NETs Biomarker Capture Platform

Liquid biopsy the need for a universal biomarker sample preparation technology

NETs technology is a sample preparation platform with the potential to revolutionise the performance of liquid biopsy diagnostic assays. Liquid biopsy can eliminate the need to carry out invasive tissue biopsies for cancer detection and treatment monitoring, since samples such as blood that contain specific, tumour-associated biomarkers can be used instead.

Analysts estimate the market potential for liquid biopsy applications at billions of dollars annually1. However, what has been lacking until now is a universal capture technology that can provide upfront enrichment of target molecules from patient samples that can be applied to any of the disease-specific targets in a scalable, rapid and cost-effective method for utilisation in high throughput pathology laboratories. Current biomarker extraction methods are suitable for research laboratories, but are often complicated, labour intensive, time consuming and require specialised equipment such as ultracentrifugation.

NETs technology provides the liquid biopsy field with a universal capture technology to overcome these hurdles and to help make the promise of liquid biopsy a reality.

The NETs technology

The patented NETs technology consists of covalently linked multilayered three-dimensional matrices (referred to as Molecular NETs) comprising a range of biomarker capture molecules, linkers and spacers that can be varied for specific and sensitive analyte capture, enrichment, purification, detection and measurement from a biofluid sample.

Placement and spacing of the capture molecules, linker molecules and spacer molecules confer a characteristic topology on the Molecular NET surface, a characteristic density within each layer, and a characteristic porosity. The porosity is a result of the choice, and method of incorporation, of the component molecules. The pores allow for size exclusion functions of the NETs and the capture molecules provide affinity binding.

The NETs matrix can be applied to any solid surface (e.g. magnetic beads, dipsticks, ELISA plate wells, etc).

A scanning electron-micrograph of the surface of one of the Molecular NETs coated on a magnetic bead, along with a diagrammatic representation of the interacting molecular components is shown below

Electron micrograph of a Molecular Net (EXO-NET) coated on a magnetic bead, and a cartoon depicting the molecular composition of the matrix.

NETs is a transformational capture technology for liquid biopsy

NETs technology allows for fast, accurate and efficient capture and isolation of biomarker-containing targets such as cells, exosomes, or molecules (e.g. proteins, DNA, RNA), from the liquid biopsy sample. The technology is highly scalable and is compatible with existing automated testing systems making it ideal for high volume clinical laboratory applications.

The NETs matrix has the following features that make it a unique universal technology to facilitate the development of a range of liquid biopsy applications:

  • Customizable for use with any sample: serum, plasma, whole blood, saliva, urine.
  • Customizable to capture any target: it has been demonstrated to capture whole cells (eg, CTCs), exosomes, proteins, peptides, viruses, carbohydrates and nucleic acids.
  • Rapid: Time from sample to target capture by NETs in < 30 mins.
  • Combines two separation technologies for viruses and exosomes: size exclusion and affinity binding for improved yield.
  • Highly specific to the target: Low non-specific binding + Enhanced signal-to-noise.
  • Demonstrated sensitivity: Up to 1000x improved detection sensitivity over competitors.
  • Adaptable to most existing detection technologies: potential for integration with emerging analytical and diagnostic technologies (qPCR, ELISA, NGS, etc.).
  • Scalable – can be applied to mass screening strategies.

NETs allows a pathology laboratory to offer a wide range of diagnostic tests (beyond cancer liquid biopsies) using the same initial sample preparation method. This is unique to the NETs technology as it is highly customizable. Examples of diagnostic applications investigated using the technology include:

  • infectious disease (HIV, dengue, MRSA),
  • oncology (breast cancer, NSCLC),
  • genetic disorders, and
  • neurological disorders (Alzheimer’s disease).

Graphic below illustrates how NETs technology overcomes the current liquid biopsy sample preparation barriers to biomarker capture and can rapidly and specifically isolate a range of biomarkers for downstream analysis.

How NETs overcomes barriers to sample preparation in pathology testing