Silva - Sensors and Biosensors, DNA based biosensors, protein based biosensors, point-of-care biosensors, antifouling coatings, drug delivery systems, nanotechnology
La Sense Group
Dr Moraes Silva’s research group, called La Sense Research Group, is highly interdisciplinary and strongly focuses on translational research. Their research aims to build new smart materials and interfaces for application in point-of-use sensors and biosensors to detect molecules of biological, medical, and environmental interest. Some of the group’s activities involve the design, engineering, and characterization of new electrochemical sensor materials. A major goal is to develop biosensors that can detect multiple biomolecules simultaneously, directly where and when the measurement needs to be done without sample pretreatment. Currently, a variety of projects are underway that focus on the development of biomolecular sensors for disease diagnostics. The group also works closely with key industry partners in the biosensors and diagnostic fields, creating a pathway to the translation of new technologies.
Research areas
Liquid biopsy for cancer monitoring
Detection of circulating microRNAS Blood-based liquid biopsy cancer biomarkers are a promising class of minimally invasive diagnostics for the early detection and surveillance of cancer. Current methodologies rely upon an intravenous blood draw and then extensive sample processing and testing in a specialised laboratory setting. We are developing a revolutionizing low-cost reagent-less, electrochemical biosensor compatible to a point-of-care setting for direct detection of several cancer biomarkers in a finger-prick volume of human blood. This is expected to provide significant benefits for the patients, especially in remote locations, enabling increased access to point-of-care devices for the early diagnosis of cancer and surveillance to track treatment efficacies.
The proposed methodology relies on an innovative electrochemical sensor designed for detection of cancer associated nucleic acids in complex biospecimens including blood. The sensor consists of a redox-reporter-modified nucleic acid probe anchored to a disposable screen-printed electrode. The sensor is a signal switchoff type of system. When the target nucleic acid binds (hybridises) to the recognition probe, the efficacy with which the attached redox-reporter can transfer electrons to the electrode surface is diminished and this reduction in signal can be measured (Figure 1). This class of biosensors targets detection of microRNAs (miRNAs) in blood of cancer patients. miRNAs are stable circulating blood biomarkers that are often overexpressed in a tissue or cancer type specific manner and released into circulating blood. As a paradigm for testing a miRNA biosensor we are targeting a known miRNA biomarker overexpressed in many neuroendocrine tumours (NETs) – miR-375. Our recent study showed that miR-375 could be used as a surveillance biomarker in Merkel cell carcinoma (MCC) patients, a highly aggressive skin cancer with neuroendocrine features. Detection of tumor associated antigens Abnormal O-glycans expressed at the surface of cancer cells consist of glycolipids(Lewis a, Lewis x and Forssman antigens) and membrane-tethered N-acetyl glactosamine (O-GalNAc) glycoproteins (T and Tn anti-gen). In particular, Tn antigen (α-O-GalNAcSer/Thr) is expressed by more than 85% of human carcinomas and usually absent in healthy tissues. This antigen has been correlated with cancer progression and poor prognosis. A key point about Tn antigen is that it can be detected in accessible bodily fluids such as serum and blood.
Using a rapid self-assembly sensing interface amenable to methods of mass production, we demonstrated the ability to detect and quantify the Tn antigen (α-O-GalNAcSer/Thr) in a small volume of blood, using a test format strip reminiscent of a blood glucose test. The detection of Tn antigen at picomolar levels could be achieved through a new transduction mechanism based on the impact of Tn antigen interactions on the molecular dynamic motion of a lectin cross-linked lubricin antifouling brush. In tests performed on retrospective blood plasma samples from patients presenting three different tumor types, differentiation between healthy and diseased patients was achieved, highlighting the clinical potential for cancer monitoring.
Chemical contaminated water: biosensors for rapid, on-the-spot detection
Detection of forever chemicals
We are developing a versatile biosensor system for rapid onsite detection and monitoring of toxic per- and poly-fluoroalkyl substances (PFAS) in contaminated waterways. PFAS are also known as the ‘forever chemicals’ and have become a major environmental pollutant that threatens human and ecological health; in Australia PFAS contamination is prevalent in both urban and rural areas, and all Australians are expected to have detectable levels of toxic PFAS in their blood. Current conventional PFAS detection methods rely on sample collection and transport to a centralized laboratory, which is expensive and time-consuming. Thus, there is a need for low-cost portable sensors for the on-spot monitoring of PFAS. In order to achieve specific molecular recognition for PFAS detection, we employ protein-based surface chemistries for specifically recognizing the target PFAS compounds.
Development of antifouling coatings
Detection of forever chemicals
Glucose meters are a great example of the impact that electrochemical biosensors, capable of functioning in whole blood, can have on the management of diseases. However, the success of these life-changing devices has not yet been expanded to the detection of many other relevant biomarkers. This is due to the issue of the nonspecific adsorption of unwanted biomolecules such as proteins or even whole cells on electrode surfaces, which leads to electrode fouling. Fouling blocks electron transfer pathways and eventually leads to sensor response loss. The issue of biosensor fouling for the detection of glucose was solved because glucose is presented in high concentrations in blood and is a small molecule that can be filtered by using membranes permeable for glucose but stop other larger biomolecules from reaching the electrode. Nevertheless, a greater number of clinically appropriate biomarkers are the same size as the fouling species, for which semi-permeable membranes cannot be applied. Hence, one of the biggest obstacles to electrochemically detecting proteins in biological fluids remains the fouling of the electrode surface. Electrochemical biosensors that use DNA, antibodies, or other proteins as recognition elements, so-called affinity-based biosensors, offer a potential alternative for inexpensive, disposable, and sensitive multiplexed point-of-care diagnostics for home healthcare. An abundance of surface chemistries and assays reported in the literature have been successfully employed for affinity-based electrochemical biosensors. However, commercialization of such technology for clinical diagnostics has been hindered by their inability to maintain sensing functionality when exposed to biological fluids such as plasma or blood. This loss of functionality is also a result of the nonspecific adsorption of unwanted biomolecules on the electrode surfaces.
To overcome these issues, we have developed an antifouling coating technology based on lubricin, a glycoprotein commonly found on the joints’ biological fluid and covering the cartilage surface in mammalian articular joints, that resulted in more stable and robust electrochemical sensors capable of efficiently functioning when challenged in complex samples such as highconcentration protein solutions, saliva, and even unprocessed whole blood.
