Category Archives: UA

Lung tissue aspiration

11 October 2017:

A new publication from CNBP researchers explores the integration of an optical coherence tomography (OCT) probe into a flexible needle for lung tissue aspiration. The paper (lead author Jiawen Li pictured), was published in the Journal of Biomedical Optics and is accessible online.

Journal: Journal of Biomedical Optics.

Publication title: Flexible needle with integrated optical coherence tomography probe for imaging during transbronchial tissue aspiration.

Authors: Jiawen Li; Bryden C. Quirk; Peter B. Noble; Rodney W. Kirk; David D. Sampson; Robert A. McLaughlin.

Abstract: Transbronchial needle aspiration (TBNA) of small lesions or lymph nodes in the lung may result in nondiagnostic tissue samples. We demonstrate the integration of an optical coherence tomography (OCT) probe into a 19-gauge flexible needle for lung tissue aspiration. This probe allows simultaneous visualization and aspiration of the tissue. By eliminating the need for insertion and withdrawal of a separate imaging probe, this integrated design minimizes the risk of dislodging the needle from the lesion prior to aspiration and may facilitate more accurate placement of the needle. Results from in situ imaging in a sheep lung show clear distinction between solid tissue and two typical constituents of nondiagnostic samples (adipose and lung parenchyma). Clinical translation of this OCT-guided aspiration needle holds promise for improving the diagnostic yield of TBNA.

Antibiotic research featured by the NHMRC

4 October 2017:

With only two new antibiotic classes being discovered and developed in the last 50 years, Professor Andrew Abell, CNBP Chief Investigator and his team at the University of Adelaide have been featured on the NHMRC website as one of the ‘ten best’ research stories of the year.

Prof Abell and team are going back to the fundamentals of chemical science in an attempt to develop a new class of antibiotics.

Motivated by a desire to understand the molecular basis of key biological processes, Professor Abell is exploring small molecules that selectively bind to bacterial proteins, as a potential mechanism for limiting bacterial survival.

Read the full story of Prof Abell’s antibiotic focused research here!

New med-tech zinc sensor developed

29 September 2017:

A new zinc sensor has been developed by CNBP researchers, which will allow for a deeper understanding of the dynamic roles that metal ions play in regulating health and disease in the living body.

The research, published in the journal ACS Omega reports that the newly designed chemical sensor can detect and measure zinc levels in cells. It also has the functionality and portability to take continuous or repeated measurements within a single biological sample.

“This makes the sensor potentially suitable for use in future diagnostic tools that could open up entirely new windows into the body,” says lead author of the research Dr Sabrina Heng (pictured), Research Fellow at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), at the University of Adelaide.

Read more at PHYS.ORG.

New med-tech zinc sensor developed

27 September 2017:

A new zinc sensor has been developed and reported by CNBP researchers, which will allow for a deeper understanding of the dynamic roles that metal ions play in regulating health and disease in the living body.

The research, published in the journal ‘ACS Omega’ reports that the newly designed chemical sensor can detect and measure zinc levels in cells. It also has the functionality and portability to take continuous or repeated measurements within a single biological sample.

“This makes the sensor potentially suitable for use in future diagnostic tools that could open up entirely new windows into the body,” says lead author of the research Dr Sabrina Heng (pictured), Research Fellow at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), at the University of Adelaide.

Read the full CNBP media release here and the publication here.

Journal: ACS Omega.

Publication title: A Rationally Designed Probe for Reversible Sensing of Zinc and Application in Endothelial Cells.

Authors: Sabrina Heng, Philipp Reineck, Achini K. Vidanapathirana, Benjamin J. Pullen, Daniel W. Drumm, Lesley J. Ritter, Nisha Schwarz, Claudine S. Bonder, Peter J. Psaltis, Jeremy G. Thompson, Brant C. Gibson , Stephen J. Nicholls, and Andrew D. Abell.

Abstract: Biologically compatible fluorescent ion sensors, particularly those that are reversible, represent a key tool for answering a range of fundamental biological questions. We report a rationally designed probe with a 6′-fluoro spiropyran scaffold (5) for the reversible sensing of zinc (Zn2+) in cells. The 6′-fluoro substituent overcomes several limitations normally associated with spiropyran-based sensors to provide an improved signal-to-background ratio and faster photoswitching times in aqueous solution. In vitro studies were performed with 5 and the 6′-nitro analogues (6) in HEK 293 and endothelial cells. The new spiropyran (5) can detect exogenous Zn2+ inside both cell types and without affecting the proliferation of endothelial cells. Studies were also performed on dying HEK 293 cells, with results demonstrating the ability of the key compound to detect endogenous Zn2+ efflux from cells undergoing apoptosis. Biocompatibility and photoswitching of 5 were demonstrated within endothelial cells but not with 6, suggesting the future applicability of sensor 5 to study intracellular Zn2+ efflux in these systems.

