Methods for segregating particles using an apparatus with a size-discriminating separation element having an elongate leading edge

摘要

The disclosure relates to an apparatus for segregating particles on the basis of their ability to flow through a stepped passageway. At least some of the particles are unable to pass through a narrower passageway bounded by a segregating step, resulting in segregation of the particles. The breadth of the leading edge of at least one step of the apparatus is significantly greater than the overall width of the passageway in which the step occurs, permitting high and rapid sample throughput. The apparatus and methods described herein can be used to segregate particles of a wide variety of types. By way of example, they can be used to segregate circulating tumor cells from a human blood sample.

主权项

1. A method of segregating circulating tumor cells (CTCs) from blood cells in a whole blood sample, wherein said method employs a device comprising:
a body and a cover that define a void therebetween, the void containing
a separation element that segregates an inlet region and an outlet region of the void, the separation element defining, together with a surface of the void,a channel that fluidly connects the inlet and outlet regions by way of a separating portion into which the separation element projects, the channel havingan overall width at the separating portion anda height defined by the distance between the separation element and the surface of the void, at least one of the body, the cover or the separation element bearing a segregating step disposed within and having a leading edge extending substantially completely across the separating portion of the channel, whereby the channel is divided into an upstream portion on the inlet side of the leading edge and a substantially lamellar downstream portion on the outlet side of the leading edge, the upstream portion of the channel being also lamellar in a region between the inlet region and the separation element; the height of the upstream portion being sufficient to facilitate passage therethrough of both said CTCs and said blood cells, the height of the downstream portion being sufficiently large to facilitate passage therethrough of said blood cells and sufficiently small to inhibit passage therethrough of said CTCs, and the leading edge having a length at least 20 times greater than the overall width of the channel at the separating portion such that the leading edge has an undulating shape; and said method comprisesurging said whole blood sample through said channel of said device from the inlet region whereby CTCs will be segregated from said blood cells due to their characteristics and inability to traverse said segregating step along the separating portion of the channel.