Tag Archives: Guozhen Liu

Cell surface sensors could advance precision medicine

1 October 2019:

Researchers have found a way to identify multiple cell signalling proteins using a single cell rather than the billions of cells used previously.

The new measurement technology, developed by researchers at the ARC Centre of Excellence for Nanoscale Biophotonics, brings precision medicine a step closer.

“Cells secrete various messenger molecules, such as cytokines. They may indicate the presence of a disease or act as a driver of key therapeutic effects,” says Dr Guozhen Liu, lead author of paper detailing the technology.

The method, termed OnCELISA, uses antibodies attached on specially engineered cell surfaces to capture cytokine molecules before they have a chance to disperse away from the cell.

The secreted messenger proteins such as cytokines are reported, at the single cell level, by using fluorescent magnetic nanoparticles.

Cytokines secreted from cells play a critical role in controlling many physiological functions, including immunity, inflammation, response to cancer, and tissue repair.

 

The image represents our sensor during the process of detecting cytokine molecules being secreted from cells. The sensor is represented by a pair of Y-shaped antibodies, the capture antibody (purple stem) and the detection antibody (pink stem).

The OnCELISA system can be used for ultrasensitive monitoring of cytokine release by individual cells, and it can also help discover cell populations with therapeutic value.

“The ability to identify and select cell populations based on their cytokine release is particularly valuable in commercial cell technologies and it can help develop unique products, such as future non-opioid pain relief” says Dr Liu.

“Importantly, our design uses commercially available reagents only, so it can be easily reproduced by others,” she adds.

While the published work focuses on specific proinflammatory cytokines IL-6 and IL-1β, the method is potentially suitable for a broad range of other secreted proteins and cell types.

The new technique represents an advance on traditional methods such as the enzyme-linked immunosorbent assays (ELISA) that detect average levels of secreted molecules from cell ensembles.

The OnCELISA takes the ELISA approach to its absolute extreme, by detecting cytokines on the surface of individual, single live cells.

The publication has been reported by prestigious iScience journal and can be found at https://www.sciencedirect.com/science/article/pii/S2589004219303578.

Journal: iScience

Publication Title: A Nanoparticle-Based Affinity Sensor that Identifies and Selects Highly Cytokine-Secreting Cells

Authors: Guozhen Liu; Christina Bursill; Siân P.Cartland; Ayad G.Anwer; Lindsay M.Parker; Kaixin Zhang; Shilun Feng; Meng He; David W.Inglis; Mary M.Kavurma; Mark R.Hutchinson; Ewa M.Goldys

Summary: We developed a universal method termed OnCELISA to detect cytokine secretion from individual cells by applying a capture technology on the cell membrane. OnCELISA uses fluorescent magnetic nanoparticles as assay reporters that enable detection on a single-cell level in microscopy and flow cytometry and fluorimetry in cell ensembles. This system is flexible and can be modified to detect different cytokines from a broad range of cytokine-secreting cells. Using OnCELISA we have been able to select and sort highly cytokine-secreting cells and identify cytokine-secreting expression profiles of different cell populations in vitro and ex vivo. We show that this system can be used for ultrasensitive monitoring of cytokines in the complex biological environment of atherosclerosis that contains multiple cell types. The ability to identify and select cell populations based on their cytokine expression characteristics is valuable in a host of applications that require the monitoring of disease progression.

Link: https://doi.org/10.1016/j.isci.2019.09.019

What is the potential for CRISPT/Cas Multiplex Biosensing?

29 May 2019:

Recent publication by CNBP PhD student Mr Yi Li and team at the University of New South Wales explores the challenges and opportunities of working with CRISPR /Cas for multiplex detection

Journal: Trends in Biotechnology

Publication TitleCRISPR/Cas Multiplexed Biosensing: A Challenge or an Insurmountable Obstacle?

