[Name of Document] REQUEST FOR PATENT
[Reference number] 33 18 10JP00
[Filing Date] 3 August 201 1
[Address] JPO Commissioner
[Int. Cl.] GOlN 37/00
GOlN 33/48
GOlN 1/10
[Inventor]
[Domicile or Residence]c/o SONY CORPORATION,
I 1-7-1 Konan, Minato-ku, Tokyo, Japan
[Name] AKIYAMA, Yuj i
I ~ [Applicant for Patent]
I [Identification Number] 000002 185
[Name] SONY CORPORATION
[Identification Number] 100 1 12874
[Patent Attorney]
Ir\ramel WATANABE, Kaoru
[Telephone Number] 03-5475-564 1
[Prepayment Ledger Number] 005094
[Amount] JPY 15,000-
. [List of Attached Documents]
[Name of Document] Description 1
[Name of Document] Claims 1
[Name of Document] Abstract 1
[Name of Document] Drawing(s) 1
[Number of General Power of Attorney] 0200464
[Name of Document] DESCRIPTION
[Title of the Invention] MICROCHIP AND PARTICLE ANANLYZING APPARATUS
[Technical Field]
[OOO 11
The present disclosure relates to microchips. More particularly, embodiments of the
present disclosure relate to a microchip used in analyzing particles such as cells or the
like.
[Background Art]
[0002]
Recently developed microchjps are provided with regions or channels which are formed
to perform a chemical or biological analysis on a substrate made of silicon, glass, or the
like by employing micromachining techniques used in the semiconductor industry.
Analysis systems using such microchips are called a micro-total-analysis system (micro-
TAS), lab-on-a-chip, biochip or the like. These analysis systems are paid attention to
as technology capable of enhancing the speed, efficiency, or integration of analysis, and
further capable of providing a compact analyzing apparatus.
[0003]
The micro-TAS is used in a case where an analysis is performed with small amount of
samples or a case where microchips are designed for disposable use, thus the micro-TAS
is particularly expected to be applied to a biological analysis which deals with valuable
and very small amount of samples or a large number of specimens. As an application
example of the micro-TAS, electrochemical detectors and compact-sized electrochemical
sensors are presented. The electrochemical detectors are used in liquid chromatography,
and the compact-sized electrochemical sensors are used in clinical or medical practice.
[0004]
As another application example of the micro-TAS, there is a technology in which
particles such as cells, micro-beads, and so on are analyzed in a channel provided on a
microchip. In this technology, the characteristics of particles are analyzed in an optical,
electrical or magnetic manner. In this particle analyzing technology, when there is a
population (group) which is determined that a predetermined condition is satisfied
according to the analyzed results, the population is separated and collected from among
particles.
[OOOS]
Patent Document 1, for example, discloses "a microchip including a flow path through
which liquid containing micro particle flows, an orifice through which the liquid flowing
through the flow path is discharged to a space outside the chip, and a light-irradiated
portion disposed in a predetermined location of the flow path for detecting an optical
property of the micro particle". The microchip disclosed in Patent Document 1 is used
to sort the micro particle determined to have a predetermined optical property by
controlling movement directions of a liquid drop containing the micro particle
discharged from the orifice.
[Prior Art Document(s)]
[Patent Document(s)]
[0006]
[Patent Document 11
[Summary of the Invention]
[Problem(s) to Be Solved by the Invention]
[0007]
In the particle analyzing microchip such as described in Patent Document 1, in order to
accurately control a flow direction of droplets ejected from an orifice and to properly
separate and sort the particles, it will be necessary to stably eject the droplets of regular
size and shape from the orifice and to maintain a steady ejecting path.
[OOOS]
In light of the foregoing, it is desirable to provide a microchip capable of steady ejecting
droplets of regular size and shape from an orifice and maintaining a steady ejecting path
in a cost-effective and easy manner without using expensive materials or undergoing
complicated molding processes.
[Means for Solving the Problem(s)]
[0009]
According to an embodiment of the present disclosure, there is provided a microchip
including a flow channel, an ejection portion, and a cutout portion. The flow channel is
configured to convey a fluid therein. The ejection portion includes an opening directed
toward an end face of a substrate layer, and the ejection portion is configured to eject the
fluid flowing through the flow channel to outside. The substrate layer is laminated to
each other. The cutout portion is formed between the opening of the ejection portion
and the end face of the substrate layer. The cutout portion has a larger diameter than
that of the opening. The microchip according to the embodiment may further include a
connection portion, configured to have a straight line shape, for connecting the flow
channel to the ejection portion.
