Biomimetic microfluid device for capturing circulating tumor cells
A method of capturing a Circulating Tumor Cell (CTC) and Circulating Cancer Cells (CSC) from a sample includes introducing a sample into a flow based multichannel device having a cell capture surface and a flow modification surface under conditions that allow a CTC to bind to a cell rolling-inducing agent and a capturing agent disposed on the cell capture surface. The invention also provides for flow based multichannel devices to capture CTCs and CSCs from a sample.
1. A microfluidic device for capturing a Circulating Tumor Cell (CTC) and a Circulating Cancer Stem Cell (CSC) from a sample, comprising:
(a) a first channel comprising a cell capture surface and a flow mobilization surface, wherein a CTC-specific or CSC-specific capturing agent and a cell rolling-inducing agent are immobilized to the cell capture surface, wherein the capturing agent is immobilized via a modified poly(amidoamine) dendrimer covalently attached to the cell capture surface agent;
(b) a second channel comprising a cell capture surface and a flow modification surface, wherein a CSC-specific or CTC-specific capturing agent and a cell rolling-inducing agent are immobilized to the cell capture surface, wherein the capturing agent is immobilized via a modified poly(amidoamine) dendrimer covalently attached to the cell capture surface agent and wherein the cell rolling-inducing agent is E-selectin or a CTC binding fragment of E-selectin.
2. The device of claim 1 , wherein the first and second channels are connected.
3. The device of claim 1 , wherein each channel has an inlet and an outlet.
4. The device of claim 1 , wherein the capturing agent is an antibody, an antibody fragment, an engineered antibody, folic acid, transferrin, a peptide, and an aptamer.
5. The device of claim 1 , wherein the capturing agent specific for CTC specifically binds a moiety on a CTC surface.
6. The device of claim 5 wherein the capturing agent is an RGD peptide.
7. The device of claim 1 wherein the capturing agent specific for CSC specifically binds a moiety on a CSC surface.
8. The device claim 1 , wherein the capturing agent is immobilized to the cell capture surface by direct attachment to the cell capture surface.
9. The device of claim 1 , wherein the capturing agent is immobilized on cell capture surface by attachment to a linker directly attached to the surface.
10. The device of claim 9 , wherein the linker is a polymeric nanolinker.
11. The device of claim 10 , wherein the polymeric nanolinker comprises a modified poly(amidoamine) dendrimer covalently attached to polyethylene glycol.
12. The device of claim 10 , wherein the polymeric nanolinker comprises polyester-n-carboxylate-1-alkyne dendron covalently attached to polyethylene glycol, wherein n is 8, 16, 32, 64, or 128.
13. The device of claim 1 , wherein the cell rolling-inducing agent and the capturing agent are arranged in a substantially uniform manner.
14. The device of claim 13 , wherein the cell capture surface of the first channel or the second channel comprises a pattern of first and second regions, the first region comprising the cell rolling-inducing agent, and the second region comprising the capture agent.
15. The device of claim 14 , wherein the first region further comprises the capture agent.
16. The device of claim 14 , wherein the first and second regions are arranged in an alternating pattern.
17. The device of claim 13 , wherein the cell capture surface of both the first channel or the second channel comprise a pattern of first and second regions, the first region comprising the cell rolling-inducing agent, and the second region comprising the capture agent.
18. The device of claim 1 , wherein the cell-rolling inducing agent is covalently attached to the cell capture surface.
19. The device of claim 1 , wherein the cell-rolling inducing agent is immobilized to a surface of the microfluidic device via a linker.
20. A method of capturing a Circulating Tumor Cell (CTC) and Circulating Cancer Stem Cell (CSC) from a sample comprising the step of introducing said sample into the device of claim 1 .