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Patent 2889372 Summary

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(12) Patent: (11) CA 2889372
(54) English Title: DIRECT SAMPLE ANALYSIS DEVICE ADAPTERS AND METHODS OF USING THEM
(54) French Title: ADAPTATEURS POUR DISPOSITIF D'ANALYSE DIRECTE D'ECHANTILLONS ET LEURS PROCEDES D'UTILISATION
Status: Granted
Bibliographic Data
(51) International Patent Classification (IPC):
  • H01J 49/04 (2006.01)
  • H01J 49/26 (2006.01)
(72) Inventors :
  • ST. CYR, PAUL L. (United States of America)
  • DELVECCHIO, MICHAEL L. (United States of America)
  • WHITEHOUSE, CRAIG M. (United States of America)
(73) Owners :
  • PERKINELMER HEALTH SCIENCES, INC. (United States of America)
(71) Applicants :
  • PERKINELMER HEALTH SCIENCES, INC. (United States of America)
(74) Agent: MARKS & CLERK
(74) Associate agent:
(45) Issued: 2022-12-06
(86) PCT Filing Date: 2013-10-27
(87) Open to Public Inspection: 2014-05-01
Examination requested: 2018-10-22
Availability of licence: N/A
(25) Language of filing: English

Patent Cooperation Treaty (PCT): Yes
(86) PCT Filing Number: PCT/US2013/066993
(87) International Publication Number: WO2014/066872
(85) National Entry: 2015-04-23

(30) Application Priority Data:
Application No. Country/Territory Date
13/662,500 United States of America 2012-10-28
13/662,745 United States of America 2012-10-29
13/662,801 United States of America 2012-10-29

Abstracts

English Abstract

Certain embodiments described herein are directed to adapters for use in coupling a direct sample analysis device to an analytical instrument such as, for example, a mass spectrometer. In some examples, the adapter can include an internal coupler separated from an external coupler through an insulator. Certain features, aspects and embodiments are directed to an adapter configured to permit coupling of a direct sample analysis device to an analytical instrument. In some embodiments, the adapter is configured to couple the direct sample analysis device to a mass spectrometer.


French Abstract

Certains modes de réalisation de l'invention concernent des adaptateurs destinés à être utilisés pour accoupler un dispositif d'analyse directe d'échantillons avec un instrument d'analyse tel qu'un spectromètre de masse par exemple. Dans certains exemples, l'adaptateur peut comprendre un système d'accouplement interne séparé d'un système d'accouplement externe par l'intermédiaire d'un isolant.

Claims

Note: Claims are shown in the official language in which they were submitted.


The embodiments of the invention in which an exclusive property or privilege
is claimed
are defined as follows:
1. An adapter for installing a direct sample analysis device on a mass
spectrometer,
wherein the adapter is configured to permit coupling of the direct sample
analysis device to the
mass spectrometer while maintaining a substantially constant vacuum pressure
in the mass
spectrometer, the adapter comprising:
an internal capillary sleeve configured to couple to a capillary inlet of the
mass
spectrometer, while maintaining the substantially constant vacuum pressure in
the mass
spectrometer, in which the internal capillary sleeve is configured to couple
to the capillary inlet
through a friction fit between outer surfaces of the capillary inlet and inner
surfaces of the
internal capillary sleeve, in which the internal capillary sleeve comprises
arms that engage the
outer surfaces of the capillary inlet;
an external sleeve coupled to the internal capillary sleeve;
an insulator between the internal capillary sleeve and the external sleeve to
electrically
decouple the internal capillary sleeve from the external sleeve, said external
sleeve coupled to
said insulator through a friction fit; and
in which the adapter is configured to provide fluidic coupling between a
sample holder of
the direct sample analysis device and the mass spectrometer through the
capillary inlet while
maintaining the substantially constant vacuum pressure in the mass
spectrometer when the
internal capillary sleeve is coupled to the capillary inlet, the external
sleeve is coupled to the
internal capillary sleeve and the direct sample analysis device is coupled to
the external sleeve.
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Date Recue/Date Received 2021-10-08

2. The adapter of claim 1, in which the external sleeve is configured to
couple to a lens
assembly.
3. The adapter of claim 2, in which the lens assembly is configured to
slidingly engage to
the external sleeve.
4. The adapter of any one of claims 1 to 3, in which the external sleeve is
configured to
slidingly engage to the internal capillary sleeve.
5. The adapter of claim 4, in which the internal capillary sleeve is
further configured to
center the capillary inlet.
6. The adapter of claim 5, in which the external sleeve is further
configured to center the
capillary inlet.
7. A system for performing direct sample analysis, the system comprising:
the direct sample analysis device; and
an adapter as claimed in any one of claims 1 to 6.
8. The system of claim 7, in which the external sleeve is configured to
couple to the lens
assembly.
23
Date Recue/Date Received 2021-10-08

9. The system of claim 8, in which the lens assembly is configured to
slidingly engage to
the external sleeve.
10. The system of either of claims 8 or 9, in which the external sleeve is
configured to
slidingly engage to the internal capillary sleeve.
11. The system of claim 10, in which the internal capillary sleeve is
further configured to
center the capillary inlet.
12. The system of claim 11, in which the external sleeve is further
configured to center the
capillary inlet.
13. A system for performing direct sample analysis, the system comprising:
the direct sample analysis device comprising a sample support; and
a mass spectrometer comprising the capillary inlet, wherein the capillary
inlet of the mass
spectrometer is fluidically coupled to the sample support of the direct sample
analysis device
through the adapter of any of claims 1 to 6.
14. The system of claim 13, in which the external sleeve is configured to
couple to the lens
assembly.
15. The system of claim 14, in which the lens assembly is configured to
slidingly engage to
the external sleeve.
24
Date Recue/Date Received 2021-10-08

16. The system of any one of claims 13 to 15, in which the external sleeve
is configured to
slidingly engage to the internal capillary sleeve.
17. The system of any one of claims 13 to 16, in which the internal
capillary sleeve is sized
and arranged to center the capillary inlet in the internal capillary sleeve.
18. A method of installing a direct sample analysis device on a mass
spectrometer while
maintaining a substantially constant vacuum pressure in the mass spectrometer,
the method
comprising:
coupling the adapter of any of claims 1 to 6 to the capillary inlet of the
mass
spectrometer; and
coupling the direct sample analysis device to the coupled adapter.
19. The method of claim 18, further comprising removing a capillary nozzle
cap prior to
coupling the adapter to the capillary inlet.
20. The method of either of claim 18 or 19, further comprising coupling the
lens assembly to
the coupled adapter.
Date Recue/Date Received 2021-10-08

Description

Note: Descriptions are shown in the official language in which they were submitted.


