Helping make brain surgery safer

19 December 2018:

Researchers from CNBP and the Institute for Photonics and Advanced Sensing, together with Sir Charles Gairdner Hospital and University of Western Australia collaborators, have demonstrated  the potential of an ‘imaging needle’ for reducing the risk of dangerous brain bleeds in patients undergoing brain biopsy. In the journal Science Advances, the researchers describe how a tiny imaging needle can detect blood vessels with a very high degree of accuracy (91.2% sensitivity and 97.7% specificity). Pictured is corresponding author of the paper CNBP Investigator Prof Robert McLaughlin, University of Adelaide.

Journal: Science Advances.

Publication title: Intraoperative detection of blood vessels with an imaging needle during neurosurgery in humans.

Authors: Hari Ramakonar, Bryden C. Quirk, Rodney W. Kirk, Jiawen Li, Angela Jacques, Christopher R. P. Lind and Robert A. McLaughlin.

Abstract: Intracranial hemorrhage can be a devastating complication associated with needle biopsies of the brain. Hemorrhage can occur to vessels located adjacent to the biopsy needle as tissue is aspirated into the needle and removed. No intraoperative technology exists to reliably identify blood vessels that are at risk of damage. To address this problem, we developed an “imaging needle” that can visualize nearby blood vessels in real time. The imaging needle contains a miniaturized optical coherence tomography probe that allows differentiation of blood flow and tissue. In 11 patients, we were able to intraoperatively detect blood vessels (diameter, >500 μm) with a sensitivity of 91.2% and a specificity of 97.7%. This is the first reported use of an optical coherence tomography needle probe in human brain in vivo. These results suggest that imaging needles may serve as a valuable tool in a range of neurosurgical needle interventions.

Cellular glycan surfaces in the central nervous system

17 December 2018:

A review paper by CNBP researchers (lead author  Sameera Iqbal pictured) reports on the examination of cellular glycan surfaces in the central nervous system and links to disorders and disease such as Alzheimer’s disease, multiple sclerosis and more.

Journal: Biochemical Society Transactions.

Publication title:  Understanding cellular glycan surfaces in the central nervous system.

Authors: Sameera Iqbal, Mina Ghanimi Fard, Arun Everest-Dass, Nicolle H. Packer, Lindsay M. Parker.

Abstract: Glycosylation, the enzymatic process by which glycans are attached to proteins and lipids, is the most abundant and functionally important type of post-translational modification associated with brain development, neurodegenerative disorders, psychopathologies and brain cancers. Glycan structures are diverse and complex; however, they have been detected and targeted in the central nervous system (CNS) by various immunohistochemical detection methods using glycan-binding proteins such as anti-glycan antibodies or lectins and/or characterized with analytical techniques such as chromatography and mass spectrometry. The glycan structures on glycoproteins and glycolipids expressed in neural stem cells play key roles in neural development, biological processes and CNS maintenance, such as cell adhesion, signal transduction, molecular trafficking and differentiation. This brief review will highlight some of the important findings on differential glycan expression across stages of CNS cell differentiation and in pathological disorders and diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, multiple sclerosis, amyotrophic lateral sclerosis, schizophrenia and brain cancer.

Super-resolution volumetric imaging

11 December 2018:

The Australian Research Council (ARC) has announced funding for a super-resolution imaging facility that will be the first of its kind in Australia.

The facility brings together a consortium of multidisciplinary researchers from leading Australian Universities, Institutes and Research Centres (including CNBP) to develop new capacities for materials science, photonics devices, engineering, and neuroscience, microbial and cardiovascular research.

At its core the A$3.0m ARC LIEF project will enable scientists to study the inner workings of cells in their native environment. This represents a step change from currently imaging isolated 2D cells cultured in a petri dish to future research that will reveal subcellular structures and cell-to-cell communications in 3D tissue in real time.

The National Volumetric Imaging Platform, as it is known, will be installed, maintained and operated by the Institute for Biomedical Materials and Devices (IBMD) at the University of Technology Sydney (UTS) and the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) at RMIT University in Melbourne. This project is scheduled to be completed in late 2019.

UTS Professor Dayong Jin, Lead Chief Investigator of the project, said that the facility will give scientists a “new way to decode the complexities of life science machinery.”

“High-resolution imaging of the large volume of single cells and functional navigation of their interactions will allow researchers to drop into a ‘street view’ and observe the details of intercellular ‘live traffic’,” he said.

