Abstract:
Ovarian cancer is the most deadly gynaecological disease that affects a quarter of a million women annually, resulting in over 140,000 deaths worldwide. Currently, detection of ovarian cancer requires time-consuming imaging techniques such as transvaginal ultrasound and MRI scans, which are generally only performed if it is already suspected that the disease is present. Although the blood sample CA-125 assay is the current most widely-employed test for ovarian cancer, it is far from ideal for providing a diagnostic conclusion by itself, especially at the early-stages of development of the disease. Also, the assay is known to generate both false negative and positive results, accordingly there is a general consensus in the medical community that there is an urgent need for disease detection based on alternative biomarkers, especially those that could be employed for assays at stages 1 and 2 in terms of disease progression. In our research on the detection of the disease, we are developing both a simple, low cost spectroscopic assay and, secondly, a detection system by biosensor configuration which could be employed for large scale screening of serum samples. Both systems are based on the sensing of the biomarker, lysophosphatidic acid (LPA), which has a sensitivity and specificity of over 90% for the disease, rendering it highly promising for use in testing for ovarian cancer. Successful detection of LPA has been achieved by HPLC-mass spectrometric methods this approach is obviously is not amenable to large scale screening. Our assays are based on the highly selective disruption of a protein complex composed of gelsolin and actin by LPA. The spectroscopic test involves the fluorescent detection of labelled actin removed by LPA present in serum with the gelsolinactin combination being attached to silica and magnetic nanoparticles. Analogous chemistry is being used to develop a high-throughput biosensor–based configuration with the protein complex being attached to the surface of an ultra-high frequency, SH-acoustic wave lithium niobate device. The latter is capable of direct operation in serum and in an anti-fouling condition.