DIRECT SAMPLE ANALYSIS DEVICE
ADAPTERS AND METHODS OF USING THEM
[0001] PRIORITY APPLICATIONS
[0002] This application claims priority to each of U.S. Application No.
13/662,500 filed on
October 28, 2012, U.S. Application No. 13/662,745 filed on October 29, 2012,
and U.S.
Application No. 13/662,801 filed on October 29, 2012.
[0003] TECHNOLOGICAL FIELD
[0004] Certain features, aspects and embodiments are directed to an adapter
configured to
permit coupling of a direct sample analysis device to an analytical
instrument. In some
embodiments, the adapter is configured to couple the direct sample analysis
device to a mass
spectrometer.
[0005] BACKGROUND
[0006] Direct sample analysis permits analysis of a sample by directly
introducing the sample
into an instrument. If desired, front-end chromatography separation can be
omitted prior to
analysis of the sample.
[0007] SUMMARY
[0008] Certain features, aspects and embodiments described herein are directed
to adapters
and/or components thereof that can couple a direct sample analysis device to
an analytical
instrument such as, for example, a mass spectrometer. The exact configuration
of the adapter can
vary and in some instances, the adapter may comprise a single integral
component or one or more
separate components which together can function to permit coupling of the
direct sample analysis
device to the analytical instrument.
[0009] In one aspect, an adapter for installing a direct sample analysis
device on a mass
spectrometer is provided. In certain examples, the adapter comprises a
capillary sleeve
configured to couple to a capillary inlet of the mass spectrometer, and an end
cap extension
configured to couple to the capillary sleeve, in which the capillary sleeve
and end cap extension
are configured to provide fluidic coupling between a sample holder and the
mass spectrometer
through the capillary inlet.
[0010] In certain embodiments, the end cap extension is configured to
couple to a lens assembly.
In other embodiments, the lens assembly is configured to slidingly engage to
the end cap extension.
In further embodiments, the end cap extension is configured to slidingly
engage to the capillary
sleeve. In some examples, the capillary sleeve couples to the capillary inlet
through a friction fit. In
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additional examples, the end cap extension couples to the capillary sleeve
through a friction fit. In
some embodiments, the capillary sleeve comprises an insulator configured to
electrically decouple
the capillary sleeve from the end cap extension. In other embodiments, the
capillary sleeve is further
configured to center the capillary inlet. In certain examples, the end cap
extension comprises an
insulator configured to electrically decouple the capillary sleeve from the
end cap extension. In
some embodiments, the end cap extension is further configured to center the
capillary inlet.
[0011] In an additional aspect, an adapter for installing a direct sample
analysis device on a mass
spectrometer, the adapter comprising an internal sleeve configured to couple
to a capillary inlet of
the mass spectrometer, an external sleeve coupled to the internal capillary
sleeve, and an insulator
between the internal sleeve and the external sleeve to electrically decouple
the internal sleeve from
the external sleeve, in which the adapter is configured to provide fluidic
coupling between a sample
holder and the mass spectrometer through the capillary inlet is disclosed.
[0012] In certain embodiments, the external sleeve is configured to couple to
a lens assembly. In
other embodiments, the lens assembly is configured to slidingly engage to the
external sleeve. In
further examples, the external sleeve is configured to slidingly engage to the
internal sleeve. In some
examples, the internal sleeve couples to the capillary inlet through a
friction fit. In additional
examples, the external sleeve couples to the internal sleeve through a
friction fit. In some
embodiments, the internal sleeve is sized and arranged to center the capillary
inlet in the internal
sleeve. In other embodiments, the insulator comprises at least one ceramic
material. In certain
examples, the adapter is configured to permit coupling of the direct sample
analysis device while
maintaining a vacuum of the mass spectrometer. In certain examples, the
adapter is configured to
permit coupling of the direct sample analysis device without removing any
lenses of the mass
spectrometer.
[0013] In another aspect, an adapter for installing a direct sample analysis
device on a mass
spectrometer, the adapter comprising an internal coupler configured to engage
a capillary inlet of the
mass spectrometer, an external coupler sized and arranged to engage a direct
sample analysis lens
assembly, and an insulator between the internal coupler and the external
coupler to electrically
decouple the internal coupler and the external coupler, in which the adapter
is configured to provide
fluidic coupling between a sample holder and the mass spectrometer through the
capillary inlet is
provided.
[0014] In some embodiments, the external coupler is configured to engage the
lens assembly
through a friction fit. In other examples, the internal coupler engages the
capillary inlet through a
friction fit. In certain examples, the internal coupler is sized and arranged
to center the capillary inlet
within the internal coupler. In further examples, the insulator comprises at
least one ceramic
2

material. In certain examples, the ceramic material is one of alumina, yttria,
titania or mixtures
thereof. In certain embodiments, each of the external coupler and the internal
coupler comprises
a substantially inert material. In other embodiments, the substantially inert
material is a stainless
steel. In some examples, the adapter is configured to permit coupling of the
direct sample
analysis device while maintaining a vacuum of the mass spectrometer. In
certain examples, the
adapter is configured to permit coupling of the direct sample analysis device
without removing
any lenses of the mass spectrometer.
[0015] In an additional aspect, an adapter for installing a direct sample
analysis device on a
mass spectrometer, the adapter comprising a coupler sized and arranged to
engage to a capillary
inlet of the mass spectrometer, the coupler comprising an internal surface
configured to engage to
the capillary of the capillary inlet and an external surface electrically
isolated from the internal
surface through an insulator, in which the adapter is configured to provide
fluidic coupling
between a sample holder and the mass spectrometer through the capillary inlet
is described.
[0016] In certain examples, the external surface of the coupler is
configured to couple to a lens
assembly through a friction fit. In certain embodiments, the internal surface
engages the capillary
inlet through a friction fit. In certain examples, the internal surface is
concentric and is sized and
arranged to center the capillary inlet within the internal coupler. In some
embodiments, the
insulator comprises at least one ceramic material. In certain examples, the
ceramic material is
one of alumina, yttria, titania or mixtures thereof. In some examples, each of
the external surface
and the internal surface comprise a substantially inert material. In some
embodiments, the
substantially inert material is a stainless steel. In other embodiments, the
adapter is configured to
permit coupling of the direct sample analysis device while maintaining a
vacuum of the mass
spectrometer. In further embodiments, the adapter is configured to permit
coupling of the direct
sample analysis device without removing any lenses of the mass spectrometer.
[0017] In another aspect, a system for performing direct sample analysis,
the system
comprising a direct sample analysis device, and an adapter for installing a
direct sample analysis
device on a mass spectrometer, the adapter comprising a capillary sleeve
configured to couple to
a capillary inlet of the mass spectrometer, and an end cap extension
configured to couple to the
capillary sleeve, in which the capillary sleeve and end cap extension are
configured to provide
fluidic coupling between a sample holder and the mass spectrometer through the
capillary inlet is
disclosed.
[0018] In certain embodiments, the end cap extension is configured to
couple to a lens assembly.
In other embodiments, the lens assembly is configured to slidingly engage to
the end cap extension.
In further embodiments, the end cap extension is configured to slidingly
engage to the capillary
sleeve. In additional embodiments, the capillary sleeve couples to the
capillary inlet through a
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friction fit. In some examples, the end cap extension couples to the capillary
sleeve through a
friction fit. In other examples, the capillary sleeve comprises an insulator
configured to electrically
decouple the capillary sleeve from the end cap extension. In further examples,
the capillary sleeve is
further configured to center the capillary inlet. In some examples, the end
cap extension comprises
an insulator configured to electrically decouple the capillary sleeve from the
end cap extension. In
other embodiments, the end cap extension is further configured to center the
capillary inlet.
[0019] In another aspect, a system for performing direct sample analysis, the
system comprising a
direct sample analysis device, and an adapter for installing a direct sample
analysis device on a mass
spectrometer, the adapter comprising an internal sleeve configured to couple
to a capillary inlet of
the mass spectrometer, an external sleeve coupled to the internal capillary
sleeve, and an insulator
between the internal sleeve and the external sleeve to electrically decouple
the internal sleeve from
the external sleeve, in which the adapter is configured to provide fluidic
coupling between a sample
holder and the mass spectrometer through the capillary inlet is provided.
[0020] In certain examples, the external sleeve is configured to couple to a
lens assembly. In some
examples, the lens assembly is configured to slidingly engage to the external
sleeve. In other
examples, the external sleeve is configured to slidingly engage to the
internal sleeve. In further
examples, the internal sleeve couples to the capillary inlet through a
friction fit. In additional
examples, the external sleeve couples to the internal sleeve through a
friction fit. In some
embodiments, the internal sleeve is sized and arranged to center the capillary
inlet in the internal
sleeve. In additional embodiments, the insulator comprises at least one
ceramic material. In other
examples, the adapter is configured to permit coupling of the direct sample
analysis device while
maintaining a vacuum of the mass spectrometer. In further examples, the
adapter is configured to
permit coupling of the direct sample analysis device without removing any
lenses of the mass
spectrometer.
[0021] In an additional aspect, a system for performing direct sample
analysis, the system
comprising a direct sample analysis device, and an adapter for installing a
direct sample analysis
device on a mass spectrometer without breaking the vacuum of the mass
spectrometer, the adapter
comprising a coupler sized and arranged to engage to a capillary inlet of the
mass spectrometer, the
coupler comprising an internal surface configured to engage to the capillary
of the capillary inlet and
an external surface electrically isolated from the internal surface through an
insulator, in which the
adapter is configured to provide fluidic coupling between a sample holder and
the mass spectrometer
through the capillary inlet is described.
[0022] In certain embodiments, the external surface of the coupler is
configured to couple to the
lens assembly through a friction fit. In other embodiments, the internal
surface engages the capillary
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inlet through a friction fit. In additional embodiments, the internal surface
is concentric and is sized
and arranged to center the capillary inlet within the adapter. In further
example, insulator comprises
at least one ceramic material. In some examples, the ceramic material is one
of alumina, yttria,
titania or mixtures thereof. In additional examples, each of the external
surface and the internal
surface comprises a substantially inert material. In some examples, the
substantially inert material is
a stainless steel. In some embodiments, the adapter is configured to permit
coupling of the direct
sample analysis device while maintaining a vacuum of the mass spectrometer. In
certain examples,
the adapter is configured to permit coupling of the direct sample analysis
device without removing
any lenses of the mass spectrometer.
[0023] In another aspect, a method of installing a direct sample analysis
device on a mass
spectrometer while maintaining a vacuum in the mass spectrometer, the method
comprising coupling
a capillary extension to the capillary inlet, and coupling an end cap
extension to the coupled capillary
extension, in which the coupled capillary extension and coupled capillary end
cap are configured to
provide fluidic coupling between a direct sample analysis sample holder and
the mass spectrometer
through the capillary inlet is provided.
[0024] In certain embodiments, the method comprises removing a capillary
nozzle cap prior to
coupling the capillary extension to the capillary inlet. In other embodiments,
the method comprises
coupling a direct sample analysis lens assembly to the coupled end cap
extension. In sonic
examples, the end cap extension comprises an insulator configured to
electrically isolate the capillary
extension from the end cap extension. In other examples, the capillary
extension comprises an
insulator configured to electrically isolate the capillary extension from the
end cap extension.
[0025] In an additional aspect, a method of installing a direct sample
analysis device on a mass
spectrometer while maintaining a vacuum in the mass spectrometer, the method
comprising coupling
an internal sleeve to a capillary inlet of the mass spectrometer, and coupling
an external sleeve to the
coupled internal capillary sleeve, the external sleeve comprising an insulator
configured to be
positioned between the internal capillary sleeve and the external sleeve to
electrically isolate the
internal sleeve from the external sleeve, in which the coupled internal and
external sleeves are
configured to provide fluidic coupling between a direct sample analysis sample
holder and the mass
spectrometer through the capillary inlet is provided.
[0026] In certain embodiments, the method comprises removing a capillary
nozzle cap prior to
coupling the internal sleeve to the capillary inlet. In other embodiments, the
method comprises
coupling a lens assembly to the coupled external sleeve. In some embodiments,
the external sleeve
comprises an insulator configured to electrically isolate the internal sleeve
from the external sleeve.

