Integrated microfluidic platform with MEMS cantilever for the early detection of prostate cancer using dry mass sensing

Prostate cancer is the most prevalent cancer in men. In the UK alone, more than 40'000 cases are diagnosed every year (www.nhs.uk). The current accepted clinical gold standard for the diagnosis of prostate cancer is the measure of the prostate-specific antigen (PSA) levels in blood. However, it is now accepted that PSA test are unreliable and can lead to over-diagnosis. These false-positive results mean that many men are subjected to invasive and painful biopsies for no reason. Our pro-ject aims to address these limitations through the development of a minimally invasive, low-cost biosensing platform to detect PCA3, a promising urinary diagnosis biomarker for prostate cancer. In order to provide a viable alternative to ultra-sensitive, yet more complex and time-consuming assays, our platform should be capable of detecting, within 15 minutes, PCA3 down to concentra-tions of 1 ng/mL in urine.

This goal will be achieved through the implementation of a simple and novel concept to enable high-resolution measurement, using ultra-sensitive mechanical sensors integrated in microfluidic devices. The concept of measurement air pockets, proposed here for the first time, will permit the capture of the analyte molecules in the liquid phase and their measurement in the gas phase; through the introduction of air pockets as measurement chambers. The measurement of liquid borne analytes in air will minimize viscous damping losses and thereby enable high-resolution, high-sensitivity measurement.

In order to facilitate the deployment of the platform in clinical settings, we will test it using clinical samples from the early development stage and we will ensure that it can be fabricated using ac-cepted manufacturing methods. After a proof-of-principle device has been demonstrated we will seek further funding, in collaboration with prostate cancer clinicians, to evaluate the platform in clin-ical settings. It is noted that the platform could be adapted for the diagnosis of other conditions and that the simple concept proposed here could be applied to other sensor for a range of applications including environmental monitoring and food safety.

The proposed project will ultimately achieve its main impact by enabling the use of ultra-sensitive MEMS flexural devices to measure and detect liquid borne analytes while retaining high measure-ment resolution through measurements in air pockets. These low-cost sensors, deployed at the point-of-care could transform healthcare systems around the world and have positive impact on the life of millions of patients. Indeed, these low-cost sensors will improve the patients quality of life by enabling earlier treatment, reducing stress and time spent at the practitioners/clinic. Cur-rently, prostate cancer is diagnosed by measuring the level of prostate-specific antigen (PSA) in blood. However, it is now accepted that PSA test are not reliable and can lead to over-diagnosis and the NHS recommends the development of other tests to diagnose prostate cancer. Our project addresses this issue through the development of a biosensing platform to detect PCA3, a long noncoding RNA (lncRNA), which has been identified as a promising new biomarker for pros-tate cancer. The smooth implementation of the project will be ensured by careful planning and management, including the consideration of ethical and regulatory matters. The development of such sensors that could also help reduce drastically healthcare costs is encouraged by the NHS.

The project is also designed to maximise the impact for UK industries as the integrated biosens-ing platforms proposed will be developed using a combination of accepted technologies compatible or easily transferable to medium scale manufacturing. We will use among others microfabrication foundries and moulding processes for the fabrication of the platform. Potential UK beneficiaries in-clude BAE system, through its Advanced Technology Centre that offers a comprehensive capability in MEMS and Barkley Plastics. Furthermore, the PI will benefit from an extensive network through his department WMG that has collaborated with over 1200 SMEs since 2007 and through his insti-tute, the Institute of Digital Healthcare (IDH), an institute specialised in translating healthcare re-search, for industrial engagement.

Academics from a range of disciplines will also benefit from a variety of advances that reflect the interdisciplinary nature of the project. In particular, the project offer the principal investigator a unique opportunity to develop a program that will give him the opportunity to build up the group and the network he needs to maximise the impact of his research.