U.S. patent application number 12/877158 was filed with the patent office on 2010-12-30 for method for manufacturing substrate for mass spectrometry.
This patent application is currently assigned to CANON KABUSHIKI KAISHA. Invention is credited to Hirokatsu Miyata, Kazuhiro Yamauchi, Kimihiro Yoshimura.
Application Number | 20100326956 12/877158 |
Document ID | / |
Family ID | 38621994 |
Filed Date | 2010-12-30 |
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United States Patent
Application |
20100326956 |
Kind Code |
A1 |
Miyata; Hirokatsu ; et
al. |
December 30, 2010 |
METHOD FOR MANUFACTURING SUBSTRATE FOR MASS SPECTROMETRY
Abstract
A substrate for mass spectrometry for effectively performing
ionization has been demanded. The substrate for mass spectrometry
includes a base, a porous film formed on the base, and an inorganic
material film formed on the porous film. The inorganic material
film has a plurality of concaves formed vertically to the base, and
the diameter of the concaves is not less than 1 nm and less than 1
.mu.m.
Inventors: |
Miyata; Hirokatsu;
(Hadano-shi, JP) ; Yamauchi; Kazuhiro; (Tokyo,
JP) ; Yoshimura; Kimihiro; (Yokohama-shi,
JP) |
Correspondence
Address: |
FITZPATRICK CELLA HARPER & SCINTO
1290 Avenue of the Americas
NEW YORK
NY
10104-3800
US
|
Assignee: |
CANON KABUSHIKI KAISHA
Tokyo
JP
|
Family ID: |
38621994 |
Appl. No.: |
12/877158 |
Filed: |
September 8, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
11775539 |
Jul 10, 2007 |
7829844 |
|
|
12877158 |
|
|
|
|
Current U.S.
Class: |
216/37 ;
427/331 |
Current CPC
Class: |
H01J 49/0418
20130101 |
Class at
Publication: |
216/37 ;
427/331 |
International
Class: |
B05D 3/10 20060101
B05D003/10; B05D 3/00 20060101 B05D003/00 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 11, 2006 |
JP |
2006-190418 |
Claims
1. A method for manufacturing a substrate for mass spectrometry,
which comprising the steps of: forming a porous film on a base;
forming an inorganic material film on the porous film; and forming,
on the surface of the inorganic material film, a plurality of
concaves having a diameter of not less than 1 nm and less than 1
.mu.m vertically to the base.
2. The method for manufacturing a substrate for mass spectrometry
according to claim 1, further comprising a step of forming, on a
surface of the inorganic material film, a substance different from
the substance comprising the inorganic material film.
3. The method for manufacturing a substrate for mass spectrometry
according to claim 1, wherein the step of forming the concaves
comprises the steps of: forming a film of a block copolymer on the
surface of the inorganic material film; developing a microphase
separation structure in the block copolymer; selectively removing
one of the components of the block copolymer which has the
microphase separation structure; and etching off the inorganic
material film by using the component of the block copolymer
remaining on the inorganic material film as a mask.
4. A method for manufacturing a substrate for mass spectrometry,
comprising the steps of: forming a porous film on a base; forming
an inorganic material film on the porous film; and forming a
plurality of convexes having a diameter of not less than 1 nm and
less than 1 .mu.m vertically to the base.
5. The method for manufacturing a substrate for mass spectrometry
according to claim 4, wherein the step of forming the convexes
comprises the steps of: forming a thin film of a block copolymer on
the surface of the inorganic material film; developing a microphase
separation structure in the block copolymer; selectively removing
one of the components of the block copolymer from the block
copolymer which has the microphase separation structure; and
etching off the inorganic material film by using the component of
the block copolymer remaining on the inorganic material film as a
mask.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a division of application Ser. No.
11/775,539, filed Jul. 10, 2007, which claims the benefit of
Japanese Patent Application No. 2006-190418, filed Jul. 11, 2006.
Both prior applications are hereby incorporated by reference herein
in their entireties.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to a substrate used for mass
spectrometry, particularly, to a substrate used for mass
spectrometry based on the laser desorption ionization method.
[0004] 2. Description of the Related Art
[0005] Mass spectrometry has long been used as one means for
identification of substances, particularly organic substances. The
principle thereof is to impart a large energy in a short time to a
sample to ionize it and analyze the mass of the ion by a detector.
As a detector, a quadrupole mass spectrometer, a time-of-flight
mass spectrometer and the like are used. Particularly, the
time-of-flight mass type detector is recently becoming mainstream.
As an energy source to cause ionization, a Curie point pyrolyzer
and a laser are used. Although mass spectrometry is favorably used
for analysis of low-molecular substances, if an object substance to
be measured has a high molecular weight, the original substance has
a tendency of being fragmented and decomposed into relatively
low-mass ions. Then, means is proposed to apply the mass
spectrometry to detection of materials having a high molecular
weight like biomolecules. This means is named Matrix Assisted Laser
Desorption Ionization Mass spectrometry (MALDI-MS). This is means
which can ionize even a substance having a high molecular weight
while preventing the fragmentation by making a mixture of the
object substance to be detected and a material named a matrix to be
a sample and subjecting the sample to the laser irradiation.
Through the spectroscopic method of MALDI-MS, the mass spectrometry
has been given attention as evaluation and identification means of
biomaterials.