Prof Brant Gibson, Co-Deputy Director and RMIT node director of CNBP said, “I am very excited to lead the RMIT University node of the National Volumetric Imaging Facility and to work in collaboration with Jin Dayong, the UTS node and all of our collaborative institutional partners. This facility will enable us to image deeper within biological samples than we ever been able to before, with nanoscale resolution and extraordinary bandwidth stretching from the near-UV (400nm) well into the infrared (1650nm) spectrum.”

Prof Mark Hutchison, Professor at the Adelaide Medical School and Director of the CNBP at the University of Adelaide said, “This is an exciting development of advanced imaging infrastructure capacity that will allow a convergence of scientists from across the country to gain an unprecedented level of molecular insights into the complex systems and arrangement of cells in biologically relevant complex 3 dimensional environments.”

Participating Organisations include: Universities: University of Technology Sydney, RMIT University, University of Wollongong, University of Sydney, The University of Queensland, The University of New South Wales, Macquarie University, The University of Adelaide.

Institutes and Centres: Institute for Biomedical and Materials Devices, ARC Research Hub for Integrated Device for End-user Analysis at Low-levels, Institute for Molecular Horizons, the Heart Research Institute, ithree Institute, Centre for Translational Neuroscience, Australian Centre for Ecogenomics, ARC Centre of Excellence for Nanoscale BioPhotonics.

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Soft-glass imaging microstructured optical fiber

10 December 2018:

A proof-of-concept fabrication of a soft-glass imaging microstructured optical fiber has been demonstrated by CNBP scientists in a new research paper published in the journal Optics Express. Lead author of the paper is Dr Stephen C. Warren-Smith, CNBP Associate Investigator at the University of Adelaide who notes that it is envisaged that the glass-based optical fibers will find potential use in applications such as in-vivo white-light and spectroscopic imaging.

Journal: Optics Express.

Publication title: Soft-glass imaging microstructured optical fibers.

Authors: Stephen C. Warren-Smith, Alastair Dowler, and Heike Ebendorff-Heidepriem.

Abstract: We demonstrate the fabrication of multi-core (imaging) microstructured optical fiber via soft-glass preform extrusion through a 3D printed titanium die. The combination of extrusion through 3D printed dies and structured element (capillary) stacking allows for unprecedented control of the optical fiber geometry. We have exploited this to demonstrate a 100 pixel rectangular array imaging microstructured fiber. Due to the high refractive index of the glass used (n = 1.62), such a fiber can theoretically have a pixel pitch as small as 1.8 µm. This opens opportunities for ultra-small, high-resolution imaging fibers fabricated from diverse glass types.

Expertise in microfluidic device development!

29 November 2018:

Meet CNBP’s Dr Lianmei Jiang in our latest ‘Quick Chat’ video! She’s developing advanced microfluidic devices for use in cancer diagnosis.

“What I love about science is the more that I learn, the more I realise how little I actually know. Science is a way to turn ‘I don’t know’ into ‘I don’t know yet’,” she says. Click to find out more!

Optimising the creation of NV centres in diamond

24 November 2018:

An improved method to convert nitrogen to nitrogen-vacancy (NV) color centers in diamond has been reported by CNBP researchers in a paper published in the journal Carbon. Lead author of the paper was CNBP student Marco Capelli (pictured).

Journal: Carbon.

Publication title: Increased nitrogen-vacancy centre creation yield in diamond through electron beam irradiation at high temperature.

Authors: M. Capelli, A.H. Heffernan, T. Ohshima, H. Abe, J. Jeske, A. Hope, A.D. Greentree, P. Reineck, B.C. Gibson.

Abstract: The nitrogen-vacancy (NV) centre is a fluorescent defect in diamond that is of critical importance for applications from ensemble sensing to biolabelling. Hence, understanding and optimising the creation of NV centres in diamond is vital for technological progress in these areas. We demonstrate that simultaneous
electron irradiation and annealing of a high-pressure high-temperature diamond sample increases the NV centre creation efficiency from substitutional nitrogen defects by up to 117 % with respect to a sample where the processes are carried out consecutively, but using the same process parameters. This increase in fluorescence is supported by visible and infrared absorption spectroscopy experiments. Our results pave the way for a more efficient creation of NV centres in diamond as well as higher overall NV densities in the future.

Modulation of the nano-environment

15 November 2018:

A new CNBP research publication (lead author Dr Roman Kostecki, University of Adelaide) describes how molecular interactions can be modulated by defining the local nano-environment to give a specific chemical outcome.

Journal: ACS Applied Materials and Interfaces.

Publication title: Control of Molecular Recognition via Modulation of the Nanoenvironment.

Authors: Roman Kostecki, Sabrina Heng, Adrian M. Mak, Heike Ebendorff-Heidepriem, Tanya M. Monro, and Andrew D. Abell.

