect enrichment—of more than 50-fold—for 10 μm particles and Jurkat cells. This work shows a clear path to achieve higher-than-ever particle concentration enhancement in a deterministic microfluidic separation system.

 

Tuning third harmonic light

27 April 2017:

Researchers from CNBP and The Institute of Photonic Technology (lead author Stephen Warren-Smith pictured), have just had a paper published on tuning third harmonic light generated within exposed-core fibres.

Journal: Optics Letters.

Publication title: Nanofilm-induced spectral tuning of third harmonic generation.

Authors: Stephen C. Warren-Smith, Mario Chemnitz, Henrik Schneidewind, Roman Kostecki, Heike Ebendorff-Heidepriem, Tanya M. Monro and Markus A. Schmidt.

Abstract: Intermodal third-harmonic generation using waveguides is an effective frequency conversion process due to the combination of long interaction lengths and strong modal confinement. Here we introduce the concept of tuning the third harmonic phase-matching condition via the use of dielectric nanofilms located on an open waveguide core. We experimentally demonstrate that tantalum oxide nanofilms coated onto the core of an exposed core fiber allow tuning the third harmonic wavelength over 30 nm, as confirmed by qualitative simulations. Due to its generic character, the presented tuning scheme can be applied to any form of exposed core waveguide and will find applications in fields including microscopy, biosensing, and quantum optics.

The paper is accessible online.

Light-triggerable liposomes

21 April 2017:

A new paper from CNBP researchers (lead author Wenjie Chen pictured) reports on the design of a new light-triggerable liposome. The work has just been published in the journal ‘Molecular Therapy: Nucleic Acid’ and is accessible online.

Journal: Molecular Therapy: Nucleic Acid.

Title: Light-triggerable liposomes for enhanced endo/lysosomal escape and gene silencing in PC12 cells.

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

Abstract: Liposomes are an effective gene/drug delivery system, widely used in biomedical applications including gene therapy and chemotherapy. Here we designed a photo-responsive liposome (lipVP) loaded with a photosensitizer verteporfin (VP). This photosensitizer is clinically approved for photodynamic therapy (PDT). LipVP was employed as a DNA carrier for pituitary adenylyl cyclase-activating polypeptide (PACAP) receptor 1 (PAC1R) gene knockdown in PC12 cells. This has been done by incorporating PAC1R antisense oligonucleotides inside the lipVP cavity. Cells which have taken up the lipVP were exposed to light from a UV light source. As a result of this exposure, reactive oxygen species (ROS) were generated from VP, destabilising the endo/lysosomal membranes and enhancing the liposomal release of antisense DNA into the cytoplasm. Endo/lysosomal escape of DNA was documented at different time points based on quantitative analysis of colocalization between fluorescently labelled DNA and endo/lysosomes. The released antisense oligonucleotides were found to silence PAC1R mRNA. The efficiency of this photo-induced gene silencing was demonstrated by a 74 ± 5% decrease in PAC1R fluorescence intensity. Following the light-induced DNA transfer into cells, cell differentiation with exposure to two kinds of PACAP peptides was observed to determine the cell phenotypic change after PAC1R gene knockdown.

Synthesis of optical spectra

3 April 2017:

A new publication from CNBP researchers (lead author Dr Ivan Maksymov pictured)  demonstrates a new scheme for synthesis of optical spectra from nonlinear ultrasound harmonics using a hybrid liquid-state and nanoplasmonic device compatible with fibre-optic technology.

The work has just been reported in the journal ‘Optics Express’ and is accessible online.

Journal: Optics Express.

Title: Synthesis of discrete phase-coherent optical spectra from nonlinear ultrasound.

Authors: Ivan S. Maksymov and Andrew D. Greentree.

Abstract: Nonlinear acoustic interactions in liquids are effectively stronger than nonlinear optical interactions in solids. Thus, harnessing these interactions will offer new possibilities in the design of ultra-compact nonlinear photonic devices. We theoretically demonstrate a new scheme for synthesis of optical spectra from nonlinear ultrasound harmonics using a hybrid liquid-state and nanoplasmonic device compatible with fibre-optic technology. The synthesised spectra consist of a set of equally spaced optical Brillouin light scattering modes having a well-defined phase relationship between each other. We suggest that these spectra may be employed as optical frequency combs whose spectral composition may be tuned by controlling the nonlinear acoustic interactions.

Nanoscale sensor to spot disease

28 March 2017:

A new nanoscale sensor has been developed that can help detect cytokines – molecules that play a critical role in cellular response to infection, inflammation, trauma and disease.

Reported in the science journal ‘Nanoscale’, the sensor consists of a modified graphene quantum dot (or GQD) which has been designed by researchers at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP). It allows ultra-small amounts of cytokines to be identified in and around cells, with the work potentially opening up an exciting new avenue of biomedical research.

“Cytokines are molecules secreted by the cells of the immune system,” explains lead CNBP project scientist Guozhen Liu, Associate Professor at Macquarie University.

“The release of certain cytokines by the body is frequently symptomatic of a disease or health related issue, such as arthritis, inflammatory disorder or even cancer. Consequently, monitoring cytokine secretions at the cellular and sub-cellular level, has enormous value in our understanding of basic physiology and how the body is actually working.”

Traditionally, cytokine molecules have been extremely hard to measure and quantify.

“This has been due to their small size and their dynamic and transient nature,” says A/Prof Liu.

“What we’ve been able to do is to design and make a sensor that is so small that it can easily penetrate inside cells. Moreover, unlike other sensors it only responds when the cytokine is present. To this aim we have connected GQDs to cytokine sensing DNA molecules known as aptamers.”