[0006] Means is also proposed to conduct mass spectrometry using a
porous substrate instead of a matrix material. This method is named
Surface Assisted Laser Desorption Ionization Mass Spectrometry
(SALDI-MS). Since this method detects no low-molecular peak
resulting from a matrix, it is said to be advantageous to the mass
spectrometry of relatively low-molecular biomaterials such as
metabolites. Techniques using a substrate having a semiconductor
porous surface for mass spectrometry are disclosed in U.S. Pat. No.
6,288,390 and U.S. Pat. No. 6,399,177. Particularly a technique
related to SALDI-MS using a porous silicon fabricated by anodic
conversion of silicon is named Desorption Ionization on Silicon
(DIOS), and is disclosed, for example, in Jing Wei, et al., Nature,
Vol. 399, pp. 243-246, 1999.
[0007] Although MALDI-MS can ionize an analytical object while
preventing fragmentation thereof, since the sample is mixed with a
matrix material for measurement, MALDI-MS has a problem that mass
peaks resulting from the matrix material are observed in large
numbers.
[0008] On the other hand, since DIOS generates almost no
low-molecular MS peaks resulting from a matrix and can prevent
fragmentation of a substance to be detected, a high-quality
spectrum is obtained.
[0009] However, in the case (U.S. Pat. No. 6,399,177) of a porous
silicon formed directly on a silicon substrate having a high
thermal conductivity, the energy absorbed in the silicon by laser
irradiation easily transfers to the silicon substrate. As a result,
there arises a problem that the efficiency of the local temperature
rise of porous parts carrying a substrate to be detected is
reduced.
[0010] Therefore, the present invention has an object to provide a
substrate for mass spectrometry whose efficiency of temperature
rise is enhanced.
SUMMARY OF THE INVENTION
[0011] The substrate for mass spectrometry according to the present
invention is characterized by including a base, a porous film
formed on the base and an inorganic material film formed on the
porous film, and the inorganic material film is characterized by
having a plurality of concaves formed vertically to the base, the
diameter of which concaves is not less than 1 nm and less than 1
.mu.m.
[0012] The manufacturing method of a substrate for mass
spectrometry according to the present invention is characterized by
including forming a porous film on a base, forming an inorganic
material film on the porous film and forming a plurality of
concaves of not less than 1 nm and less than 1 .mu.m in diameter on
the surface of the inorganic material film vertically to the
base.
[0013] The present invention provides a substrate for mass
spectrometry which smoothly causes the desorption process because
the efficiency of the temperature rise can be enhanced since the
substrate has a porous film.
[0014] Further features of the present invention will become
apparent from the following description of exemplary embodiments
with reference to the attached drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIGS. 1A and 1B are illustrative views of a substrate for
mass spectrometry according to the present invention on whose
surface fine concaves are formed.
[0016] FIGS. 2A and 2B are illustrative views of a substrate for
mass spectrometry according to the present invention on whose
surface fine convexes are formed.
[0017] FIGS. 3A, 3B, 3C, 3D and 3E are illustrative views
illustrating an example of a manufacturing process of a substrate
for mass spectrometry according to the present invention.
[0018] FIGS. 4A, 4B, 4C, 4D, 4E, 4F and 4G are illustrative views
illustrating another example of a manufacturing process of a
substrate for mass spectrometry according to the present
invention.
DESCRIPTION OF THE EMBODIMENTS
[0019] Hereinafter, exemplary embodiments of the present invention
will be described.
[0020] A typical constitution of the substrate for mass
spectrometry according to the present invention is illustratively
shown in FIGS. 1A and 1B.
[0021] The substrate for mass spectrometry according to the present
invention has a base 11, a porous film 12 of a porous substance
formed on the base 11 and an inorganic material film 13 formed on
the porous film 12.
[0022] The material of the base 11 is not especially limited as
long as withstanding fabrication processes of a porous film and an
inorganic material film described later, and can be common
materials. The examples include glass, ceramics and metals.
[0023] Then, the porous film 12 of a porous substance formed on the
base 11 will be described. Substances containing silicon as a
component and inorganic substances such as oxides are favorably
used as the porous substance, but the porous substance is not
limited thereto; as an oxide, silica, titania, tin oxide, silicon
dioxide and the like can be used. Porous substances have a low
thermal conductivity because having pores, and enhance the effect
of enclosing heat in an inorganic material film. This enables a
sample carried on the inorganic material film to be efficiently
ionized. Further, there is also a demand for the porous film 12 to
be such that a film of an inorganic material described later can be
continuously and flatly formed on the porous film.
[0024] As a porous film, a thin film of a mesoporous material can
be especially used which is fabricated by removing an organic
component (surfactant) from an organic-inorganic composite formed
with clusters of the surfactant made to be a template. The
mesoporous material can be formed as a favorable continuous film on
a base by a simple process such as the sol-gel method. A material
of a porous substance to be favorably used contains silicon in view
of the cost and the easiness of the process, and silica can be
especially used. Fabrication methods of mesoporous silica thin
films are disclosed in some documents, for example, Advanced
Functional Materials, Vol. 14, p. 311 and Current Opinion in
colloid & Interface Science, Vol. 4, p. 420.
