U.S. patent application number 16/751332 was filed with the patent office on 2020-05-28 for analysis system for testing a sample.
This patent application is currently assigned to Boehringer Ingelheim Vetmedica GmbH. The applicant listed for this patent is Boehringer Ingelheim Vetmedica GmbH. Invention is credited to Axel Niemeyer, Hannah Schmolke.
Application Number | 20200164372 16/751332 |
Document ID | / |
Family ID | 57132958 |
Filed Date | 2020-05-28 |
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United States Patent
Application |
20200164372 |
Kind Code |
A1 |
Niemeyer; Axel ; et
al. |
May 28, 2020 |
ANALYSIS SYSTEM FOR TESTING A SAMPLE
Abstract
An analysis system for testing a biological sample wherein a
sensor cover can be or is pneumatically lowered onto a sensor
apparatus in order to detect an analyte of the sample. A sensor
array having a plurality of sensor fields are fluidically separated
from one another by lowering the sensor cover. The sensor apparatus
has a housing that is sealingly mounted on the sensor cover in an
edge region, the housing surrounding a chip or support of the
sensor apparatus at least partially. The sensor cover has a raised
portion in a center on a side remote or opposite from the sensor
apparatus or is centrally reinforced.
Inventors: |
Niemeyer; Axel; (Bielefeld,
DE) ; Schmolke; Hannah; (Didderse, DE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Boehringer Ingelheim Vetmedica GmbH |
Ingelheim am Rhein |
|
DE |
|
|
Assignee: |
Boehringer Ingelheim Vetmedica
GmbH
Ingelheim am Rhein
DE
|
Family ID: |
57132958 |
Appl. No.: |
16/751332 |
Filed: |
January 24, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
15725336 |
Oct 5, 2017 |
|
|
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16751332 |
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B01L 3/5027 20130101;
B01J 2219/00333 20130101; B01L 2300/0627 20130101; B01L 2300/0645
20130101; B01J 19/0093 20130101; B01L 2300/123 20130101; G01N
33/483 20130101; B01L 2300/0636 20130101; B01L 2400/0487 20130101;
B01L 2300/0816 20130101; F16K 2099/0084 20130101; B01L 3/502715
20130101; B01L 2300/0819 20130101; C12Q 1/6825 20130101; F04B
19/006 20130101 |
International
Class: |
B01L 3/00 20060101
B01L003/00; G01N 33/483 20060101 G01N033/483; F04B 19/00 20060101
F04B019/00; C12Q 1/6825 20060101 C12Q001/6825; B01J 19/00 20060101
B01J019/00 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 7, 2016 |
EP |
16 020 377.4 |
Claims
1. An analysis system for testing a sample, comprising: a main body
having a plurality of channels, and a sensor arrangement for
detecting an analyte of the sample, the sensor arrangement
comprising a sensor apparatus having capture molecules and a sensor
cover that is flexible at least in part for covering the sensor
apparatus, the sensor cover being lowerable onto or towards the
sensor apparatus in an actuated state, wherein, in an unactuated
state, the sensor cover is at least substantially planar or flat on
a side facing the sensor apparatus and wherein the sensor cover has
a raised portion in a center on a side remote or opposite from the
sensor apparatus or is centrally reinforced.
2. The analysis system according to claim 1, further comprising
pneumatic means for lowering the sensor cover.
3. The analysis system according to claim 1, wherein the sensor
apparatus is pressed or sealed against the sensor cover in an edge
region of the sensor cover.
4. The analysis system according to claim 1, wherein sensor
apparatus has a housing that is sealingly mounted on the sensor
cover in an edge region, the housing at least partially surrounding
a chip or support.
5. The analysis system according to claim 4, wherein the chip or
support is integrally cast in the housing.
6. The analysis system according to claim 4, wherein the sensor
array of the chip or support not covered by the housing on a
measuring side.
7. The analysis system according to claim 1, further comprising a
pneumatic connection for supplying a working medium to at least one
of the analysis system and the sensor cover.
8. The analysis system according to claim 7, wherein the pneumatic
connection is connected for supplying a pressure chamber with the
working medium.
9. The analysis system according to claim 8, wherein the sensor
cover is arranged between the pressure chamber and the sensor
apparatus and fluidically separates the pressure chamber from the
sensor arrangement.
10. The analysis system according to claim 1, wherein the sensor
cover is made of an elastomer.
11. The analysis system according to claim 8, wherein the sensor
cover comprises a cover part that is lowerable onto the sensor
apparatus, a side part and a connecting part that is flexible, and
wherein the cover part is connected to the side part by means of
the connecting part.
12. The analysis system according to claim 11, wherein the cover
part is thicker and/or more rigid than at least one of the
connecting part and the side part.
13. The analysis system according to claim 11, wherein the
connecting part is thinner than the side part.
14. The analysis system according to claim 11, wherein the side
part surrounds the cover part in a collar-shaped manner.
15. The analysis system according to claim 11, wherein the side
part is held directly between the sensor apparatus and the main
body,
16. The analysis system according to claim 11, wherein the side
part forms a seal for at least one of the sensor apparatus, a
sensor compartment and the pressure chamber.
17. The analysis system according to claim 11, wherein at least one
of an inlet and an outlet extend through the side part.
18. The analysis system according to claim 1, wherein the sensor
arrangement comprises a sensor compartment between the sensor
apparatus and the sensor cover, an inlet into the sensor
compartment and an outlet out of the sensor compartment, at least
one of the inlet and the outlet extending through the sensor
cover.
19. The analysis system according claim 18, wherein at last one of
the inlet and the outlet diverge towards the sensor
compartment.
20. The analysis system according to claim 1, wherein the sensor
arrangement comprises a sensor compartment that is delimited or
defined by the sensor cover and the sensor apparatus.
21. The analysis system according to claim 20, wherein a fluid flow
path is provided through the sensor compartment at least
substantially vertically in a normal operating position of the
cartridge.
22. The analysis system according to claim 1, wherein at least one
of the sensor apparatus and the sensor cover are held in a
depression or receptacle by means of heat staking the main
body.
23. The analysis system according to claim 1, wherein the sensor
apparatus electrochemically detects analytes bonded to the capture
molecules.
24. The analysis system according to claim 1, wherein the sensor
apparatus comprises a sensor array having a plurality of sensor
fields, wherein the sensor fields are fluidically separated from
one another by lowering the sensor cover.
25. The analysis system according to claim 1, wherein the sample is
a biological sample.
26. An analysis system for testing a sample, comprising: a main
body having a plurality of channels, and a sensor arrangement for
detecting an analyte of the sample, wherein the sensor arrangement
comprises a sensor apparatus having capture molecules and a sensor
cover that is flexible at least in part for covering the sensor
apparatus, the sensor cover being lowerable onto or towards the
sensor apparatus in an actuated state, and wherein the sensor
apparatus has a housing that is sealingly mounted on the sensor
cover in an edge region, the housing surrounding a chip or support
of the sensor apparatus at least partially.
27. The analysis system according to claim 26, wherein the chip or
support is integrally cast in the housing.
28. The analysis system according to claim 26, wherein a sensor
array of the chip or support is not covered by the housing on a
measuring side.
29. The analysis system according to claim 26, wherein the sensor
apparatus comprises a plurality of electrical contacts or contact
surfaces.
