The current research areas, methods and achievements of Professor Liu and her team are as follows:
1. Advanced biosensing techniques
1）Cytokine sensing
Cytokines are small cell signalling proteins that aid cell to cell communication in immune responses. Monitoring cell-to-cell communication through cytokine secretions provide significant insight into physiological processes and disease pathways, and the secreted cytokines can serve as biomarkers for various diseases.
2）Cortisol sensing
Cortisol is a hormone that is secreted from the adrenal glands located above the kidneys. Cortisol is the end product of the hypothalamic–pituitary–adrenal (HPA) axis, which is the main component of the human body’s adaptive system to maintain regulated physiological processes under changing environmental factors. It also plays an important role in homeostasis of the cardiovascular, immune, renal, skeletal and endocrine system. The most dominating effect on cortisol variation comes from psychological/emotional stress, which is why cortisol is popularly called the “stress-hormone".
3）Lactate sensing
Lactate is a key metabolite of the anaerobic metabolic pathway. When the energy demand by tissues cannot be met by aerobic respiration, an increase in lactate concentration will occur from the anaerobic metabolism. Without adequate clearance by liver and kidney, the accumulated concentration of lactic acid results in lactic acidosis. Therefore, lactate level in body is used as a key parameter in the clinical diagnostics for assessing patient health conditions like hemorrhage, respiratory failure, hepatic disease, sepsis and tissue hypoxia. The baseline lactate level in blood ranges from 0.5 to 1.5 mmol/l at rest but can rise up to 25 mmol/L during the intense exertion. We target to develop a sensitive biosensor for non-invasive continuous screening of lactate in body fluids.
4）Insulin sensing
Insulin is a major hormone produced in the pancreas that regulates glucose metabolism in the body. Elevated blood insulin is an incredibly common condition that is responsible for some of the most common health problems today. High insulin levels are a major cause of obesity, diabetes, cardiovascular disease and may also increase the risk of breast cancer and infertility. Insulin level is We are interested in developing accurate and non-invasive point-of-care devices for detection of insulin in saliva to help people with metabolic syndrome/prediabetes.
5）Glucose sensing
Diabetes mellitus is the most common endocrine disorder of carbohydrate metabolism. It is a major health problem worldwide. The prevalence of diabetes continues to increase. Monitoring of glucose levels has been established as a valuable tool in diabetes management. During the last 50 years, glucose biosensor technology including point-of-care devices, continuous glucose monitoring systems and noninvasive glucose monitoring systems has been significantly improved. However, there continues to be several challenges related to the achievement of accurate and reliable glucose monitoring. Further technical improvements in glucose biosensors, standardization of the analytical goals for their performance, and continuously assessing and training lay users are required. We are interested in developing reliable and non-invasive glucose monitoring systems for point-of-care testing.
6）MicroRNA sensing
MicroRNAs are small, highly conserved non-coding RNA molecules involved in the regulation of gene expression. Detailed knowledge of the microRNA pathways is essential for understanding their physiological role and the implications associated with dysfunction and dysregulation. MicroRNAs (especially circulating miRNAs and exosomal miRNAs) have been implicated in a number of diseases including a broad range of cancers, heart disease and neurological diseases. Consequently, microRNAs are intensely studied as candidates for diagnostic and prognostic biomarkers and predictors of drug response.
Our fundamental technology targets:
•High sensitivity and specificity
•Ultrasmall sample volumes
•Deployable devices
•Multiplex with spatial resolution
•In-vivo continuous monitoring
Our sensing approaches:
•Immunosensing
•Aptamer based biosensing
•CRISPR/Cas systems based biosensing
•Molecularly imprinted polymers based biosensing
Our signal readout platforms:
•Smartphone readout (fluorescence, colorimetry)
•Consumer electronics such as glucose meters (electrochemistry)
•Fluorescence or laser scanning microscopy
•Wireless/Clouds
We have developed a range of sensing platforms for detection of cancer biomarkers, hormones, and cell secreted products, such as cytokines, insulin, glucose, cortisol, HbA1c, botulinum neurotoxin type A, troponin-I and exosomes. These sensing platforms are universal, and can be re-purposed for detection of a spectrum of analytes.