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In other embodiments, the internal sleeve comprises an insulator configured to
electrically isolate the
internal sleeve from the external sleeve.
[0027] In another aspect, a method of installing a direct sample analysis
device on a mass
spectrometer comprising a capillary inlet while maintaining a vacuum in the
mass spectrometer, the
method comprising coupling an adapter comprising a coupler sized and arranged
to engage to a
capillary inlet of the mass spectrometer, the coupler comprising an internal
surface configured to
engage to the capillary of the capillary inlet and an external surface
electrically isolated from the
internal surface through an insulator, in which the adapter is configured to
provide fluidic coupling
between a sample holder and the mass spectrometer through the capillary inlet
is described.
[0028] In certain examples, the method comprises removing a capillary nozzle
cap prior to
coupling the internal surface to the capillary inlet. In other examples, the
method comprises
coupling a lens assembly to the coupled external surface. In certain
embodiments, the method
comprises initiating sample analysis of a sample on a direct sample analysis
sample support
substantially immediately after coupling the lens assembly to the external
surface of the adapter. In
other embodiments, the method comprises maintaining a substantially constant
vacuum pressure in
the mass spectrometer during the coupling of the adapter.
[0029] In another aspect, a method of coupling a direct sample analysis device
to a mass
spectrometer, the method comprising coupling an adapter comprising a coupler
sized and arranged to
engage to a capillary inlet of the mass spectrometer to provide fluidic
coupling between the capillary
inlet and a direct sample analysis sample support to permit substantially
immediate sample analysis
of sample on the direct sample analysis sample support after coupling of the
adapter is provided.
[0030] In certain embodiments, the adapter comprises an internal sleeve, an
external sleeve and an
insulator between the internal sleeve and the external sleeve. In other
embodiments, the method
comprises maintaining an operating pressure of the mass spectrometer during
coupling of the coupler
to the capillary inlet. In further embodiments, the method comprises coupling
a lens assembly to the
coupled adapter and initiating the sample analysis substantially immediately
subsequent to coupling
of the lens assembly. In some examples, the method comprises configuring the
adapter to comprise a
separate internal coupler and a separate external coupler.
[0031] In another aspect, the adapters described herein can be packaged in the
form of a kit that
comprises one or more of the adapters described herein. In other embodiments,
the kit may comprise
two or more of the adapters described herein.
[0032] Other aspects and attributes will become apparent to those skilled in
the art after review of
the detailed description and accompanying drawings.
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[0033] BRIEF DESCRIPTION OF FIGURES
[0034] Certain configurations are provided below for illustrative purposes
only with reference to
the accompanying figures in which:
[0035] FIG. 1 is an illustration of an adapter comprising an internal coupler
and an external
coupler, in accordance with certain examples;
[0036] FIG. 2 is an illustration of an adapter comprising an internal coupler,
an external coupler
and an insulator between the internal coupler and the external coupler, in
accordance with certain
examples;
[0037] FIG. 3 is an illustration of a capillary sleeve, in accordance with
certain examples;
[0038] FIG. 4 is an illustration of the capillary sleeve of FIG. 3 coupled to
a capillary housing, in
accordance with certain examples;
[0039] FIG. 5 is an illustration of an end cap coupled to a capillary sleeve,
in accordance with
certain examples;
[0040] FIG. 6 is an illustration of an insulator between a coupled end cap and
a capillary sleeve, in
accordance with certain examples;
[0041] FIG. 7 is an illustration of an adapter configured as a unitary device
and comprising an
internal sleeve and an external sleeve, in accordance with certain examples;
[0042] FIG. 8 is an illustration of an adapter configured as a unitary device
and comprising an
internal sleeve, an external sleeve and an insulating layer or sleeve between
the internal sleeve and
the external sleeve, in accordance with certain examples;
[0043] FIG. 9 is a block diagram of an instrument comprising a direct sample
analysis device, in
accordance with certain examples;
[0044] FIGS 10A-10D schematically show installation of an adapter and lens
assembly on a mass
spectrometer, in accordance with certain examples;
[0045] FIG. 11 is an illustration of a direct sample analysis device coupled
to a mass spectrometer,
in accordance with certain examples; and
[0046] FIG. 12 is an illustration of a the system of FIG. 11 showing the
sample support between
an ion gun and a lens assembly, in accordance with certain examples.
[0047] Additional features, aspects and embodiments are described in more
detail below. It will
be recognized by the person of ordinary skill in the art, given the benefit of
this disclosure, that the
lengths and dimensions shown in the figures are not limiting and that many
different lengths and
dimensions can be used depending on the size of the adapter, the system which
the adapter is to be
used in and other factors.
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[0048] DETAILED DESCRIPTION
[0049] Certain embodiments of adapters are described below can include one or
more components
that can facilitate fluidic coupling of a direct sample analysis device to an
inlet of a mass
spectrometer or other analytical instrument that can receive a fluid stream.
The exact configuration
of the adapters including, for example, the length and width of the adapter
components, size and
configuration of the openings of the adapters and materials used in the
adapters, or components
thereof, can vary depending on the particular instrument the adapters are to
be used with and/or
depending on the nature of the sample to be analyzed. Where direct sample
analysis is referred to
below, no particular configuration of a direct sample analysis device or
system is intended to be
required as being necessary for properly using the adapters. For illustration
purposes, some
configurations of a direct sample analysis device or system are described
herein. The term sample
support, as used in certain instances herein, refers to a holder, device or
other structure that is
effective to retain a sample, for at least some period, to permit analysis of
the sample. In some
instances, the sample support may be configured to receive a mesh, screen or
other material that is
effective to receive and retain a sample for analysis.
[0050] In certain examples, the adapters described herein can be configured to
slip onto a fluid
inlet of an analytical device to permit coupling of one or more other
components to the adapter. For
example, the adapter can be sized and arranged to permit a lens assembly to be
placed over the
adapter while permitting fluidic coupling of a sample support to the fluid
inlet. In embodiments
where the fluid inlet is part of a mass spectrometer, the adapter can permit
coupling of the direct
sample analysis device without breaking the vacuum of the mass spectrometer.
In certain
embodiments, a mass spectrometer may have an operating pressure of about 10 9
Ton or less. Where
existing sample introduction systems are coupled to the mass spectrometer, the
vacuum seal is
broken requiring pumping of the instrument back down to operating pressure and
a substantial delay,
e.g., about 8 hours or more, before sample can be analyzed. In addition, where
capillary inlets are
present, it is often required that the existing capillary be removed and
replaced with a longer
capillary. Replacement of the capillary with a longer one often requires
removal of the source block
and subsequent realignment before the instrument may be used. In certain
embodiments of the
adapters described herein, a direct sample analysis device can be coupled to a
mass spectrometer
without removal of the source block. In other embodiments of the adapter
described herein, a direct
sample analysis device can be coupled to a mass spectrometer without
lengthening of the capillary of
the capillary inlet. In further embodiments of the adapter described herein, a
direct sample analysis
device can be coupled to a mass spectrometer without breaking of the vacuum of
the mass
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spectrometer. In other embodiments, the adapter is configured to permit
coupling of the direct
sample analysis device without removing any lenses of the mass spectrometer.
100511 In certain embodiments, an adapter comprising an internal coupler
and an external
coupler can be used to fluidically couple a direct sample analysis device to
an analytical instrument,
e.g., a mass spectrometer. Referring to FIG. 1, an adapter is shown comprising
an internal coupler
110 and an external coupler 120. The exact configuration of the internal
coupler can vary, and in
some examples the internal coupler is configured to permit fluidic coupling
from the outside of the
adapter to a capillary inlet of the analytical system. For example, the
internal coupler 110 can be
configured to engage a capillary inlet of the mass spectrometer such that
sample from a sample
support can be provided to the capillary inlet. In some embodiments, the
external coupler 120 can be
sized and arranged to engage another component of the analytical instrument
such as, for example, a
direct sample analysis lens assembly 130. In certain embodiments, the internal
coupler 110 and the
external coupler 120 are integral to the adapter, e.g., the adapter is a one-
piece adapter. In use of a
one-piece adapter, an end cap is typically removed from the capillary inlet,
and the adapter is slid
onto the capillary inlet in place of the end cap. The lens assembly 130, or
other component, may be
slid or placed over the adapter to prepare the instrument for sample analysis.
In some examples, the
internal coupler 110 and the external coupler 120 are two separate components
which may engage
each other in a suitable manner to provide the fluidic coupling. For example,
the internal coupler
110 may first be slid or placed onto the capillary inlet followed by placement
of the external coupler
120 over the internal coupler 110. The lens assembly 130 may be placed over
the external coupler
120 to permit use of the direct sample analysis device with the instrument for
sample analysis.
100521 In certain examples, the internal coupler 110 and the external coupler
120 may be placed in
direct contact with each other without any intervening component or device
between them. In other
embodiments, the internal coupler 110 and the external coupler 120 can be
separated by one or more
other components, e.g., a spacer or insulator. For example, a spacer can be
placed between the
internal coupler 110 and the external coupler 120 in instances where the
internal diameter of the
external coupler 120 is larger than the outer diameter of the internal coupler
110. Use of a spacer can
permit physical contact of the internal coupler 110 and external coupler 120
through the spacer to
provide electrical coupling between the coupler 110 and the coupler 120. In
other embodiments, it
may be desirable to electrically decouple the internal spacer 110 and the
external spacer 120. For
example and referring to FIG. 2, an adapter comprises an internal coupler 210
comprising a capillary
channel 205. The adapter also includes an external coupler 220 configured to
permit coupling of a
lens assembly (not shown) to the mass spectrometer. The adapter also comprises
an insulator 215
which is effective to electrically decouple the external coupler 220 and any
installed lens assembly
9

