Modern medicine has been tackling cancer-related problems for decades. Even though diagnosis and treatment methods have progressed significantly, cancer is still considered as one of the most deadly diseases in the world. Although there is no cure for cancer, detecting and treating the disease at early stages is crucial for patients’ survival. For example, when diagnosed at its earliest stage, all individuals with melanoma skin cancer survive for five years or more. When diagnosed late, only 1/4 women and 1/10 of men survive (Source: Cancer Research UK).
Our project is focusing on developing a patient-friendly device that will detect cancer at early stages. The idea is to combine an imperceptible micro-needle array with micro-electrode array technology to monitor electrical impedance of cancer tissue. Electrical impedance describes the relationship between current and voltage flowing through an electrical circuit. In simple terms it describes how well the system conducts electricity.
A number of studies have shown the significant contrast between electrical properties of benign and malignant tissues. The contrast is due to morphological differences between normal and cancer tissue. This method shows promise for detecting cancers that may have previously gone undetected. One potential application is a biopsy needle with electrical impedance sensor array that can provide localised and accurate characterisation of biological tissue at the needle tip. Our project investigates a potential application of 3D microelectrode arrays for cancer detection.
Comparison between healthy tissue and cancerous tissue
In May 2019, we had an opportunity to take part in the OpenPlant Biomaker Challenge to develop a low-cost biological sensor. This was an excellent opportunity to try out our idea. For the first phase of the challenge, we constructed a system that contained a two-pin electrode a 2x2-electrode array integrated into a recording circuit based on components provided by Biomaker. These probes were made from subdermal needles which are commonly used for nerve monitoring or stimulation.
Experimental probe design using subdermal needles
Our detection system is powered by a DC (direct current) signal. Impedance is a concept used for AC (alternating current) signal and resistance is the DC equivalent. For that reason, we could only measure electrical resistance or, its inverse, electrical conductivity. After constructing the hardware, we calibrated the electrodes and tested it on phantom tissue – an artificial biological systems that mimics electrical properties of normal and cancerous tissues. We were able to detect areas of increased conductivity that corresponded to phantom cancer.
Building hardware and testing on artificial tissue (below right)
We have now started the second phase of the challenge. Thanks to the follow-on funding of £2000, we are now targeting to construct an advanced detection system. Firstly, we will incorporate industry-designed 3D microelectrode arrays and run tests on phantom tissue containing both normal and cancerous tissue. It will enable us to measure spatial distribution of conductivity in a mixed sample. Another crucial milestone will be shifting from DC to AC signal processing. Biological tissues have an additional capacitive nature due to presence of thin lipid bilayer with leaky ion-channels. A capacitor ‘blocks’ DC current but not AC current flow. Hence, impedance measurements is the conventional way for characterisation of biological tissue.
The 3D micro-electrode array from Multi Channel SystemsTM
Finally, we want to investigate if microelectrode arrays can be used to detect changes not only in tissue structure but also in neuronal activities. One of the characteristics of the cancer microenvironment, which drives cancer development, is the altered activity of neurons surrounding the cancer lesion. We are interested in exploring the changes in neuronal activity as a potential biomarker for early stage cancer. By monitoring neuronal activity, we could potentially improve sensitivity and specificity of the device.
The development of an accurate detection method is associated with a number of challenges. Background noise, sensitivity, false positives, false negatives, and specificity are the prime challenges that we need to tackle to ensure that our product can be classified as a medical device for cancer diagnosis. There is an exciting journey ahead of us. At the end, we hope to deliver a form of self-test device available to people off the shelf at their local pharmacy.
By Marta Wylot and Saksham Sharma, University of Cambridge