[0025] A mesoporous silica thin film can be fabricated by various
methods, such as means including dip coat, spin coat and mist coat
based on the sol-gel method described before and means based on the
inhomogeneous nucleus generation-nucleus growth on a base. In the
present invention, fabrication methods are not especially limited
as long as they can form a continuous film having a flat surface
and few generated cracks. In the mesoporous material described
above, since pores are formed with clusters of surfactant molecules
made to be a template, and the sizes of the molecular clusters are
uniform, a porous substance having a substantially uniform pore
size is formed. Some methods are known, which remove the surfactant
from the pores, and include, for example, baking, ultraviolet
irradiation, oxidative removal by ozone, extraction by a solvent
and extraction by a supercritical fluid. In the present invention,
any of these methods may be used.
[0026] In the substrate for mass spectrometry according to the
present invention, the porous film 12 can have at least one
diffraction peak in the angular region corresponding to the
structural period of not less than 1 nm in the X-ray diffraction
analysis. The fine porous structure of the mesoporous silica can be
optional. Usable examples are mesoporous silicas having a
two-dimensional hexagonal structure including tubular pores, and a
cubic structure and a tree-dimensional hexagonal structure
including spherical pores.
[0027] Then, in the substrate for mass spectrometry according to
the present invention, the inorganic material film 13 formed on the
porous film 12 described above will be described. Formation methods
of the inorganic material film can use various vacuum deposition
methods, but are not necessarily limited thereto. As a vacuum
deposition method, methods such as resistance heating vacuum
deposition, electron beam deposition, sputtering, arc deposition
and chemical vapor deposition (CVD) can be used. Materials for an
inorganic material used for the inorganic material film 13 are not
especially limited, but semiconductors and metals can be especially
used. The semiconductors include silicon, germanium and oxide
semiconductors, but in the present invention, silicon can be
especially used. Silicon can be favorably used for any of amorphous
silicon films, polycrystalline silicon films and the like, and an
optimum means is used out of the plasma CVD, low-pressure CVD and
the like depending on the purposes. Here, a film formation method
may be selected so that the base 11 to be used and the porous film
of a porous substance formed on the base are not adversely affected
by the formation process of the inorganic material film. If
exemplified, in the case of formation of an amorphous silicon film,
for example, the high-frequency plasma CVD method can be used. In
the case of formation of a low-temperature polysilicon film, for
example, the plasma CVD can be used. In the present invention,
there are especially no limitations on the form, structure, film
formation method and the like of silicon used for the inorganic
material film, and an optimum material is formed as a film by an
optimum method depending on the purposes. The thickness of silicon
has also no limitation, but too thick a silicon thickness reduces
the effect on the thermal block by the porous film underneath the
inorganic material film, which will be described later. By
contrast, too thin a silicon thickness sometimes raises problems
that the laser energy cannot be efficiently absorbed, that
decomposition of a substance to be detected in the ionization
process by the laser irradiation cannot be prevented, and the like.
Therefore, the thickness can be optimized depending on the
material.
[0028] On the other hand, when a metal is used as an inorganic
material used for the inorganic material film 13, a relatively
common metal can be used. Examples include iron, nickel, chromium,
copper, silver, gold, platinum and palladium. Here, when a material
which is relatively easily oxidized in the air is used for a
substrate for mass spectrometry, if required in consideration of
formation of an oxide, a treatment such as removal of the oxide
layer is sometimes necessary. The metal is formed on the porous
film 12 by methods such as resistance heating deposition, electron
beam deposition, sputtering and arc deposition. A material such as
titanium, which improves the adhesiveness of a metal and an
underlying layer, may optionally be deposited prior to the film
formation of the object metal.
[0029] Then, the inorganic material film 13 formed on the porous
film 12 in such a way is subjected to a process of forming a
plurality of concaves or a plurality of convexes of not less than 1
nm and less than 1 .mu.m in diameter vertically to the base. Here,
a substrate for mass spectrometry on which concaves 14 are formed
is illustrated in FIGS. 1A and 1B; and a substrate for mass
spectrometry on which convexes 24 are formed is illustrated in
FIGS. 2A and 2B. As a result of extensive studies on the irregular
structures formed on a base, the present inventors have confirmed
that the case where the concaves or convexes have a diameter of not
less than 1 nm and less than 1 .mu.m provides a mass spectrum with
a favorable sensitivity and with a suppressed fragmentation.
[0030] Application of the general-purpose photolithography to the
formation of concaves or convexes on an inorganic material film is
difficult because their diameter is not less than 1 nm and less
than 1 .mu.m. Hence, concaves or convexes of the substrate for mass
spectrometry according to the present invention can be fabricated
by a process utilizing the self-assembly of a material. However,
any process which can form the similar structure can be applied to
the fabrication of the substrate for mass spectrometry according to
the present invention. A process utilizing the self-assembly of a
material can be especially a method whereby a pattern having a
microphase separation structure of a block copolymer is transferred
to an inorganic material film, and this technique is disclosed, for
example, in Japanese Patent Application Laid-Open No. 2001-151834.
A method whereby a structure of a block copolymer is transferred to
a base will be described below.
[0031] A block copolymer means a polymer compound in which a
plurality of polymer segments having different properties is bonded
by covalent bond. Use of a precise polymerization such as living
polymerization allows synthesis of a block copolymer having a very
narrow molecular weight distribution, and such a block copolymer is
known to generate the microphase separation of components on the
nanometer scale. The microphase separation structure is known to be
able to take a highly regular structure, and the structure is
determined depending on the molecular weight ratio of a plurality
of segments contained in a molecule and the degree of the
compatibility between the plurality of segments. Examples include a
structure in which a secondary component is dispersed in a
spherical shape in a matrix of a first component, a structure in
which a secondary component is dispersed in a cylindrical shape in
a matrix of a first component, and a structure in which a first
component and a second component are separated in a lamellar shape.