from the internal coupler 210. In some embodiments, the insulator 220 may be a
separate
component that is coupled to the internal coupler 210 prior to coupling of the
external coupler
220. In other embodiments, the insulator 220 may be integral to the internal
coupler 210 such
that coupling of the internal coupler 210 to the capillary inlet acts to
suitably position the
insulator 215 between the internal coupler 210 and the external coupler 220.
In other examples,
the insulator 215 may be integral to the external coupler 220 such that
coupling of the external
coupler 220 to the internal coupler 210 acts to suitably position the
insulator 215 between the
internal coupler 210 and the external coupler 220. It may be desirable to
electrically decouple the
internal coupler 210 from the external coupler 220 such that no unwanted
electrical fields are
provided. For example, the lens assembly that is coupled to the external
coupler 220 may be
electrically charged to assist in entry of only certain ions or atoms into the
capillary inlet. It may
be desirable to prevent the charge on the lens assembly from reaching the
internal coupler 210.
The insulator 215 can be effective to electrically isolate the internal
coupler 210 from the external
coupler 220 and/or any lens assembly.
[0053] In
certain embodiments, the internal coupler 210 is configured to engage the
capillary
inlet through a friction fit, whereas in other embodiments the internal
coupler 210 can couple to
the capillary inlet through threads or other fittings. In some embodiments,
the internal coupler
210 can be sized and arranged to center the capillary inlet within the
internal coupler 210 to
provide a fluid flow path at a desired angle or plane. In some examples, the
external coupler 220
may couple to the internal coupler 210 through a friction fit or through the
use of threads or
fittings. Similarly, the external coupler 220 can engage the lens assembly
through a friction fit or
through threads or other fittings. Where an insulator 215 is present, it can
engage the internal
coupler 210 and/or external coupler 220 through a friction fit or through
threads or other fittings.
In some embodiments, the insulator 215 may be produced from, or may include,
any non-
conductive material including, but not limited to, ceramics such as, for
example, alumina, yttria,
titania or mixtures thereof. As described herein, the internal and external
couplers can be
produced with one or more substantially inert materials such as, for example,
the plastics and/or
stainless steel materials described herein.
[0054] In certain examples, the external surface of the internal coupler 210
can be
configured as non-conductive, e.g., can include a non-conductive coating or
layer that
physically contacts an inner surface of the external coupler 220. In other
embodiments,
the internal surface of the external coupler 220 can be configured as non-
conductive, e.g.,
can include a non-conductive coating or layer that physically contacts an
outer surface of
the internal coupler 210. If desired, the internal surface of the internal
coupler 210 may
comprise a non-conductive material or a substantially inert material, either
of which can
take the form of a coating or layer, to reduce the likelihood of sample
contamination by
the internal coupler 210. In some embodiments, the internal surface of the
internal
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coupler 210 can be concentric and sized and arranged to center the capillary
inlet within the internal
coupler 210. For example, it may be desirable to align the center of the
capillary inlet with the center
of the adapter inlet to ensure ions traveling into the adapter inlet are
provided to the capillary inlet
without hitting the internal surfaces of the adapter inlet. In certain
examples, the adapter need not
perfectly center the capillary inlet but can place the capillary inlet
substantially in the center of the
adapter.
[0055] In certain embodiments, an adapter comprising a capillary sleeve and an
end cap extension
can be used to install a direct sample analysis device on a mass spectrometer.
Referring to HG. 3, a
capillary sleeve 300 is shown as including a generally cylindrical body with a
first portion 310 and a
second portion 320. The sleeve 3110 comprises an internal channel 315 that can
fluidically couple to
the capillary inlet of the mass spectrometer at an end 317. "The other end 319
of the channel 315 may
be fluidically coupled to a sample support (not shown) to receive sample into
the channel 315. The
portion 310 of the sleeve 300 can be sized and arranged to slide over and
around the capillary
housing until the surface of the sleeve 300 that is adjacent to the end 317
contact the capillary
housing. Such contact places the end 317 proximal to the end of the capillary
inlet and provides
fluidic coupling between the end 319 and the capillary inlet. For example and
referring to HG. 4, a
capillary housing 410 comprising a capillary 415 is shown as being coupled to
the capillary sleeve
300. The surface adjacent to the opening 317 abuts the surface of the
capillary housing 410. The
portion 310 of the capillary sleeve can include arms or projections 312, 314
that can engage the outer
surface of the capillary housing 410 to provide contact of increased surface
area of the housing 410
by the inner surfaces of the capillary sleeve 300. In some embodiments, one
end of the capillary
sleeve 300 can be configured to couple to the capillary inlet and is pushed
into the capillary housing
410 until it encounters resistance by the capillary housing 410. Placement of
the sleeve 300 onto the
housing 410 until resistance is encountered can provide the fluidic coupling
between the ends of the
capillary sleeve 300 and the capillary 415.
[0056] In certain examples, an end cap extension may then be coupled to the
capillary sleeve, e.g.,
slid onto and around the capillary sleeve. Referring to FIG. 5, an end cap
extension 510 is shown as
being coupled to the capillary sleeve 300. The extension 510 is slid onto the
capillary sleeve 300
and engages the capillary sleeve 300 through a friction fit at the portion 320
of the capillary sleeve
300. The extension 510 is placed on the sleeve 300 and slid in a direction
toward the interior of the
instrument until it encounters resistance when it contacts internal surfaces
of the instrument at arrows
512 and 514. Once resistance is encountered, insertion is halted and the
coupled capillary sleeve 300
and extension 510 are ready for analysis or ready to be coupled to another
component of the system.
In certain embodiments, the end cap extension 510 can assist with the fluidic
coupling between a
11