In the microchip according to the embodiment, the cutout portion is provided between
the opening of the ejection portion and the end face of the substrate layer, and the
ejection portion is provided at a position recessed inwardly by a predetermined distance
from the end face of the substrate layer susceptible to molding defect due to injection
molding. The opening of the ejection portion therefore can be prevented from being
irregular in shape, thereby forming the ejection portion having a desired shape.
.In the microchip of the embodiment, the ejection portion is provided at a position
recessed inwardly by a predetermined distance from the end face of the substrate layer - -
susceptible to deformation due to thermocompression bonding. The shape of the
ejection portion and the shape of the connection portion arranged to connect the flow
channel with the ejection portion thus can be prevented from being deformed. Also,
the ejection portion and flow channel having desired shapes can be formed.
In the microchip of the embodiment, the cutout portion preferably has a width of 0.2
millimeters or more in corresponding with a distance between the opening and the end
face.
The cutout portion having a width of 0.2 millimeters or more allows molding defect
caused due to injection molding or deformation caused due to thermocompression
bonding to be prevented certainly.
The microchip according to the embodiment of the present disclosure is prefer+!y used
/
in analyzing particles. There is also provided a particle analyzing apparat@ having the
/'
microchip mounted thereon. //
[OO 1 01
As used herein, the term "perticle(s)" should be broadponstrued to include
bioparticles such as cell, microorganism, and liposome as well as synthetic particles
such as latex particles, gel particles, and industrial particles. Examples of the
bioparticles include chromosome, liposome, mitochondria, and organelle (cell
compartment) constituting various cells. Examples of the cells include animal cells
(e.g., blood corpuscle cells) and plant cells. Examples of the microorganisms include
bacteria such as colon bacillus, viruses such as tobacco mosaic virus, and fungi such as
yeast. Examples of the microscopic bioparticles include microscopic biopolymers such
as nucleic acid, proteins, and complexes thereof. The industrial particles may be, for
example, organic or inorganic polymer materials, metals or the like. The organic
polymer materials include polystyrene, stylene-vinyl benzene, and polymethyl
methacrylate. Examples of the inorganic polymer materials include glass, silica, and
magnetic materials. Examples of the metals include gold colloid and alumina. The
shapes of these particles are typically spherical, but may be non-spherical. In addition,
'embodiments of the present disclosure are not particularly limited to factors such as
particle size or mass.
[Effect(s) of the Invention]
[OO 111
According to the embodiments of the present disclosure, there is provided a microchip
capable of stably ejecting droplets of regular size and shape from an orifice and
maintaining a steady ejecting path in a cost-effective and easy manner without using
expensive materials or undergoing complicated molding processes.
[Brief Description of the Drawing(s)]
[OO 1 21
[Fig. 11 Fig. 1 is chematic diagrams illustrating a configuration of a particle
analyzing apparatus A according to an embodiment of the present disclosure;
[Fig. 21 Fig. 2 is a schematic diagram illustrating a configuration of the particle
analyzing apparatus A according to an embodiment of the present disclosure;
[Fig. 31 Fig. 3 is a schematic diagram illustrating a configuration of the particle
analyzing apparatus A according to an embodiment of the present disclosure;
[Fig. 41 Fig. 4 is a schematic diagram illustrating a configuration of the particle
analyzing apparatus A according to an embodiment of the present disclosure;
[Fig. 5) Fig. 5 is schematic diagrams illustrating a configuration of a microchip
1 according to an embodiment of the present disclosure;
[Fig. 61 Figs. 6 is schematic diagrams illustrating a configuration of an orifice
12 according to an embodiment of the present disclosure;
[Fig. 71 Fig. 7 is a schematic diagram illustrating a droplet D ejected from the
orifice 12 according to an embodiment of the present disclosure;
[Fig. 81 Fig. 8 is a schematic diagram illustrating a particle sorting operation of
the particle analyzing apparatus A according to an embodiment of the present disclosure;
[Fig. 91 Fig. 9 is a photograph showing a typical example of the shape of
droplets ejected from the microchip 1 (A) according to the embodiment of the present
disclosure and a typical example of the shape of droplets ejected from a microchip in
the related art shown in Fig. 10 (B); and
[Fig. 101 Fig. 10 is schematic diagrams illustrating a configuration of an orifice
*of the microchip in the related art.
