News Express: UM develops new drug screening technology for precision medicine
新聞快訊:澳大成功研發新型精準醫療藥篩技術
精準醫療藥物篩選示意圖
A schematic of drug screening on digital microfluidics for cancer precision medicine
澳大成功研發新型精準醫療藥篩技術
澳門大學微電子研究院助理教授賈豔偉領導的研究團隊研發出一種利用原代癌症細胞進行藥物篩選的微流控系統,該系統可針對個體癌症患者進行藥物篩選並給出治療方案,確保最佳治療效果。系統將有望用於臨床醫生用藥指導,實現科技成果轉化,助力粵港澳大灣區科技創新建設。研究成果已獲國際知名期刊《Nature Communications》刊登。
近年來,精準醫療已成為醫學領域的熱門話題。它是一種基於個體差異的醫療模式,依據患者內在生物學資訊或臨床體徵等資訊,為每一位患者量身定製醫療方案和臨床決策。迄今為止,大多數精準醫療都是基於每位患者的基因異常,為具有某些基因突變的患者開出一些藥物以獲得最佳反應,而其他具有特定突變的患者則不會開出這些藥物,因為預計反應性會降低或不良反應的風險較高。然而,臨床資料表明,越來越多的基因參與癌症對某種藥物的反應,使得基於基因的精準醫療的治療效果並不令人滿意。也有人提出對來自患者活檢或腫瘤切除樣本的原發性腫瘤細胞進行藥物篩選,可獲得有關特定腫瘤的藥物敏感資訊。然而,活檢樣本僅包含非常少量的細胞,難以用傳統的96孔板進行藥篩。雖然多次活檢可以提供足夠的腫瘤細胞,但也增加了癌症轉移的風險和患者的痛苦。
因此,澳大此項研究通過開發一個用戶友好的藥篩設備,易於臨床醫生使用,可立即對新鮮的高活性癌症細胞進行採集和藥物篩選。該設備基於數字微流控技術,因其微型化、集成化、消耗小等優勢,可對微小樣本進行操作。即使是單次活檢得到的微量細胞樣本,已足夠用數字微流控晶片得出藥篩結果,避免了反覆活檢給患者帶來的風險和痛苦。該設備已應用於臨床肝癌病人樣品的靶向藥物篩選,得出的結果與基因測序的結果一致,並且更加直接地反映了特定病人對藥物的反應。
研究團隊表示,該項技術能夠為臨床醫生和病人提供可靠的用藥指導,相比基因測序,設備成本低廉,有望實現大規模生產,實現全民精準醫療。該項技術同時為科研人員提供了可進行高通量藥篩並且大幅節省樣本和試劑的研究平台,有助於探索新治療策略以及新藥開發,以進一步提高臨床療效。另外,該項技術已實現科技成果轉化,並成功創辦了 “珠海普羅精準醫療科技有限公司”的高科技服務機構,專注於精準醫療設備的研發、生產和銷售,助力大灣區科技創新建設。
是次研究的通訊作者為賈豔偉,博士後翟蛟和博士研究生劉瑩瑩為共同第一作者;北京科技大學教授姚海龍和中山三院主任醫師易述紅為共同通訊作者;澳大教授馬許願和麥沛然,模擬與混合信號超大規模集成電路國家重點實驗室的技術和管理團隊為該研究作出了重要貢獻。
該項研究由澳門特別行政區科學技術發展基金(檔案編號:0029/2021/A1和004/2023/SKL)、澳門大學(檔案編號:MYRG2020-00078-IME和MYRG-GRG2023-00034-IME)、何鴻燊博士醫療拓展基金會(檔案編號:SHMDF-OIRFS/2024/001)、珠海華發集團(檔案編號:HF-006-2021)、國家自然科學基金重點專案(檔案編號:62034005)和國家自然科學基金(檔案編號:61974084)資助。原文可瀏覽:https://www.nature.com/articles/s41467-024-48616-3。
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UM develops new drug screening technology for precision medicine
A research team led by Jia Yanwei, assistant professor in the Institute of Microelectronics at the University of Macau (UM), has developed a microfluidic system for drug screening using primary tumour cells, which can offer individual cancer patients a tailored treatment plan that exhibits the best therapeutic results. The system is expected to be used by clinicians in medication guidance, thereby realising the commercialisation of research results and facilitating technological innovation in the Guangdong-Hong Kong-Macao Greater Bay Area. The research findings have been published in the internationally renowned journal Nature Communications.
