In Vivo Capture of Circulating Tumor Cells Based on Transfusion with a Vein Indwelling Needle

Abstract

Detection of circulating tumor cells (CTCs) could be used as a "liquid biopsy" for tracking the spread of cancer. In vitro detection methods based on blood sampling and in vitro CTC capture often suffer from the small sampling volume and sampling error. Here, the in vivo capture of CTCs based on transfusion with a surface-modified vein indwelling needle is proposed. When the needle was applied to transfusion in the vein, the simultaneous capture of CTCs was performed. To investigate the actual capture efficiency of the in vivo capture method, labeled MCF-7 cells were directly injected into the veins of rabbits, wild type mice, and nude mice and could be successfully captured. Two of 5 MCF-7 cells injected into the veins of nude mice were successfully captured. To investigate the CTC capture of mouse tumor model and compare with the in vitro method, mice were subcutaneous inoculated with metastatic 4T1 cells. Seven and 21 days after inoculation, CTCs were captured for the first time using in vivo and in vitro methods, respectively. This predicted that the in vivo method could be more suitable for use of early diagnosis of cancer than the in vitro method. As CTC capture can be performed at the same time as transfusion and does not cause further bodily harm, it would be easily accepted by patients. This efficient, simple, and less damaging method involving the use of a vein indwelling needle could be popularized easily in the clinic.

Current detection technologies for circulating tumor cells

“…In order to overcome this problem, Zhang et al developed a method of in vivo CTC enrichment based on transfusion with a vein indwelling needle (Figure 5). 32 The vein indwelling needle was modified with an anti-EpCAM antibody, which could specifically recognize the EpCAM antigen on the surface of CTCs (Figure 5a). When this surface modified vein indwelling needle was applied for transfusion in the vein, the simultaneous capture of CTCs was performed.…”

A Novel Pathogen Capturing Device for Removal and Detection

“…circulating tumor cells or bacteria) for in vivo diagnostics and therapeutic purposes 5–7, 12, 13 . The simple tube arrangement described in this manuscript was tested for in vivo pathogen removal in a rat model.…”

“…These efforts are motivated by the need to quickly capture pathogens for detection of bloodborne infections 5–7 , for detection of pathogens in food products 8–11 , or even for therapeutic purposes 12–18 . Some indicative examples include extracorporeal blood circulation methods to capture target pathogens (e.g.…”

“…Some indicative examples include extracorporeal blood circulation methods to capture target pathogens (e.g. circulating tumor cells) using immunocapturing techniques reported for in vivo diagnostics and therapies 5–7 and immunomagnetic concentration technologies for food pathogens 11 . Recently, a microfluidic device that relies on immunomagnetic separation (IMS) technology using an engineered antibody 13 was used to remove bacteria and toxins from blood.…”

“…A hemofiltration cartridge was developed using the same engineered antibody 12 . It is evident that there is a multitude of applications and the specific parameters for each may vary (for instance some applications require high volume pathogen removal, such as food pathogen testing and environmental testing 1, 2 , while others require ability to capture low quantities of pathogens, such as blood infection diagnosis and circulating tumor cell detection 4, 6, 7 ). However, the overarching need for a simple and inexpensive way to remove pathogens from liquid media remains due to the common needs these applications share, which are: ability to capture the majority of the pathogens present in the liquid media irrespective of the total quantity of the pathogens and the media volume, ability to process samples with complex constituents, ability to perform capturing in a rapid manner.…”