University of Bath

Cancer diagnostic aptasensors using modified interdigitated electrodes

This Royal Society Mobility Award allows the partners at Bath and Malaysia to join forces to develop novel biosensors for prostate cancer diagnostics.

Prostate cancer (PCa) is the second most common form of malignancy among men. Prostate-specific antigen (PSA) is the main tumour biomarker used for screening and diagnosing prostate cancer. If the PSA levels in blood are higher than 4 ng/mL, further investigation is recommended.

80% of all diagnosed prostate cancer is found in men aged 65 and older. At this age and late diagnosis, standard cancer therapies have severe secondary effects on the patients and treatment is not as effective. Furthermore, there is both an economic and emotional impact on the patients and their families. The best way to control and improve mortality rate from PCa is to detect the disease at early stage, while it is localised and organ-confined.

Biosensors offer interesting cancer detection methods

Interdigitated electrode (IDE)-based capacitive biosensors offer label-free detection of biomolecule interactions. They are also known for their high sensitivity. IDE consists of a series of parallel electrodes connected and separated to alternating interlocked electrode by an insulator. This forms a set of interdigitated fingers. The IDE sensor's detection mechanism is based on the change in the dielectric constant. This is caused by binding target molecules to receptors (antibodies, DNA, proteins, and other bio-recognition elements) immobilised on the surface of the electrodes. Higher sensitivity can be achieved with:

  1. using IDE arrays as it increases the active area for the binding events
  2. small distances between the finger electrodes

But, smaller distances between the finger electrodes involve costly and time-consuming processes such as e-beam lithography. Alternatively, higher sensitivity can be achieved with deposition of nano-particles between the finger electrodes of an IDE. This shortens the distance between fingers. The modulation of potential from the substrate on the active sensing areas on the IDE sensors is achieved with the presence of a back-gate electrode. This results in amplifying the detection signal. By applying a small amplitude sinusoidal excitation signal, the IDE sensors can also be operated as electrochemical impedence sensors.

Using IDE-based sensors to detect prostate cancer

Our research collaboration aims to fabricate and characterise IDE-based sensors for low-concentration detection of PSA to diagnose prostate cancer using DNA aptameters as the recognition probes. Aptamers are synthetic DNA sequences that bind to an analyte with high affinity and specificity. They have the advantage of low cost (compared to antibodies), stability and ease of manipulation for the functionalisation of the IDEs. We will fabricate the device at UniMAP on silicon wafer substrates. We will use a standard lithography process to form the interdigitated fingers from conductive metal or heavily doped silicon. The metal oxide nanoparticles will then be deposited on the surface. We will functionalise the surface with DNA aptameters specific to PSA. We'll do this using a range of surface chemistries developed at UBath.

Finally, we will test the PSA detection under different buffer conditions and in spiked serum samples. We will validate the results with standard techniques. Then we will adapt the sensors to other biomarkers by using different aptamers. Array format will enable us to detect a panel of biomarkers for better cancer diagnosis. Our research visits between the two institutions will involve training research students and knowledge transfer.