2. Continuous molecular monitering
The design of a biosensor capable of continuously measuring specific molecules in vivo is difficult because such sensing schemes must meet the following requirements:
1) selective rejection of false signals that arise from interferences present in the complex environments found in vivo;
2) reagentless operation, without any exogenous reagents beyond those provided in situ by the organism;
3) continuous operation without any additional steps, such as separations, washing or incubation;
4) reversible response, reflecting physiologically varying target concentrations.
Biomolecular switches are one of the approaches used by nature to solve the problem of real-time molecular sensing in complex environments. These biomolecules undergo binding-induced changes in conformation or oligomerization state to transduce chemical information into specific signal outputs. There is a growing recognition that structure-switching aptasensing technology is a promising and versatile strategy for molecular monitoring of key analytes in vivo. We are interested in developing structure-switching molecule based biosensing platforms for continuous monitoring of a spectrum of analytes under physiological conditions. Specifically we are focusing on applying these real-time cytokine sensing platforms for continuous inflammation monitoring (CIM).
Publications:
C. Cao, et al., G. Liu*, Acta Biomater., 2020, 101, 372-383
S. Ni, et al., G. Liu*, Electrochimica Acta, 2020, 331, 136321
G. Liu*, et al., Microsys. Nanoeng., 2019, 35, 1-11
Cao, et al., G. Liu*, ACS Appl. Mater. Interfaces, 2018, 10 (39), 33078–33087
K. Ma, et al.,G. Liu*, ACS Sens., 2018, 3(2), 320-326
C. Cao, et al., G. Liu*, TrAC Trends Anal. Chem., 2018, 102, 379-396
G. Liu*, et al., Nanoscale, 2017, 9(15), 4934-4943
Collaborators:
Prof Xin Chen, Xi'an Jiaotong University, China
Prof Howard Young, National Institute of Health, USA
3. Intellignet nano-particles
This program aims to develop a suite of intelligent nanoparticles (iNPs) – novel interactive in vivo tools for neuroscience. With their sophisticated adaptive behaviors and context-dependent functions, the intelligent nanoparticles will sense key molecules in the brain in real-time, and respond by precise delivery of small molecules to functionally activated cells. This will make a critical difference in the leading neuroscience approach of chemogenetics where it will help unravel causal relationships between molecular events and high-level brain activity.
The iNPs will help solve key problems of chemical neuroreceptor control, by providing
(i) spatial selectivity in the presence of multiple unknown cell types;
(ii) ways to establish causation, by the capacity for in vivomonitoring of molecular processes in real time;
(iii) adaptive, conditional responses driven by molecules secreted by cells;
(iv) immunity to complex background interference.These technological barriers currently prevent and /or limit the determination of functional brain circuits underpinning physiology and behavior.
The iNPs will have broad impact beyond neuroscience. With their capacity for real time sensing and precise delivery in complex biological samples, they will address the challenges of the current molecular diagnostic technology. They will be able to selectively perform their actions in a functionally heterogeneous mixture of different cell types communicating via secreted products (signalling molecules, cytokines, exosomes etc). Such environments are highly relevant across the whole spectrum of the life sciences, including for the study of the immune system, for biomarker diagnostics, and in the rapidly advancing areas of commercial cell technologies and food safety.
Publications:
1. G. Liu*, et al., iScience, 2019, 20, 137-147.
2. K. Ma, G. Liu*, Nanomedicine, 2019, 14(9). 1-11
3. K. Wen, et al., G. Liu, H. Huang*, ACS Appl. Mater. Interfaces, 2019, 11, 19, 17884-17893
4. T. Jiang, et al., G. Liu, P. Zhang*, Anal. Chem., 2019, 91, 11, 6996-7000
5. K. Ma, et al.,G. Liu*, ACS Sens., 2018, 3(2), 320-326
6. G. Liu*, et al., Nanoscale, 2017, 9(15), 4934-4943
Collaborators:
Prof Hong Qiao, Sydney University
Prof Guojun Liu, ANSTO
Prof Pengfei Zhang, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Prof Hui Huang, University of Chinese Academy of Sciences
4. Microfludic paper-based Point-of-Care biosensing devices
Paper is biocompatible with DNA, RNA, proteins, and various clinical samples, favoring its use in diagnostics of biological samples. Paper-based diagnostic tools, such as lateral flow assays, dipstick assays, and microfluidic paper-based analytical devices (µPAD) are emerging as a promising lightweight, disposable and cost-effective format, especially for developing countries and Point-of-Care (POC) testing.
Smartphones are able to bring conventional biomedical tests from specialised laboratories to POC, due to their growing imaging capabilities and significant computing power (about 70% of a typical laptop). The mobile phone devices are capable of quantitative fluorimetric and colorimetric diagnostic assays. In principle, with minimal modifications and/or added hardware, smartphones are capable to carry out assay readouts of a wide variety of diagnostic applications.
We are targeting to development of paper based analytical devices with smartphone readouts, which are able to replace the currently widely used ELISA to realise the digital health management.
Publications:
1. Z. Luo, et al. G. Liu*, Angewandte Chemie International Edition, 2020, 59,1-7
2. L. Liu, D. Yang, G. Liu*, Biosens. Bioelectron., 2019, 136, 60-75
Collaborators:
Prof Bin Liu, Shenzhen University, China
Prof Margaret Morris, UNSW
A/Prof Wen Hu, UNSW
Prof Tony Jun Huang, Duke University, USA
Prof Zhaowei Zhang, Oil Crops Research Institute of the Chinese Academy of Agricultural Sciences, China
5. Wearable biosenors
Sweat contains a wealth of chemical information that could potentially indicate the body’s deeper biomolecular state. Wearable biosensors have received tremendous attention over the past decade owing to their great potential in predictive analytics and treatment toward personalized medicine. Unlike most reported wearable sensors that mainly track physical activities and vital signs, the new generation of wearable and flexible chemical biosensors enables real-time, continuous and fast detection of accessible biomarkers from the human body, and allows for the collection of large-scale information about the individual's dynamic health status at the molecular level. We target to develop wearable and flexible biosensors toward continuous and non-invasive molecular analysis in sweat, tears, saliva, interstitial fluid, blood, wound exudate as well as exhaled breath.
Collaborators:
Prof Kourosh Kalanta-zadeh, UNSW
Prof Nigel Lovell, UNSW
6. In vivo devices-brain chip
In vivo monitoring of physiology in real time using implanted electrochemical or optical devices or chips wirelessly communicating with personal electronic devices represents the next technology frontier. Being able to continuously read biochemical indicators of physiology would make it possible to realise novel medical interventions with close feedback between the physiological readout and drug delivery, thus effectively treating physiological dysregulation. The challenges with in vivo sensing include sensitivity (low level of analytes), selectivity (biological environment), delivery of readout signal coupled with low power operation, biocompatibility and minimisation of implant-induced foreign body response. We target to develop the implantable brain chip for continuous monitoring of neurochemicals to understand the neuroimmune interface.
Collaborators:
Prof Mark Hutchinson, University of Adelaide, Australia
Dr Michael Barrata, University of Colorado Boulder, USA
Prof Xin Chen, Xi'an Jiaotong University, China
Dr Howard Young, National Cancer Institute, NIH USA
7. Single cell Analysis
Cell selection technology
Cell-to-cell variation is a universal property of multi-cellular organisms, which contain diverse cell types characterized by different functions, morphologies, and gene expression profiles. It is important therefore to analyse them one at a time to determine these differences. Monitoring cell functions and cell-to-cell communication in the cellular environment has enormous implications for cell biology and regenerative medicine. Additionally, in detection of cell-based diseases, it is important to develop methods of extreme sensitivity down to single cells to gain the best ability for diagnosis, cell signaling, and monitoring of disease development and progression.
Publications:
1. G. Liu*, et al., iScience, 2019, 20, 137-147.
