Methods and systems for cancer diagnosis and prognosis

• US 10,495,644 B2
• Filed: 04/01/2015
• Issued: 12/03/2019
• Est. Priority Date: 04/01/2014
• Status: Active Grant

• Current Assignee: Academia Sinica (Government of The Republic of China)
• Original Assignee: Academia Sinica (Government of The Republic of China)
• Inventors: Chang, Ying-Chih, Lai, Jr-Ming, Wu, Jen-Chia, Chen, Huai-Lu, Shao, Hung-Jen
• Primary Examiner(s): Martinez, Rebecca L
• Application Number:
  US14/781,165
• Publication Number:
  US 20170219593A1
• Time in Patent Office: 1,707 Days
• Field of Search: None
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502769 characterised by multiphase flow arrangements
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/57492 involving compounds localized on the membrane of tumor or cancer cells

Abstract

The disclosure provides for compositions and methods of making and using a foam composition and its utility in clinical applications.

Claims

1. A method of releasing target cells from a blood sample captured on a surface of a microfluidic channel, the method comprising:

flowing a foam composition across the surface, wherein the surface comprises a lipid bi-layer coupled to a binding moiety selective for said target cells and the target cells are captured in association with said binding moiety coupled to the lipid bi-layer; and

detaching at least a part of the lipid bi-layer, thereby releasing the target cells captured on the lipid bi-layer,

wherein the foam composition comprises a plurality of air bubbles, a majority of which has a diameter smaller than a width of the microfluidic channel or a height of the microfluidic channel.

2. The method of claim 1, wherein the captured target cells are released with at least 40% efficiency and 40% viability.

3. The method of claim 1, further comprising a) staining the target cells with a panel of antibodies and b) identifying an origin source based on the staining result.

4. The method of claim 3, wherein the panel of antibodies comprises at least two of anti-panCK, anti-CK18, anti-CK7, anti-TTF-1, anti-CK20 mixed with anti-CDX-2, anti-PSA mixed with anti-PSMA.

5. The method of claim 1, further comprising analyzing the released target cells thereby assessing a presence, absence, severity, metastasis, or tissue of origin of a condition in a subject.

6. The method of claim 5, wherein the condition is cancer and assessing the severity comprises determining a cancer stage.

7. The method of claim 5, wherein the target cells are CTCs, and wherein analyzing comprises enumerating CTCs, enumerating viable CTCs, or performing a molecular analysis assay on the CTCs.

8. The method of claim 5, wherein the analyzing comprises comparing a number of released viable target cells to a cutoff value.

9. The method of claim 1, wherein the blood sample has a volume equal to or less than 6 mL.

10. The method of claim 9, wherein the blood sample has a volume equal to or less than 2 mL.

11. The method of claim 1, wherein at least 50% of said air bubbles comprise a diameter from 10 to 100 microns.

12. The method of claim 1, wherein the majority of the air bubbles has a diameter smaller than ½

a width of the microfluidic channel or ½

a height of the microfluidic channel.

13. The method of claim 1, wherein said flowing comprises flowing the foam composition at a linear velocity of at least 2.5 mm/s.

14. The method of claim 1, wherein said flowing comprises flowing the foam composition at a linear velocity of at most 4 mm/s.

15. The method of claim 1, wherein said flowing removes greater than 60% of said lipid bi-layer.

16. The method of claim 1, wherein a ratio of liquid to air in said composition is at least 1.5:

1.

17. The method of claim 1, wherein the foam composition comprises a protein-containing solution mixed with air.