30. An analysis system for testing a sample, comprising a main body
having a plurality of channels, and a sensor arrangement for
detecting an analyte of the sample, wherein the sensor arrangement
comprises: a sensor apparatus having capture molecules and a sensor
cover that is flexible at least in part for covering the sensor
apparatus, the sensor cover being lowerable onto or towards the
sensor apparatus in an actuated state, and a sensor array having a
plurality of sensor fields, the sensor fields being fluidically
separated from one another by lowering the sensor cover.
31. The analysis system according to claim 30, wherein the sensor
apparatus is adapted for electrochemically detecting analytes
bonded to the capture molecules.
32. The analysis system according to claim 30, further comprising
pneumatic means for lowering the sensor cover.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a Continuation of U.S. patent
application Ser. No. 15/725,336 filed Oct. 5, 2017, which claims
the benefit of priority to European Patent No. 16020377.4 filed
Oct. 7, 2016, the contents of which are incorporated herein by
reference in their entirety.
BACKGROUND OF THE INVENTION
Field of the Invention
[0002] The present invention relates to an analysis system, in
particular a cartridge, for testing a biological sample, the
analysis system comprising a main body having a plurality of
channels, and comprising a sensor arrangement for detecting an
analyte of the sample.
[0003] Preferably, the present invention deals with analyzing and
testing a sample, in particular from a human or animal,
particularly preferably for analytics and diagnostics, for example
with regard to the presence of diseases and/or pathogens and/or for
determining blood counts, antibodies, hormones, steroids or the
like. Therefore, the present invention is in particular within the
field of bioanalytics. A food sample, environmental sample or
another sample may optionally also be tested, in particular for
environmental analytics or food safety and/or for detecting other
substances.
[0004] Preferably, by means of the present invention, at least one
analyte (target analyte) of a sample can be determined, identified
or detected. In particular, the sample can be tested for
qualitatively or quantitatively determining at least one analyte,
for example in order for it to be possible to detect or identify a
disease and/or pathogen.
[0005] Within the meaning of the present invention, analytes are in
particular nucleic-acid sequences, in particular DNA sequences
and/or RNA sequences, and/or proteins, in particular antigens
and/or antibodies. In particular, by means of the present
invention, nucleic-acid sequences can be determined, identified or
detected as analytes of a sample, and/or proteins can be
determined, identified or detected as analytes of the sample. More
particularly preferably, the present invention deals with systems,
devices and other apparatuses for carrying out a nucleic-acid assay
for detecting a nucleic-acid sequence and/or a protein assay for
detecting or identifying a protein.
[0006] The present invention deals in particular with what are
known as point-of-care systems, i.e. within particular mobile
systems, devices and other apparatuses, and deals with methods for
carrying out tests on a sample at the sampling site and/or
independently or away from a central laboratory or the like.
Preferably, point-of-care systems can be operated autonomously or
independently of a mains network for supplying electrical
power.
Description of Related Art
[0007] U.S. Pat. No. 5,096,669 discloses a point-of-care system for
testing a biological sample, in particular a blood sample. The
system comprises a single-use cartridge and an analysis device.
Once the sample has been received, the cartridge is inserted into
the analysis device in order to carry out the test. The cartridge
comprises a microfluidic system and a sensor apparatus comprising
electrodes, which apparatus is calibrated by means of a calibration
liquid and is then used to test the sample.
[0008] Furthermore, International Patent Application Publication WO
2006/125767 A1 and corresponding U.S. Pat. No. 9,110,044 B2
disclose a point-of-care system for integrated and automated DNA or
protein analysis, comprising a single-use cartridge and an analysis
device for fully automatically processing and evaluating
molecular-diagnostic analyzes using the single-use cartridge. The
cartridge is designed to receive a sample, in particular blood, and
in particular allows cell disruption, PCR and detection of PCR
amplification products, which are bonded to capture molecules and
provided with a label enzyme, in order for it to be possible to
detect bonded PCR amplification products or nucleic-acid sequences
as target analytes in what is known as a redox cycling process.
[0009] German Patent DE 100 58 394 C1 and corresponding U.S. Pat.
No. 7,838,261 B2 disclose a method for testing a sample using a
reaction array comprising at least two reaction compartments for
receiving substances that react with one another, the reaction
compartments being interconnected by means of a supply space. In
order to measure the substances, an exchange of substances and thus
chemical crosstalk between the individual reaction compartments is
prevented by lowering a sensor cover. In this way, the detection
sensitivity of the method is increased.
[0010] German Paten Application DE 10 2014 200 483 A1 discloses a
microfluidic chip for analyzing a sample. A fluid can be displaced
from a reaction chamber by lowering a flexible membrane in the
chamber. The membrane separates the reaction chamber from an air
chamber and is lowered or pressed down by applying pressure to the
membrane via the air chamber. The membrane has a given, constant
thickness and, thus does not allow optimized operation
characteristics.
[0011] International Patent Application Publication WO 2007/089587
A2 and corresponding U.S. Pat. No. 8,039,269 B2 disclose a
microfluidic device for detection and analysis of interactions
between molecules Chambers in which molecules can be trapped and
analyzed are formed by flexible membranes adhered to a plane glass
substrate. The sides of the membranes facing the substrate have
concave recesses so that the chambers are formed between the
concave recesses and the plane substrate. Molecules to be analyzed
can be mechanically trapped by pneumatically pressing down the
membrane. The form of the membranes does not allow optimized
operation.
[0012] International Patent Application Publication WO 2008/135564
A2 and corresponding U.S. Pat. No. 8,633,013 B2 disclose a
microfluidic device for performing assays. Channels for a sample
are defined between a rigid substrate and a deformable substrate
being made of flexible material, both substrates being generally
planar. A sample can be moved within the microfluidic device by
pressing down the deformable substrate with a roller. The
substrates are shown to have at least essentially constant
thicknesses. It is not explained how the substrates are connected.
The form of the substrate does not allow optimized operation.
SUMMARY OF THE INVENTION
[0013] The problem addressed by the present invention is to provide
an improved analysis system and an improved method for testing a
sample, a simple, compact, stable and/or cost-effective design of
the analysis system and/or efficient, rapid, reliable and/or
precise testing of the sample and/or reliable sealing of individual
positions or fields of a sensor array being made possible or
facilitated.
[0014] The above problem is solved by an analysis system as
described herein.
[0015] The proposed analysis system for testing an in particular
biological sample preferably comprises a sensor arrangement for
identifying or detecting an analyte of the sample, the sensor
arrangement preferably comprising a sensor apparatus having capture
molecules and a sensor cover that is flexible at least in part for
covering the sensor apparatus.
[0016] The sensor apparatus is preferably designed to carry out a
protein assay and/or a nucleic-acid assay. In particular, the
sensor apparatus comprises capture proteins as capture molecules
for detecting or identifying a target protein and/or comprises
capture nucleic-acid sequences as capture molecules for detecting
or identifying a target nucleic-acid sequence, in particular in
order to bond corresponding target proteins to the capture proteins
and to bond corresponding target nucleic-acid sequences to the
capture nucleic-acid sequences.
[0017] The sensor apparatus is preferably designed for
electrochemically detecting analytes bonded to the capture
molecules. The sensor apparatus preferably comprises a sensor array
comprising a plurality of sensor fields and/or electrodes.
[0018] One aspect of the present invention is that the sensor cover
can be actuated and/or lowered onto the sensor apparatus preferably
pneumatically, in particular by means of a working medium such as
gas, in particular in order to seal and/or fluidically separate
individual positions and/or sensor fields of the sensor apparatus
from one another.