Children’s University Regional Lecture Series

17 September 2017:

Georgina Sylvia, CNBP researcher, was recently involved in two outreach events organised as part of the Children’s University Regional Lecture Series, which aims to stimulate interest in Science, Technology, Engineering and Mathematics (STEM subjects) for school children in Years 6-9.

At the first event at Renmark, she presented exciting chemistry demonstrations to year 7 and 8 students from the local community at the McCormick Centre for the Environment. The students were engaged in groups of 25 and encouraged to participate in the experiments and to ask and discuss science related queries.

The best quote of the day heard by Georgina – “Chemistry is awesome!”

The second outreach event was held at ‘Riverland Field Days’, 15-16th September, 2017. This community event is held annually “showcasing horticultural, agricultural and general farming products and services along with many general exhibitors.”

Children’s University, as a part of the Regional Lecture Series, set up a stall where Georgina and other researchers demonstrated and engaged kids in activities such as Engineering (building catapults from popsicle sticks), Chemistry (Slime making) and Biology (an aroma-sensory panel activity).

Feedback from Georgina – “The best part of this event was encouraging parents and caregivers to get involved in the activities with their kids, and to learn things together. Another great experience for me was encouraging a little girl to get involved in the catapult-making engineering activity, and seeing her so excited to participate!”

Below – Georgina (second right) at the Field Days event.

Concordia students visit CNBP labs

14 September 2017:

Eighty Concordia College students with an interest in STEM undertook a series of educational tours at CNBP laboratories at the University of Adelaide—forty students visiting Wednesday 6th September and a further forty students visiting Wednesday 13th September, 2017.

The students were hosted by a number of CNBP researchers, undertaking laboratory tours in both the Braggs and Health and Medical Sciences buildings.

As well as getting an introduction to CNBP and biophotonic related science, the students were shown a range of CNBP activity and work-spaces. This included demonstrations of advanced needle probes and optical imaging systems, hands-on demonstrations of near-infrared light scanners, use of a 3D metal printer and tours of the Centre’s glass and optical fibre fabrication facilities, as well as tours of the  embryology laboratory where embryo culture and cryopreservation techniques were also able to be shown.

Emily Johnson, Middle Years Programme Coordinator from Concordia College noted, “All of the students (and teachers) really enjoyed the sessions. They came back quite buzzing and extremely interested in what they saw.”

Feedback from the CNBP researchers was also extremely positive with many noting the excellent questions posed by the students during the lab tour demonstrations and activity.

First reversible ‘turn-off’ sensor for Glutathione

6 September 2017:

The first reversible ‘turn-off’ sensor for Glutathione has been reported by CNBP researchers in a paper published in the science journal Biosensors.

The paper is accessible online (open access).

Dr Sabrina Heng notes:

γ-Glutamyl-cysteinyl-glycine (GSH) plays a critical role in maintaining redox homeostasis in biological systems and a decrease in its cellular levels is associated with disease. Many diseases including Parkinson’s, cancer, heart diseases and Alzheimer’s are indicated by a decrease in GSH levels. In this case, a ‘turn on’ sensor would result in reduced fluorescence relative to healthy cells. An important advance would come from the development of a sensor that is measurably turned off by GSH and back on by a lower level of GSH. This would then provide an opportunity to sense reduced GSH levels during the onset of important diseases.

With that in mind we have rationally designed, to the best of our knowledge, the first reversible, reaction-based ‘turn-off’ probe that is suitable for sensing decreasing levels of GSH, a situation known to occur at the onset of various diseases.  We have demonstrated that the sensor can be used to detect changes of intracellular GSH in live HEK 293 cells to provide a potentially regenerable sensor for monitoring lower levels of intracellular GSH as associated with the onset of important diseases.

Journal: Biosensors.

Publication title: A Rationally Designed Reversible ‘Turn-Off’ Sensor for Glutathione.

Authors: Sabrina Heng (pictured), Xiaozhou Zhang, Jinxin Pei and Andrew D. Abell.

