(411f) Collision Dynamics of Microparticles in Microfluidic Obstacle Arrays

The enrichment and capture of rare cells in blood is a topic of widespread clinical relevance, with potential applications including prenatal diagnostics, patient-specific chemotherapeutics, and non-invasive ?liquid biopsies.? ^{[1, 2, 3]} Several designs for microfluidic immunocapture devices exist, including straight and curved channels and micro-pillar arrays. The latter have been shown to be successful in capturing rare populations of circulating tumor cells (CTCs)^{[1, 2]} and fetal nucleated red blood cells.^[3] While initial results are promising, optimization of the device geometry is required to achieve the capture efficiency and population purity required for genetic analysis and diagnostic efficacy.

Immunocapture is only possible when target cells are brought into contact with antibody-coated surfaces. As such, controlling the cell transport with fluid mechanical design principles is crucial to the success of microfluidic immunocapture devices. A recent advance in the design of these devices has been demonstrated using geometrically-enhanced differential immunocapture (GEDI).^[3] This technique uses an obstacle array geometry designed such that there is differential transport of particles to the immunocoated surfaces, maximizing the target cells' interaction with the surface, while minimizing the interaction with other species. The result is a one-step immunocapture device with significantly improved capture efficiency and population purity as compared to the previous state-of-the-art.

We approach the problem of designing such a capture device by tracking and maximizing the collisions between the particles and immunocoated obstacles. We have developed numerical simulations to model the behavior of particle populations as they flow through an obstacle array; these simulations predict the particles' path and track when collisions occur. These simulations have demonstrated that the obstacle array geometry significantly affects the transport of these particles through post arrays and transport/collision modes are observed. To understand these collision modes, we developed an analytical model to enable the rapid design and optimization of future microfluidic capture devices. Our analytical model predicts the transport mode and collision dynamics of particles in a post array, and shows close agreement to our numerical simulations. This work is crucial for the design of immunocapture devices, but also relevant in the larger context of devices for microscale separation of particles by lateral displacement as it corrects for inaccurate predictions of other models using quasi-1D approximations.

Our use of a numerical simulation to track individual particles and their interactions with an immunocoated obstacle is a novel technique, leading to the design of microfluidic capture devices with improved capture efficiency and population purity. Furthermore, the detailed analytical model we have developed can be applied to rapidly develop immunocapture devices optimized for specific target populations. These advances will result in an improved generation of immunocapture devices with the performance required to gain widespread clinical adoption.

[1] Nagrath, et al. Nature, 2007, 450: 1235-1239

[2] Gleghorn, et al. Lab on a Chip, 2010, 10: 27-29

[3] Huang, et al. Prenatal Diagnosis, 2008, 28: 892-899

[4] Inglis, et al. Lab on a Chip, 2006, 6: 655-658