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sample holder and a mass spectrometer capillary inlet and/or may be sized and
arranged to receive a
lens assembly for selection of certain ions or atoms in the ionized sample. In
certain examples, the
end cap extension 510 is configured to slidingly engage to the capillary
sleeve 300. In some
embodiments, the lens assembly is configured to slidinely engage to the end
cap extension 510. If
desired, the components of the adapter can couple to each other through a
friction fit.
[0057] In certain embodiments, one or both of the capillary sleeve 300 and the
end cap extension
510 can include an insulator to electrically decouple or isolate the capillary
sleeve 300 from the end
cap extension 510. For example and referring to FIG. 6, an insulator 610 can
be coupled to the
sleeve 300 prior to coupling of the end cap extension 510. Where it is
desirable to use an insulator
610, the dimensions of the end cap extension 510 can be altered such that a
friction fit is provided
between the end cap extension 510 and the insulator 610. Without wishing to be
bound by any
particular scientific theory, the insulator 610 may be effective to
electrically decouple the sleeve 300
from the end cap extension 510. In some analytical methods, the end cap
extension 510 may include
an electrical voltage or current that can be isolated from the capillary
sleeve 300. In certain
instances, the capillary sleeve 303 or capillary inlet may have its own
voltage, which can be different
than the voltage of the end cap extension 510. The insulator 610 permits
independent control of the
voltages on each of the sleeve 300 and the end cap extension 510. In some
embodiments, the
insulator 610 may be produced from, or may include, one or more nonconductive
materials such as,
for example, alumina or other ceramics. The end cap extension 510, the
capillary sleeve 300 or both
may be effective to assist in centering the capillary inlet in the adapter
inlet. By centering the
capillary inlet opening, more reproducible results can be achieved and overall
accuracy
improvements can be realized. In certain embodiments, a lens assembly (not
shown) can be coupled
to the end cap extension 510. In some examples, the lens assembly may be
effective to select or
guide certain ions into the capillary inlet, e.g., at a desired angle, and
reject or deflect unwanted ions.
The adapter components shown in FIGS. 3-6 can be used with additional
components in other
analytical systems if desired. In addition, the overall dimensions including
the width, length and
geometry of the components can be varied to permit fluidic coupling of a
direct sample analysis
device to an instrument.
[0058] In certain embodiments, the adapter may be configured as a unitary
device with an internal
sleeve and an external sleeve. For example and referring to FIG. 7, the
adapter 700 comprises an
internal sleeve 710 and an external sleeve 720. The internal sleeve 710 can be
configured similar to
the capillary sleeve 300, e.g., can be configured to couple to a capillary
housing and provide fluidic
coupling between a sample support and a capillary inlet of an instrument. The
external sleeve 720
can be configured similar to the end cap extension 510, e.g., can be
configured to couple to a lens
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assembly. In some embodiments, the internal sleeve 710 may be electrically
isolated from the
external sleeve 720 by an insulative material between the sleeve 710 and the
sleeve 720. For
example and referring to FIG. 8, an insulator 830 can be present between an
internal sleeve 810 and
an external sleeve 820 to electrically decouple the internal sleeve 810 from
the external sleeve 820.
In some embodiments, the insulator 830 is configured to permit each of the
internal sleeve 810 and
the external sleeve 820 to receive or provide a different voltage or no
voltage. Where a unitary
adapter is used, an end cap of the capillary inlet can be removed and the
unitary adapter may be
coupled to the capillary inlet by inserting the adapter until resistance is
encountered. In other
configurations, the unitary adapter can include threads or other fittings to
assist in retention of the
adapter to the capillary inlet. After coupling of the adapter, a lens assembly
may be coupled to the
coupled adapter and sample analysis may be immediately initiated without
having to wait for the
instrument to be pumped down to a desired operating pressure.
[0059] In certain embodiments, the adapter comprising the sleeves can be
configured to slidin2ly
engage to a lens assembly, e.g., through a friction fit. In some embodiments,
the sleeves may be
configured as separate sleeves that can be coupled to each other through a
friction fit by sliding the
external sleeve over the internal sleeve. Where two or more sleeves are
present, the internal sleeve,
the external sleeve or both can be configured as substantially concentric
sleeve that are effective to
generally center the capillary inlet. In certain examples, the sleeves of the
adapter can be coupled to
the mass spectrometer without removing any lenses of the mass spectrometer. If
desired, one or
more insulating sleeves can be inserted between the internal sleeve and the
external sleeve.
[0060] In some embodiments, coupling of the adapters and/or lens assemblies
permit substantially
immediate sample analysis to be initiated. For example, unlike existing
devices that are used to
couple a direct sample analysis device to an instrument, such as a mass
spectrometer, which may
require hours of pumping to reach an operating pressure, e.g., a vacuum
pressure, the adapters
described herein permit sample analysis to begin within about 30 seconds of
coupling of the adapter,
more particularly within about 1 minute, 2 minutes, 3 minutes, 4 minutes or
about 5 minutes of
coupling the adapter and/or lens assembly. In some instances, after coupling
of the lens assembly, a
sample support comprising sample can be loaded onto a sample platform. The
sample platform with
coupled sample support can be lowered and translated into a position such that
one or more of the
apertures of the sample support are placed between an ion source, e.g., an ion
gun, and an aperture or
opening of the coupled lens assembly/adapter. The ion source can impact the
sample and ionized
sample may exit the sample support and be provided to the capillary inlet of a
mass spectrometer
through the aperture of the coupled lens assembly/adapter. Illustrative sample
supports suitable for
use with the adapters described herein are described in commonly assigned U.S.
Patent Application
13

