开发出微滴芯片来筛选抗药性癌干细胞（附原文）

zorro

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   来自新加坡生物工程与纳米技术研究所(Institute of Bioengineering and Nanotechnology, IBN)的研究人员开发出一种微型芯片技术来研究药物对癌干细胞(cancer stem cells, CSCs)的影响.这项技术有望促进人们开发出更加有效的抗癌药物.相关研究结果于近期发表在Nano Today期刊上,论文标题为"Elucidating drug resistance properties in scarce cancer stem cells using droplet microarray".3 I' _! ^5 i* v2 `* F# w- Z1 Z

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/ [0 ^0 |9 t0 s2 r- _2 J   在肿瘤中,CSCs形成一小部分不同类型的更加抵抗化疗的癌细胞.类似于在人组织中发现的干细胞,CSCs能够产生和分化为不同类型的癌细胞.如果CSCS不能被根除,那么它们能够重新入驻肿瘤中,并导致癌症复发.因此对研究人员而言,理解抗癌药物抵抗CSCs的效果是非常重要的.然而,因为CSCs极其稀少,它们大约占肿瘤中全部癌细胞的1%,所以对它们的研究一直受阻于常规药物筛选方法,这是因为常规药物筛选方法需要大量生物样品,而且耗时和成本高昂.
) Q0 `; R2 z* }' S3 R    生物工程与纳米技术研究所(IBN)行政主管Jackie Y. Ying教授领导的一个研究小组开发出一种被称作微滴芯片(Droplet Array)的微型生物检测方法以便利用有限的样品来开展更加便宜、更加快速和更加方便的药物筛选.
2 ~8 {% _- |- A* b, L    在传统的生物检测方法中,人们经常使用微孔板(microplate)---含有多个用于放置样品的孔的平板---,而且每个孔需要放置至少2500或5000个细胞以便进行有效的分析.作为对比,IBN开发的微滴芯片是一块长方形的平板,在它上面分布着一系列直径为2毫米的点.用移液管将样品加入到这些微小的点上,使得它们看起来像微滴那样.接着,这块平板被包被一层专门油以便阻止在清洗期间样品蒸发和样品微滴之间发生的交叉污染.研究人员也开发出一台与之配套的台式设备来对平板进行自动化清洗过程.在IBN开发出的微滴芯片上每个点的大小是标准微孔板上一个孔的五分之一,只需要500个细胞就可进行药物筛选.这种样品量的大幅减少不仅节省资金,而且特别便于研究数量稀少的靶细胞,如CSCs.' t# y$ ^' A, ~
    IBN研究人员利用微滴芯片来研究从乳腺癌、肝癌和结肠癌中提取的CSCs对药物产生的反应.他们发现化疗药物,如通常诱导肝癌细胞死亡的阿霉素(doxorubicin),对肝癌中的CSCs效果不佳.来自乳腺癌和结肠癌的CSCs也拥有更大的能力来抵抗抗癌药物.6 ^! a5 {/ C* q- o1 C% t/ L- c) J
    开展的动物研究也证实在微滴芯片上取得的发现.来自肝癌中的CSCs和非CSCs同时被移植到两组不同的小鼠体内.6周之后,接受CSCs移植的小鼠产生肿瘤,而接受非CSCs移植的小鼠则不产生任何肿瘤.从接受CSCs移植的小鼠中提取的肿瘤也表现出血管形成,从而证实CSCs拥有自我更新的性质.3 w( R& b- H  E) x( ^
    最近几年,CSCs的抗药性被人们广泛地讨论过,但是直到现在,量化这种抗药性一直是个挑战.IBN研究人员利用微滴芯片成功地证实CSCs能够抵抗化疗和促进肿瘤转移.
5 i+ ]( |/ [9 n2 t    Jackie Y. Ying教授说,"微滴芯片标记着纳米技术和实验室芯片方面的一项重大突破,并提供一种有效的平台来加速药物筛选和开发.特别令人激动的是,这种技术能够被学术界和制药行业用来开展癌干细胞(CSCs)研究.我们希望这项发现将促进人们开发出更有效的抗癌药物.我们也希望利用这种微滴芯片的性能来补充或替换用于药物毒理学测试的动物模型和开发出新的癌症诊断方法."( |. z* j8 Z/ {$ q
    这种易于使用的微型生物芯片能够兼容于现存的实验室设备如酶标仪(plate reader)和显微镜,从而降低适应这种新技术所需购买的额外设备的成本.这种微滴芯片技术当前正被IBN的第一家子公司Curiox生物系统私营有限公司(Curiox Biosystems Pte Ltd)命名为DropArray来进行商业化.2 m* N+ H* t4 R) z. h: t
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Droplet array sheds light on drug-resistant cancer stem cells
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Researchers at the Institute of Bioengineering and Nanotechnology (IBN) have developed a miniaturized biochip for investigating the effect of drugs on cancer stem cells (CSCs). Published recently in Nano Today, this new technology could boost the development of more effective cancer drugs.
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) y7 l1 f1 w1 S/ WIn a tumor, CSCs form a small and distinct class of cancer cells that are more resistant to chemotherapy. Similar to stem cells found in human tissues, CSCs can produce and differentiate into different cell types. If CSCs are not eradicated, they can repopulate the tumor and lead to cancer recurrence. Hence, it is important for researchers to understand the efficacy of anti-cancer drugs against CSCs. However, since CSCs are so scarce – they make up approximately 1% of cancer cells – their study has been hampered by conventional drug screening methods, which require large sample volumes and are slow and expensive.
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9 g. b4 i8 c. M( F. n" ]A team of researchers led by IBN Executive Director, Professor Jackie Y. Ying, has developed a miniaturized biological assay called the Droplet Array to perform cheaper, faster and more convenient drug screening using limited samples.
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In traditional biological assays, microplates – a flat plate with multiple wells in which samples are placed – are commonly used, and each well requires at least 2,500 or 5,000 cells, to be present for viable analysis. By comparison, IBN’s Droplet Array is a flat, rectangular glass plate on which a series of spots, each 2 millimeters in diameter, are arranged. The samples are pipetted into these tiny spots, making them appear like droplets. The plate is then coated with a layer of proprietary oil to prevent evaporation and cross contamination between the sample droplets during the rinsing process. An accompanying bench-top device to automate the rinsing process of the plate has also been developed. Being one-fifth the size of a well in a standard microplate, each spot on IBN’s Droplet Array requires only 500 cells for screening. This massive reduction in sample volume not only saves money, but is also particularly advantageous for studying scarce quantities of target cells, such as CSCs.
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Using the Droplet Array, the IBN researchers investigated the drug responses of CSCs extracted from breast, liver and colon cancer cells. It was found that chemotherapeutic drugs such as doxorubicin, which usually induce cell death in liver cancer cells, demonstrated poor efficacy in liver CSCs. The CSCs from the breast and colon tumors also showed much greater ability to survive the effects of anti-cancer drugs.
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7 f7 A. H: p6 Q* jAnimal studies were conducted to validate the findings of the Droplet Array. CSCs and non-CSCs from liver tumors were implanted into two different sets of mice at the same time. After 6 weeks, tumors were formed in the mice implanted with CSCs, whereas the mice without CSCs did not develop any tumors. Tumors extracted from the mice with CSCs also showed blood vessel formation, which confirmed the self-renewal property of these cells.
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+ y% p) e. Y6 B- x$ {$ w5 ]$ }The drug resistance properties of CSCs have been widely discussed in recent years but until now, it has been challenging to quantify this correlation. Using the Droplet Array, IBN researchers have successfully demonstrated that CSCs can survive chemotherapy and drive metastasis.
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Professor Jackie Y. Ying said, “The Droplet Array marks a significant breakthrough in nanotechnology and lab-on-a-chip concepts, and provides an efficient platform for accelerating drug screening and development. The study of cancer stem cells, in particular, is an exciting application of this technology for both the academic and pharmaceutical industries. We hope that this finding will facilitate the development of more effective cancer drugs. We also hope to leverage on the Droplet Array’s capabilities to complement/replace animal models for drug toxicity testing, and develop new cancer diagnostics.”
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Designed for ease of use, this miniaturized biochip is compatible with existing laboratory instruments, such as plate readers and microscopes, and reduces the set-up cost and the need to purchase additional equipment when adapting to this new technology. The Droplet Array technology is currently being commercialized by IBN’s first spinoff company, Curiox Biosystems Pte Ltd, as DropArray.2 L1 _+ J7 r7 ?1 u5 N* u' R2 q

