Smart Personalized Medical Platform for Cancer Diseases

这项研究方案包括设计嵌入在芯片上器官系统中的新一代光学分子成像系统。成像系统的目标是实时测量神经递质浓度，以了解癌细胞对大脑神经网络的影响，以及商业化抗癌药物在治疗脑癌细胞方面的效率。我们提出的传感器的创新之处在于，它使用了嵌入高密度微流体微腔阵列中的功能化和选择性的超稳定纳米颗粒，从一侧成像癌细胞在脑组织中生长时的神经递质浓度分布，从另一侧研究抗癌药物的有效性。从技术角度来看，该传感器是基于微流控/电子/微电子、光学、MEMS技术和纳米颗粒在一个单一系统中的混合集成。我们特别感兴趣的是检测功能化的超稳定金纳米颗粒与神经递质特异性适配子的吸收位移的偏移。我们的目标是能够使用标准相机创造出一种分子成像传感器。因此，它相当于显微镜的电子透镜，能够检测分子活动。目前用光学透镜观察分子的唯一方法是添加荧光标记。这涉及到对原始溶液的修改和分辨率的损失，在大多数显微镜下，分辨率被限制在200纳米。我们提议开发的系统的目的是通过捕捉与纳米颗粒结合的适体来捕获分子，从而超过这一分辨率限制。这将改变分子的直径，从而改变吸收位移。因此，通过检测这种变化，可以确定神经递质浓度。我们的目标是在研究的这个阶段能够检测到至少两种神经递质(多巴胺和抗坏血酸)在纳米分子级别的浓度。我们还将复制5-羟色胺、β-氨基丁酸、乙酰胆碱和谷氨酸神经递质的过程。因此，我们将实现第一个用于神经递质的选择性金纳米颗粒的图像传感器。这种技术可以在神经科学之外得到更广泛的应用，例如在药物和水毒素的检测中。

This research proposal consists in the design of a new generation of an optical molecular imaging system embedded in an organ-on-chip system. The goal of the imaging system is to measure the neurotransmitter concentration in real time to understand the impact of cancer cells on the brain's neural network and the efficiency of commercialized anti-cancer drugs in the treatment of brain cancer cells. The sensor we are proposing is original in that it uses a functionalized and selective ultra-stable nanoparticle embedded in a high density microfluid micro-cavity array to image neurotransmitter concentration distribution when cancer cells grow in brain tissue from one side and from the other side ton investigate the efficiency of cancer drug. From a technological standpoint, the sensor is based on the hybrid integration of microfluidic/electronic/microelectronic, optic, MEMS technologies and nanoparticles in one single system. We are especially interested in detecting the offset of the absorption shift of the functionalized ultra-stable gold nanoparticles with aptamers specific to neurotransmitters. Our goal is to be able to create a molecular imaging sensor using standard cameras. As such, it is the equivalent of the electronic lens of a microscope being able to detect molecular activity. The only way to currently observe molecules with optic lenses is by adding fluorophore markers. This involves the modification of the original solution and the loss of resolution, which is limited to 200 nm in most microscopes. The purpose of the system we are proposing to develop is to exceed this resolution limit by capturing the molecules with aptamers tied to the nanoparticles. This will modify the diameter of the molecule and thus absorption shift. Therefore, by detecting this shift, the neurotransmitter concentration can be determined. Our goal is to be able to detect the concentrations of at least two neurotransmitters (dopamine and ascorbic acid) in the order of the nanomoles at this stage of the research. We will also replicate the process for the serotonin, ?-aminobutyric acid, acetylcholine and glutamate neurotransmitters. We will therefore implement the first image sensor from selective gold nanoparticles for neurotransmitters. Such technology could be more widely used, beyond neuroscience, for example in the detection of drugs and water toxins.