[Mode(s) for Carrying out the Invention]
[00 1 31
Hereinafter, preferred embodiments of the present disclosure will be described in detail
with reference to the appended drawings. Note that, in this specification and the
appended drawings, structural elements that have substantially the same function and
structure are denoted with the same reference numerals, and repeated explanation of
these structural elements is omitted.
The description wili be given in the following order.
1. Particle Analyzing Apparatus
2. Microchip
3. Operation of Particle Analyzing apparatus
[00 141
1. Particle Analyzing Apparatus
Figs. 1 to 4 are schematic diagrams illustrating configurations of a particle analyzing
apparatus according to an embodiment of the present disclosure. In these figures, the
particle analyzing apparatus A includes a particle sorting region protected by a cover A2
of a main body A1. This particle sorting region is further protected by a sorting cover
A3. The particle sorting region is configured to include a microchip 1 which is inserted
and mounted into a top opening of 'the sorting cover A3. In Fig. 2, a block-shaped
arrow indicates an insertion direction along which a microchip module is inserted into
the sorting cover A3. The microchip module includes the microchip 1 as a constituent
element thereof. The illustration of the sorting cover A3 is omitted in Fig. 3 for the
convenience of explanation. Further, only the microchip 1 of the microchip module
inserted into the sorting cover A3 is shown in Fig. 3, and other portions of the microchip
module are qmitted.
[00 151
The particle sorting region includes the microchip 1, an optical detection unit 3, a pair of
electrodes 4, 4 and three collection units (containers 51, 52, and 53). The optical
detection unit 3 irradiates a light onto a predetermined area of the microchip 1. The
.optical detection unit 3 and the pair of electrodes 4, 4 are provided in the main body A1.
-Each of the containers 51, 52 and 53 is detachably mounted to the main body A1.
[00 161
A configuration of the particle sorting region will be described in detail below with
reference to Fig. 4. Fig. 4 illustrates the microchip 1, the optical detection unit 3, the
pair of electrodes 4, 4, the container 51 to 53, and so on. As shown in Fig. 4, a
vibrating device 2 is provided on the microchip 1. Electrodes 6, 6 are connected to the
ground.
[00 171
The microchip 1 includes a sample flow channel 11. A stream of fluid containing the
particle to be sorted flows through the sample flow channel 11 (the fluid is referred to
hereinafter as a "sample fluid"). The optical detection unit 3 irradiates a light onto a
predetermined area of the sample flow channel 11 (the light is referred to hereinafter as
a "measuring light"). The optical detection unit 3 also detects a light emitted from the
particles flowing through the sample flow channel 11 (the light is referred to hereinafter
as a "light to be measured"). The area which is irradiated with the measuring light by
the optical detection unit 3 in the sample flow channel 11 is hereinafter referred to as a
"light irradiation area".
[00 1 81
The optical detection unit 3 may be structurally similar to that used in a particle
analyzing apparatus in the related art. More specifically, the optical detection unit 3
includes a laser light source, an irradiation system, and a detection system. The
irradiation system includes a condensing lens or diachronic mirror configured to
condense and irradiate a laser light onto particles, and a band pass filter. The detection
system is arranged to detect the light to be measured which is emitted from the particles
in response to the irradiation of the laser light. The detection system is configured to
include a photo multiplier tube (PMT), or an area image-capturing device such as a
charge coupled device (CCD) or complementary metal-oxide semiconductor (CMOS)
device. In the Fig. 4, only the condensing lens is illustrated as the optical detection
unit 3. In Fig. 4, the irradiation and detection systems are arranged so that they have a
common flow channel, but the irradiation and detection systems may be arranged to have
the respective flow channels.
[00 191
.The light to be measured is detected by the detection system of the optical detection unit
3 and is emitted from the particles in response to the irradiation of the laser light.
Examples of the light to be measured may include a forward scatter, a side scatter, a
scattered light such as Rayleigh scattering or Mie scattering, or fluorescence. The light
to be measured is converted into electrical signals. The optical characteristics of the
particles are detected on the basis of the electrical signal.
