Circulating tumor cell capture and single cell analysis prototype developed successfully in Dalian

Circulating tumor cell capture and single cell analysis prototype developed successfully in Dalian

October 26, 2018 Source: Ministry of Science and Technology

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Led by Dalian Medical University, and cooperated with the Shenzhen Institute of Advanced Technology and Research, Chinese Academy of Sciences, and under the support of the National Science and Technology Program, after three years of research and development, successfully constructed a circulating tumor cell (CTC) with independent intellectual property rights. Capture and single cell analysis prototypes show good application prospects.

CTC is a general term for various types of tumor cells existing in the peripheral blood of patients. Capturing and sorting them can help predict and judge the risk of tumor metastasis, and provide information on important diseases such as treatment response and prognosis. At the cellular level, gene sequencing and other analyses are conducted to guide individualized medication and achieve precise treatment of tumors. Unlike tissue biopsy, CTC is the main component of liquid biopsy. It only needs to extract a few milliliters of peripheral venous blood, which has the advantages of non-invasive, convenient and repeatable operation. However, due to the scarcity and heterogeneity of CTCs, there are huge technical challenges in CTC capture and sorting, which has become a major bottleneck restricting its application in clinical practice. Microfluidic chip technology has the outstanding advantages of precise manipulation of target cells, high detection precision and low cost. It has become a key technology in CTC efficient detection.

The team applied microfluidic chip technology to build three functional CTC capture devices and a single cell detection device (see figure below). They are “Deterministic lateral displacement (DLD) single chip capture device”, “DLD chip and magnetic field negative sorting chip integrated joint capture device” and “CTC capture and in situ identification combined device”. The DLD single chip capture device uses the principle of deterministic lateral displacement array to separate CTC and blood cells, the sorting efficiency is over 95.26%, and the leukocyte removal rate can reach above 96.5%. In order to improve the purity of CTC sorting and eliminate the interference of white blood cells to the greatest extent, the integrated combined capture device was constructed by combining DLD chip and magnetic field negative sorting chip. The sorting performance was removed again on the basis of DLD chip sorting. % of white blood cells. The CTC capture and in situ identification combination device sequentially recognizes CTC capture recognition and fluorescent immunostaining in a single fence structure chip, and realizes the integration of enrichment, capture and identification analysis.

Compared with the internationally recognized CTC capture device Cellsearch sorting system, they not only have excellent detection efficiency, but also have the advantages of less blood volume, low cost and short time. It has been applied by many clinical units such as the Second Affiliated Hospital of Dalian Medical University and the People's Hospital of Peking University, and the capture efficiency of the device is over 95%.

The “single cell detection device” developed by the company realizes the efficient and pollution-free single cell sorting of CTC in the microfluidic chip closed system by identifying the single cell impedance pulse signal, which provides a guarantee for further single cell analysis. . Through the testing of lung cancer cells, the device can perform accurate sorting and analysis of individual cells.

At present, the core technology related to the prototype has applied for 22 patents, including 14 invention patents and 7 approvals.

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