[0019] The analysis system is in particular portable, mobile and/or
is a point-of-care system and/or can be used in particular at the
sampling site and/or away from a central laboratory.
[0020] The analysis system preferably comprises an analysis device
and a cartridge for testing the sample, the cartridge preferably
being designed for receiving the sample and the analysis device
preferably being designed for receiving the cartridge.
[0021] Particularly preferably, the analysis device is designed to
receive the cartridge or to connect said cartridge electrically,
thermally and/or pneumatically.
[0022] Particularly preferably, the analysis device is fluidically,
in particular pneumatically, connected or connectable to the
cartridge and/or is designed to supply the cartridge with a working
medium, in particular gas, in order to actuate the sensor cover
and/or to lower said cover onto the sensor apparatus.
[0023] The pneumatic actuation of the sensor cover allows
particularly reliable and rapid actuation of the sensor cover.
Furthermore, a construction of this kind allows or facilitates a
particularly simple and compact design of the analysis system
and/or of the cartridge. In particular, no mechanical and/or
movable components are required for actuating the sensor cover.
[0024] The sensor cover preferably comprises a cover part, a side
part and a connecting part that is flexible and/or extensible at
least in part, the cover part preferably being able to be lowered
onto the sensor apparatus and/or sensor fields, and/or being
connected to the side part by means of the connecting part.
Particularly preferably, the sensor cover is formed in one piece or
the sensor cover forms a unit. In particular, the sensor cover is
made of and/or injection-molded from plastics material,
particularly preferably from an elastomer.
[0025] According to another aspect of the present invention, which
can also be implemented independently, when it is unactuated and/or
moved away from the sensor apparatus, the sensor cover has a raised
portion in the center on a side remote from the sensor apparatus
and is at least substantially flat or planar on a side facing the
sensor apparatus.
[0026] Particularly preferably, the sensor cover, in particular the
cover part, is reinforced.
[0027] A construction of this kind makes it possible to lower the
sensor cover and/or the cover part onto the sensor apparatus at
least substantially evenly and/or in an uncurved manner and/or with
a planar flat side, and/or to close and/or fluidically separate all
the sensor fields of the sensor apparatus from one another at least
substantially simultaneously. In particular, the center of the
sensor cover and/or the cover part is not or at least substantially
not curved or bent during actuation.
[0028] The central raised portion and/or reinforcement of the
sensor cover in particular ensures that the sensor fields in the
edge region of the sensor apparatus are also closed and/or sealed
by the sensor cover and/or the cover part.
[0029] According to another aspect of the present invention, which
can also be implemented independently, in the edge region, the
sensor apparatus is pressed against the sensor cover and/or the
side part and/or is sealingly mounted on the sensor cover and/or
the side part in the edge region.
[0030] The side part holds or surrounds the cover part, preferably
peripherally and/or in a frame-like or collar-like manner In
particular, the sensor cover is held and/or clamped in the analysis
system and/or in the cartridge at the edge and/or by the side
part.
[0031] Particularly preferably, the sensor cover and/or the side
part forms a seal for the sensor apparatus. In particular, the
sensor cover is designed and/or installed so as to close the sensor
fields and to seal the sensor apparatus at the edge. This allows or
facilitates a particularly compact design of the analysis system
and/or of the cartridge.
[0032] The cartridge preferably comprises an in particular at least
substantially planar, flat, plate-shaped and/or card-like main
body, the sensor cover and the sensor apparatus preferably being
received in the main body. Particularly preferably, the sensor
apparatus is held by the main body and/or pressed against the
sensor cover in a form-fit or interlocking manner in the edge
region, in particular such that the sensor apparatus is sealingly
mounted on the sensor cover and/or on the side part of the sensor
cover in the edge region.
[0033] According to another aspect of the present invention, which
can also be implemented independently, the sensor arrangement
comprises a sensor compartment delimited or defined by the sensor
apparatus and the sensor cover, an inlet into the sensor
compartment and an outlet out of the sensor compartment, the inlet
and/or outlet extending through the sensor cover, in particular the
side part, at least in portions. In particular, the inlet and/or
the outlet is/are sealed by the sensor cover and/or the side part.
This allows or facilitates a particularly compact design and
reliable sealing of the sensor compartment.
[0034] In the proposed method for testing an in particular
biological sample, analytes of the sample are bonded to capture
molecules of a sensor apparatus, and the bonded analytes are
detected, preferably electrochemically or by means of redox
cycling, a sensor cover that is preferably flexible at least in
part being lowered onto the sensor apparatus for the detection, in
particular in order to seal and/or fluidically separate sensor
fields of the sensor apparatus from one another. The sensor cover
is preferably actuated pneumatically and/or by means of pressurized
air. This results in corresponding advantages.
[0035] Preferably, in the method, the sample is placed into a
cartridge, and the cartridge containing the sample is received by
an analysis device at least in part. The analysis device is (then)
preferably pneumatically connected to the cartridge, in particular
to a sensor arrangement of the cartridge, in order to actuate the
sensor cover and/or to lower said cover onto the sensor apparatus
in order to detect the bonded analytes.
[0036] Preferably, a working medium, in particular a gas, is
pressurized by the analysis device and is fed to the cartridge from
the outside. In particular, the pressure is generated outside the
cartridge and/or by means of the analysis device. Advantageously,
the complexity of the cartridge is thus reduced.
[0037] The term "analysis device" is preferably understood to mean
an instrument which is in particular mobile and/or can be used on
site, and/or which is designed to chemically, biologically and/or
physically test and/or analyze a sample or a component thereof,
preferably in and/or by means of a cartridge. In particular, the
analysis device controls the pretreatment and/or testing of the
sample in the cartridge.
[0038] The term "cartridge" is preferably understood to mean a
structural apparatus or unit designed to receive, to store, to
physically, chemically and/or biologically treat and/or prepare
and/or to measure a sample, preferably in order to make it possible
to detect, identify or determine at least one analyte, in
particular a protein and/or a nucleic-acid sequence, of the
sample.
[0039] A cartridge within the meaning of the present invention
preferably comprises a fluid system having a plurality of channels,
cavities and/or valves for controlling the flow through the
channels and/or cavities.
[0040] In particular, within the meaning of the present invention,
a cartridge is designed to be at least substantially planar and/or
card-like, in particular is designed as a (micro)fluidic card
and/or is designed as a main body or container that can preferably
be closed and/or said cartridge can be inserted and/or plugged into
a proposed analysis device when it contains the sample.
[0041] The above-mentioned aspects and features of the present
invention and the aspects and features of the present invention
that will become apparent from the claims and the following
description can in principle be implemented independently from one
another, but also in any combination or order.