[0020]
The sample fluid is passed through the light irradiation area and then is ejected from an
orifice 12 to the outside of the microchip. The orifice 12 (also referred to as an
ejection portion) is provided at one end of the sample flow channel 11. In this case,
The microchip 1 is vibrated by the vibrating device 2 such as a piezo-electric element
and thus the sample fluid can be broken into individual droplets and be ejected to the
outside of the microchip. That is, the droplet D is ejected to the outside of the
microchip.
[002 11
The droplet D may contain respective particles to be sorted. The pair of electrodes 4, 4
are arranged along the flow direction of droplets ejected to the outside of the microchip.
The pair of electrodes 4, 4 are arranged to be faced each other so that the droplets may
4k
be passed between the electrodes. An electric charge applying device (not shown)
applies electric charge to the ejected droplet. The flow directions of droplets are
controlled by an electrostatic repulsive force (or an electrostatic attractive force) acting
between the pair of electrode 4, 4 and the droplet which is charged with any electric
charge. The pair of electrode 4, 4 allows the droplets to be diverted and guided into
respective corresponding one of the containers 5 1, 52, and 53.
[0022]
The flow directions of droplets containing individual particles are controlled by the pair
of electrode 4, 4 based on the optical characteristics of individual particles detected by
the optical detection unit 3. Thus, the particle analyzing apparatus A can collect and
sort the particles with desired characteristics into respective corresponding one of the
containers 5 1 to 53.
[0023]
In the particle analyzing apparatus A, electric or magnetic detection device may be used
.instead of the optical detection unit 3. When the characteristics of particles are
intended to be detected in an electrical or magnetic manner, microelectrodes are
arranged to be faced each other and the sample flow channel 11 is placed between the
microelectrodes, thereby measuring resistance, capacitance, inductances, impedance,
variations in electric field between the electrodes, magnetization, variations in magnetic
field, variations in magnetic field, and so on. In this case, the particles are sorted on
the basis of electrical or magnetic characteristics of the particles.
[0024]
2. Microchip
Figs. 5A and 5B are schematic diagrams illustrating a configuration of the microchip 1.
Fig. 5A shows a schematic top view and Fig. 5B shows a schematic sectional view taken
along the line P-P of Fig. 5A. Figs. 6A, 6B and 6C are schematic diagrams illustrating
a configuration of the orifice 12 of the microchip 1. Fig. 6A shows a schematic top
view, Fig. 6B shows a schematic sectional view taken along the line P-P of Fig. 5A, and
Fig. 6C shows a front view.
[0025]
In the microchip 1, substrate layers la, lb are bonded to each other so as to form the
sample flow channel 11. The sample flow channel 11 can be formed by injection
&
molding of a thermoplastic resin using a mold. The sample flow channel 11 may be
formed at either one or both of the substrate layers la, lb. In the case where the
sample flow channel 11 is formed( at both of the substrate layers 1 a, I by respective parts
of the sample flow channel are partially formed on both layers.
[0026]
As a material used in forming a typical microchip, the thermoplastic resin can employ a
known plastic material such as polycarbonate, polymethyl methacrylate (PMMA), cyclic
polyolefin, polyethylene, polystyrene, polypropylene, and polydimethyl siloxane
(PDMS).
[0027]
The injection molding may be implemented in the usual way. For example, when
injection molding process is done by polyolefin (ZEONEX 1060R manufactured by Zeon
Corporation) using the injection molding machine (SE75DU manufactured by Sumitomo
Heavy Industries, Ltd.), the typical molding process is performed under conditions
.involving a resin temperature of 270 deg C, a mold temperature of 80 deg C, and a mold
clamping force of 500 kilo-Newton (kN).
[002 81
The substrate layers la, 1 b forming the sample flow channel 11 are bonded to each other
by thermocompression bonding using well known processes. For example, when the
substrate layers made of polyolefin are bonded together by thermocompression bonding
using the nano-imprint machine (Eitre618 manufactured by Canon Inc.), the typical
compression bonding process is performed by pressing the substrate layers for several
minutes under conditions involving a bonding temperature of 95 deg C and a pressing
force of 10 kilo-Newton .