Abstract: γ-Glutamyl-cysteinyl-glycine (GSH) plays a critical role in maintaining redox homeostasis in biological systems and a decrease in its cellular levels is associated with diseases. Existing fluorescence-based chemosensors for GSH acts as irreversible reaction-based probes that exhibit a maximum fluorescence (‘turn-on’) once the reaction is complete, regardless of the actual concentration of GSH. A reversible, reaction-based ‘turn-off’ probe (1) is reported here to sense the decreasing levels of GSH, a situation known to occur at the onset of various diseases. The more fluorescent merocyanine (MC) isomer of 1 exists in aqueous solution and this reacts with GSH to induce formation of the ring-closed spiropyran (SP) isomer, with a measurable decrease in absorbance and fluorescence (‘turn-off’). Sensor 1 has good aqueous solubility and shows an excellent selectivity for GSH over other biologically relevant metal ions and aminothiol analytes. The sensor permeates HEK 293 cells and an increase in fluorescence is observed on adding buthionine sulfoximine, an inhibitor of GSH synthesis.

Charge transfer in helical peptides

1 September 2017:

Understanding the electronic properties inherent to peptides is crucial for controlling charge transfer, and precursory to the design and fabrication of bio-inspired next generation electronic components.

However, to achieve this objective one must first be able to predict and control the associated charge transfer mechanisms.

Here CNBP researchers demonstrate for the first time a controllable mechanistic transition in peptides resulting directly from the introduction of a side-bridge.

Journal: RSC Advances.

Publication title: A controllable mechanistic transition of charge transfer in helical peptides: from hopping to superexchange.

Authors: Jingxian Yu (pictured), John R. Horsley and Andrew D. Abell.

For more information, access the paper here.

School tour of Braggs labs

31 August 2017:

Caritas College students visiting the University of Adelaide for a ‘science day’ were shown around laboratory spaces in the Braggs Building by CNBP PHD students Kathryn Palasis (pictured) and Georgina Sylvia.

The 23 Year 9 school students were given a tour through a synthetic chemistry lab and then spoke with both CNBP researchers about the work being done and their journeys through University. This was followed by a further tour through a fibre-optics laboratory.

According to Kathryn, “The students seemed engaged and interested, particularly with the fibre-optics tour. And feedback from Amy (who organised the day) was that the students enjoyed it and that the teachers were very appreciative. Personally I spoke to a girl who said she was interested in studying science at university which was very pleasing to hear, and hopefully we encouraged others to see it as an appealing career path as well.”

New technique to aid IVF embryo selection

28 August 2017:

Researchers at the ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP) have successfully developed an advanced new imaging technique, which can help assess the quality of early-stage embryos.

The research, reported in the journal ‘Human Reproduction’ has the potential to significantly benefit the IVF industry of the future, improving assisted reproduction outcomes for women.

“We use a special type of imaging to show differences in the metabolism and chemical make-up of embryos before they’ve been implanted,” says lead author Dr Mel Sutton-McDowall (pictured).

“This technique can give us an objective measure of which embryo to choose as part of the IVF process.”

This ‘hyperspectral imaging’ measures light that cells naturally produce during their normal activities. The light or ‘autoflorescence’ produced changes according to the chemical reactions or metabolism going on in the cell.

Being able to measure embryo metabolism is viewed by many researchers as one of the most important factors as to whether a particular IVF program will be successful.

However, says Dr Sutton-McDowall, fertility specialists take a largely subjective approach in deciding which embryos should be used.

“Pre-implantation screening of embryos generally takes place under a normal optical microscope. Although it’s quite easy to discern poor embryos (due to differences in uniformity), it is far harder for the clinician to determine objectively, the viability of the other embryos,” she says.

“The challenge is how to choose the single healthiest embryo out of this group to maximise the chances of pregnancy.”

Dr Sutton-McDowall sees the use of hyperspectral imaging as a new tool that can be combined with other diagnostic methods to provide a more accurate and objective embryo viability assessment.

“The benefit of hyperspectral imaging is that it can capture information-rich content of inspected objects. It analyses every pixel in an image for its light intensity at differing wavelengths,” she says

“This lets us drill down and analyse the hyperspectral signature of each individual embryo, looking for known or anomalous characteristics. It lets us discriminate between embryos, but also measuring metabolic differences within individual embryos. We predict that embryos that have cells with homogeneous (uniform) metabolic profiles are the healthier ones.”

