Early diagnosis is crucial for the treatment and cure of a range of pathologies including cancers. The challenge diagnosis is to quantify the level of biomarkers at very low concentrations. In the diagnostic devices focus area of the ACN, researchers are developing a range of biosensors that are capable of detecting ultralow concentrations of important cancer biomarkers. These biomarkers are all present in whole blood and are hence consistent with the idea of the liquid biopsy. The basis of these technologies are the development of nanomaterials that can both preconcentrate and detect the biomarker of interest combined with well-defined surface chemistry to ensure the sensor only detects the desired biomarker. Projects include detecting microRNA in whole blood at attomolar levels, detecting low levels of protein biomarkers such as prostate specific antigen and detecting heterogeneity in rare cancer cells. The technologies can be applied for both early detection and treatment efficacy.
Detecting microRNA as a cancer biomarker
MicroRNAs are post transcriptional gene regulator that are found directly from circulating blood. The levels of the many different microRNAs can be up or down regulated with a range of pathologies including cancer. The analytical challenge is these biomarkers must be detected in the picomolar to nanomolar range. We have developed the concept of nucleic acid modified gold coated magnetic nanoparticles (referred to as dispersible electrodes) that can capture and detect specific microRNA sequences in whole blood over a broad dynamic range of nanomolar down to 10 attomolar. This unprecedented performance sees this as a promising technology for detecting these important biomarkers.
Detecting single protein biomarkers
Sensors that can detect and count single molecules not only have the ultimate detection sensitivity but also can be calibration free. We are developing such a technology based on a nanopore. Our unique technology is referred to as a nanopore blockade sensor and is different to other nanopore sensors in that a magnetic nanoparticle captures the rare protein of interest, and brings it to the nanopore which is then blocked by the nanoparticle. The benefits of the nanopore blockade sensor is that is can detect ultralow levels of protein in whole blood, something not previously possible with conventional nanopores where proteins translocate through the nanopore.
The capture and release of rare cells
Understanding the heterogeneity of cancer cells is important in both understanding and treating cancer. With metastasis occurring via the circulating of rare cancer tumour cells in the blood stream, tools are needed for understanding the heterogeneity of these cells. We have developed a unique antibody modified surface for capturing these rare cancer cells that can then release individual cells without harm. In this way drug response of captured cells can be investigated before the release of cells that respond anomalously.