LO02 91
The sample fluid flowing out from a sample fluid inlet 13 joins the sheath fluid flowing
out from a sheath fluid inlet 14. The joined stream passes through the sample flow
channel 11. More specifically, the sheath fluid flowing out from the sheath fluid inlet
14 branches into two directions and then joins the sample fluid flowing out from the
sample fluid inlet 13 at a joining point, so that the sample fluid may be sandwiched
between the two directional flows of the sheath fluid. Thus, the sample fluid is placed
midway between the flows of the sheath fluid, thereby forming three-dimensional
laminar flow.
[0030]
When there are some clogging materials or bubbles within the sample flow channel 11, a
suction channel 15 removes any clogging material or bubbles by causing the stream in
i the sample flow channel 11 to be temporarily flowed in the reverse direction. The
reversing of the flow direction is implemented by a negative pressure applied to the the
sample flow channel 11. A suction outlet 151 is formed at one end of the suction
channel 15. The suction outlet 151 is connected to a negative pressure source such as a
vacuum pump. The other end of the suction channel 15 is communicated with the
sample flow channel 11 through a communicating port 152.
[003 11
The three-dimensional laminar flow is passed through a tapered portion 16 1 (see Fig. 5)
or 162 (see Fig. 6) which is gradually thinned down along a fluid flowing direction, and
.then the three-dimensional laminar flow is ejected from the orifice 12 provided at one
'end of the sample flow channel. The tapered portion is formed such that the cross
section profile of the tapered portion perpendicular to the fluid flowing direction is
narrowed down in a gradual or stepwise manner according to the fluid flowing direction.
As shown in Fig. 7, the droplet D is ejected from the orifice 12 to the outside of the
microchip. In Fig. 7, the droplet D is ejected from the orifice 12 in an ejection
direction F.
[(I0321
A straight portion 17 connects the sample flow channel 11 to the orifice 12 and is formed
in a straight line shape. The straight portion 17 allows the droplet D to be ejected
straight from the orifice 12 in the direction F indicated by an arrow. The straight
portion 17 has a length (denoted as "k" in Fig. 6B) in a range from 100 micrometers to
500 micrometers when the orifice 12 has an opening diameter (denoted as "I" in Fig. 6C),
for example, in a range from 30 micrometers to 250 micrometers. If the straight
portion 17 has a length of 100 micrometers, then the ejection direction of the droplet D
may be not constant. In this case, it will be difficult to precisely control the ejection
direction of the droplet being ejected to the outside of the microchip.
COO331
The orifice 12 is opened toward the end face of the substrate layers la, lb. A cutout
(1. portion 121 is provided between the opening of the orifice 12 and the end face of the
substrate layers. The cutout portion 121 is formed by cutting out the substrate layers
la, Ib between the opening of the orifice 12 and the end face of the substrate layers so
that a diameter L of the cutout portion 121 may be larger than the opening diameter 1 of
the orifice 12 (see Fig. 6C). The diameter L of the cutout portion 121 is preferably
more than two times larger than the opening diameter I of the orifice 12 so that the flow
of the droplets ejected from the orifice 12 may be prevented from being obstructed.
However, if the diameter L of the cutout portion 121 is too large, then uniformity of a
temperature or pressure distribution becomes worse, or gas is gathered in the cutout
portion 121, and this becomes the cause of shape irregularity of the orifice 12.
Therefore, the cutout portion 121 preferably has the diameter L in a range from 400
micrometers to about 2 millimeters, when the orifice 12 typically has the opening
diameter I of about 200 micrometers.
[0034]
In this embodiment, the opening of the orifice 12 has a circular shape and the cutout
portion 121 is formed by cutting the substrate layers 1 a, I b in an octagonal prism shape.
However, the opening of the orifice 12 is not limited to a circular shape, and may be
oval, square, rectangular, or polygonal. The opening of the orifice 12 preferably has a
symmetric shape so as to achieve symmetries of thermal conduction and pressure
loading when the substrate layers la, lb are bonded through thermocompression. The
cutout portion 121 is not limited to an octagonal prism shape, and may be any shape as
long as a space communicating with the opening of the orifice 12 is formed and the
shape does not-inhibit .the flow of the droplet ejected from the orifice 1.2. , .The cutout
portion 121 is preferably placed coaxial with the orifice 12, but the embodiment is not
limited to this. If the thickness of the microchip 1 is thin, then the cutout portion 121
may be formed by cutting off all the end face of the substrate layers la, lb in the
thickness direction.