In recent years, precision medicine has emerged as a hot topic in the medical field. It represents a model of individualised healthcare that tailors the treatment plan and clinical decision for each patient based on the patient’s intrinsic biological information or clinical signs and symptoms. To date, the majority of precision medicine approaches have been based on the genetic abnormalities of each patient. Some drugs are prescribed to patients with certain genetic mutations with the aim of achieving an optimal response, whereas some other patients with specific mutations are not prescribed these drugs due to predicted reduced responsiveness or a high risk of adverse effects. However, clinical data have indicated that an increasing number of genes are involved in the cancer response to a certain drug, making the therapeutic effect based on genetic precision medicine unsatisfying. An alternative approach is to perform drug screening on primary tumour cells derived from patient biopsies or tumour resection samples. This provides direct information on the drug susceptibility of the specific tumour. However, biopsy samples contain only a limited number of cells, which makes drug screening with traditional 96-well microplates challenging. While multiple biopsies could provide sufficient tumour cells, this also carries an increased risk of cancer metastasis and causes the patient to experience more pain.
The research team has therefore developed a novel clinician-friendly drug screening device that enables the immediate collection of highly active cancer cells and on-site drug screening. It is a portable digital microfluidic (DMF) device with low power consumption that integrates all the controls into a handheld box with user-friendly control panels, enabling the handling of tiny samples. A single biopsy of a small quantity of cell samples is sufficient to produce drug screening results with the DMF chip, thus avoiding the risks and discomfort associated with repeated biopsies for patients. The device has been applied to clinical liver cancer samples for targeted drug screening. The results obtained are consistent with those derived from genetic sequencing and provide a more direct reflection of the individual patient’s response to the drug.
According to the research team, the DMF technology can provide clinicians and patients with reliable medication guidance, and low cost of equipment in comparison with that of gene sequencing. The technology should enable mass production and the realisation of precision medicine for all. It also provides researchers with a platform for high-throughput drug screening and significant savings in samples and reagents, which can help explore new therapeutic strategies and develop new drugs to further improve treatment efficacy. In addition, the DMF technology has been commercialised, resulting in the establishment of a high-tech service organisation called Promedicine Technology, which specialises in the research, development, production, and retail of precision medical equipment, contributing to technological innovation in the Greater Bay Area.
The corresponding author of the paper is Prof Jia, while UM postdoctoral fellow Zhai Jiao and UM doctoral student Liu Yingying are the co-first authors. Yao Hailong, professor at the University of Science and Technology Beijing, and Yi Shuhong, chief physician at the Third Affiliated Hospital of Sun Yat-Sen University, are the co-corresponding authors. UM professors Rui Martins and Mak Pui In, and the technical and management team of the State Key Laboratory of Analog and Mixed-Signal VLSI also made significant contributions to the study.
The research project was supported by the Science and Technology Development Fund of the Macao SAR (File no: 0029/2021/A1 and 004/2023/SKL), UM (File no: MYRG2020-00078-IME and MYRG-GRG2023-00034-IME), Dr Stanley Ho Medical Development Foundation (File no: SHMDF-OIRFS/2024/001), Zhuhai Huafa Group (File no: HF-006-2021), the Key Program of the National Natural Science Foundation of China (File no: 62034005), and the National Natural Science Foundation of China (File no: 61974084). The full version of the research article is available at https://www.nature.com/articles/s41467-024-48616-3.
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