Methods and apparatus for generating and utilizing linear moving optical gradients

48 Pages·2013·4.09 MB·English

US 20020160470A1
(19) United States
(12) Patent Application Publication (10) Pub. N0.: US 2002/0160470 A1
Zhang (43) Pub. Date: Oct. 31, 2002
(54) METHODS AND APPARATUS FOR (52) US. Cl. ........................................... .. 435/1731; 435/2
GENERATING AND UTILIZING LINEAR
MOVING OPTICAL GRADIENTS
(75) Inventor: Haichuan Zhang, San Diego, CA (US) (57) ABSTRACT
Correspondence Address:
LYON & LYON LLP
633 WEST FIFTH STREET Apparatus and methods are provided for interacting light
SUITE 4700 With particles, including but not limited to biological matter
LOS ANGELES, CA 90071 (US) such as cells, in unique and highly useful Ways. Optophore
sis consists of subjecting particles to various optical forces,
(73) Assignee: GenoptiX
especially optical gradient forces, and more particularly
moving optical gradient forces, so as to obtain useful results.
(21) Appl. No.: 10/053,507
In one implementation, a population of particles, comprising
(22) Filed: Jan. 17, 2002 tWo or more differing particles, e.g., red blood cells and
White blood cells, are illuminated by a line of light Which is
Related US. Application Data moved sloWly relative to the particle population. The par
ticles are moved With the line until the population is aligned.
(63) Continuation-in-part of application No. 09/993,377, Next, the line of particles is subject to relative motion of
?led on Nov. 14, 2001, Which is a continuation-in-part light relative to the particles, such as by rapidly moving the
of application No. 09/845,245, ?led on Apr. 27, 2001.
line of illumination relative to the physical position of the
particles. By moving the line aWay from the particles at a
(60) Provisional application No. 60/248,451, ?led on Nov.
rate great enough that certain particles remain behind, effec
13, 2000.
tive separation, characterization and/or identi?cation of the
Publication Classi?cation particles may be made. Optionally, the direction of the loW
initial scan is in a direction opposition to the more rapid scan
(51) Int. Cl? ........................... .. A01N 1/02; C12N 13/00 after the particles have been aligned.
Patent Application Publication Oct. 31, 2002 Sheet 1 0f 25 US 2002/0160470 A1
Focused Beam
Cross-Section
of Intensity
76
Particle
l0
(QB-MM)
FV =2n'r3 a + 225
FV = Optical force on particle towards higher intensity
r = Radius of particle
85 = Dielectric constant of backround medium
a = Dielectric constant of particle
| = Light intensity (Wlcm 2)
V = Spatial derivative
, FIG. 1
Patent Application Publication Oct. 31, 2002 Sheet 2 0f 25 US 2002/0160470 A1
FIG. 2
22
Km
22
/\/ 22
26 w a 40
.32
28
52
_50_
FIG. 3
90 92
i0. 82 9%
Ci 96'? W8 M8
Q Jk94 112 I14
105M116
84 35 110
720 “402
704 Microscope Objective
706
FIG. 4 I08
Patent Application Publication Oct. 31, 2002 Sheet 3 0f 25 US 2002/0160470 A1
Microscope Objective
Y I
Levitated Particle
[I M Mic>>ope Slide
Microscope Objective
FIG. 4A
Patent Application Publication Oct. 31, 2002 Sheet 4 0f 25 US 2002/0160470 A1
6528
E556
E
Ȥ
vm3202i5
§.
vNI\\11I1Q\1 3 ;R
mmms5,
m“m3.m%:
w,ke2“:
m?céywz?m.
(MUl5:M !
_
NE:?
5 22; 955:a
VmmA10% :
3m@?uzszMl 5m
Patent Application Publication Oct. 31, 2002 Sheet 5 0f 25 US 2002/0160470 A1
gm 6528
25.H55
8
VNmew2
_3m 8w
5
§(
5walk
8%?”
@262
20%
595%:;
AQP2
_
.65m@2%
aVm:Qm :2
Patent Application Publication Oct. 31, 2002 Sheet 6 0f 25 US 2002/0160470 A1
FIG. 7
)
‘ 252 w
230
234v/
FROM -—->~ 248 SOURCE
CONTROL
240 P
238
242
244 IR FILTER 246
Patent Application Publication Oct. 31, 2002 Sheet 7 0f 25 US 2002/0160470 A1
280
/ 255
FIG. 9A
Patent Application Publication Oct. 31, 2002 Sheet 8 0f 25 US 2002/0160470 A1
296 290
290 \ 292
2;; t: ~90
#292
i i) i k l“
294
FI G. 1 0
406
406 406
ulmensity) lZ\/\\ FIG. 1 1A
. 407
402
lFuForce) FIG. 11B
474
“W otentia "M/ / N FIG. 11C
4 08
Patent Application Publication Oct. 31, 2002 Sheet 9 0f 25 US 2002/0160470 A1
@ 300
FIG. 12A
502
@ M304
@
FIG. 1215’ FIG. 12C
u (POTENTlAL)
578
FIG. 1315’ FIG. 13C