Abstract: Many biological processes are driven by the interaction of a host with a guest molecule. We show such interactions can be modulated by carefully defining the local molecular environment to give a specific chemical outcome. Particularly, the selectivity of a host toward two different ions (Ca2+ and Al3+) is defined by it being in solution or the physisorbed state. In solution, the host displays greater selectivity toward Ca2+. When physisorbed, the selectivity profile of the host is reversed with enhanced binding of Al3+. This demonstrates a single host molecule can be tailored to selectively bind multiple guests by altering its nanoenvironment.

Optical fiber based immunosensor detects cytokines

13 November 2018:

An immunosensor created on an optical fiber surface has been developed by CNBP researchers that has successfully detected cytokine proteins in a rat’s spinal cord. The result indicates that such fiber sensors can be used as an effective and sensitive tool for localised detection of cytokines in vivo, in a range of research and clinical applications. Lead author on the published research paper was CNBP’s Kaixin Zhang.

Journal: Sensors and Actuators B: Chemical.

Publication title: An optical fiber based immunosensor for localized detection of IL-1 in rat spinal cord.

Authors: Kaixin Zhang, Azim Arman, Ayad G. Anwer, Mark R. Hutchinson, Ewa M. Goldys.

Abstract: Sensitive and localized measurements of cytokines is important in biomedicine as cytokines are produced locally where needed to induce an immune reaction. Here, we present a novel immunosensor deposited on the optical fiber surface. The sensor is capable of localized detection of interleukin-1beta (IL-1β) in the rat spinal cord. In this immunosensor, a stable immunocapture surface was formed via a biotin-streptavidin coupling strategy and fluorescent carboxylated supermagnetic iron oxide (SPIO)-IL-1β detection antibody conjugates were used for signal amplification. Under the optimal condition, the proposed immunosensor can be used for the estimation of IL-1β in vitro in the range from 3.13 pg.mL-1 to 400 pg.mL-1 with a detection limit of 1.12 pg.mL-1. Furthermore, the performance of the fiber sensor was firstly assessed by ex-vivo monitoring the secretions of the rat macrophages stimulated by lipopolysaccharide (LPS), and the results demonstrated significant correlations with a commercial ELISA kit. Furthermore, the fiber sensor was successfully utilized to carry out a localized measurement of IL-1β in a spinal cord of an anesthetized rat. The result indicates that such fiber sensors can be used as an effective and sensitive tool for localised detection of IL-1β in vivo, in a range of research and clinical applications.

A spiropyran-based nanocarrier

10 November 2018:

CNBP researchers have published a new science paper reporting on a new zinc responsive delivery system with real-time intracellular sensing capabilities. Lead author of the publication is Dr Sabrina Heng (pictured).

Journal: Chemistry.

Publication title: Spiropyran‐based Nanocarrier: A New Zn2+‐Responsive Delivery System with Real Time Intracellular Sensing Capabilities.

Authors: Sabrina Heng, Xiaozhou Zhang, Jinxin Pei, Alaknanda Adwal, Philipp Reineck, Brant Gibson, Mark Hutchinson, Andrew Abell.

Abstract: A new spiropyran‐based stimuli‐responsive delivery system is presented that encapsulates and then releases an extraneous compound in response to elevated levels of Zn2+, a critical factor in cell apoptosis. A C12‐alkyl substituent on the spiropyran promotes self‐assembly into a micelle‐like nanocarrier in aqueous media, with nanoprecipitation and encapsulation of added payload. Zn2+ binding occurs to an appended bis(2‐pyridylmethyl)amine group at biologically relevant micromolar concentration. This leads to switching of the spiropyran (SP) isomer to the strongly fluorescent ring opened merocyanine‐Zn2+ (MC‐Zn2+) complex, with associated expansion of the nanocarriers to release the encapsulated payload. Payload release is demonstrated in solution and in HEK293 cells by encapsulation of a blue fluorophore, 7‐hydroxycoumarin, and monitoring its release using fluorescence spectroscopy and microscopy. Furthermore, we demonstrate the use of the nanocarriers to deliver a caspase inhibitor, Azure B, into apoptotic cells in response to an elevated Zn2+ concentration. This then inhibits intracellular caspase activity, as evidenced by confocal microscopy and in real‐time by time‐lapsed microscopy. Finally, the nanocarriers are shown to release an encapsulated proteasome inhibitor (5) in Zn2+‐treated breast carcinoma cell line models. This then inhibits intracellular proteasome and induces cytotoxicity to the carcinoma cells.