Micro size rocket fabrication, anti-body loading and treatment with the cancer cells.

2. • History and outcome
• Implementing into physiological media
• Antibody binding strategy to the surface
• Function in different cancerous cell condition and
it’s detection
2

3. Why not use chemistry to drive tiny engines
and to operate tiny machines in the liquid
phase, in much the same way that Nature
has been using biochemistry to power a
myriad of biological motors and machines?
-Richard P. Feynman

4. 4
Autonomous movement and self‐assembly
R. F. Ismagilov et al, Angew. Chem. Intl. Ed., 41, 652-654 (2002)

5. Y.Shirai et al, Nano Letters, 5, 2330-2334 (2005)
C.Cheng et al, ACS Nano, 3, 3069-3076 (2009)55
S.Balasubramanian et al, Angew. Chem. Int. ed., 50, 4161-4164 (2011)

6. Uncontrolled and unregulated growth of the cell is known as cancer.
This results in malignant tumors and invade nearby parts of the body
through the lymphatic system or bloodstream
Circulating Tumor Cells(CTCs) are the primary entities responsible
for spawning cancer cell metastasis
CTCs are cells that have detached from a primary tumor and
circulate in the bloodstream
Detection of CTCs provides an indicator for the clinical diagnosis and
prognosis of various types of cancers
E.I. Galanzha et al, Nat. Nanotechnol., 4, 855-860 (2009)

7. 7
Y. Wang et al, Langmuir, 22, 10451-10456 (2006)

8. 8
Y. Wang et al, Langmuir, 22, 10451-10456 (2006)

9. Funnel shaped platinum-gold micro jet engines
Manesh KM et al, ACS Nano, 4, 1799-1804 (2010)

10. Cathode Au, E0
Au+/Au= 1.68 V ; Anode Pt, E0
Pt+2/Pt= 1.2 V
Cathodic reaction- Anodic reaction-
H2O2 + e- OH- + OH. H2O2 - e- H+ +HO2
.
OH. + e- OH- HO2
. - e- H+ + O2
The chain reaction could also occur
OH. + H2O2 HO2
. + H2O HO2
. + H2O2 OH. + H2O + O2
with the termination-step, OH. + HO2
. H2O + O2
The overall electrode reactions were then,
Cathodic, H2O2 + 2H+ +2 e- 2H2O
Anodic, H2O2 O2 + 2H+ + 2 e-
D.W. McKEE, Journal Of Catalysis, 14, 355-364 (1969)

11. 11
A. Bubble propulsion mechanism for driving motion
B. Bipolar electrophoresis(electro kinetic) mechanism for driving motion
A
B
Y. Wang et al, Langmuir, 22, 10451-10456 (2006)

12. (A) Etched 50 m diameter Ag wire, (B) Pt-Au tubular microcone following the Ag dissolution
Manesh KM et al, ACS Nano, 4, 1799-1804 (2010)

13. 1.6 sec
0.4 sec
0 sec
1.2 sec0.8 sec
2 sec
Manesh KM et al, ACS Nano, 4, 1799-1804 (2010)

14. Red and black curve represent microrockets with diameter of 5 and 2 m respectively
http://phys.org/news/2012-01-bubble-propelled-microrockets-human-stomach.html

15. a. Overall dimension of microrocket
b. Size of the metal segments
c. Choice of metals
d. Concentration and viscosity of H2O2
e. Surfactant additives
f. pH
g. Ionic strength
15
Manesh KM et al, ACS Nano, 4, 1799-1804 (2010)

16. I. Such nano-motors are highly incompatible with
the high-ionic strength of biological fluids
II. It does not have the necessary towing force to
carry the large mammalian cells
III. Locomotion of this kind of microjet engine is
highly non-functionalized and also it can’t carry
antibody for any specific antigen
16
Manesh KM et al, ACS Nano, 4, 1799-1804 (2010)