Professor at Macquarie University, Ewa Goldys, Deputy Director at the Centre for Nanoscale BioPhotonics, also on the project team, noted that the detection of cytokines in body fluids, cells, tissues and organisms was attracting considerable attention in the biomedical research field. “Being able to track cytokine levels in real time opens new ways to monitor body physiology. This will ultimately lead to new diagnostic tools and new ways of treatment monitoring.”

Goldys believes that the innovative GQD sensing technology developed by the CNBP has potential widespread applications, due to the universal nature of the sensor design.

“We see these graphene quantum dot sensors as being excellent candidates for many other biomedical applications such as DNA and protein analysis, intracellular tracking as well as for monitoring of other cell secreted products in the body.”

Although still some years away from clinical study Goldys and Liu are both excited by the research. “Operating at the nanoscale we’re creating entirely new windows into the body and will gain valuable insights into the body, health, wellbeing and disease,” concludes Goldys.

RESEARCH PAPER:
http://pubs.rsc.org/en/content/articlelanding/2017/nr/c6nr09381g#!divAbstract

Below: CNBP Researcher A/Prof Guozhen Liu. Click on the image to access image download.

Gold nanoparticles for bioimaging

22 March 2017:

A new publication from CNBP researchers (lead author Sandhya Clement pictured) reports on a more effective and less harmful gold-based nano-agent for bioimaging and photodynamic therapy treatment for deep tissue tumors.

The work has just been reported in the journal ‘Microchimica Acta ’ and is accessible online.

Journal: Microchimica Acta.

Title: Verteprofin conjugated to gold nanoparticles for fluorescent cellular bioimaging and X-ray mediated photodynamic therapy.

Authors: Sandhya Clement, Wenjie Chen, Ayad G. Anwer & Ewa M. Goldys.

Abstract: Photodynamic therapy (PDT) uses photosensitizers, light and molecular oxygen to generate cytotoxic reactive oxygen species. Its effectiveness is limited to <1 cm due to the limited penetration depth of light. The present study compares the PDT effectivity of the photosensitizer verteporfin (VP) conjugated to gold nanoparticles (AuNPs) (a) by using deeply penetrating X-rays administered in standard radiotherapy doses, and (b) by using red light (690 nm). VP was conjugated to AuNPs of around 12 nm size to enhance the interaction of ionizing radiation with PS. For comparison, VP also was directly exposed to X-rays. It is found that VP alone is stimulated by X-rays to generate singlet oxygen. The conjugate to AuNPs also generated a significant amount of singlet oxygen on irradiation with X-rays in comparison to illumination with 690-nm light. It is also found that the rate of singlet oxygen generation is amplified in case of AuNP-conjugated VP compared to VP alone. The performance of the AuNP-VP conjugate and of the VP alone was tested in Panc 1 cells. Their viability was impaired much more in these two scenarios than with the X-ray radiation only. This suggests excellent perspectives for PDT based on VP and with X-ray stimulation, both as a stand-alone photosensitizer and in Au-NP conjugates. Moreover, both VP and AuNP-VP conjugates show bright fluorescence in physiological media for excitation/emission wavelengths in the range of 405/690 nm; hence they can also be used for simultaneous bioimaging.

Microscopy meet ‘big data’

22 March 2017:

Cell Systems has published an invited preview article authored by CNBP Research Fellow Dr Antony Orth along with collaborators from Harvard University and Massachussetts General Hospital.

The commentary article discusses how data-driven methods are poised to shake-up how we approach bio-microscopy. Microscopy-based assays can be made more informative and more predictive when paired with a library of reference images. The preview puts new results in this field into context and suggests further avenues of research.

The article is accessible online although a subscription is required.

 

Generating whispering gallery mode spectra

9 March 2017:

A new publication from CNBP researchers (lead author Jonathan Hall pictured) presents a new model for generating whispering gallery mode spectra for multilayer microspheres.

The work has just been reported in the journal ‘Optics Express’ and is accessible online.

Journal: Optics Express.

Title: Unified theory of whispering gallery multilayer microspheres with single dipole or active layer sources.

Authors: Jonathan M. M. Hall, Tess Reynolds, Matthew R. Henderson, Nicolas Riesen, Tanya M. Monro, and Shahraam Afshar.

Abstract: The development of a fast and reliable whispering gallery mode (WGM) simulator capable of generating spectra that are comparable with experiment is an important step forward for designing microresonators. We present a new model for generating WGM spectra for multilayer microspheres, which allows for an arbitrary number of concentric dielectric layers, and any number of embedded dipole sources or uniform distributions of dipole sources to be modeled. The mode excitation methods model embedded nanoparticles, or fluorescent dye coatings, from which normalized power spectra with accurate representation of the mode coupling efficiencies can be derived. In each case, the emitted power is expressed conveniently as a function of wavelength, with minimal computational load. The model makes use of the transfer-matrix approach, incorporating improvements to its stability, resulting in a reliable, general set of formulae for calculating whispering gallery mode spectra. In the specific cases of the dielectric microsphere and the single-layer coated microsphere, our model simplifies to confirmed formulae in the literature.

Breaking apart sugars

9 March 2017:

CNBP scientists Chris Ashwood and Prof Nicki Packer at Macquarie University have shown alternative ways to break apart sugars, improving their characterisation in their latest publication in the area of mass spectrometry (Enhancing structural characterisation of glucuronidated O-linked glycans using negative mode ion trap higher energy collision-induced dissociation mass spectrometry).

The work was published online in the journal Rapid Communications in Mass Spectrometry on 9th March 2017 and was funded by the Australian Research Council Centre of Excellence for Nanoscale BioPhotonics.