MTL Annual Report

Figure 1: Schematic illustration of the experimental set-up for TASR including the assembly fluid (in which variable chemistry and shape-matching are implemented through the choice of materials and component/template geometry) and the 1.7-MHz ultrasonic transducer that introduces mechanical forces to the selective removal system.

This work presents the size-selective sorting of single biological cells using Templated Assembly by Selective Removal (TASR). We have demonstrated the selective self-assembly of single SF9 cells (clonal isolate derived from Spodoptera frugiperda IPLB-Sf21-AE cells) into patterned hemispherical sites on rigid assembly templates using TASR. Experimental success with SF9 cells, which are nearly spherical and resistant to shear, suggests that self-assembly using TASR can also be extended to other cells and biological materials that are spherical.  Examples include white blood cells and, in general, cells that maintain a well-defined morphology for short durations when dispersed in culture media, agitated mildly using megasonic excitation, and allowed to settle on a patterned substrate. Therefore, TASR-based biological self-assembly holds potential for several applications, such as cell-sorting for medical research or diagnostics, or isolation of single cells for studying their biological and mechanical behavior.

Figure 2: Optical micrograph of SF9 insect cells with mean diameter of 15 microns, stained with methylene blue and self-assembled (a) selectively into patterned hemispherical sites with alternating diameters of 12 and 22 microns (b) uniformly into patterned hemispherical sites with a diameter of 15 microns on a templated silicon surface using TASR.

In TASR, the system’s free energy is minimized when objects assemble in holes that match their shapes and sizes on the template’s surface (Figure 1). A combination of chemical and mechanical effects selectively removes objects from poorly matched holes. Previous work on TASR has shown that microcomponents made from relatively rigid materials such as silica ^[1] [2] and deformable materials like polystyrene ^[3] can be assembled effectively on similarly rigid patterned templates using this technique. In an extension of the application of TASR to biological systems, SF9 cells (which come in a range of sizes with a mean diameter of 15 microns) were successfully assembled using TASR onto patterned silicon templates. The assembly sites comprised holes with nearly hemispherical profiles etched in a silicon substrate using DRIE. Figure 2 shows optical micrographs of the assembly and demonstrates the size-selectivity of the process as well as the high yield of cell assembly using this technique.

1. S. Jung and C. Livermore, “Achieving selective assembly with template topography and ultrasonically induced fluid forces,” Nanoletters, vol. 5, no. 11, pp. 2188-94, 2005. [↩]
2. F. Eid, S. Jung, and C. Livermore, “Templated assembly by selective removal : simultaneous, selective assembly and model verification,” Nanotechnology vol. 19 p. 285602, 2008. [↩]
3. G. Agarwal, A. Servi, F. Eid, and C. Livermore, “Shape Selective Assembly in Deformable Systems using Templated Assembly by Selective Removal,” Proc. of the Foundations of Nanoscience Conference- Self-Assembled Architectures and Devices, Snowbird, Utah, 2009. [↩]