No. 13/662,500 filed on October 28, 2012, published as US2014-0116160A1.
Illustrative
sample platforms suitable for use with the adapters described herein are
described in commonly
assigned U.S. Patent Application No. 13/662,801 filed on October 29, 2012,
published as
US2014-0116161A1.
[0061] In certain embodiments, a system for performing direct sample analysis
can include
one of the adapters described herein. Referring to FIG. 9, a system 900
comprising a direct
sample analysis (DSA) device 910 coupled to an analytical device 920 is shown.
The DSA
device 910 may be fluidically coupled to the analytical device 920 and/or
physically coupled to
the analytical device 920. In certain embodiments, the analytical device 920
may take many
forms including mass spectrometers, optical absorbance or emission detectors,
plasma based
analytical systems or other systems. In direct sample analysis, the sample can
be directly
analyzed without undergoing pre-sample preparation or purification, e.g.,
without being subjected
to one or more purification steps, chromatographic separation steps or the
like. In a typical
operation, the sample is ionized after collision with an energized ion or
atom, e.g., an
electronically excited ion or atom. The collisional atoms are typically
provided by an ion source
such as, for example, an electron ionization source, a chemical ionization
source, an electrospray
ionization source, an atmospheric-pressure chemical ionization source, a
plasma (e.g., inductively
coupled plasma), glow discharge sources, field desorption sources, fast atom
bombardment
sources, thermospray sources, desorption/ionization on silicon sources,
secondary ion mass
spectrometry sources, spark ionization sources, thermal ionization sources,
ion attachment
ionization sources, photoionization or other suitable ion sources. Energy
transfer can occur
between excited molecules from the ion source and the sample which can cause
ejection of
charged sample species from the sample support. The ejected species may be
provided to the
analytical device 920 or system, e.g., a mass analyzer, for detection. In a
typical setup, the ions
which are provided to the analytical device 920 pass through an interface (not
shown) which may
include one or more ion guides or lenses to select an analyte of a desired
mass-to-charge ratio
and/or remove any interfering or unwanted species.
[0062] In certain embodiments where the analytical device 920 takes the form
of a
mass spectrometer, many different types of mass analyzers can be used with the
sample
support holders described herein. For example, sector field mass analyzers,
time of flight
mass analyzers, quadrupole mass filters, ion traps, linear quadrupole ion
traps, orbitraps
or cyclotrons, e.g., Fourier transform ion cyclotron resonance or other
suitable mass
analyzers can be used. As selected ions exit the mass analyzer they can be
provided to a
detector to detect a change in charge or a current that is produced as the
ions impact or
travel by a surface, for example. Illustrative detectors include, but are not
limited to,
electron multipliers, Faraday cups, ion-to-photon detectors, microchannel
plate
14
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detectors, an inductive detector or other suitable detectors may be used. The
mass spectrometer
typically will include a display that can provide a spectrum for review by the
user. While not
described, the mass spectrometer typically would include numerous other
components including a
vacuum system, one or more interfaces and many other components commonly found
in mass
spectrometers in use.
l00631 In some embodiments, the system 900 can include the DSA device 910 and
an adapter for
installing the DSA device on a mass spectrometer. In some embodiments, the
adapter comprises a
capillary sleeve configured to couple to a capillary inlet of the mass
spectrometer, and an end cap
extension configured to couple to the capillary sleeve, in which the capillary
sleeve and end cap
extension are configured to provide fluidic coupling between a sample support
of the DSA device
910 and the mass spectrometer through the capillary inlet. In certain
examples, the end cap
extension used in the system 900 can be configured to couple to a lens
assembly. In some examples,
the lens assembly can be configured to slidingly engage to the end cap
extension. In other examples,
the end cap extension can be configured to slidingly engage to the capillary
sleeve. In some
embodiments, the capillary sleeve couples to the capillary inlet through a
friction fit. In certain
instances, the end cap extension couples to the capillary sleeve through a
friction fit. In certain
examples, the capillary sleeve comprises an insulator configured to
electrically decouple the
capillary sleeve from the end cap extension. In other embodiments, the
capillary sleeve is further
configured to center the capillary inlet. In some examples, the end cap
extension comprises an
insulator configured to electrically decouple the capillary sleeve from the
end cap extension. In
further example, the end cap extension is further configured to center the
capillary inlet.
1-00641 In other embodiments, the DSA device 910 can include an adapter
comprising an internal
sleeve configured to couple to a capillary inlet of the mass spectrometer, an
external sleeve coupled
to the internal capillary sleeve, and an insulator between the internal sleeve
and the external sleeve to
electrically decouple the internal sleeve from the external sleeve, in which
the adapter is configured
to provide fluidic coupling between a sample support and the mass spectrometer
through the
capillary inlet. In some examples, the external sleeve of the adapter used in
the system 900 can be
configured to couple to a lens assembly. In certain examples, the lens
assembly can be configured to
slidingly engage to the external sleeve of the adapter. In other embodiments,
the external sleeve can
be configured to slidingly engage to the internal sleeve. In some examples,
the internal sleeve
couples to the capillary inlet through a friction fit. In some embodiments,
the external sleeve couples
to the internal sleeve through a friction fit. In additional examples, the
internal sleeve can be sized
and arranged to center the capillary inlet in the internal sleeve. In some
examples, the insulator
comprises at least one ceramic material. In other examples, the adapter can be
configured to permit