[003 51
It is generally known that the molding defect called as "burr" or "undercut" are probably
occurred at a portion which is contact with the mold of the thermoplastic resin when the
substrate layer is fabricated by injection molding. In particular, the gas generated at
the time of molding will cause any portions which will be the end face of the substrate
Cv layer and its surroundings to be significantly deformed. For this reason, if the opening
of the orifice is formed at the end face of the substrate layer, then the molding defect
makes it easier to cause the orifice to become more irregular in shape.
[0036]
In the microchip 1 of the embodiment, the cutout portion 121 is provided between the
opening of the orifice 12 and the end face of the substrate layer, and the orifice 12 is
provided at a position recessed inwardly by a predetermined distance from the end face
I of the substrate layer. Therefore, even though molding defect is occurred at the end
I face of the substrate layer and its surroundings, such molding defect does not have an
influence on the shape of the orifice 12. As a result, the opening of the orifice 12 can
be accurately molded into a desired shape and the droplet D of regular size and shape
can be ejected from the orifice 12.
[003 71
- In order to be completely free from the influence of molding defect occurred at the end
-face of the substrate layer and its surroundings, a width (denoted as "w" in Fig. 6B) of
the cutout portion may be set to correspond to the distance from the opening of the
orifice 12 to the end face of the substrate layer. As an example, when a width (denoted
as "W" in Fig. 5) of the microchip 1 in the direction from the orifice 12 to the end face
of the substrate layer is 75 millimeters (the microchip size: 75 millimeters, 25
millimeters and 2 millimeters in width, length, and thickness, respectively), the width of
the cutout portion is preferably 0.2 millimeters or more. The "burr" or gas occurred
when performing an injection molding process depends on the types or conditions of the
thermoplastic resin, and thusathe width w of the cutout portion 121 is preferably set to be - , c . r -
changed over a wide range and to be optimized, depending on the types or conditions of
the thermoplastic resin.
[003 81
It has been known that the end face of the substrate layer and its surrounding edges are
likely to be susceptible to deformation due to thermal contraction as compared to a
middle portion of the substrate layer, when a thermocompression bonding process is
performed on the substrate layer. Thus, when the opening of the orifice or a flow
channel connected thereto is provided at the end face of the substrate layer and its
vicinities, the shape of the molded orifice or flow channel is likely to be deformed due
0 to the thermal contraction.
[0039]
In the microchip 1 of the embodiment, the cutout portion 121 is provided between the
opening of the orifice 12 and the end face of the substrate layer, and the orifice 12 is
provided at a position recessed inwardly by a predetermined distance from the end face
of the substrate layer. Therefore, when a thermocompression bonding process is
performed on the substrate layer, the shape of the orifice or flow channel connected
thereto will not be deformed. As a result, in the microchip 1, the shapes of the orifice
12 and straight portion 17 can be maintained in the desired shape and the droplet D of
regular size and shape can be ejected straight from the orifice 12.
[0040]
For comparison, an orifice configuration of a microchip 9 in the related art will be
described with reference to Fig. 10. The microchip 9 in the related art does not include
any mechanism that may be corresponded to the cutout portion 121 of the present
.embodiment. For reference, Fig. 9 shows the shape of droplets ejected from the
microchip 1 according to the embodiment of the present disclosure and the shape of
droplets ejected from the microchip 9 in the related art. Fig. 9A shows a typical
example of shapes of droplets ejected from the microchip 1 and Fig. 9B shows a typical
example of shapes of droplets ejected from the microchip 9.
[004 11
The microchip according to the embodiment of the present disclosure includes the cutout
portion allowing the shape irregularity or deformation of the orifice and flow channel
caused due to injection~molding~~atnhde.r mocom~ressionb onding in the substrate layer . , 5 --
to be prevented. According to the microchip of the embodiment, the droplets of regular
size and shape can be stably ejected from the uniform shaped orifice in a steady ejecting
path.
[0042]
In the microchip according to the embodiment of the present disclosure, the orifice and
flow channel having a uniform shape can be formed by injection molding and
thermocompression bonding processes using thermoplastic resin without performing the
polishing process on expensive quartz and ceramic such as alumina and zirconia, thereby
saving the cost and increasing the productivity. Furthermore, According .to the .-
microchip of the embodiment of the present disclosure, the orifice is not provided at the
distal end of the microchip, and thus breakage of the orifice due to an accidental contact
probably occurred during the manufacturing process is unlikely to happen, thereby
increasing the productivity.