17. 17

18. Demonstrating a new kind of micro-rocket
Compatible with high ionic- having the necessary towing force
strength of biological fluid to carry the large mammalian cells
Locomotion of this micro-rocket is highly functionalized with an antibody specific for
antigenic surface proteins expressed on cancer cells
18
S.Balasubramanian et al, Angew. Chem. Int. ed., 50, 4161-4164 (2011)

19. i. Baked at 115C for 60 sec
ii. Exposed to UV-light
iii. Metallic layers were deposited
i. removal of exposed
photoresist layer
ii. ~60 nm gold layer was
sputtered onto the rolled-up
micro tubes
S.Balasubramanian et al, Angew. Chem. Int. ed., 50, 4161-4164 (2011)
Positive photoresist Microposit S1827
Spin coated on
Silicon-wafer

20. 20

21. i. Binary mixture of MUA and
MCH in absolute ethanol
21
B.L.Frey and R.M.Corn, Anal. Chem., 68, 3187-3193 (1996)
i. Anti-CEA mAb in PBS
ii. Stored in ethanolamine
iii. Washing for use
Microrockets Self-assembled monolayer (SAM)
N
CH3
CH3
CH3
N C N

22. 22

23. Motion of an anti-CEA mAb coated microrocket in human serum at 2 S intervals with 85 ms-1 speed(a-c)
23
S.Balasubramanian et al, Angew. Chem. Int. ed., 50, 4161-4164 (2011)

24. 24

25. Pick-up and transport of a CEA+ pancreatic cancer cell by an anti-CEA mAb modified microrocket
25
S.Balasubramanian et al, Angew. Chem. Int. ed., 50, 4161-4164 (2011)

26. From Stokes’ law,
Fd=6rv,
where =solution viscosity, r=cell-radius, v=linear velocity of the cell (16ms-1),
Fd =drag force that a cell would experience at a cont. velocity of one body-length/second
26
S.Balasubramanian et al, Angew. Chem. Int. ed., 50, 4161-4164 (2011)

27. 27

28. Approaching a cylindrical shape of microrocket, Stokes’ drag law for
cylinder becomes
Where, R=radius of the microrocket=2.5m
L=length of the microrocket=60m
The shear stress (s) as a result of microrocket interaction with the cell
can be written as,
where, A=interaction area
28

29. • indicates the anti-CEA mAb-modified microrocket moving in the bottom plane
This result is similar to that obtained for cell capture using microchip
technology. 29

30. 30

31. Anti-CEA mAb-modified (a-d) and unmodified (e-h) microrockets with
CEA+ cancer cells (a,b,e and f ) and CEA- cancer cells (c,d,g and h)
S.Balasubramanian et al, Angew. Chem. Int. ed., 50, 4161-4164 (2011)

32. Red arrows indicate trypan blue stained dead cells 32
S.Balasubramanian et al, Angew. Chem. Int. ed., 50, 4161-4164 (2011)

33. CEA-
Cancer
cells
CEA+
Cancer cells
Microrockets
33
S.Balasubramanian et al, Angew. Chem. Int. ed., 50, 4161-4164 (2011)

34. In the search for biologically friendly fuels, initials steps
has been taken where carbon fibers decorated with
glucose-oxides and bilirubin-oxidase enzymes were
propelled in the presence of a glucose solution.
Hopefully in near future this technique will be applicable
to accumulate cancer cells inside human-body with much
more compatible bio-friendly and efficient fuels.
34
Nicolas Mano and Adam Heller, JACS, 127, 11574-11575 (2005)
Manesh KM et al, ACS Nano, 4, 1799-1804 (2010)

35. i. We could increase the efficiency of viable cell
separation process by controlling the shear stress
ii. This can be readily incorporated in micro channel
networks for creating integrated microchip devices
a. For high capture efficiency and single step isolation of
CTCs
b. Can be extended to accumulating CTCs in a pre-defined
collection area by detaching the cancer cells
35

36. Thanks for
giving
attention and
time!
36