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Microarray of non-connected gold pads used as high density electric traps for parallelized pairing and fusion of cells

机译:非连接金焊盘的微阵列用作高密度电阱用于细胞的平行配对和融合

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摘要

Cell fusion consists of inducing the formation of a hybridoma cell containing the genetic properties of the progenitor cells. Such an operation is usually performed chemically or electrically. The latter method, named electrofusion, is considered as having a strong potential, due to its efficiency and non-toxicity, but deserves further investigations prior to being applicable for key applications like antibody production and cancer immunotherapy. Indeed, to envision such applications, a high amount of hybrid cells is needed. In this context, we present in this paper a device for massive cell pairing and electrofusion, using a microarray of non-connected conductive pads. The electrofusion chamber––or channel––exposes cells to an inhomogeneous electric field, caused by the pads array, enabling the trapping and pairing of cells with dielectrophoresis (DEP) forces prior to electrofusion. Compared to a mechanical trapping, such electric trapping is fully reversible (on/off handling). The DEP force is contactless and thus eases the release of the produced hybridoma. Moreover, the absence of wire connections on the pads permits the high density trapping and electrofusion of cells. In this paper, the electric field mapping, the effect of metallic pads thickness, and the transmembrane potential of cells are studied based on a numerical model to optimize the device. Electric calculations and experiments were conducted to evaluate the trapping force. The structure was finally validated for cell pairing and electrofusion of arrays of cells. We believe that our approach of fully electric trapping with a simple structure is a promising method for massive production of electrofused hybridoma.
机译:细胞融合包括诱导杂交瘤细胞的形成,该杂交瘤细胞包含祖细胞的遗传特性。这种操作通常以化学或电方式进行。由于后者的效率和无毒性,后一种方法被称为电融合,被认为具有很强的潜力,但在将其应用于抗体生产和癌症免疫疗法等关键应用之前,值得进一步研究。实际上,为了设想这样的应用,需要大量的杂交细胞。在这种情况下,我们在本文中介绍了一种使用未连接的导电焊盘的微阵列进行大规模细胞配对和电融合的设备。电融合室(或通道)将细胞暴露于由电极垫阵列引起的不均匀电场,从而在电融合之前用介电电泳(DEP)力捕获和配对细胞。与机械捕集相比,这种电捕集是完全可逆的(开/关处理)。 DEP力是非接触的,因此易于释放产生的杂交瘤。而且,在垫上没有电线连接允许细胞的高密度捕获和电融合。本文基于数值模型研究了电场映射,金属焊盘厚度的影响以及细胞的跨膜电位,以优化器件。进行电学计算和实验以评估诱捕力。该结构最终经过验证,可用于细胞配对和细胞阵列的电融合。我们认为,采用简单结构进行完全电捕获的方法是大规模生产电融合杂交瘤的有前途的方法。

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