Microchips for optimized FISH
screenii
ing in myeloma
Vincent Sieben
Carina Debes-Marun
Patrick Pilarski
Govind Kaigala
Dr. Andrew Belch
Dr. Linda Pilarski
Dr. Christopher Backhouse
Department of Electrical Engineering,
XI International
Department of Oncology,
Myeloma Workshop
Cross Cancer Institute,
Kos, Greece
June 29, 2007
Vincent Sieben - FISH & CHIPS (S11.2, 8:15 A.M.)
1
University of Alberta, Canada
June 2007
Lab-on-a-chip ... Microfluidics
· Etched out channels
enclosed in glass.
· Nano- to micrometer
physical dimensions.
· Permit sophisticated
fluid control
June 29, 2007
Vincent Sieben - FISH & CHIPS (S11.2, 8:15 A.M.)
2
Advantages of miniaturization
Portability
+ Low cost
1947
2007
= Mass usage
& Personalized
Personalized
treatment
June 29, 2007
Vincent Sieben - FISH & CHIPS (S11.2, 8:15 A.M.)
3
The BIG picture for FISH
· FISH (several probes) cost is $1000 / pati
ti
t
en .
· Not feasible
feasible for clinical
clinical testing (PCRs
(PCRs under dollar).
June 29, 2007
Vincent Sieben - FISH & CHIPS (S11.2, 8:15 A.M.)
4
Aggenda
1. Ot
Our current FISH
FISH chi
hips
2. On-chip results
3. Other aspects of our FISH project
(integration, software, clinical testing)
4. Conclusions
June 29, 2007
Vincent Sieben - FISH & CHIPS (S11.2, 8:15 A.M.)
5
Our first "simple" chip
pp
1/10th the
the reagent,
efficient probe usage
10-fold higher
throughp
gput
Cells
Wasted
probe
Conventi
ti
l
ona slide-bd
based FISH
FISH
On-chip FISH
June 29, 2007
Vincent Sieben - FISH & CHIPS (S11.2, 8:15 A.M.)
6
Cell adhesion
Immobilizing cells
cells not
easily implemented in
sealed
microchannels.
Our temperature treatment
increased adhesion.
June 29, 2007
Vincent Sieben - FISH & CHIPS (S11.2, 8:15 A.M.)
7
On-chip FISH imag
pges
Sieben et al. IET Nanobiotechnology, vol. 1(3), pp. 27-35, June 2007.
June 29, 2007
Vincent Sieben - FISH & CHIPS (S11.2, 8:15 A.M.)
8
Robustness of on-chip FISH
t(4 14)(
;
1
p 6
16 3
.
32)
;q
13 14
q
.3 d l
e
14 32
q
b
k
rea apart
Te
Tested
sted with several
probe, patient, and cell
line combinations
53
p
d l
e
June 29, 2007
Vincent Sieben - FISH & CHIPS (S11.2, 8:15 A.M.)
9
Chip 2: On-chip p
ppumping
·On-chip p
ppumps and valves to circulate probe
· FISH in 4 hours; but quality control study required
June 29, 2007
Vincent Sieben - FISH & CHIPS (S11.2, 8:15 A.M.)
10
Chip 3: On-chip heaters
· Built in t
t
empera ure
t
con
l
ro (Vi
(Vi t
e Hoang, PCR).
· Permits automation.
53
p
probe
June 29, 2007
Vincent Sieben - FISH & CHIPS (S11.2, 8:15 A.M.)
11
Chip 4: On-chip cell sorting
pg
· We are integrating
sample preparation
(Chris Sims).
· Magnetically labeled
cells trapped.
· Unwanted cells/debris
pass through.
June 29, 2007
Vincent Sieben - FISH & CHIPS (S11.2, 8:15 A.M.)
12
Software: computer vision
· Automated classification system
(Patrick Pilarski)
· Portable device duplicates many skills
of qualified technician
FOUND PROBES
June 29, 2007
Vincent Sieben - FISH & CHIPS (S11.2, 8:15 A.M.)
13
Conclusions
On-chip FISH:
· tested with patient samples
· 10-times more cost-effective
· 10-fold higher throughput
· Significant time reduction through a combination of
Mi i
x ng
It
Int
t
egra i
tion
At
Aut
t
oma i
tion
June 29, 2007
Vincent Sieben - FISH & CHIPS (S11.2, 8:15 A.M.)
14
Discussion and Questions
Alberta Cancer
Board
June 29, 2007
Vincent Sieben - FISH & CHIPS (S11.2, 8:15 A.M.)
15