If the magnitude of the molecular weight ratios of the first
component and the second component reverses, a structure in which a
first component is dispersed in a matrix of a second component is
formed. Although the above exemplified structures are found in
diblock copolymers including two components, block copolymers
having three or more components form more complicate and much
diversified structures.
[0032] Development of the phase separation structure of a block
copolymer can be achieved by a very simple process. For example, a
simple process in which a block copolymer dissolved in a solvent is
cast on a base, and heated while the solvent is being dried, can
cause the microphase separation.
[0033] From the microphase separation structure of the block
copolymer formed above a base in such a way, a specific component
can be selectively removed utilizing the difference in chemical
properties between components. By this step, for example, a porous
film (i.e., porous film 12) is formed above a base. Structures
having a cylindrical shape and a spherical shape can be formed on a
base by removing selectively matrix components. In such a way,
holes and cylindrical structures vertical to the film surface can
be formed.
[0034] By using a film of a block copolymer, formed on an inorganic
material film in such a way, from which a specific component has
been removed, a pattern of the microphase separation structure can
be transferred to the inorganic material film. As the simplest
case, there is a method whereby the inorganic material film is
etched using as a mask a polymer component remaining on the
inorganic material film. In this case, the process must be
optimized depending on the materials constituting a substrate for
mass spectrometry, etching means and a composition of a block
copolymer to be used. The problem is the ratio of the etching rates
of one polymer component remaining on the inorganic material film
and an underlying inorganic material film. In the case where this
ratio cannot be made large, deep irregular structures cannot
sometimes be formed because the polymer on the inorganic material
film is also removed by etching in the stage of a shallow etching
of the inorganic material film. In such a case, one component of a
block copolymer is not used directly as a mask, but the structure
of the block copolymer may be replaced by another material which is
largely different in the etching rate from a material comprised in
the inorganic material film which is an object of etching.
Thereafter, a process can be used in which the inorganic material
film is etched using as a mask the another material replaced by in
such a way.
[0035] These two processes will be in detail described by way of
drawings.
[0036] A first process will be first described in which a specific
component of a phase separation structure of a block copolymer is
selectively removed, and an inorganic material film is etched using
a remaining component as a mask. The flow of this process is
illustrated in FIGS. 3A to 3E.
[0037] As illustrated in FIG. 3A, first, an inorganic material film
13 is formed on a porous film 12 on a base 11, and a block
copolymer film 34 is cast on the inorganic material film 13.
[0038] Then, as illustrated in FIG. 3B, a structure illustrated in
FIG. 3A is heated to dry a solvent in the block copolymer film and
to develop a microphase separation structure of the block
copolymer. Thus, the block copolymer is separated as micophases
into domains 31 including one component of the block copolymer
causing the microphase separation (hereinafter, simply referred to
as domains 31) and a matrix 32 including the other component of the
block copolymer causing the microphase separation (hereinafter,
simply referred to as matrix 32).
[0039] Then, as illustrated in FIG. 3C, the domains 31 are
selectively removed by a treatment such as dry etching under
certain conditions.
[0040] Further, as illustrated in FIG. 3D, by using as a mask the
matrix 32 remaining on the inorganic material film 13, the
inorganic material film 13 on the base 11 is etched by dry etching
or the like under other conditions.
[0041] Finally, as illustrated in FIG. 3E, the matrix 32 having
been used as a mask is removed.
[0042] In this process, for example, by reversing the ratio of the
molecular weights in the block copolymer to be used, either of
concaves and convexes can be formed on a substrate for mass
spectrometry.
[0043] Next, a process will be described referring to FIGS. 4A to
4G in which process a structure of a block copolymer is replaced by
another material which is largely different in the etching rate
from a material which is an object of etching (inorganic material
film), and the inorganic material film is etched using the another
material as a mask.
[0044] Since the steps of FIGS. 4A to 4C are the same as the steps
of FIGS. 3A to 3C in the first process described above, their
description is omitted.
[0045] As illustrated in FIG. 4D, after the domains 31 are removed,
a mask material 41 having a large etching contrast against the
underlying inorganic material film 13 is formed by vapor deposition
and the like in the state of the pattern of the polymer being
formed on the inorganic material film.
[0046] Then, as illustrated in FIG. 4E, the matrix 32 on the
inorganic material film and the mask material 41 formed on the
matrix 32 are removed.
[0047] Then, as illustrated in FIG. 4F, the inorganic material film
13 is etched using the mask material 41 as a mask by dry etching
and the like under other conditions.
[0048] Finally, as illustrated in FIG. 4G, the mask material 41 on
the inorganic material film is removed.
[0049] The substrate for mass spectrometry according to the present
invention may be fabricated using either of the two processes
described above. This step is not essential, and the substrate for
mass spectrometry can be used in the state that the substance
deposited on the surface remains.
[0050] These two fabrication processes will be further in detail
described.
[0051] As a block copolymer used for manufacture of the substrate
for mass spectrometry according to the present invention, block
copolymers having common compositions can be used. They include,
for example, the following, but are not limited thereto.
[0052] Polystyrene-polymethyl methacrylate (PS-b-PMMA) [0053]
Polystyrene-polyphenyl methacrylate (PS-b-PPhMA) [0054]
Polystyrene-polyisoprene (PS-b-PI) [0055] Polystyrene-polybutadiene
(PS-b-PB)
[0056] A combination of a plurality of components constituting a
block copolymer which exhibits a sufficient etching contrast in the
etching process described later can be especially used for the
first process illustrated in FIGS. 3A to 3E.
