Levitational Image Cytometry with Temporal Resolution.
Levitational Image Cytometry with Temporal Resolution.
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DOI：
10.1002/adma.201405660
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发表时间：
2015-07-08
期刊：
影响因子：
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通讯作者：
Demirci U
中科院分区：
文献类型：
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作者：
Tasoglu S;Khoory JA;Tekin HC;Thomas C;Karnoub AE;Ghiran IC;Demirci U
各种各样的细胞过程，无论是生理的还是病理的，都伴随着细胞作为生物材料的基本特征的瞬时或永久性变化：(I)体积质量密度或(Ii)由于细胞内顺磁反应物种(如活性氧(ROS)和活性氮(RNS)的形成或猝灭而产生的磁特征。这些事件包括细胞周期阶段[1]、分化[2]、细胞死亡(凋亡/坏死)[3]、恶性肿瘤、疾病状态[4]、激活、吞噬、体内和体外细胞老化(如红细胞)、病毒感染以及对药物的特异性和非特异性反应。因此，为高空间分辨率、实时监测和量化细胞的磁性特征和体积质量密度而设计的可靠工具将有助于阐明复杂的细胞机制[5]。其中一项技术涉及提供低吞吐量的纳米级悬浮微通道谐振器，以及使用复杂的泵机构在不同密度的流体之间传输细胞的必要性[5]。其他方法包括相移干涉术[7]、数字全息显微镜[8]、四波横向剪切干涉术[9]和定量相位层析成像[10]。尽管这些技术在量化细胞密度方面取得了成功，但在监测细微的形态变化、操纵细胞或触发和量化各种细胞事件方面存在局限性，而不需要复杂的制造或组件。另一种方法是利用磁泳法根据细胞的天然磁性分离细胞，例如从全血中分离脱氧红细胞[11]，从健康红细胞中分离感染疟疾的红细胞[12]。磁斥力也被用于在磁性溶液中添加细胞的大小、弹性和磁性的无标记分离[13]。然而，这些技术不能分析各种细胞群体。而且到目前为止，
A wide variety of cellular processes, both physiological and pathological, are accompanied by transient or permanent changes in a cell’s fundamental characteristics as a biological material (i) volumetric mass density or (ii) magnetic signature due to formation or quenching of intracellular paramagnetic reactive species such as, reactive oxygen species (ROS) and reactive nitrogen species (RNS). These events include cell-cycle stage [1], differentiation [2], cell-death (apoptosis/necrosis)[3], malignancy, disease state [4], activation, phagocytosis, in vivo and ex vivo cell aging (eg, red blood cells), viral infection, and specific as well as non-specific responses to drugs. Therefore, reliable tools designed for high spatial resolution, real-time monitoring and quantification of magnetic signatures and volumetric mass densities of cells will help elucidate the intricate cellular mechanisms [5].Hitherto, there have been attempts to measure the fundamental material properties of biological living materials with high precision such as the density of single living cells [6]. One such technology involves nanofabricated, suspended microchannel resonators that offers low throughput, and the necessity to use a sophisticated pump mechanism to transfer cells between fluids with different densities [5]. Other approaches include phase-shifting interferometry [7], digital holographic microscopy [8], quadriwave lateral shearing interferometry [9], and quantitative phase tomography [10]. Despite its success in quantifying cellular density, these technology has limitations in monitoring subtle morphological changes, manipulating cells or triggering and quantifying various cellular events without requiring sophisticated fabrication or components. Alternatively, magnetophoresis was used to separate cells based on their native magnetic properties, such as deoxygenated red blood cells (RBCs) from whole blood [11] and malaria-infected RBCs from healthy RBCs [12]. Magnetic repulsion was also used for label-free separation of cells spiked in magnetic solutions with respect to their size, elasticity and magnetic property [13]. However, these technologies are not capable to analyze various cell populations. Moreover, up until now,