Authors: Yi Li, Linyang Liu, Guozhen Liu

Abstract:  Performing multiplex detection is still an elusive goal for molecular diagnostics. CRISPR/Cas-based biosensing has demonstrated potential for multiplex detection. Instead of being an insurmountable obstacle, CRISPR/Cas multiplexed biosensing is a realistic challenge with some recent successful applications. Strategic considerations are required to fully explore its potential in multiplex diagnostics.

Key Words:

CRISPR/Cas; multiplex; biosensing; diagnostics; nucleic acid detection

 

Amperometric sensing device to detect cytokines

10 September 2018:

A new paper with CNBP co-authors Prof Mark Hutchinson, Prof Ewa Goldys and Dr Guozhen Liu demonstrates an amperometric sensing device based on graphene oxide (GO) and structure-switching aptamers for long-term detection of cytokines in a living organism.

Journal: ACS Applied Materials and Interfaces.

Publication title: Graphene Oxide Based Recyclable in Vivo Device for Amperometric Monitoring of Interferon-γ in Inflammatory Mice.

Authors: Chaomin Cao, Ronghua Jin, Hui Wei, Wenchao Yang, Ewa M. Goldys, Mark R. Hutchinson, Shiyu Liu, Xin Chen, Guangfu Yang, and Guozhen Liu.

Abstract: Cytokine sensing is challenging due to their typically low abundances in physiological conditions. Nanomaterial fabricated interfaces demonstrated unique advantages in ultrasensitive sensing. Here, we demonstrate an amperometric sensing device based on graphene oxide (GO) and structure-switching aptamers for long-term detection of cytokines in a living organism. The device incorporates a single layer of GO acting as a signal amplifier on glassy carbon electrodes. The hairpin aptamers specific to interferon-γ (IFN-γ), which were loaded with redox probes, are covalently attached to GO to serve as biorecognition moieties. IFN-γ was able to trigger the configuration change of aptamers while releasing the trapped redox probes to introduce the electrochemical signal. This in vivo device was capable of quantitatively and dynamically detecting IFN-γ down to 1.3 pg mL–1 secreted by immune cells in cell culture medium with no baseline drift even at a high concentration of other nonspecific proteins. The biocompatible devices were also implanted into subcutaneous tissue of enteritis mice, where they performed precise detection of IFN-γ over 48 h without using physical barriers or active drift correction algorithms. Moreover, the device could be reused even after multiple rounds of regeneration of the sensing interface.

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.

Aptasensors and cytokine detection

10 March 2018:

A new review paper summarising recent advances in aptamer-based biosensors with a specific focus on cytokine sensing has been published in the journal ‘Trends in Analytical Chemistry’. The paper includes CNBP coauthors Fuyuan Zhang, Ewa M.Goldys and Guozhen Liu (pictured).

Journal: Trends in Analytical Chemistry.

Publication title: Advances in Structure-Switching Aptasensing Towards Real Time Detection of Cytokines.

Authors: C. Cao, F. Zhang, E.M. Goldys, G. Liu.

Abstract: Structure-switching aptamer-based biosensors (aptasensors) provide a promising strategy for real-time or near real-time monitoring of analytes in vivo, owing to their reversibility, the versatility of methods available to engineer the aptamer switches, and the ability to tune their dynamic range. Monitoring cell-to-cell communication through cytokine secretions has enormous value in biology and medicine. However, cytokine detection is challenging due to the extremely dynamic, transient cytokine secretion process, and typically low abundances in physiological conditions. Here, we summarise recent advances in structure-switching signaling aptamer-based biosensing with specific focus on cytokine sensing. This Review begins with the survey of cytokine-specific aptamers followed by the designs of elegant sensing platforms based on structure-switching aptamers with different signal readouts such as optic, electrochemistry, and other types. We describe the strategies of signal amplification in aptasensors, and highlight future perspectives of aptasensors for real-time or near real-time detection of cytokines.