[0057] The ratio of the molecular weights of the block copolymer
has no limitation. For example, if the block copolymer is a diblock
copolymer, the ratios including 20/80, 30/70, 80/20 and 70/30 can
be used, and may be a ratio therebetween. The microphase separation
structure of a block copolymer changes depending on these
composition ratios, and a structure in which spherical domains are
dispersed and a structure in which cylindrical domains are
dispersed are favorably used. However, in a block copolymer having
a composition whose phase separation structure exhibits a lamella
structure, since the lamella structure is generally formed parallel
with a base and the selective removal of one component is almost
impossible, application of the block copolymer to the present
invention is difficult. Which component out of a plurality of
components is made to be a matrix and which one is made to be
dispersed domains are suitably selected depending on the surface
shape of an object substrate.
[0058] Various means are applicable to remove a specific component
in a phase separation structure of a block copolymer. For example,
in the case of using a block copolymer having a structure
containing oxygen as a component of the block copolymer, the means
include a method whereby the component containing oxygen is
selectively removed by the dry etching using oxygen as an etching
gas. In the present invention, a method of selectively removing a
component is not especially limited as long as the method can
favorably achieve the removal of an object component, and an
optimum method is selected depending on a component to be
removed.
[0059] Then, processes will be described in which an underlying
inorganic material film is etched using a block copolymer film
after a specific component has been removed. As described above,
the processes have two types.
[0060] First, a method, which is illustrated in FIGS. 3A to 3E,
will be described whereby an inorganic material film is etched
using directly as a mask a matrix after a specific component
remaining on an inorganic material film has been removed.
[0061] Transfer of a pattern of a component separated as
microphases of a block copolymer to an inorganic material film
commonly uses an etching process. For fabrication of the substrate
for mass spectrometry according to the present invention, either of
the dry etching and wet etching processes can be used, but the dry
etching process often achieves a favorable transfer. However, a
process used for fabrication of the substrate for mass spectrometry
according to the present invention is not any more limited as long
as the process provides a desired shape. For example, when the
inorganic material film is silicon, the dry etching using a mixed
gas of SF.sub.6/CHF.sub.3 uses the matrix 32 as a mask, and the
inorganic material film of silicon and the like can be favorably
etched. The dry etching, since the directional controllability at
etching can be made favorable, can form concaves vertical to the
base. If viewed from a structure finally formed, this is also
regarded as convexes vertical to the base being formed.
[0062] Next, a process, illustrated in FIGS. 4A to 4G, will be
described in which a structure of a block copolymer is replaced by
another material which is largely different in the etching rate
from a material which is an object of etching (inorganic material
film), and the inorganic material film is etched using the another
material as a mask. With the block copolymer (i.e. matrix 32) after
removal of a specific component being left on the inorganic
material film, for example, a metal (i.e. mask material 41) is
vapor deposited. A deposited substance is not limited to a metal as
long as the substance withstands a process described later and can
be favorably removed from the inorganic material film after the dry
etching. An example of a metal includes chromium.
[0063] After the deposition step of the mask material 41, the block
copolymer (matrix 32) and the deposited material (mask material 41)
formed thereon are removed. This removal step may be performed, for
example, by dissolving in a solvent the component of the block
copolymer remaining on the inorganic material film and removing it
with the solvent. By this step, the deposit (mask material 41 of
FIG. 4E) deposited on parts on the inorganic material film where
the block copolymer is not present is made to remain. By this step,
a deposit pattern having the same shape as the matrix 32 having the
phase separation structure of the block copolymer formed on the
inorganic material film, is transferred and formed.
[0064] Then, by using this pattern, concaves or convexes are formed
on the underlying inorganic material film. This step can be
performed by the etching process as in the first process described
above. Either of processes of dry etching and wet etching may be
used for this etching step, but the dry etching process can often
achieve a favorable transfer. However, a process used for
fabrication of the substrate for mass spectrometry according to the
present invention is not any more limited as long as it provides a
desired shape. For example, in the case of an inorganic material
film of silicon, silicon in the area where the deposited material
pattern (mask material 41) is not formed is selectively etched to
form concaves by the dry etching using a mixed gas of
SF.sub.6/CHF.sub.3. This process is more complicated than the
method whereby an inorganic material film is etched using a
component of a block copolymer (matrix 32) directly as a mask, but
can form deep irregularity. This is because a material (mask
material 41) largely ratio in the etching rate from the underlying
inorganic material film is selected as a deposition material to be
transferred from the phase separation structure of the block
copolymer.
[0065] Lastly, the deposited material used as a mask for etching is
subjected to a step of removing it.
[0066] This step is not an essential one to fabricate the substrate
for mass spectrometry according to the present invention.
Therefore, if the measurement sample and the mass spectrometry are
not adversely affected, the deposited material can be made to
remain on the surface. When mass spectrometry is conducted by the
surface assisted laser desorption ionization mass spectrometry,
there is a case where a higher electric conductivity of the surface
provides a more favorable spectrum measurement. Particularly in
such a case, there is a case where a more favorable substrate for
mass spectrometry can be fabricated by using a metal as a
deposition material and using it as it is allowed to remain on the
surface. In this case, a conductive material different from a
material comprised in the inorganic material film may be on
concaves or convexes. For removal of the deposited material, common
means are used. Especially using the wet etching allows to simply
remove a deposited material. As a substance used for etching, an
optimum one is selected depending on the deposited material. For
example, in the case of chromium as a deposited material, the
chromium can be removed using a cerium ammonium nitrate solution.