[0043]
3. Operation of Particle Analyzing Apparatus
An operation of the particle analyzing apparatus A will be described with reference to
Fig. 8.
[0044]
The joined sample and sheath fluids, which are passed through the light irradiation area
of the sample flow channel 11, are ejected from the orifice 12 to the outside of the
microchip 1. In the light irradiation area, the optical detection unit detects the optical
characteristics of the particles and simultaneously detects the fluid flowing speed (flow
rate) of the particles and the interval between the particles. The optical characteristics,
.flow rate, interval and the like of the particles detected by the optical detection unit are
converted into respective electrical signals. The electrical signals are outputted to a
controller (not shown) configured to control the entire apparatus. The controller
controls a vibration frequency of the vibrating device 2 (see Fig. 4) based on the
electrical signals, and the controller vibrates the microchip 1 in such a way that the
particle P is suspended in the droplet D one particle at a time.
COO451
In addition, the controller causes the polarity of electric charge applied to each of the
sheath and sample fluids flowing through the sample flow channel 11 to be changed in
synchronization with the vibration frequency of the vibrating device 2. Thus,
individual droplets formed in the orifice 12 can be electrically charged by the controller
and will carry a positive or negative charge.
[0046]
The optical characteristics of the particle detected by the optical detection unit are
converted into the electrical signal. The electrical signal is outputted to the controller.
The controller determines which electric charge will be applied to the droplet based on
the electrical signal, in accordance with the optical characteristics of the particle
contained in each of the droplets. More specifically, when the droplets are electrically --
'ib charged by the controller, the droplet containing the particle to be sorted with desired
I characteristics may be positively charged, and the droplet which is not containing the
particle to be sorted may be negatively charged.
In this case, in order to stabilize the electrically charged state of the droplet D;in the
particle analyzing apparatus A, the ground electrodes 6, 6 are disposed in the vicinity of
the orifice 12 along the flow direction of the droplet being ejected to the outside of the
microchip. The ground electrodes 6, 6 are arranged to be faced each other and to allow
the droplets to be flowed between the electrodes. The ground electrodes 6, 6 are
disposed between the orifice 12 and a pair of electrodes 41, 42. The pair of electrodes
41, 42 controls the flow direction of the droplets.
[0048]
The flow direction of the charged droplet D ejected from the orifice 12 is controlled by
electrostatic force acting between the electrodes 41 and 42. In this case, the stable
.application of the electric charge to the droplet is necessary in order to accurately
control the flow direction of the droplet. At this time, a very high voltage is applied
between the pair of electrodes 41 and 42, and thus the electrically charged state of the
droplet D is likely to become unstable. To overcome this, in the particle analyzing
apparatus A, the ground electrodes 6, 6 are disposed between the orifice 12 and the pair
of electrode 41, 42, thereby eliminating the influence of the high potential applied
between the pair of electrode 41, 42.
[0049]
_ ,- Controlling the flow direction of the droplet D ejected-from the orifice 12, for example,
is carried out as follows. In the previous described case where the droplet containing
the particle to be sorted may be positively charged and the droplet not containing the
particle to be sorted may be negatively charged, when the electrode 41 is positively
charged and the electrode 42 is negatively charged, the droplet containing the particle to
be sorted can be deflected and sorted into the container 53. More specifically, when the
droplet containing the particle to be sorted is positively charged, the flow of the
positively charged droplet is deflected into a direction indicated by an arrow f3 by the
electrostatic repulsive force acting between the electrode 41 and the droplet and by the
electrostatic attractive force acting between the electrode 42 and the droplet. The
JI deflected droplet then moves toward the container 53. On the other hand, when the
droplet not containing the particle to be sorted is negatively charged, the flow of the
negatively charged droplet is deflected into a direction indicated by an arrow f2, and
then the droplet moves toward the container 52.