[0042] Other aspects, advantages, features and properties of the
present invention will become apparent from the claims and the
following description of a preferred embodiment with reference to
the drawings, in which:
BRIEF DESCRIPTION OF THE DRAWINGS
[0043] FIG. 1 is a schematic view of a proposed analysis system
and/or analysis device comprising a proposed cartridge received
therein;
[0044] FIG. 2 is a schematic view of the cartridge;
[0045] FIG. 3 is a schematic front view of a proposed sensor
apparatus of the analysis system and/or cartridge;
[0046] FIG. 4 is an enlarged detail from FIG. 3 illustrating a
sensor field of the sensor apparatus;
[0047] FIG. 5 is a schematic rear view of the sensor apparatus;
[0048] FIG. 6 is a schematic sectional view of a sensor arrangement
comprising the sensor apparatus and a sensor cover that has been
moved away;
[0049] FIG. 7 is a schematic sectional view of the sensor
arrangement according to FIG. 6, with the sensor cover lowered;
[0050] FIG. 8 is an enlarged view of the cartridge in the region of
the sensor arrangement;
[0051] FIG. 9 is a schematic sectional view of the cartridge in the
region of the sensor arrangement, along the sectional line IX-IX
shown in FIG. 8;
[0052] FIG. 10 is a schematic sectional view of the cartridge in
the region of the sensor arrangement, along the sectional line X-X
shown in FIG. 8;
[0053] FIG. 11 is a schematic sectional view of the cartridge in
the region of a pneumatic connection comprising a connection
element that has been moved away; and
[0054] FIG. 12 is a schematic sectional view of the cartridge
according to FIG. 11, with the connection element connected.
DETAILED DESCRIPTION OF THE INVENTION
[0055] In the Figures, which are only schematic and sometimes not
to scale, the same reference signs are used for the same or similar
parts and components, corresponding or comparable properties and
advantages being achieved even if these are not repeatedly
described.
[0056] FIG. 1 is a highly schematic view of a proposed analysis
system 1 and analysis device 200 for testing, in particular, a
biological sample P, preferably by means of or in an apparatus or
cartridge 100.
[0057] FIG. 2 is a schematic view of a preferred embodiment of the
proposed apparatus or cartridge 100 for testing the sample P. The
apparatus or cartridge 100 in particular forms a handheld unit, and
in the following is merely referred to as a cartridge.
[0058] The term "sample" is preferably understood to mean the
sample material to be tested, which is in particular taken from a
human or animal. In particular, within the meaning of the present
invention, a sample is a fluid, such as saliva, blood, urine or
another liquid, preferably from a human or animal, or a component
thereof. Within the meaning of the present invention, a sample may
be pretreated or prepared if necessary, or may come directly from a
human or animal or the like, for example. A food sample,
environmental sample or another sample may optionally also be
tested, in particular for environmental analytics, food safety
and/or for detecting other substances, preferably natural
substances, but also biological or chemical warfare agents, poisons
or the like.
[0059] Preferably, the analysis system 1 or analysis device 200
controls the testing of the sample P in particular in or on the
cartridge 100 and/or is used to evaluate the testing or the
collection, processing and/or storage of measured values from the
test.
[0060] By means of the proposed analysis system 1, analysis device
200 and/or the cartridge 100 and/or using the proposed method for
testing the sample P, preferably an analyte A of the sample P, in
particular a (certain) nucleic-acid sequence and/or a (certain)
protein, or particularly preferably a plurality of analytes A of
the sample P, can be determined, identified or detected. Said
analytes are in particular detected and/or measured not only
qualitatively, but particularly preferably also quantitatively.
[0061] Therefore, the sample P can in particular be tested for
qualitatively or quantitatively determining at least one analyte A,
for example in order for it to be possible to detect a disease
and/or pathogen or to determine other values, which are important
for diagnostics, for example.
[0062] Particularly preferably, a molecular-biological test is made
possible by means of the analysis system 1 and/or analysis device
200 and/or by means of the cartridge 100.
[0063] Particularly preferably, a nucleic-acid assay for detecting
or identifying a nucleic-acid sequence, in particular a DNA
sequence and/or RNA sequence, and/or a protein assay for detecting
or identifying a protein, in particular an antigen and/or antibody,
are made possible or are carried out.
[0064] Preferably, the sample P or individual components of the
sample P or analyte A can be amplified if necessary, in particular
by means of PCR, and tested, identified or detected in the analysis
system 1, analysis device 200 and/or in the cartridge 100, and/or
for the purpose of carrying out the nucleic-acid assay. Preferably,
amplification products of the analyte A or analytes A are thus
produced.
[0065] In the following, further details are first given on a
preferred construction of the cartridge 100, with features of the
cartridge 100 preferably also directly representing features of the
analysis system 1, in particular even without any further explicit
explanation.
[0066] The cartridge 100 is preferably at least substantially
planar, flat and/or plate-shaped and/or card-like.
[0067] The cartridge 100 preferably comprises an in particular at
least substantially planar, flat, plate-shaped and/or card-like
main body or support 101, the main body or support 101 in
particular being made of and/or injection-molded from plastics
material, particularly preferably polypropylene.
[0068] The cartridge 100 preferably comprises at least one film or
cover 102 for covering the main body 101 and/or cavities and/or
channels formed therein at least in part, in particular on the
front, and/or for forming valves or the like, as shown by dashed
lines in FIG. 2.
[0069] The analysis system 1 or cartridge 100 or the main body 101
thereof, in particular together with the cover 102, preferably
forms and/or comprises a fluidic system 103, referred to in the
following as the fluid system 103.
[0070] The cartridge 100, the main body 101 and/or the fluid system
103 are preferably at least substantially vertically oriented in
the operating position and/or during the test, in particular in the
analysis device 200, as shown schematically in FIG. 1. In
particular, the main plane or surface extension of the cartridge
100 thus extends at least substantially vertically in the operating
position.
[0071] The cartridge 100 and/or the fluid system 103 preferably
comprises a plurality of cavities, in particular at least one
receiving cavity 104, at least one metering cavity 105, at least
one intermediate cavity 106, at least one mixing cavity 107, at
least one storage cavity 108, at least one reaction cavity 109, at
least one intermediate temperature-control cavity 110 and/or at
least one collection cavity 111, as shown in FIGS. 1 and 2.
[0072] The cartridge 100 and/or the fluid system 103 also
preferably comprises at least one pump apparatus 112 and/or at
least one sensor arrangement or sensor apparatus 113.
[0073] Some, most or all of the cavities are preferably formed by
chambers and/or channels or other depressions in the cartridge 100
and/or the main body 101, and particularly preferably are covered
or closed by the cover 102. However, other structural solutions are
also possible.
[0074] In the example shown, the cartridge 100 or the fluid system
103 preferably comprises two metering cavities 105A and 105B, a
plurality of intermediate cavities 106A to 106G, a plurality of
storage cavities 108A to 108E and/or a plurality of reaction
cavities 109, which can preferably be loaded separately from one
another, in particular a first reaction cavity 109A, a second
reaction cavity 109B and an optional third reaction cavity 109C, as
can be seen in FIG. 2.
[0075] The reaction cavity/cavities 109 is/are used in particular
to carry out an amplification reaction, in particular PCR, or
several, preferably different, amplification reactions, in
particular PCRs. It is preferable to carry out several, preferably
different, PCRs, i.e., PCRs having different primer combinations or
primer pairs, in parallel and/or independently and/or in different
reaction cavities 109.
[0076] To carry out the nucleic-acid assay, preferably nucleic-acid
sequences, as analytes A of the sample P, are amplified in the
reaction cavity/cavities 109 by means of an amplification reaction,
in particular in order to produce amplification products for the
subsequent detection in the sensor arrangement or sensor apparatus
113.
[0077] Within the meaning of the present invention, amplification
reactions are in particular molecular-biological reactions in which
an analyte A, in particular a nucleic-acid sequence, is
amplified/copied and/or in which amplification products, in
particular nucleic-acid products, of an analyte A are produced.
Particularly preferably, PCRs are amplification reactions within
the meaning of the present invention.
