TERACELL: Integrated Microwave-to-Terahertz Sensors for label-free circulating tumour cell detection

TERACELL：集成微波到太赫兹传感器，用于无标记循环肿瘤细胞检测

基本信息

批准号：
EP/M001121/1
负责人：
Norbert Klein
金额：
$ 159.91万
依托单位：
Imperial College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FM001121%2F1
关键词：
TERACELL Integrated Microwave Terahertz Sensors

项目摘要

Label-free detection of circulating tumour cells (CTCs) is considered to be one of the holy grails of biosensing. CTCs are malignant cells shed into the bloodstream from a tumour, which have the potential to establish metastases. The separation and subsequent characterization of these cells is of vital importance for cancer diagnosis and development of personalized cancer therapies. Biochemical CTC separation methods have proven to be highly inefficient and, therefore, preventive screening by sole blood analysis is currently not reliable. Microwave-to-terahertz dielectric measurements were successfully used for the identification of cancer cells; their capability for tumour tissue imaging is clinically established as a viable alternative to X-rays and MRI. The frequency range from 10 GHz up to about 1 THz is extremely promising for the detection of single tumour cells. Due to the diminishing cell membrane polarization effects, the cell membrane becomes transparent, but cell scattering is still negligible, in contrast to that found in the visible and near/medium-infrared range. Due to the high electromagnetic absorption of water up to about 1 THz, electromagnetic resonators with high quality factors and highly concentrated electric field within a small integrated microfluidic reservoir (previously demonstrated by the team), which essentially contains one cell at a time, represent an ideal system for fast and accurate dielectric measurements. This is because the single cell lies within their natural liquid environment. In order to tackle the problem of extremely low abundance of CTCs in blood samples, we intend to combine microfluidic separation techniques with integrated microwave-to-terahertz resonators on one chip or as a multichip combination, aiming towards a lab-on-chip approach for clinical applications. In order to achieve this ambitious goal, within this three-year project, we suggest a multidisciplinary approach, based on the expertise of the associated members of Imperial's Centre for Terahertz Science and Engineering (made up of academics and researchers from the Depts. of Materials, Electrical and Electronic Engineering and Physics), along with selected groups from dedicated areas of Life Sciences (which includes cancer cell biology and cell biosensing), plus the expertise of oncologists from Imperial's Faculty of Medicine. A variety of tumour cell suspension of defined concentration based on whole blood, serum or water being derived from a murine model will be our gold standard approach for the generation of a database of dielectric properties of different types of tumour cells, for the optimization of different sensor chip approaches, and for the development of cell detection methods. As a key milestone, towards the end of the project, we will demonstrate CTC detection in human blood samples.As the main engineering challenge of this project, three different electromagnetic resonator approaches will be investigated, based on our previous work on silicon MEMS technology for nanolitre liquid measurements: dielectric resonators, photonic crystals and spoof plasmon-based metamaterials. Advanced micro- and nano-machining techniques like deep reactive ion etching, e-beam lithography and focussed ion-beam etching will be employed for the manufacturing of fully-integrated (sub-) THz resonator-microfluidic systems.On the way towards the grand challenge of CTC detection, we intend to investigate two potential applications, which may generate clinical impact on a shorter timescale: Label-free detection of leukaemia cells within a murine model and bladder cancer cell detection in human urine samples. In both cases, the expected cell abundance is much higher than in the case of CTC, but the methods of dielectric cell recognition are identical to CTC detection. Follow-up projects including clinical studies plus stronger involvement of industry are likely to be launched during the time-span of this project.