[0050]
When the droplet containing the particle to be sorted remains uncharged, the droplet not
containing the particle to be sorted is positively or negatively charged, and each of the
electrodes 41, 42 are either positively or negatively charged, then the droplet containing
the particle to -be sorted can be deflected and sorted into the container 51. The
application of the electric charge to the droplet D and the control of the droplet flowing
direction by the electrodes 41, 42 can be performed using various kinds of combinations
in a similar way to the flow cytometry in the related art. It is noted that two or more
containers for receiving the droplets D may be provided and the number of containers is
not limited to three. In addition, the container may be configured to work as an
ejection channel for ejecting the collected droplets without accommodating the collected
droplets. When the particle not to be sorted is collected, the particle may be discarded.
[005 11
As described above, according to the microchip 1, the droplet D of regular size and
shape can be stably ejected from the uniform shaped orifice 12 in a steady ejecting path.
Thus, according to the microchip 1; the flow direction of the droplet D can be precisely
controlled and the particles with desired characteristics can be correctly sorted.
[0052]
*&.. >* The description has been given with respect to -the case where positive or negative
electric charge is correspondingly applied to individual droplets depending on the
characteristics of the particle contained in the droplet and then the droplet is sorted.
Even when the optical detection unit is replaced with an electrical or magnetic detecting
mechanism, controlling of the flow direction of the droplet based on electrical or
magnetic characteristics allows sorting of the droplet, thus the particles with desired
characteristics can be diverted and sorted into the individual containers.
Additionally, the present technology may also be configured as below.
(1) A microchip including: . .
* a flow channel configured to convey a fluid therein;
an ejection portion including an opening directed toward an end face of a substrate layer,
the ejection portion configured to eject the fluid flowing through the flow channel to
outside, the substrate layer being laminated to each other; and
a cutout portion formed between the opening of the ejection portion and the end face of
the substrate layer, the cutout portion having a larger diameter than that of the opening.
(2) The microchip according to claim 1, further including:
a connection portion, configured to have a straight line shape, for connecting the flow
channel to the ejection portion.
(3) The microchip according to claim 2, wherein
the substrate layer is formed by injection molding.
(4) The microchip according to claim 3, wherein
the substrate layer is laminated by thermocompression bonding.
( 5 ) The microchip according to claim 4, wherein
.the cutout portion has a width of 0.2 millimeters or more in corresponding with a
distance between the opening and the end face. -- -
(6) The microchip according to claim 5, wherein
the microchip is used in analyzing particles.
(7) A particle analyzing apparatus having the microchip as recited in claim 6
mounted thereon.
[Reference Signs List]
[0054]
. I =. .*- *- A-Particle analyzing apparatus
Al Main body
A2 Cover
A3 Sorting cover
D droplet
P Particle(s)
1 Microchip
1 a, 1 b Substrate layer
11 Sample flow channel
J. 12 Orifice
12 1 Cutout portion
13 Sample fluid inlet
14 Sheath fluid inlet
15 Suction channel
15 1 Suction outlet
152 Communicating port
16 1, 162 Tapered portion
17 Straight portion
2 Vibrating device
3 Optical detection unit
4, 41, 42 Paired Electrode
51, 52, 53 Collection vessel (container)
6 Ground electrode

[Claim I]
[Claim 21
[Claim 31
[Claim 41
[Claim 51
[Claim 61
[Claim 71
Claims
A microchip comprising:
a flow channel configured to convey a fluid therein;
an ejection portion including an opening directed toward an end face of
a substrate layer, the ejection portion configured to eject the fluid
flowing through the flow channel to outside, the substrate layer being
laminated to each other; and
a cutout portion formed between the opening of the ejection portion and
the end face of the substrate layer, the cutout portion having a larger
diameter than that of the opening.
The microchip according to claim 1, further comprising:
a connection portion, configured to have a straight line shape, for
connecting the flow channel to the ejection portion.
The microchip according to claim 2, wherein
the substrate layer is formed by injection molding.
The microchip according to claim 3, wherein
the substrate layer is laminated by thermocompression bonding.
The microchip according to claim 4, wherein
the cutout portion has a width of 0.2 millimeters or more in corresponding
with a distance between the opening and the end face.
The microchip according to claim 5, wherein
the microchip is used in analyzing particles.
A particle analyzing apparatus having the microchip as recited in claim
6 mounted thereon.
Dated this 28.01.2014
[S WATI PAHUJA]
OF REMFRY & SAGAR
ATTORNEY FOR THE APPLICANT[S]