[0078] "PCR" stands for polymerase chain reaction and is a
molecular-biological method by means of which certain analytes A,
in particular portions of RNA or RNA sequences or DNA or DNA
sequences, of a sample P are amplified, preferably in several
cycles, using polymerases or enzymes, in particular in order to
then test and/or detect the amplification products or nucleic-acid
products. If RNA is intended to be tested and/or amplified, before
the PCR is carried out, a cDNA is produced starting from the RNA,
in particular using reverse transcriptase. The cDNA is used as a
template for the subsequent PCR.
[0079] Preferably, during a PCR, a sample P is first denatured by
the addition of heat in order to separate the strands of DNA or
cDNA. Preferably, primers or nucleotides are then deposited on the
separated single strands of DNA or cDNA, and a desired DNA or cDNA
sequence is replicated by means of polymerase and/or the missing
strand is replaced by means of polymerase. This process is
preferably repeated in a plurality of cycles until the desired
quantity of the DNA or cDNA sequence is available.
[0080] For the PCR, marker primers are preferably used, i.e.
primers which (additionally) produce a marker or a label, in
particular biotin, on the amplified analyte A or amplification
product. This allows or facilitates detection. Preferably, the
primers used are biotinylated and/or comprise or form in particular
covalently bonded biotin as the label.
[0081] The amplification products and/or other portions of the
sample P produced in the one or more reaction cavities 109 can be
conducted or fed to the connected sensor arrangement or sensor
apparatus 113, in particular by means of the pump apparatus
112.
[0082] The sensor apparatus 113 is used in particular for
detecting, particularly preferably qualitatively and/or
quantitatively determining, the analyte A or analytes A of the
sample P, in this case particularly preferably the nucleic-acid
sequences and/or proteins as the analytes A. Alternatively or
additionally, however, other values may also be collected or
determined.
[0083] As already explained at the outset, in particular
nucleic-acid sequences, preferably DNA sequences and/or RNA
sequences, and/or proteins, in particular antigens and/or
antibodies, are preferably qualitatively and/or quantitatively
determined as analytes A of the sample P. In the following,
however, a distinction is not made between nucleic-acid sequences
and proteins, or between the nucleic-acid assay for detecting
nucleic-acid sequences and the protein assay for detecting
proteins.
[0084] In particular, the pump apparatus 112 comprises or forms a
tube-like or bead-like raised portion, in particular by means of
the film or cover 102, particularly preferably on the back 100B of
the cartridge 100, as shown schematically in FIG. 1.
[0085] The cartridge 100, the main body 101 and/or the fluid system
103 preferably comprise a plurality of channels 114 and/or valves
115, as shown in FIG. 2.
[0086] By means of the channels 114 and/or valves 115, the cavities
104 to 111, the pump apparatus 112 and/or the sensor arrangement
and/or sensor apparatus 113 can be temporarily and/or permanently
fluidically interconnected and/or fluidically separated from one
another, as required and/or optionally or selectively, in
particular such that they are controlled by the analysis system 1
or the analysis device 200.
[0087] The cavities 104 to 111 are preferably each fluidically
linked or interconnected by a plurality of channels 114.
Particularly preferably, each cavity is linked or connected by at
least two associated channels 114, in order to make it possible for
fluid to fill, flow through and/or drain from the respective
cavities as required.
[0088] The fluid transport or the fluid system 103 is preferably
not based on capillary forces, or is not exclusively based on said
forces, but in particular is essentially based on the effects of
gravity and/or pumping forces and/or compressive forces and/or
suction forces that arise, which are particularly preferably
generated by the pump or pump apparatus 112. In this case, the
flows of fluid or the fluid transport and the metering are
controlled by accordingly opening and closing the valves 115 and/or
by accordingly operating the pump or pump apparatus 112, in
particular by means of a pump drive 202 of the analysis device
200.
[0089] Preferably, each of the cavities 104 to 110 has an inlet at
the top and an outlet at the bottom in the operating position.
Therefore, if required, only liquid from the respective cavities
can be removed via the outlet.
[0090] In the operating position, the liquids from the respective
cavities are preferably removed, in particular drawn out, via the
outlet that is at the bottom in each case, it preferably being
possible for gas or air to flow and/or be pumped into the
respective cavities via the inlet that is in particular at the top.
In particular, relevant vacuums in the cavities can thus be
prevented or at least minimized when conveying the liquids.
[0091] In particular, the cavities, particularly preferably the
storage cavity/cavities 108, the mixing cavity 107 and/or the
receiving cavity 104, are each dimensioned and/or oriented in the
normal operating position such that, when said cavities are filled
with liquid, bubbles of gas or air that may potentially form rise
upwards in the operating position, such that the liquid collects
above the outlet without bubbles. However, other solutions are also
possible here.
[0092] The receiving cavity 104 preferably comprises a connection
104A for introducing the sample P. In particular, the sample P may
for example be introduced into the receiving cavity 104 and/or
cartridge 100 via the connection 104A by means of a pipette,
syringe or other instrument.
[0093] The receiving cavity 104 preferably comprises an inlet 104B,
an outlet 104C and an optional intermediate connection 104D, it
preferably being possible for the sample P or a portion thereof to
be removed and/or conveyed further via the outlet 104C and/or the
optional intermediate connection 104D. Gas, air or another fluid
can flow in and/or be pumped in via the inlet 104B, as already
explained.
[0094] Preferably, the sample P or a portion thereof can be
removed, optionally and/or depending on the assay to be carried
out, via the outlet 104C or the optional intermediate connection
104D of the receiving cavity 104. In particular, a supernatant of
the sample P, such as blood plasma or blood serum, can be conducted
away or removed via the optional intermediate connection 104D, in
particular for carrying out the protein assay.
[0095] Preferably, at least one valve 115 is assigned to each
cavity, the pump apparatus 112 and/or the sensor apparatus 113
and/or is arranged upstream of the respective inlets and/or
downstream of the respective outlets.
[0096] Preferably, the cavities 104 to 111 or sequences of cavities
104 to 111, through which fluid flows in series or in succession
for example, can be selectively released and/or fluid can
selectively flow therethrough by the assigned valves 115 being
actuated, and/or said cavities can be fluidically connected to the
fluid system 103 and/or to other cavities.
[0097] In particular, the valves 115 are formed by the main body
101 and the film or cover 102 and/or are formed in another manner,
for example by additional layers, depressions or the like.
[0098] Particularly preferably, one or more valves 115A are
provided which are preferably tightly closed initially or when in
storage, particularly preferably in order to seal liquids or liquid
reagents F, located in the storage cavities 108, and/or the fluid
system 103 from the open receiving cavity 104 in a storage-stable
manner
[0099] Preferably, an initially closed valve 115A is arranged
upstream and downstream of each storage cavity 108. Said valves are
preferably only opened, in particular automatically, when the
cartridge 100 is actually being used and/or while inserting the
cartridge 100 into the analysis device 200 and/or for carrying out
the assay.
[0100] A plurality of valves 115A, in particular three valves in
this case, are preferably assigned to the receiving cavity 104, in
particular if the intermediate connection 104D is provided in
addition to the inlet 104B and the outlet 104C. Depending on the
use, in addition to the valve 115A on the inlet 104B, then
preferably only the valve 115A either at the outlet 104C or at the
intermediate connection 104D is opened.
[0101] The valves 115A assigned to the receiving cavity 104 seal
the fluid system 103 and/or the cartridge 100 in particular
fluidically and/or in a gas-tight manner until the sample P is
inserted and the receiving cavity 104 or a connection 104A of the
receiving cavity 104 is closed.
