1. Field
The present disclosure relates to methods of separating a target cell in a biological sample.
2. Description of the Related Art
The majority of deaths associated with malignant tumors are due to the metastasis of primary tumor cells to tissues and organs distant from the initial tumor. Accordingly, early diagnosis of metastasis is a critical factor for the survival of a cancer patient, and early diagnosis of a tumor and monitoring of tumor growth are considered to be very important factors for successful treatment of a cancer patient. Cancer diagnosis usually involves diagnosis techniques related to histopathology. A histopathological diagnosis technique is a method of using a tissue sample from a living subject to diagnose cancer. Such a histopathological approach allows a tumor cell to be directly observed. However, the histopathological approach may be inaccurate in determining whether there is a tumor, since only data about the particular tissue sample site is obtained. Thus it can be difficult to know whether a tumor has metastasized to another site. For this reason, the applicability of the histopathological diagnosis technique in diagnosing and monitoring tumors may be limited.
Circulating tumor cells (CTCs) may be found in a patient before a tumor is initially detected. Accordingly, CTCs may play an important role in early diagnosis and prognosis of cancers. In addition, because cancer usually metastasizes through the blood, a CTC may be a marker for determining whether cancer has metastasized. Even after cancer cells have been removed by surgery, CTCs may still be found. In this case, this may indicate that cancer may reoccur. However, very small numbers of these CTCs are found in blood. It is thus very difficult to detect and quantify CTCs. Accordingly, there remains a need for a diagnostic method that is highly sensitive with respect to detection of CTCs, cancer cells, or cancer stem cells in a patient.
The related art discloses a method of separating red blood cells, white blood cells, circulating cancer cells, and serum. However, white blood cells and circulating cancer cells are not separated from each other and exist as a mixture when the technology is used, and thus the method is disadvantageous in that the separation efficiency of white blood cells and circulating cancer cells is theoretically limited.
Other related art discloses cell margination and multi-orifice separation based on the principles of fluid dynamics. The former is a technology whereby the number of small cells, such as red blood cells, is decreased and the number of other cells is increased using a phenomenon which occurs in actual blood vessels in which small particles gather in the inner part of the blood vessels and large particles move outside. The latter is a principle whereby a channel along which fluid flows has an expanded tube section to gather large particles and small particles outside and in the middle of the channel, respectively, according to Reynolds number. However, it is difficult to selectively separate a desired target cell from actual blood using this principle, and there is limitation in treating a volume of several ml because the fluid flow rate is slow. However, it is necessary to dilute a fluid by several hundred times in order to control the Reynolds number, and thus there is a limitation in that samples of several hundred ml should be actually treated.
Accordingly, although the related art may be used, there still remains a need for a method of efficiently separating a target cell in a biological sample.
USPTO Backgrounds
USPTO Backgrounds