To date, this imaging technology has only been tested on cattle embryos but Dr Sutton-McDowall notes that the technique is extremely promising.

“It offers benefits of being a non-invasive imaging approach that provides real-time information to the clinician,” she says.

The paper is accessible online.

Journal: Human Reproduction.

Publication title: Hyperspectral microscopy can detect metabolic heterogeneity within bovine post-compaction embryos incubated under two oxygen concentrations (7% versus 20%).

Authors: Melanie L. Sutton-McDowall, Martin Gosnell, Ayad G. Anwer, Melissa White, Malcolm Purdey, Andrew D. Abell, Ewa M. Goldys, Jeremy G. Thompson.

Abstract: 

STUDY QUESTION
Can we separate embryos cultured under either 7% or 20% oxygen atmospheres by measuring their metabolic heterogeneity?

SUMMARY ANSWER
Metabolic heterogeneity and changes in metabolic profiles in morula exposed to two different oxygen concentrations were not detectable using traditional fluorophore and two-channel autofluorescence but were detectable using hyperspectral microscopy.

WHAT IS KNOWN ALREADY
Increased genetic and morphological blastomere heterogeneity is associated with compromised developmental competence of embryos and currently forms the basis for embryo scoring within the clinic. However, there remains uncertainty over the accuracy of current techniques, such as PGS and time-lapse microscopy, to predict subsequent pregnancy establishment.

STUDY DESIGN, SIZE, DURATION
The impact of two oxygen concentrations (7% = optimal and 20% = stressed) during post-fertilisation embryo culture was assessed. Cattle embryos were exposed to the different oxygen concentrations for 8 days (D8; embryo developmental competence) or 5 days (D5; metabolism measurements). Between 3 and 4 experimental replicates were performed, with 40–50 embryos per replicate used for the developmental competency experiment, 10–20 embryos per replicate for the fluorophore and two-channel autofluorescence experiments and a total of 21–22 embryos used for the hyperspectral microscopy study.

PARTICIPANTS/MATERIALS, SETTING, METHODS
In-vitro produced (IVP) cattle embryos were utilised for this study. Post-fertilisation, embryos were exposed to 7% or 20% oxygen. To determine impact of oxygen concentrations on embryo viability, blastocyst development was assessed on D8. On D5, metabolic heterogeneity was assessed in morula (on-time) embryos using fluorophores probes (active mitochondria, hydrogen peroxide and reduced glutathione), two-channel autofluorescence (FAD and NAD(P)H) and 18-channel hyperspectral microscopy.

MAIN RESULTS AND THE ROLE OF CHANCE
Exposure to 20% oxygen following fertilisation significantly reduced total blastocyst, expanded and hatched blastocyst rates by 1.4-, 1.9- and 2.8-fold, respectively, compared to 7% oxygen (P < 0.05), demonstrating that atmospheric oxygen was a viable model for studying mild metabolic stress. The metabolic profiles of D5 embryos was determined and although metabolic heterogeneity was evident within the cleavage stage (i.e. arrested) embryos exposed to fluorophores, there were no detectable difference in fluorescence intensity and pattern localisation in morula exposed to the two different oxygen concentrations (P > 0.05). While there were no significant differences in two-channel autofluorescent profiles of morula exposed to 7% and 20% oxygen (main effect, P > 0.05), morula that subsequently progressed to the blastocyst stage had significantly higher levels of FAD and NAD(P)H fluorescence compared to arrested morula (P < 0.05), with no change in the redox ratio. Hyperspectral autofluorescence imaging (in 18-spectral channels) of the D5 morula revealed highly significant differences in four features of the metabolic profiles of morula exposed to the two different oxygen concentrations (P < 0.001). These four features were weighted and their linear combination revealed clear discrimination between the two treatment groups.

LIMITATIONS, REASONS FOR CAUTION
Metabolic profiles were assessed at a single time point (morula), and as such further investigation is required to determine if differences in hyperspectral signatures can be detected in pre-compaction embryos and oocytes, using both cattle and subsequently human models. Furthermore, embryo transfers should be performed to determine the relationship between metabolic profiles and pregnancy success.

WIDER IMPLICATIONS OF THE FINDINGS
Advanced autofluorescence imaging techniques, such as hyperspectral microscopy, may provide clinics with additional tools to improve the assessment of embryos prior to transfer.