However, if the material used for the wet etching remains on the
substrate for mass spectrometry, the material has a risk of
generating a peak derived from a contamination on the mass
spectrometry spectrum. Therefore, the substrate for mass
spectrometry after the wet etching may optionally be well washed
using ultrapure water and the like.
[0067] By the steps described above, the substrate for mass
spectrometry according to the present invention can be
fabricated.
[0068] The substrate for mass spectrometry according to the present
invention can be used for mass spectrometry using a commercially
available MALDI-MS apparatus. The substrate for mass spectrometry
according to the present invention is used as a sample stage on
which a sample of a measurement object is mounted to conduct mass
spectrometry. Here, an additional step of working the surface of
the sample stage such that the heights of the surfaces of the
sample stage and the substrate coincide may be necessary, and the
working step is optionally added.
[0069] As described above, according to the present invention, fine
irregularity of the nanometer scale can be formed on a substrate
without using an electrochemical means using hydrofluoric acid. In
the substrate for mass spectrometry according to the present
invention, a porous material having a very low thermal conductivity
is formed underneath an inorganic material film of silicon and the
like. This prevents the energy which the inorganic material film
has acquired by absorbing laser from moving into a base and
reducing the utilization efficiency of energy, and finally prevents
the sensitivity from decreasing.
[0070] Since the present invention can dispenses with using silicon
wafers, many structures can be formed on a large substrate surface,
and substrates for mass spectrometry can be inexpensively
manufactured.
EXAMPLES
[0071] Hereinafter, the present invention will be further in detail
described by way of examples, but the present invention is not
limited to these contents of the examples.
Example 1
[0072] In Example 1, a polycrystalline silicon film was formed on a
mesoporous silica thin film formed on a glass base, and a
microphase separation structure of a block copolymer film of a
polystyrene-polymethyl methacrylate (PS-b-PMMA) was used. Example 1
was an example in which fine concaves were formed on the surface of
the polycrystalline silicon, and the substrate was used as a
substrate for SALDI-MS.
[0073] A base made of quartz glass of 50 mm.times.50 mm and 1 mm in
thickness was washed with acetone, isopropyl alcohol and pure
water, and subjected to the UV-ozone treatment to clean its
surface.
[0074] A mixed solution prepared by adding 13.8 g of ethanol with
1.80 g of 0.1-M diluted hydrochloric acid was added and vigorously
agitated with 20.8 g of tetraethoxysilane to prepare a homogenous
solution, and then the resultant solution was heated at 70.degree.
C. for 1 h to fabricate a sol.
[0075] 0.95 g of a block copolymer surfactant PluronicP123 (BASF
AG) was dissolved in 1.97 g of ethanol, and the resultant solution
was added in 20 g of the sol and added further with 3.95 g of
0.01-M diluted hydrochloric acid to prepare a homogeneous precursor
solution.
[0076] The homogeneous precursor solution was applied on the
above-mentioned base made of quartz glass by the dip coat method
and dried in room temperature.
[0077] The resultant film was baked in the air at 450.degree. C.
for 5 h to remove the surfactant. The film after the removal of the
surfactant was transparent and had no cracks observed. The film
after baking was evaluated by the X-ray diffractometry, and as a
result, a clear diffraction peak was observed at an angle
corresponding to d=5.8 nm. Results by a high-resolution scanning
electron microscope (FE-SEM), a transmission electron microscope
(TEM) and the like revealed that the film had a two-dimensional
hexagonal structure formed by honeycomb packing of tubular pores.
However, a detailed analysis revealed that since the structural
period in the film thickness direction is selectively small, the
hexagonal structure deviated from a complete one.
[0078] Next, a polycrystalline silicon film was formed on the
mesoporous silica thin film. The formation of the polycrystalline
silica film was performed under the following conditions using the
chemical vacuum deposition (CVD) using a low-temperature
plasma.
[0079] Flow rate: 100 sccm (SiH.sub.4); 9,000 sccm (H.sub.2) [0080]
Pressure: 2,000 Pa [0081] Power: 200 W [0082] Frequency: 105 MHz
[0083] Temperature: 300.degree. C.
[0084] Thus, a polycrystalline silicon film of 200 nm in thickness
was fabricated on the mesoporous silica film. The surface of the
fabricated polycrystalline silicon film exhibited specular
reflection, and the smoothness of the surface was confirmed by an
FE-SEM.
[0085] Then, a block copolymer was thinly applied on the
polycrystalline silicon film. A diblock copolymer of a
polystyrene-polymethyl methacrylate (PS-b-PMMA) (molecular weight
ratio=PS 163.5 k:PMMA 67.2 k) was dissolved in the following
solvent to prepare a 2-mass % solution.
[0086] The solvent was propylene glycol mono-methyl ethyl acetate
(PGMEA).
[0087] The solution was applied on the polycrystalline silicon film
at a rotation frequency of 1,000 rpm by spin coat. The film
obtained by spin coat was annealed in vacuum at 180.degree. C. for
1 h for developing a microphase separation structure. The film
surface after annealing was observed using the phase mode of an
atomic force microscope (AFM), and as a result, a structure was
observed in which domains of PMMA were dispersed in a matrix of PS.