CNBP at ‘Science meets Policymakers’

8 August 2017:

CNBP was well represented at the STA ‘Science meets Policymakers’ event held in Canberra, August 8, 2017.

Researchers A/Prof Guozhen Liu, Dr Alf Garcia-Bennett, Dr Sanam Mustafa and Dr Hannah Brown all attended and heard a number of talks on topics ranging from ‘A Whole Government approach to Science Policy’, to ‘A Crash-course in STEM and Policy Making’ through to discussion on ‘Positive and Meaningful Contributions to Policy.’

A/Prof Guozhen Liu particularly enjoyed the ‘Working Round Table’ discussion. “We discussed the 2030 Strategic Plan for the Australian Innovation, Science and Research System, which will help shape future science activity in Australia. It was emphasized that Australia encourages both fundamental and applied research, and that research excellence is key.”

A/Prof Liu also noted the importance of effective communication between stakeholders. “Methods and approaches to drive effective and engaged connections between Universities, Government and Industry were topics that were explored and discussed in depth throughout the day.”

The ‘Science meets Policymakers’ event brought together researchers and practitioners from a range of science and technology disciplines, with policymakers from across government departments and agencies. Objectives included to make connections and to examine the intersection between the evidence base and actual policy development.

Nanotechnology meets bioengineering

29 June 2017:

The Fudan-UH-MQ Workshop on ‘Nanotechnology meets Bioengineering’ was well supported by CNBP researchers at Macquarie University,  Wed 28th June – Thu 29th June.

A joint workshop, organised within the framework of University wide trilateral collaboration between Fudan, Hamburg and Macquarie, the event aimed to enhance collaborations between all three universities as well as generate potential cotutelle PhD candidates.

CNBP researchers presenting at the workshop included:

Prof. Nicolle H. Packer (CNBP Chief Investigator, pictured)
Cellular glycosylation: opportunities for discovering new molecular targets.

A/Prof. Anwar Sunna (CNBP Associate Investigator)
A platform technology for the self assembly of functional materials.

A/Prof. Guozhen Liu (CNBP Associate Investigator)
Nanotools for in vivo cytokine monitoring in neuroscience.

Dr. Nicole Cordina (CNBP Research Fellow)
Functionalisation of fluorescent nanodiamonds for bio-imaging applications.

Below: Prof. Nicolle Packer presents her talk on glycans.

China visit by Centre researcher

16 May 2017:

On a recent trip to China, CNBP Research Fellow A/Prof Guozhen Liu undertook a number of visits and talks, discussing her advanced sensing, nano-particle and bio-imaging work. This included:

5 May-8 May: Attendance at the International Congress on Analytical Sciences 2017 (ICAS2017) at Kaikou, China. Here Guozhen gave an oral presentation with the title “Engineering reduced graphen oxides towards a label-free electrochemical immunosensor for detection of tumor necrosis factor-alpha.”

11 May: Guozhen gave an invited talk titled, “Nanotools for cytokine monitoring in neuroscience” at Prof Zhihong Zhang’s research team at Huazhong University of Science and Technology, Wuhan. Prof Zhang is one of CNBP’s Partner Investigators at HUST.

13-14 May: Guozhen provided a keynote speech, titled, “An optical fibre based ex-vivo device for detection of cytokines” at the 2nd International Congress on Biomedical Imaging and Signal Processing (ICBISP 2017) at Wuhan.

Below: A/Prof Guozhen Liu (right) visiting CNBP Partner Investigator Prof Zhihong Zhang.

 

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.

 

Nanoscale sensor detects disease

28 March 2017:

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

Leader of the project A/Prof Guozhen Liu (pictured) said the release of certain cytokines by the body is frequently symptomatic of a disease or health-related issue. “Monitoring cytokine secretions at the cellular and subcellular level has enormous value in our understanding of basic physiology and how the body is actually working.”

The research featured in the online publication Photonics.com.