Gencline's Technology & Process

The patented Gencline separation technology is applicable to a broad range of applications involving product recovery, separation, concentration or stratification. The unique process does not involve trapping particles and is generally independent of particle density. As a result, the Gencline process has distinct advantages over conventional methods. Potential applications can involve processing of cells, cellular fragments or components, cell aggregates, proteins and solid particles composed of various substances such as precipitates, crystal particles, rock/sediment. The suspending fluid can have any form including liquid or gas.

History

Harnessing the power of numerous small influences to create a large summative effect is the general principle that led to Gencline's separation technology. The observation from blood flow biomechanics that platelets in small blood vessels concentrate in regions very near the vessel wall inspired our first attempt at using the general principle to separate cells. The platelet concentrating effect (margination) is the result of numerous small interactions between platelets and red blood cells that collectively drive the platelets to a region near the vessel wall. In the early 1990's Gencline demonstrated a separation technology that utilized obstacles in the form of fixed pillars or fibers placed in rectangular channels and a US patent was filed in 1995. As microfluidic fabrication became readily available, the obstacle based separation approach became more practical. In the mid 2000's an implementation of obstacle based separation in a microfluidic diagnostic device was developed for the isolation of select cells from whole blood based on size. While effective, that early separation technology has limitations and requires long channels to achieve sufficient lateral separation. Nevertheless, it demonstrates the practicality of using numerous small influences to drive a separation process.

More recently it was realized that if the small influences were directional, then the collective result could provide an even larger overall effect. That realization led to our new and recently patented technique for cell separation based on obstacles that shift cells directionally or asymmetrically relative to the flow. Furthermore, the asymmetrical nature of those shifts can be based on cell surface markers creating a highly specific biologically based separation.

Methodology

Gencline technologies employ obstacle based methods and range from sized based separation to highly selective surface marker based separations. Additionally, a broad range of target cell or particle physical attributes can be utilized to drive the separation processes.

More specifically, the separation technology involves interactions between the cells or particles and individual obstacles placed in the path of a flowing suspension. These interactions can shift the cells or particles symmetrically or asymmetrically about the individual obstacles relative to the fluid flow. A field or pattern of obstacles are positioned within a channel to realize the overall separation process. As the suspension of cells or particles is forced past the specifically designed obstacle field, target cells or particles migrate in a preferential direction and are collected downstream.

Obstacle Induced Preferential Dispersion

One Gencline process is based on obstacle induced preferential diffusion (OIPD). In this process, the mixture or suspension to be separated is forced past an obstacle field. The obstacle field causes a preferential dispersion or migration of the particles so that they are separated from the fluid. In particular, a non-uniform obstacle field has a spatial density that varies in a given direction. For example, consider a flow along an X axis through a field of obstacles whose spatial density increases in the Y direction, i.e., there are more obstacles as one travels in the +Y direction. When a particle encounters an obstacle it is shifted in either the +Y or -Y direction relative to the flow. If the particle is shifted in the +Y direction there is an increased probability of encountering another obstacle and being shifted back to its original path. If the particle is shifted in the -Y direction, there is a decreased probability of the particle encountering an obstacle and being shifted back to its original path. Thus, the particles will tend to migrate in the -Y direction. This migration is referred to as obstacle induced preferential dispersion (OIPD). In addition, the magnitude of the particle path shift from a single obstacle is dependent on the particle properties; therefore, the rate of migration will also be a function of particle characteristics.

Varying the spatial density of the obstacle field as described above is one useful approach when accurately controlling the placement of specific obstacles is not practical. Of course when the position of each obstacle can be precisely controlled, other approaches are also available. Positioning obstacles to force "streaming" of the particles is possible by having each shift successively move the particle relative to the next obstacle and continuously drive the particle in one direction. This is very similar to the approach that has been used for decades in sand separators and louvered dust separators.