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

前列腺癌是男性最常见的癌症。仅在英国，每年就有超过4万例确诊病例(www.nhs.uk)。目前公认的诊断前列腺癌的临床金标准是测量血液中的前列腺特异性抗原(PSA)水平。然而，现在人们普遍认为PSA检测是不可靠的，可能会导致过度诊断。这些假阳性结果意味着许多男性无缘无故地遭受侵入性和痛苦的活组织检查。我们的项目旨在通过开发一种微创、低成本的生物传感平台来检测PCA3，这是一种有前途的前列腺癌尿路诊断生物标志物，旨在解决这些局限性。为了提供一种可行的替代超敏感、但更复杂和耗时的分析方法，我们的平台应该能够在15分钟内检测到尿液中PCA3的浓度降至1 ng/mL。这一目标将通过实施一种简单而新颖的概念来实现，以实现高分辨率测量，使用集成在微流控设备中的超灵敏机械传感器。这里首次提出了测量气囊的概念，通过引入气囊作为测量室，可以捕获液相中的分析物分子，并在气相中测量它们。对空气中液态分析物的测量将最大限度地减少粘性阻尼损失，从而实现高分辨率、高灵敏度的测量。为了便于在临床环境中部署该平台，我们将使用早期开发阶段的临床样本对其进行测试，并确保可以使用公认的制造方法来制造它。在原理验证设备被证明后，我们将寻求与前列腺癌临床医生合作的进一步资金，以在临床环境中评估该平台。值得注意的是，该平台可用于其他情况的诊断，这里提出的简单概念可应用于其他传感器，用于包括环境监测和食品安全在内的各种应用。

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.