The observed structure had an average size of the domains of 58.7
nm and an average pitch thereof of 79.9 nm.
[0088] Then, from the block copolymer developing the microphase
separation structure, one component was selectively removed. This
step was performed using the dry etching using oxygen as an etching
gas. In Example 1, etching was performed by setting the machine
power of the dry etching at 50 W, the bias power at 10 W and the
etching time at 60 sec from the film thickness of the block
copolymer film and the etching rates of PS and PMMA, which were in
advance measured. The block copolymer film after etching was
observed by an atomic force microscope (AFM), and as a result,
domains of PMMA were observed to be selectively removed.
[0089] Then, by using as a mask the polymer film having a large
number of holes of the nanometer scale, fine irregularity was
formed on the surface of the polycrystalline silicon film. This
step was accomplished by the dry etching using SF.sub.6/CHF.sub.3
as an etching gas. Also in this case, etching was favorably
performed by optimizing the etching conditions as follows in
consideration of the film thickness of the remaining PS.
[0090] Mixing ratio of SF.sub.6/CHF.sub.3 :1/5 [0091] Machine
power: 50 W [0092] Bias power: 10 W [0093] Etching time: 120
sec
[0094] Observation of this film by an AFM and an electron
microscope confirmed that concaves of 80 nm in depth were formed on
the substrate. The structure was one corresponding to the structure
illustrated in FIGS. 1A and 1B. The size and pitch of the concaves
substantially coincided with the above-mentioned microphase
separation structure. The wall surfaces of the concaves were nearly
vertical to the base surface, and the superiority of the
directional controllability of etching in the dry etching process
was considered to be reflected.
[0095] Lastly, the PS slightly remaining on the polycrystalline
silicon was removed. The PS was favorably removed using ethyl
acetate.
[0096] The substrate on which the irregularity was formed was dried
in nitrogen gas at 120.degree. C. to provide as a substrate for
mass spectrometry. Triacetyl-b-cyclodextrin was used as a sample
and silver trifluoroacetate was used as an ionization promoter. The
ionization promoter and a 0.1-mM THF solution of the sample were
dropped on the substrate and the measurement was conducted after
drying in air. The molecular size of triacetyl-b-cyclodextrin is
about 2 nm and the molecular weight is 2017.75.
[0097] The measurement was conducted using an N.sub.2 laser of 377
nm as an excitation light source and a time-of-flight type
detector. As a result, by using the substrate fabricated in Example
1, the mass peak of triacetyl-b-cyclodextrin added with Ag.sup.+
was clearly observed with a high S/N ratio. No peak corresponding
to a mass of a low molecular weight was observed and the
suppression of fragmentation was confirmed.
Example 2
[0098] Example 2 was an example in which, contrary to Example 1 in
which concaves were formed, fine convexes were formed using a
microphase separation structure of a block copolymer on a
substrate, which was used as a substrate for mass spectrometry.
[0099] A mesoporous silica film and a polycrystalline silicon layer
were formed on a base made of quartz glass by using the same
procedures and same materials as those in Example 1. A diblock
copolymer of PS-b-PMMA having a molecular weight ratio of PS 78.0
k:PMMA 169.6 k was formed as a film on the polycrystalline silicon
layer by the same procedures as those in Example 1 to develop a
microphase separation structure by the same procedure. The film
thickness was 80 nm like in Example 1.
[0100] The surface of the film was observed by an atomic force
microscope (AFM) phase mode, and as a result, a structure was
observed in which domains of PS were dispersed in a matrix of PMMA.
The observed structure had an average size of the domains of 47.1
nm and an average pitch thereof of 67.9 nm.
[0101] The block copolymer film was subjected to the oxygen dry
etching to remove the matrix. The conditions of the dry etching
were as in Example 1. A state was confirmed in which by this step,
PMMA of the matrix was removed and the domains of PS were dotted on
the polycrystalline silicon film.
[0102] This structure was subjected to the dry etching using
SF.sub.6/CHF.sub.3 as an etching gas under the same conditions as
those in Example 1 to remove parts of the silicon layer where PS is
not present. By this step, the silicon layer was etched by about 80
nm, and as a result, convexes of 80 nm were formed on the
substrate. This structure was one illustrated in FIGS. 2A and
2B.
[0103] The size and pitch of the convexes substantially coincided
with the above-mentioned domains having the microphase separation
structure. The wall surfaces of the convexes were nearly vertical
to the base surface and the superiority of the directional
controllability of etching of the dry etching process was
considered to be reflected.
[0104] Lastly, the PS slightly remaining on the polycrystalline
silicon film was removed by the same procedure as that in Example
1.
[0105] By using the substrate for mass spectrometry thus fabricated
on which a large number of fine convexes were formed, the mass
spectrometry similar to that in Example 1 was attempted.
[0106] As a result, as in Example 1, a peak of a sample was
observed with a high S/N ratio, thus verifying a highly sensitive
detection of the sample. Further, almost no peak by the
fragmentation was observed in the region of low molecular
weights.
Example 3
[0107] In Example 3, the same block copolymer as that in Example 1
was used and PMMA was selectively removed by the dry etching using
oxygen as an etching gas; thereafter a metal was vapor deposited on
parts where PMMA had been removed and PS was further removed.
Thereafter, the polycrystalline silicon film was etched using the
metal as a mask. The substrate for mass spectrometry thus obtained
according to the present invention had convexes having a higher
aspect ratio than that of the structure of Example 2, and was an
example obtained by modifying the surface of a substrate for mass
spectrometry.