[0102] As an alternative or in addition to the valves 115A (which
are initially closed), one or more valves 115B are preferably
provided which are not closed in a storage-stable manner and/or
which are open initially and/or which can be closed by actuation.
These valves are used in particular to control the flows of fluid
during the test.
[0103] The cartridge 100 is preferably designed as a microfluidic
card and/or the fluid system 103 is preferably designed as a
microfluidic system. In the present invention, the term
"microfluidic" is preferably understood to mean that the respective
volumes of individual cavities, some of the cavities or all of the
cavities 104 to 111 and/or channels 114 are, separately or
cumulatively, less than 5 ml or 2 ml, particularly preferably less
than 1 ml or 800 .mu.l, in particular less than 600 .mu.l or 300
.mu.l, more particularly preferably less than 200 .mu.l or 100
.mu.l.
[0104] Particularly preferably, a sample P having a maximum volume
of 5 ml, 2 ml or 1 ml can be introduced into the cartridge 100
and/or the fluid system 103, in particular the receiving cavity
104.
[0105] Reagents and liquids which are preferably introduced or
provided before the test in liquid form as liquids or liquid
reagents F and/or in dry form as dry reagents S are required for
testing the sample P, as shown in the schematic view according to
FIG. 2 by reference signs F1 to F5 and S1 to S10.
[0106] Furthermore, other liquids F, in particular in the form of a
wash buffer, solvent for dry reagents S and/or a substrate SU, for
example in order to form detection molecules and/or a redox system,
are also preferably required for the test, the detection process
and/or for other purposes, and are in particular provided in the
cartridge 100, i.e. are likewise introduced before use, in
particular before delivery. At some points in the following, a
distinction is not made between liquid reagents and other liquids,
and therefore the respective explanations are accordingly also
mutually applicable.
[0107] The analysis system 1 and/or the cartridge 100 preferably
contains all the reagents and liquids required for pretreating the
sample P and/or for carrying out the test or assay, in particular
for carrying out one or more amplification reactions or PCRs, and
therefore, particularly preferably, it is only necessary to receive
the optionally pretreated sample P.
[0108] The cartridge 100 and/or the fluid system 103 preferably
comprises a bypass 114A that can optionally be used, in order for
it to be possible, if necessary, to conduct or convey the sample P
or components thereof past the reaction cavities 109 and/or, by
bypassing the optional intermediate temperature-control cavity 110,
also directly to the sensor apparatus 113.
[0109] The cartridge 100, the fluid system 103 and/or the channels
114 preferably comprise sensor portions 116 or other apparatuses
for detecting liquid fronts and/or flows of fluid.
[0110] It is noted that various components, such as the channels
114, the valves 115, in particular the valves 115A that are
initially closed and the valves 115B that are initially open, and
the sensor portions 116 in FIG. 2 are, for reasons of clarity, only
labelled in some cases, but the same symbols are used in FIG. 2 for
each of these components.
[0111] The collection cavity 111 is preferably used for receiving
excess or used reagents and liquids and volumes of the sample,
and/or for providing gas or air in order to empty individual
cavities and/or channels.
[0112] In particular, the collection cavity 111 can optionally be
connected to individual cavities and channels or other apparatuses
fluidically in order to remove reagents and liquids from said
cavities, channels or other apparatuses and/or to replace said
reagents and liquids with gas or air. The collection cavity 111 is
preferably given appropriate large dimensions.
[0113] Once the sample P has been introduced into the receiving
cavity 104 and the connection 104A has been closed, the cartridge
100 can be inserted into and/or received in the proposed analysis
device 200 in order to test the sample P, as shown in FIG. 1.
Alternatively, the sample P could also be fed in later.
[0114] FIG. 1 shows the analysis system 1 in a ready-to-use state
for carrying out a test or assay on the sample P received in the
cartridge 100. In this state, the cartridge 100 is therefore linked
to, received by and/or inserted into the analysis device 200.
[0115] In the following, some features and aspects of the analysis
device 200 are first explained in greater detail, in particular on
the basis of FIG. 1. The features and aspects relating to said
device are preferably also directly features and aspects of the
proposed analysis system 1, in particular even without any further
explicit explanation.
[0116] The analysis system 1 or analysis device 200 preferably
comprises a mount or receptacle 201 for mounting and/or receiving
the cartridge 100.
[0117] Preferably, the cartridge 100 is fluidically, in particular
hydraulically, separated or isolated from the analysis device 200.
In particular, the cartridge 100 forms a preferably independent and
in particular closed or sealed fluidic and/or hydraulic system 103
for the sample P and the reagents and other liquids. In this way,
the analysis device 200 does not come into direct contact with the
sample P and can in particular be reused for another test without
being disinfected and/or cleaned first.
[0118] It is however provided that the analysis device 200 can be
connected or coupled mechanically, electrically, thermally and/or
pneumatically to the cartridge 100.
[0119] In particular, the analysis device 200 is designed to have a
mechanical effect or act mechanically on the cartridge 100, in
particular for actuating the pump apparatus 112 and/or the valves
115, and/or to have a thermal effect or act thermally on the
cartridge 100, in particular for temperature-controlling the
reaction cavity/cavities 109 and/or the intermediate
temperature-control cavity 110.
[0120] In addition, the analysis device 200 can preferably be
pneumatically connected to the cartridge 100, in particular in
order to actuate individual apparatus, and/or can be electrically
connected to the cartridge 100, in particular in order to collect
and/or transmit measured values, for example from the sensor
apparatus 113 and/or sensor portions 116.
[0121] The analysis system 1 or analysis device 200 preferably
comprises a pump drive 202, the pump drive 202 in particular being
designed for mechanically actuating the pump apparatus 112.
[0122] Preferably, a head of the pump drive 202 can be rotated in
order to rotationally axially depress the preferably bead-like
raised portion of the pump apparatus 112. Particularly preferably,
the pump drive 202 and pump apparatus 112 together form a pump, in
particular in the manner of a hose pump or peristaltic pump and/or
a metering pump, for the fluid system 103 and/or the cartridge
100.
[0123] Particularly preferably, the pump is constructed as
described in DE 10 2011 015 184 B4 and corresponding U.S. Pat. No.
8,950,424 B2. However, other structural solutions are also
possible.
[0124] Preferably, the capacity and/or discharge rate of the pump
can be controlled and/or the conveying direction of the pump and/or
pump drive 202 can be switched. Preferably, fluid can thus be
pumped forwards or backwards as desired.
[0125] The analysis system 1 or analysis device 200 preferably
comprises a connection apparatus 203 for in particular electrically
and/or thermally connecting the cartridge 100 and/or the sensor
arrangement or sensor apparatus 113.
[0126] As shown in FIG. 1, the connection apparatus 203 preferably
comprises a plurality of electrical contact elements 203A, the
cartridge 100, in particular the sensor arrangement or sensor
apparatus 113, preferably being electrically connected or
connectable to the analysis device 200 by the contact elements
203A.
[0127] The analysis system 1 or analysis device 200 preferably
comprises one or more temperature-control apparatuses 204 for
temperature-controlling the cartridge 100 and/or having a thermal
effect on the cartridge 100, in particular for heating and/or
cooling, the temperature-control apparatus(es) 204 (each)
preferably comprising or being formed by a heating resistor or a
Peltier element.