无标记的循环肿瘤细胞（CTC）被认为是生物传感的圣杯之一。 CTC是从肿瘤中流入血液中的恶性细胞，有可能建立转移酶。这些细胞的分离和后续表征对于个性化癌症疗法的癌症诊断和发展至关重要。事实证明，生化CTC分离方法已被证明高效，因此，通过唯一血液分析进行预防性筛查目前不可靠。微波到terahertz的介电测量成功用于鉴定癌细胞。它们的肿瘤组织成像能力在临床上被确定为X射线和MRI的可行替代品。从10 GHz到约1 THz的频率范围对于检测单个肿瘤细胞非常有前途。由于细胞膜极化的效应减少，细胞膜变得透明，但是与在可见的和接近/中含量的范围内发现的相比，细胞散射仍然可以忽略不计。由于水的高电磁吸收高达约1 THz，电磁谐振器具有高质量的因子和高度集中的微流体储层（以前由团队所证明的），该储层基本上包含一个单元，一次包含一个单元，代表快速和准确的介电测量系统的理想系统。这是因为单个细胞位于其自然液体环境中。为了解决血液样本中CTC丰度极低的问题，我们打算将微流体分离技术与一个芯片或多芯片组合的集成微波与terahertz共振器相结合，旨在朝着实验室芯片方法进行临床应用。为了实现这一雄心勃勃的目标，在这个为期三年的项目中，我们建议采用多学科的方法，基于帝国帝国科学与工程中心的相关成员的专业知识（由材料，电气和电子工程学系的学者和研究人员组成）以及来自生命科学的专业生物学（包括生命癌症）的专业群体以及包括生命癌症的专业群体的群体以及细胞的专业群体的专业知识（由材料，电子和物理学组成），以及范围内的专业群体。来自帝国医学院。基于全血，从鼠模型中得出的全血，血清或水的各种肿瘤细胞悬浮液将是我们的黄金标准方法，用于生成不同类型的肿瘤细胞的介电性能数据库，以优化不同的传感器芯片方法，以及细胞检测方法的开发。作为一个关键的里程碑，在项目结束时，我们将在人类血液样本中证明CTC检测。作为该项目的主要工程挑战，将根据我们先前在纳米层液体液体液体测量的硅MEM技术的工作中研究三种不同的电磁谐振器方法：介电晶晶晶体晶体晶体晶体，光子水晶和Spoof Plapasmems MetAmpatials MetAmpals MetAmpatials。先进的微型和纳米缓冲技术，例如深层反应离子蚀刻，电子束光刻和集中的离子束蚀刻，将用于制造完全集成（子）THZ谐振器 - 微荧光系统。在对CTC检测的巨大挑战中，我们有可能进行临床的范围，这可能是在ctc检测中的巨大挑战，我们可能会在研究中进行研究，这可能会造成生成的应用程序，这可能会生成一定的生成，这可能是生成的，这可能是一定的。在鼠模型中检测白血病细胞和人类尿液样品中的膀胱癌细胞检测。在这两种情况下，预期的细胞丰度都比CTC高得多，但是介电细胞识别方法与CTC检测相同。在该项目的时间范围内，可能会推出包括临床研究以及行业更强大参与在内的后续项目。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Dielectric measurements of nanoliter liquids with a photonic crystal resonator at terahertz frequencies

DOI：
10.1063/1.4927242
发表时间：
2015-07-20
期刊：
APPLIED PHYSICS LETTERS
影响因子：
4
作者：
Hanham, S. M.;Watts, C.;Klein, N.
通讯作者：
Klein, N.

3D printed 1.1 THz waveguides

DOI：
10.1049/el.2016.4662
发表时间：
2017-02
期刊：
Electronics Letters
影响因子：
1.1
作者：
W. J. Otter;N. Ridler;Hiroyuki Yasukochi;Kentaro Soeda;K. Konishi;J. Yumoto;M. Kuwata-Gonokami;S. Lucyszyn
通讯作者：
W. J. Otter;N. Ridler;Hiroyuki Yasukochi;Kentaro Soeda;K. Konishi;J. Yumoto;M. Kuwata-Gonokami;S. Lucyszyn

Polymer-Based 3-D Printed Ku-Band Steerable Phased-Array Antenna Subsystem

基于聚合物的 3D 打印 Ku 波段可操纵相控阵天线子系统