[0108] A film of PS, similar to that formed in Example 1, on which
dotted fine holes were formed was formed on the polycrystalline
silicon film formed on the mesoporous silica thin film by using the
same base material, the same block copolymer and the same
procedures as those in Example 1.
[0109] Chromium was vapor deposited by 100 nm on the film by the
electron beam vapor deposition. The structure with the deposited
chromium was immersed in ethyl acetate, heated at 40.degree. C. to
dissolve and remove the PS matrix and simultaneously remove the
chromium formed on the PS. After this step, the surface of the film
thus obtained was observed by an AFM, and as a result, fine dots of
chromium like those observed in Example 2 were confirmed to be
formed on the polycrystalline silicon film.
[0110] Thereafter, the dry etching was performed under the same
conditions as those in Example 1 to etch the polycrystalline
silicon film. The etching time was set 240 sec, which was longer
than that in Examples 1 and 2.
[0111] After the etching of the polycrystalline silicon film, the
etched polycrystalline silicon film was immersed in an aqueous
solution of cerium ammonium nitrate and perchloric acid for 15 sec
to etch chromium, fully washed with ultrapure water, and then
heated and dried in nitrogen at 120.degree. C.
[0112] As a result of observation of this substrate by an AFM,
formation of fine convexes as illustrated in FIGS. 2A and 2B were
confirmed with the height of the convexes of about 140 nm.
[0113] Then, this structure was put in a closed vessel, and exposed
to the vapor of n-propyl triethoxysilane for 1 h. By this step, a
structure was obtained to which an organic group derived from
n-propyl triethoxysilane was bonded. This treatment prevents the
decrease in the sensitivity of the mass spectrometry spectrum
because the surface of silicon is otherwise oxidized when left in
the air, leading to the decrease in the sensitivity.
[0114] By using this structure as a substrate for mass
spectrometry, the mass spectrometry spectrum was measured under the
same conditions as those in Examples 1 and 2. As a result, a sample
was detected with high sensitivity as in Examples 1 and 2, and it
was revealed that no peak was observed at a low molecular weight
region other than a peak possibly due to a slight fragment of the
silane coupling agent, thus suppressing the fragmentation. The
measured spectrum exhibited a slightly higher S/N ratio than those
in Examples 1 and 2 regardless of the same concentration of the
sample, thus exhibiting the highly sensitive measurement of the
sample.
[0115] The substrate after preserved in synthetic air for two
months was similarly measured, and the signal/noise ratio and the
like of the measured spectrum were not inferior to the substrate
immediately after the fabrication.
Example 4
[0116] Example 4 was an example in which by using gold as an
inorganic material film in place of silicon, and using the phase
separation structure of a block copolymer as a mask, a fine
irregular structure was formed on the gold film to be applied to a
substrate for mass spectrometry.
[0117] The same mesoporous silica thin film as that fabricated in
Examples 1 to 3 was formed on the base made of quartz glass used in
Examples 1 to 3, and gold of 200 nm was vapor deposited on the
mesoporous silica thin film by the electron beam deposition. The
surface of the gold after the deposition exhibited the specular
reflection, and the result of observation by an FE-SEM revealed the
surface having a flat shape.
[0118] The same block copolymer as that used in Example 2 was
applied on the deposited gold film; a microphase separation
structure was developed by the same procedures; and the dry etching
was performed using oxygen as an etching gas under the same
conditions as those in Examples 1 to 3 to selectively remove the
matrix of PMMA. In the state that a large number of PS dots
remained on the deposited gold film, chromium was vapor deposited
by 100 nm on the PS dots as in Example 3. Then, as in Example 3,
the PS was dissolved using ethyl acetate to remove the PS and the
chromium formed thereon. By this step, on the deposited gold film,
a thin chromium film in which a large number of fine holes were
formed was formed. The result of observation of this film by an AFM
confirmed that the microphase separation structure of the polymer
was completely transferred to the chromium film.
[0119] By using as a mask the chromium film having a large number
of fine holes, the gold was etched by the dry etching. The dry
etching used CF.sub.4 as an etching gas, and was performed at a
power of 150 W for 5 min. The etching rate of gold with CF.sub.4 is
three or more times that of chromium, so the gold was favorably
etched by using chromium as a mask.
[0120] After this step, chromium was removed by etching with the
same etchant and under the same etching condition as those used in
Example 3. The surface of the gold after etching was observed by an
AFM, and as a result, a state was observed in which a large number
of fine concaves were formed on the deposited gold film, thus
confirming that the phase separation structure of the block
copolymer was favorably transferred to the deposited gold film. The
depth of fine concaves was about 150 nm.
[0121] After this substrate was dried in a nitrogen atmosphere at
120.degree. C., the mass spectrometry as in Examples 1 to 3 was
attempted. As a result, as in Examples 1 to 3, it was confirmed
that a sample was highly sensitively detected, and that almost no
peak due to the fragmentation occurred in the low molecular weight
region. Example 4 exhibited that the thin metal film on whose
surface the irregularity was formed can also be favorably used as a
substrate for measurement by SALDI-MS.
[0122] While the present invention has been described with
reference to exemplary embodiments, it is to be understood that the
invention is not limited to the disclosed exemplary embodiments.
The scope of the following claims is to be accorded the broadest
interpretation so as to encompass all such modifications and
equivalent structures and functions.
* * * * *