CA 02889372 2015-04-23
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coupling of the direct sample analysis device while maintaining a vacuum of
the mass spectrometer.
In some examples, the adapter can be configured to permit coupling of the
direct sample analysis
device without removing any lenses of the mass spectrometer.
100651 In certain examples, the adapter of the system 910 may comprise an
adapter for installing a
direct sample analysis device on a mass spectrometer without breaking the
vacuum of the mass
spectrometer. For example, the adapter may comprises a coupler sized and
arranged to engage to a
capillary inlet of the mass spectrometer and comprising an internal surface
configured to engage to
the capillary of the capillary inlet and an external surface electrically
isolated from the internal
surface through an insulator. In some embodiments, the adapter can be
configured to provide fluidic
coupling between a sample support, e.g., a DSA sample support, and the mass
spectrometer through
the capillary inlet. In some embodiments, the external surface of the coupler
can be configured to
couple to the lens assembly through a friction fit. In other embodiments, the
internal surface engages
the capillary inlet through a friction fit. In certain examples, the internal
surface is concentric, e.g., it
may be sized and arranged to center the capillary inlet within the adapter. In
some embodiments, the
insulator comprises at least one ceramic material. In other embodiments, the
ceramic material is one
of alumina, yttria, titania or mixtures thereof. In further examples, each of
the external surface and
the internal surface comprises a substantially inert material. In some
examples, the substantially
inert material is a stainless steel. In other embodiments, the adapter is
configured to permit coupling
of the direct sample analysis device while maintaining a vacuum of the mass
spectrometer. In some
embodiments, the adapter is configured to permit coupling of the direct sample
analysis device
without removing any lenses of the mass spectrometer.
100661 In certain embodiments, the adapters described herein can be used to
permit exchange of an
existing ionization device in a mass spectrometer with a direct sample
analysis device. For example,
one or more ionization systems commonly used in a mass spectrometer can be
removed and replaced
with a direct sample analysis device. Illustrative types of ionization devices
that can be replaced
with a direct sample analysis device include, but are not limited to, devices
including a source
selected from an electron ionization source (ESI), a chemical ionization
source, an clectrospray
ionization source, an atmospheric-pressure chemical ionization source, a
plasma (e.g., inductively
coupled plasma), glow discharge sources, field desorption sources, fast atom
bombardment sources,
thermospray sources, desorption/ionization on silicon sources, secondary ion
mass spectrometry
sources, spark ionization sources, thermal ionization sources, ion attachment
ionization sources,
photoionization or other suitable ion sources. Referring to FIGS. 10A-10D, a
series of figures are
shown pictorially representing the process of replacing an electrospray
ionization source of a mass
spectrometer with a direct sample analysis device. The ESI door assembly 1010
(see FIG. 10A) is
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removed from the mass spectrometer 1020 by opening the ESI door 1010 and
lifting the door 1010
upward. A nozzle cap 1030 (see FIG. 10B) is then removed by grasping the
nozzle cap 1030 and
moving it away from the capillary housing in the general direction of arrow
1032. An adapter 1040
is then coupled to the capillary housing (see FIG. 10C) by inserting the
adapter 1040 in the direction
of arrow 1042 until it encounters resistance from the capillary housing. A
lens assembly 1050 (see
FIG. 10D) can then be installed over the adapter 1040 in the direction of
arrow 1052. The adapter
1040 may be any of the adapters described herein. For example, the adapter can
be configured with
capillary extension and an end cap extension that is coupled capillary
extension. It desired, an
insulator can be placed between the capillary extension and the end cap
extension. In other
embodiments, the adapter can include and internal sleeve and an external
sleeve that can couple to
the internal sleeve. Optionally an insulator may be between the internal and
external sleeves.
Adapters comprising other configurations may also be used to permit coupling
of a lens assembly of
a direct sample analysis device to a mass spectrometer.
[0067] In certain embodiments, once the lens assembly is installed, the system
is ready to analyze
sample by direct sample analysis. Referring to FIG. 11, a cut away view of a
direct sample analysis
device 1100 is shown. The DSA device 1100 includes a sample holder assembly
1110 including a
sample support 1115 coupled to a sample platform. A sealing device 1120, e.2.,
a door or cover, is
shown as being present in an open position to permit loading of the sample
support 1115 onto the
sample platform. The DSA device 1100 also comprises a lens assembly 1125,
which is similar to, or
the same as, the lens assembly 1050 of FIG. 10D, and an ion source or ion gun
1130. Referring also
to FIG. 12, once the sample support 1115 is loaded onto the sample platform,
the sample platform is
lowered into the DSA device 1100 and moved toward the right of the figure to
align one of the
apertures of the sample support 1115 with the ion gun 1130 and the lens
assembly 1125. Ions from
the ion gun 1130 impact the sample on the sample support 1115, and ionized
sample exits the sample
support on an opposite side of the sample support 1115 and enters the lens
assembly 1125. The lens
assembly 1125 is fluidically coupled to the analytical device through an
adapter (not shown), as
described herein, to provide ionized sample from the DSA device to the
analytical device, e.g., to the
mass spectrometer through a capillary inlet of the mass spectrometer.
[0068] In a typical sampling operation, the sample can be added to the sample
support, e.g., either
directly or by suspending the sample in a liquid or dissolving the sample in a
solvent, where it is
retained at least for a sufficient period to permit analysis of the sample.
Where the sample is a solid,
it may be crushed, pulverized, homogenized or otherwise rendered into powder
or crystalline form to
be loaded onto the sample support. A diluent or carrier can be added to the
powder to clump or
agglomerate the powder to facilitate loading onto the sample support. Where
diluents or carriers are
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used, suitable materials are selected so they do not create species that may
interfere with any analysis
of the sample. Where the sample is a liquid, it may be sprayed on, dropped on,
pipetted on or
otherwise introduced onto the sample support. In some embodiments, the sample
support can be
dipped into a liquid or liquids to load the samples onto the sample support.
For example, the sample
support can be configured with individual sections that are separated by
openings and configured to
be dipped or disposed into an individual receptacle, e.g., an individual
microwell, to permit dipping
of the sample support into a plurality of wells in a microwell plate. Such
sample supports would
permit automated sample loading and decrease the overall time needed to load
samples onto the
sample support.
[0069] In certain embodiments, the adapters and components of the adapters
described herein can
be produced using one or more suitable materials that are generally inert so
as to not substantially
interfere with, or contaminate, any sample analysis. In some embodiments, the
materials may be, or
may include, one or more plastic materials including thermoplastics and
thermosets. In some
embodiments, the plastic material desirably has a melting temperature of
greater than 250 degrees
Celsius, more particularly greater than 300 degrees Celsius. In certain
embodiments, any one or
more of the adapter components herein can include a thermoplastic comprising
an acrylic polymer, a
fluoroplastic polymer, a polyoxymethylene polymer, a polyacrylate polymer, a
polycarbonate
polymer, a polyethylene terephthalate polymer, a polyester polymer, a
polyetheretherketone polymer,
a polyamide polymer, a polyimidc polymer, a polyamidc-imidc polymer, a
polyaryletherketone
polymer or combinations and copolymers thereof. If desired metallic or
conductive particles can be
included in the thermoplastic to facilitate electrical coupling of the sample
support to an electrical
ground. In some embodiments, the thermoplastic used is substantially
transparent when viewed with
the human eye to facilitate, for example, coupling of the adapter to the
capillary housing. In certain
embodiments, the components of the adapters can be produced using one or more
substantially inert
metal materials including, for example, Inconel alloys, titanium and titanium
alloys, aluminum and
aluminum alloys, stainless steels, refractories or other suitable materials
that include metals and
which are substantially inert in the use environment of the adapters.
[0070] In certain embodiments, some components of adapters can be produced
using materials
other than inert materials if desired. For example, portions of the adapters
may generally be out of
the fluid stream that contacts the sample and can be produced using materials
other than non-inert
materials. If desired, the different components of the adapters can be
produced using different
materials. Where an insulator is present in the adapters to electrically
isolate the internal coupler or
sleeve from the external coupler or sleeve, the insulator may be any
nonconductive material and is
desirably a substantially inert nonconductive material to avoid any
contamination of the sample.
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Illustrative insulating materials include non-conductive materials, ceramics
such as, for example,
alumina, yttri a, titania, machinable ceramics, non-machinable ceramics or
other suitable ceramics
and other suitable insulating materials. In some embodiments, the components
of the adapters
described herein can include a material that can withstand a cleaning
operation such as, for example,
sonication, solvent washes or other cleaners can be used to clean and/or
remove any residue from the
adapters prior to reuse. In some configurations, the materials of the adapters
can withstand such
washing steps and substantially no deterioration occurs after washing.
f00711 In certain embodiments, the adapters, or components of the adapters,
described herein can
be packaged or grouped into a kit. In some examples, a kit comprises an
adapter comprising a
capillary sleeve configured to couple to a capillary inlet of the mass
spectrometer, and an end cap
extension configured to couple to the capillary sleeve, in which the capillary
sleeve and end cap
extension are configured to provide fluidic coupling between a sample holder
and the mass
spectrometer through the capillary inlet. In other examples, a kit comprises
an adapter comprising an
internal sleeve configured to couple to a capillary inlet of the mass
spectrometer, an external sleeve
coupled to the internal capillary sleeve, and an insulator between the
internal sleeve and the external
sleeve to electrically decouple the internal sleeve from the external sleeve,
in which the adapter is
configured to provide fluidic coupling between a sample holder and the mass
spectrometer through
the capillary inlet. In sonic embodiments, a kit comprises an adapter
comprising an internal coupler
configured to engage a capillary inlet of the mass spectrometer, an external
coupler sized and
arranged to engage a direct sample analysis lens assembly, and an insulator
between the internal
coupler and the external coupler to electrically decouple the internal coupler
and the external
coupler, in which the adapter is configured to provide fluidic coupling
between a sample holder and
the mass spectrometer through the capillary inlet. In other examples, a kit
comprises a coupler sized
and arranged to engage to a capillary inlet of the mass spectrometer, the
coupler comprising an
internal surface configured to engage to the capillary of the capillary inlet
and an external surface
electrically isolated from the internal surface through an insulator, in which
the adapter is configured
to provide fluidic coupling between a sample holder and the mass spectrometer
through the capillary
inlet. If desired, the kit can include two or more different adapters that can
be used to couple a direct
sample analysis device to an analytical instrument such as a mass
spectrometer.
f00721 In certain examples, a method of installing a direct sample analysis
device on a mass
spectrometer while maintaining a vacuum in the mass spectrometer is provided.
In certain
embodiments, the method comprises coupling a capillary extension to the
capillary inlet, and
coupling an end cap extension to the coupled capillary extension, in which the
coupled capillary
extension and coupled capillary end cap are configured to provide fluidic
coupling between a direct
19

