Nondestructive optical assay method for nanoscale biological particles in solution

In this paper, we present an optical system for non-destructive assay of nanoscale biological particles (viruses) in fluids. This method is part of the design of a novel lab-on-chip device that enables microbiologists to purify, isolate and assay mixtures of viruses without the use of destructive labeling techniques or direct observations using electron microscopy. Our approach is based on the fabrication of large (10³ scale) and very dense (100 nm scale) electrode arrays using the semiconductor layers of a lab on-chip die. This array, see figure 1, is the platform for dielectrophoresis (DEP) based methods for sorting the mixtures of bioparticles and arranging the particles by type into groups at various regions of the electrode array. Based on the DEP field configuration, each group of particles organizes into a set of lines between specific pairs of electrodes with the lines repeated in a spatially periodic pattern. These lines of particles, shown in figure 2, along with the electrodes themselves, form a diffraction grating, where the efficiency of the grating is directly related to the density of the particles captured between the electrodes. By measuring the optical power in the 1st order diffraction mode of the grating before and after a separation (with and without particles) we can make an indirect measurement of the density of particles trapped in that region of the electrode array. The method works in both reflective mode, for CMOS 3D-IC chip stacks (figure 1) or transmissive mode for SoS-based transparent substrate devices (Figure 3a).