The rapidly growing field of micro and nanotechnology to measure living cells
The rapidly growing field of micro and nanotechnology to measure living cells
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用于测量活细胞的微米和纳米技术领域快速发展
DOI：
10.1002/aic.11615
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
A. Minerick
中科院分区：
文献类型：
--
作者：
A. Minerick
活细胞是复杂的生物反应器，具有过多的多阶段反应序列，所有这些反应序列都一致发生以维持生命工厂。随着化学工程师与电气工程师和化学家合作开发更复杂的纳米结构和微器件，测量和监测这些细胞和亚细胞过程的能力正在成为现实。在过去25年中使用的传统细胞分析工具主要在宏观尺度上进行。然而，硅革命的尾随技术是芯片上的微制造实验室（芯片实验室），能够将微米级事件和传感器与细胞群连接起来。纳米技术注入到这个平台是最近才开始的，在国家纳米技术倡议（NNI）在这一领域的研究热潮之后。今天，微米和纳米技术通常用于探测和操纵活细胞。虽然目前在消费市场上有一些平台，但经济增长的潜力很大。这一观点主要集中在利用微型设备和纳米技术探测活细胞的应用，如医疗诊断，病原体或生物恐怖主义检测，药物筛选和癌症检测等方面取得的进展。微器件（也称为芯片实验室（Lab-on-a-Chip，缩写为LAB）和微型全分析系统（micro Total Analytical Systems，缩写为mTAS））正在地球仪的实验室中进行开发，因为它们有潜力为广泛的生物和化学应用提供高分辨率、低成本和快速的小样本量分析。这种微器件被设计成通过利用制造到聚合物或玻璃芯片中的微通道和微室来模拟微升和纳升体积的实验室过程。活细胞可以在这个平台上进行研究，因为精确控制的环境条件和单细胞操作现在是可能的。大多数细胞操作技术利用微观尺度上发生的物体相互作用的显著不同概率。例如，检查约4英寸的10 cm切片。直径(100 mm）管，发现管的内表面积为0.03m2，相应体积为0.0008m2。该大通道的表面积与体积比仅为约40 μ m，而对于直径为100微米且同样为10 cm长的微通道，表面积和体积分别小三个和六个数量级，但表面积与体积比大三个数量级（540，000 μ m）。对于球形颗粒以及通道，这种趋势简要地记录在表1中。这意味着液体/固体相互作用更加普遍，因此，表面可用于对通道内的流体和细胞施加力。当将三个数量级更小的移动到纳米颗粒时，可以进一步利用这种表面到体积的属性。例如，人们可以用超过300万个1 nm的颗粒（没有空隙空间5400万）涂覆1微米的球形电池。使纳米颗粒功能化是相当简单的，因为超过300个1埃分子可以适合1 nm的颗粒（没有空隙空间5400）。用于功能化表面的分子需要对其靶分子的高亲和力和特异性。抗体，一种高度专业化的生物（免疫）识别标签，是最常用的分子用于这些目的。从这个角度来看，讨论将集中在微流控装置技术探测细胞水平的过程中，分子对细胞反应的影响，和细胞与纳米粒子的相互作用。
L iving cells are complicated bioreactors with a plethora of multistage reaction sequences all occurring in concert to sustain the factory of life. As chemical engineers develop more sophisticated nanostructures and microdevices in coordination with electrical engineers and chemists, the ability to measure and monitor these cellular and subcellular processes is becoming a reality. Traditional cell analysis tools utilized over the last 25 years have predominantly been conducted at the macroscale. However, the trailing technology of the Silicon Revolution has been microfabricated laboratories on a chip (Lab-on-a-Chip), with the ability to interface micron-scale events and sensors with cell populations. The infusion of nanotechnology into this platform is even more recent and began after the National Nanotechnology Initiative’s (NNI) flurry of research in this area. Today, micro and nanoscale technologies are routinely used to probe and manipulate living cells. Although a few platforms are currently available on consumer markets, the potential for economic growth is significant. This perspective focuses primarily on the progress made utilizing microscale devices and nanotechnology to probe living cells for applications as diverse as medical diagnostics, pathogen or bioterrorism detection, pharmaceutical screening and cancer detection. Microdevices (also called Lab-on-a-Chip (LOC), and micro Total Analytical Systems (mTAS)) are under development in labs across the globe because they have the potential to provide high-resolution, low-cost, and rapid analysis with small sample volumes for a wide range of biological and chemical applications. Such microdevices are designed to mimic laboratory processes in micro and nanoliter volumes by utilizing microchannels and microchambers fabricated into polymer or glass chips. Living cells can be studied within this platform as precisely controlled environmental conditions and single-cell manipulations are now possible. Most cell manipulation technology takes advantage of the significantly different probability of object interactions that occur at the microscale. For example, examining a 10 cm section of an approximately 4 in. dia. (100 mm) pipe, one finds that the inner surface area of the pipe is 0.03 m with a corresponding volume of 0.0008 m. The surface to volume ratio for this large channel is only about 40 m, while for a microchannel with a diameter of 100 microns and the same 10 cm long, the surface area and volume are three and six orders of magnitude smaller, respectively, but the ratio of surface area to volume is three orders of magnitude larger (540,000 m). This trend is briefly captured in Table 1 for spherical particles, as well as for channels. This means that liquid/solid interactions are much more prevalent, and as such, the surfaces can be utilized to impart forces on the fluid and the cells within the channel. This surface to volume attribute can be exploited further when moving three orders of magnitude smaller to nanoparticles. For instance, one can coat a 1-micron spherical cell with over 3 million 1 nm particles (no void space 5 4 million). Functionalizing a nanoparticle is fairly straightforward, as well because over 300 1-Angstrom molecules can fit on a 1 nm particle (no void space 5 400). Molecules that are used to functionalize surfaces require a high affinity and specificity for their target molecules. Antibodies, a highly specialized biological (immunological) recognition tag, are the most commonly utilized molecules for these purposes. In this perspective, discussions will focus on microfluidic device technologies for probing cellular level processes, molecular influences on cell responses, and cell to nanoparticle interactions.
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