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More information: 1.    Y. Y. Lee, K. Narayanan, S. J. Gao and J. Y. Ying, “Elucidating Drug Resistance Properties in Scarce Cancer Stem Cells Using Droplet Microarray,” Nano Today, 7 (2012) 29-34.
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! m7 }1 H, @. a" i1 O2.    H. Zhang, Y. Y. Lee, K. J. Leck, N. Y. Kim and J. Y. Ying, “Recyclable Hydrophilic-Hydrophobic Micropatterns on Glass for Microarray Applications,” Langmuir, 23 (2007) 4728-4731.. U9 F, d( v( H7 h/ g( K. E
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yuhaoze

这个虽然好，不过看起来传统的用96孔板配合红色染料来筛选药物的方法也没什么不好

evial

能检测500个目标细胞!真的很好，我们能够分出来的CSC也就几千几万个，这样就够用啦！这可不是一般的传统检测能做到的！

naturalkillerce

回复 zorro 的帖子. {- n3 ~' q$ L* u  U( {

) Z' t7 h* }$ M4 Q新闻出处：3 B. u% v) n+ a3 [( q8 T# D$ J
开发出微滴芯片来筛选抗药性癌干细胞
, [0 ^" s) S$ f2 O/ v7 A% q时间：2012-05-10 08:23:03 来源：生物无忧 作者：davidtower

bin

路过看看！