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Microfluidic micropipette aspiration for measuring the deformability of single cells

机译:微流控微量移液器测量单细胞的可变形性

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We present a microfluidic technique for measuring the deformability of single cells using the pressure required to deform such cells through micrometre-scale tapered constrictions. Our technique is equivalent to whole-cell micropipette aspiration, but involves considerably simpler operation, less specialized equipment, and less technical skill. Single cells are infused into a microfluidic channel, and then deformed through a series of funnel-shaped constrictions. The constriction openings are sized to create a temporary seal with each cell as it passes through the constriction, replicating the interaction with the orifice of a micropipette. Precisely controlled deformation pressures are generated using an external source and then attenuated 100 : 1 using an on-chip microfluidic circuit. Our apparatus is capable of generating precisely controlled pressures as small as 0.3 Pa in a closed microchannel network, which is impervious to evaporative losses that normally limit the precision of such equipment. Intrinsic cell deformability, expressed as cortical tension, is determined from the threshold deformation pressure using the liquid-drop model. We measured the deformability of several types of nucleated cells and determined the optimal range of constriction openings. The cortical tension of passive human neutrophils was measured to be 37.0 + 4.8 pN μm~(-1), which is consistent with previous micropipette aspiration studies. The cortical tensions of human lymphocytes, R.T4 human bladder cancer cells, and L1210 mouse lymphoma cells were measured to be 74.7 + 9.8,185.4 + 25.3, and 235.4 ±31.0 pN μm~(-1) respectively. The precision and usability of our technique demonstrates its potential as a biomechanical assay for wide-spread use in biological and clinical laboratories.
机译:我们提出了一种微流体技术,用于测量单个细胞的变形能力,该技术使用通过微米尺度的锥形收缩使此类细胞变形所需的压力。我们的技术等效于全细胞微量移液器抽吸,但涉及的操作相当简单,专用设备较少,并且技术技能较低。将单细胞注入微流体通道,然后通过一系列漏斗形的收缩物变形。收缩口的尺寸可设置成在每个细胞通过收缩口时与每个细胞建立临时密封,从而复制与微量移液器孔口的相互作用。使用外部源可精确控制变形压力,然后使用片上微流体电路将其压缩100:1。我们的设备能够在封闭的微通道网络中产生精确控制的压力,压力低至0.3 Pa,这不受蒸发损耗的影响,而蒸发损耗通常会限制此类设备的精度。使用液滴模型从阈值变形压力确定固有细胞可变形性,表示为皮质张力。我们测量了几种类型的有核细胞的可变形性,并确定了狭窄开口的最佳范围。被动人类嗜中性粒细胞的皮质张力经测量为37.0 + 4.8 pNμm〜(-1),这与以前的微量移液器吸取研究一致。经测定,人淋巴细胞,R.T4人膀胱癌细胞和L1210小鼠淋巴瘤细胞的皮质张力分别为74.7 + 9.8、185.4 + 25.3和235.4±31.0 pNμm〜(-1)。我们技术的精确性和可用性证明了其作为生物力学测定方法的潜力,可广泛用于生物学和临床实验室。

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