[0128] Individual temperature-control apparatuses 204, some of
these apparatuses or all of these apparatuses can preferably be
positioned against the cartridge 100, the main body 101, the cover
102, the sensor arrangement, sensor apparatus 113 and/or individual
cavities and/or can be thermally coupled thereto and/or can be
integrated therein and/or in particular can be operated or
controlled electrically by the analysis device 200. In the example
shown, in particular the temperature-control apparatuses 204A, 204B
and/or 204C are provided.
[0129] Preferably, the temperature-control apparatus 204A, referred
to in the following as the reaction temperature-control apparatus
204A, is assigned to the reaction cavity 109 or to a plurality of
reaction cavities 109, in particular in order for it to be possible
to carry out one or more amplification reactions therein.
[0130] The reaction cavities 109 are preferably
temperature-controlled simultaneously and/or uniformly, in
particular by means of one common reaction temperature-control
apparatus 204A or two reaction temperature-control apparatuses
204A.
[0131] More particularly preferably, the reaction cavity/cavities
109 can be temperature-controlled from two different sides and/or
by means of two or the reaction temperature-control apparatuses
204A that are preferably arranged on opposite sides.
[0132] Alternatively, each reaction cavity 109 can be
temperature-controlled independently and/or individually.
[0133] The temperature-control apparatus 204B, referred to in the
following as the intermediate temperature-control apparatus 204B,
is preferably assigned to the intermediate temperature-control
cavity 110 and/or is designed to (actively) temperature-control
and/or heat the intermediate temperature-control cavity 110 or a
fluid located therein, in particular the amplification products,
preferably to a preheat temperature.
[0134] The intermediate temperature-control cavity 110 and/or
intermediate temperature-control apparatus 204B is preferably
arranged upstream of or (immediately) before the sensor arrangement
or sensor apparatus 113, in particular in order for it to be
possible to temperature-control and/or preheat, in a desired
manner, fluids to be fed to the sensor arrangement or sensor
apparatus 113, in particular analytes A and/or amplification
products, particularly preferably immediately before said fluids
are fed.
[0135] Particularly preferably, the intermediate
temperature-control cavity 110 and/or intermediate
temperature-control apparatus 204B is designed or intended to
denature the sample P or analytes A and/or the amplification
products produced, and/or to divide any double-stranded analytes A
or amplification products into single strands and/or to counteract
premature bonding and/or hybridizing of the amplification products,
in particular by the addition of heat.
[0136] Preferably, the analysis system 1, analysis device 200
and/or the cartridge 100 and/or one or each temperature-control
apparatus 204 comprise/comprises a temperature detector and/or
temperature sensor (not shown), in particular in order to make it
possible to control and/or regulate temperature.
[0137] One or more temperature sensors may for example be assigned
to the sensor portions 116 and/or to individual channel portions or
cavities, i.e. may be thermally coupled thereto.
[0138] The temperature-control apparatus 204C, referred to in the
following as the sensor temperature-control apparatus 204C, is in
particular assigned to the sensor apparatus 113 and/or is designed
to (actively) temperature-control and/or heat fluids located in or
on the sensor arrangement or sensor apparatus 113, in particular
analytes A and/or amplification products, reagents or the like, in
a desired manner, preferably to a hybridization temperature.
[0139] The sensor temperature-control apparatus 204C is preferably
planar and/or has a contact surface which is preferably rectangular
and/or corresponds to the dimensions of the sensor arrangement or
sensor apparatus 113, the contact surface allowing for heat
transfer between the sensor temperature-control apparatus 204C and
the sensor apparatus 113.
[0140] Preferably, the analysis device 200 comprises the sensor
temperature-control apparatus 204C. However, other structural
solutions are also possible in which the sensor temperature-control
apparatus 204C is integrated in the cartridge 100, in particular
the sensor arrangement or sensor apparatus 113.
[0141] Particularly preferably, the connection apparatus 203
comprises the sensor temperature-control apparatus 204C, and/or the
connection apparatus 203 together with the sensor
temperature-control apparatus 204C can be linked to, in particular
pressed against, the cartridge 100, in particular the sensor
arrangement or sensor apparatus 113.
[0142] More particularly preferably, the connection apparatus 203
and the sensor temperature-control apparatus 204C (together) can be
moved toward and/or relative to the cartridge 100, in particular
the sensor arrangement or sensor apparatus 113, and/or can be
positioned against said cartridge, preferably in order to both
electrically and thermally couple the analysis device 200 to the
cartridge 100, in particular the sensor arrangement or sensor
apparatus 113 or the support 113D thereof.
[0143] Preferably, the sensor temperature-control apparatus 204C is
arranged centrally on the connection apparatus 203 or a support
thereof and/or is arranged between the contact elements 203A.
[0144] In particular, the contact elements 203A are arranged in an
edge region of the connection apparatus 203 or a support thereof or
are arranged around the sensor temperature-control apparatus 204C,
preferably such that the connection apparatus 203 is connected or
connectable to the sensor apparatus 113 thermally in the center and
electrically on the outside or in the edge region. However, other
solutions are also possible here.
[0145] The analysis system 1 or analysis device 200 preferably
comprises one or more actuators 205 for actuating the valves 115.
Particularly preferably, different (types or groups of) actuators
205A and 205B are provided which are assigned to the different
(types or groups of) valves 115A and 115B for actuating each of
said valves, respectively.
[0146] The analysis system 1 or analysis device 200 preferably
comprises one or more sensors 206. In particular, sensors 206A are
designed or intended to detect liquid fronts and/or flows of fluid
in the fluid system 103. Particularly preferably, the sensors 206A
are designed to measure or detect, for example optically and/or
capacitively, a liquid front and/or the presence, the speed, the
mass flow rate/volume flow rate, the temperature and/or another
value of a fluid in a channel and/or a cavity, in particular in a
respectively assigned sensor portion 116, which is in particular
formed by a planar and/or widened channel portion of the fluid
system 103.
[0147] Particularly preferably, the sensor portions 116 are each
oriented and/or incorporated in the fluid system 103 and/or fluid
flows against or through the sensor portions 116 such that, in the
operating position of the cartridge 100, fluid flows through the
sensor portions 116 in the vertical direction and/or from the
bottom to the top, or vice versa, in particular in order to make it
possible or easier to accurately detect liquid.
[0148] Alternatively or additionally, the analysis device 200
preferably comprises (other or additional) sensors 206B for
detecting the ambient temperature, internal temperature,
atmospheric humidity, position, and/or alignment, for example by
means of a GPS sensor, and/or the orientation and/or inclination of
the analysis device 200 and/or the cartridge 100.
[0149] The analysis system 1 or analysis device 200 preferably
comprises a control apparatus 207, in particular comprising an
internal clock or time base for controlling the sequence of a test
or assay and/or for collecting, evaluating and/or outputting or
providing measured values in particular from the sensor apparatus
113, and/or from test results and/or other data or values.
[0150] The control apparatus 207 preferably controls or regulates
the pump drive 202, the temperature-control apparatuses 204 and/or
actuators 205, in particular taking into account or depending on
the desired test and/or measured values from the sensor arrangement
or sensor apparatus 113 and/or sensors 206.
[0151] The flows of fluid are controlled in particular by
accordingly activating the pump or pump apparatus 112 and actuating
the valves 115.
[0152] Particularly preferably, the pump drive 202 comprises a
stepper motor, or a drive calibrated in another way, such that
desired metering can be achieved, at least in principle, by means
of appropriate activation.