CA 02889372 2015-04-23
WO 2014/066872 PCT/US2013/066993
sample analysis sample support and the mass spectrometer through the capillary
inlet. In some
examples, the method comprises removing a capillary nozzle cap prior to
coupling the capillary
extension to the capillary inlet. In certain embodiments, the method comprises
coupling a direct
sample analysis lens assembly to the coupled end cap extension. In additional
embodiments, the end
cap extension comprises an insulator configured to electrically isolate the
capillary extension from
the end cap extension. In further embodiments, the capillary extension
comprises an insulator
configured to electrically isolate the capillary extension from the end cap
extension.
[0073] In certain embodiments, the method comprises coupling an internal
sleeve to a capillary
inlet of the mass spectrometer, and coupling an external sleeve to the coupled
internal capillary
sleeve, the external sleeve comprising an insulator configured to be
positioned between the internal
capillary sleeve and the external sleeve to electrically isolate the internal
sleeve from the external
sleeve, in which the coupled internal and external sleeves are configured to
provide fluidic coupling
between a direct sample analysis sample support and the mass spectrometer
through the capillary
inlet. In some examples, the method comprises removing a capillary nozzle cap
prior to coupling the
internal sleeve to the capillary inlet. In other examples, the method
comprises coupling a lens
assembly to the coupled external sleeve. In additional examples, the external
sleeve comprises an
insulator configured to electrically isolate the internal sleeve from the
external sleeve. In some
embodiments, the internal sleeve comprises an insulator configured to
electrically isolate the internal
sleeve from the external sleeve.
[0074] In some examples, the method comprises coupling an adapter comprising a
coupler sized
and arranged to engage to a capillary inlet of the mass spectrometer, the
coupler comprising an
internal surface configured to engage to the capillary of the capillary inlet
and an external surface
electrically isolated from the internal surface through an insulator, in which
the adapter is configured
to provide fluidic coupling between a sample support and the mass spectrometer
through the
capillary inlet. In certain examples, the method comprises removing a
capillary nozzle cap prior to
coupling the internal surface to the capillary inlet. In other examples, the
method comprises
coupling a lens assembly to the coupled external surface. In additional
embodiments, the method
comprises initiating sample analysis of a sample on a direct sample analysis
sample support
substantially immediately after coupling the lens assembly to the external
surface of the adapter. In
additional embodiments, the method comprises maintaining a substantially
constant vacuum pressure
in the mass spectrometer during the coupling of the adapter.
[0075] In certain embodiments, a method of coupling a direct sample analysis
device to a mass
spectrometer is disclosed. In certain examples, the method comprises coupling
an adapter
comprising a coupler sized and arranged to engage to a capillary inlet of the
mass spectrometer to

CA 02889372 2015-04-23
WO 2014/066872 PCT/US2013/066993
provide fluidic coupling between the capillary inlet and a direct sample
analysis sample support to
permit substantially immediate sample analysis of sample on the direct sample
analysis sample
support after coupling of the adapter. In certain examples, the adapter
comprises an internal sleeve,
an external sleeve and an insulator between the internal sleeve and the
external sleeve. In some
embodiments, the method comprises maintaining an operating pressure of the
mass spectrometer
during coupling of the coupler to the capillary inlet. In other embodiments,
the method comprises
coupling a lens assembly to the coupled adapter and initiating the sample
analysis substantially
immediately subsequent to coupling of the lens assembly. In certain examples,
the method
comprises configuring the adapter to comprise a separate internal coupler and
a separate external
coupler.
[0076] When introducing elements of the aspects, embodiments and examples
disclosed herein,
the articles "a," "an," "the" and "said" are intended to mean that there are
one or more of the
elements. The terms "comprising," "including" and "having" are intended to be
open-ended and
mean that there may be additional elements other than the listed elements. It
will be recognized by
the person of ordinary skill in the art, given the benefit of this disclosure,
that various components of
the examples can be interchanged or substituted with various components in
other examples.
[0077] Although certain aspects, examples and embodiments have been described
above, it will be
recognized by the person of ordinary skill in the art, given the benefit of
this disclosure, that
additions, substitutions, modifications, and alterations of the disclosed
illustrative aspects, examples
and embodiments are possible.
21

Representative Drawing
A single figure which represents the drawing illustrating the invention.
Administrative Status

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Administrative Status

Title Date
Forecasted Issue Date 2022-12-06
(86) PCT Filing Date 2013-10-27
(87) PCT Publication Date 2014-05-01
(85) National Entry 2015-04-23
Examination Requested 2018-10-22
(45) Issued 2022-12-06

Abandonment History

There is no abandonment history.

Maintenance Fee

Last Payment of $203.59 was received on 2022-09-22


 Upcoming maintenance fee amounts

Description Date Amount
Next Payment if small entity fee 2023-10-27 $125.00
Next Payment if standard fee 2023-10-27 $347.00

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Payment History

Fee Type Anniversary Year Due Date Amount Paid Paid Date
Application Fee $400.00 2015-04-23
Maintenance Fee - Application - New Act 2 2015-10-27 $100.00 2015-04-23
Maintenance Fee - Application - New Act 3 2016-10-27 $100.00 2016-10-04
Maintenance Fee - Application - New Act 4 2017-10-27 $100.00 2017-10-04
Maintenance Fee - Application - New Act 5 2018-10-29 $200.00 2018-10-04
Request for Examination $800.00 2018-10-22
Maintenance Fee - Application - New Act 6 2019-10-28 $200.00 2019-10-02
Maintenance Fee - Application - New Act 7 2020-10-27 $200.00 2020-09-22
Maintenance Fee - Application - New Act 8 2021-10-27 $204.00 2021-09-27
Final Fee 2022-09-20 $305.39 2022-09-16
Maintenance Fee - Application - New Act 9 2022-10-27 $203.59 2022-09-22
Owners on Record

Note: Records showing the ownership history in alphabetical order.

Current Owners on Record
PERKINELMER HEALTH SCIENCES, INC.
Past Owners on Record
None
Past Owners that do not appear in the "Owners on Record" listing will appear in other documentation within the application.
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Document
Description 
Date
(yyyy-mm-dd) 
Number of pages   Size of Image (KB) 
Amendment 2020-03-17 41 1,363
Description 2020-03-17 21 1,317
Claims 2020-03-17 13 344
Examiner Requisition 2020-08-28 6 263
Amendment 2020-12-24 26 791
Claims 2020-12-24 3 98
Examiner Requisition 2021-06-11 3 142
Electronic Grant Certificate 2022-12-06 1 2,527
Amendment 2021-10-08 13 343
Claims 2021-10-08 4 100
Final Fee 2022-09-16 3 101
Representative Drawing 2022-11-04 1 14
Cover Page 2022-11-04 1 49
Abstract 2015-04-23 2 81
Claims 2015-04-23 11 343
Drawings 2015-04-23 12 445
Description 2015-04-23 21 1,297
Representative Drawing 2015-05-05 1 16
Cover Page 2015-05-13 1 49
Request for Examination 2018-10-22 1 32
Examiner Requisition 2019-09-17 5 271
PCT 2015-04-23 16 1,171
Assignment 2015-04-23 2 98