[0153] Additionally or alternatively, the sensors 206A are used to
detect liquid fronts or flows of fluid, in particular in
cooperation with the assigned sensor portions 116, in order to
achieve the desired fluidic sequence and the desired metering by
accordingly controlling the pump or pump apparatus 112 and
accordingly activating the valves 115.
[0154] Optionally, the analysis system 1 or analysis device 200
comprises an input apparatus 208, such as a keyboard, a touch
screen or the like, and/or a display apparatus 209, such as a
screen.
[0155] The analysis system 1 or analysis device 200 preferably
comprises at least one interface 210, for example for controlling,
for communicating and/or for outputting measured data or test
results and/or for linking to other devices, such as a printer, an
external power supply or the like. This may in particular be a
wired or wireless interface 210.
[0156] The analysis system 1 or analysis device 200 preferably
comprises a power supply 211, preferably a battery or an
accumulator, which is in particular integrated and/or externally
connected or connectable.
[0157] Preferably, an integrated accumulator is provided as a power
supply 211 and is (re)charged by an external charging device (not
shown) via a connection 211A and/or is interchangeable.
[0158] The analysis system 1 or analysis device 200 preferably
comprises a housing 212, all the components and/or some or all of
the apparatuses preferably being integrated in the housing 212.
Particularly preferably, the cartridge 100 can be inserted or slid
into the housing 212, and/or can be received by the analysis device
200, through an opening 213 which can in particular be closed, such
as a slot or the like.
[0159] The analysis system 1 or analysis device 200 is preferably
portable or mobile. Particularly preferably, the analysis device
200 weighs less than 25 kg or 20 kg, particularly preferably less
than 15 kg or 10 kg, in particular less than 9 kg or 6 kg.
[0160] The fluidic, in particular pneumatic, coupling between the
cartridge 100 and the analysis device 200 will be explained in
greater detail in the following, it being possible for the
following aspects to be implemented independently from the
preceding aspects.
[0161] As already explained, the analysis device 200 can preferably
be pneumatically linked to the cartridge 100, in particular to the
sensor arrangement and/or to the pump apparatus 112.
[0162] Particularly preferably, the analysis device 200 is designed
to supply the cartridge 100, in particular the sensor arrangement
and/or the pump apparatus 112, with a working medium, in particular
gas or air.
[0163] Preferably, the working medium can be compressed and/or
pressurized in the analysis device 200 or by means of the analysis
device 200.
[0164] Preferably, the analysis device 200 comprises a pressurized
gas supply 214 for this purpose, in particular a pressure generator
or compressor, preferably in order to compress, condense and/or
pressurize the working medium.
[0165] The pressurized gas supply 214 is preferably integrated in
the analysis device 200 or the housing 212 and/or can be controlled
or regulated by means of the control apparatus 207.
[0166] Preferably, the pressurized gas supply 214 is electrically
operated or can be operated by electrical power. In particular, the
pressurized gas supply 214 can be supplied with electrical power by
means of the power supply 211.
[0167] The analysis device 200 or pressurized gas supply 214 is
preferably designed to compress the working medium to a pressure of
more than 100 kPa, particularly preferably more than 150 kPa or 250
kPa, in particular more than 300 kPa or 350 kPa, and/or of less
than 1 MPa, particularly preferably less than 900 kPa or 800 kPa,
in particular less than 700 kPa and/or to feed said medium to the
cartridge 100 at said pressure.
[0168] Preferably, air can be drawn in, in particular from the
surroundings, as the working medium by means of the analysis device
200 or pressurized gas supply 214. In particular, the analysis
device 200 or pressurized gas supply 214 is designed to use the
surroundings as a reservoir for the working medium or the air.
However, other solutions are also possible here, in particular
those in which the analysis device 200 and/or pressurized gas
supply 214 comprises a preferably closed or delimited reservoir,
such as a tank or container, comprising the working medium, and/or
is connected or connectable thereto.
[0169] Preferably, the analysis device 200 or pressurized gas
supply 214 comprises an inlet, the working medium in particular
being able to be drawn in and/or conducted in or to the pressurized
gas supply 214 via the inlet.
[0170] Preferably, the analysis device 200 and/or pressurized gas
supply 214 comprises a filter, the filter preferably being
integrated in the inlet and/or it preferably being possible for the
working medium to be filtered by means of the filter and/or it
preferably being possible for particles to be separated from the
working medium by means of the filter.
[0171] The filter is preferably designed as a micro filter or as a
fine particulate air filter. Preferably, particles having a
particle diameter of more than 10 .mu.m, particularly preferably
more than 8 .mu.m or 9 .mu.m, in particular more than 6 .mu.m or 7
.mu.m, more particularly preferably more than 4 .mu.m or 5 .mu.m,
can be separated by means of the filter, the particle diameter
preferably being the maximum or average diameter of the respective
particles. This ensures that the channels or lines in the cartridge
that convey the working medium do not become contaminated or
clogged and/or that no undesired pressure loss occurs.
[0172] The analysis device 200 or pressurized gas supply 214
preferably comprises a connection element 214A, in particular in
order to pneumatically connect the analysis device 200 and/or
pressurized gas supply 214 to the cartridge 100, as will be
explained in greater detail with reference to FIGS. 11 and 12.
[0173] In the following, further details are given on a preferred
construction of the sensor arrangement and sensor apparatus 113
with reference to FIGS. 3 to 10.
[0174] FIG. 3 is a plan view of the sensor array 113A or the
measuring side of the sensor apparatus 113. FIG. 4 is an enlarged
detail from FIG. 3. FIG. 5 shows the connection side of the sensor
arrangement or the sensor apparatus 113. FIG. 6 and FIG. 7 are each
schematic sections through the sensor arrangement. FIG. 8 is an
enlarged detail of the back 100B of the cartridge 100 illustrating
the sensor arrangement. FIG. 9 is a section through the sensor
arrangement along the line IX-IX from FIG. 8. FIG. 10 is a
schematic section through the sensor arrangement along the line X-X
from FIG. 8.
[0175] The sensor arrangement preferably comprises the sensor
apparatus 113, a sensor cover 117 for the sensor apparatus 113, a
sensor compartment 118, an inlet 119 into the sensor compartment
118 and/or an outlet 120 out of the sensor compartment 118, as
shown in FIGS. 6, 7, 9 and 10.
[0176] The sensor arrangement, in particular the sensor apparatus
113, is preferably designed for electrochemically measuring or
detecting analytes A of the sample P.
[0177] In particular, the sensor arrangement or sensor apparatus
113 is designed to identify, to detect and/or to determine
(identical or different) analytes A bonded to capture molecules M
or products derived therefrom, in particular amplification products
of the analyte A or different analytes A.
[0178] The sensor arrangement is preferably designed as a
multiple-part module, the sensor apparatus 113 and the sensor cover
117 preferably each forming a component of the sensor arrangement
or module.
[0179] Preferably, the sensor arrangement has a layered
construction, the sensor apparatus 113 preferably forming a base of
the sensor arrangement and the sensor cover 117 being directly
connected to the sensor apparatus 113, at least at the edge, and/or
resting thereon.
[0180] The sensor apparatus 113 and the sensor cover 117 define or
delimit the sensor compartment 118, preferably on the flat sides.
In particular, the sensor compartment 118 is formed or arranged
between the sensor apparatus 113 and the sensor cover 117.
[0181] The sensor compartment 118 preferably has, in particular
when the sensor cover 117 is not actuated and/or has been moved
away, a volume of greater than 0.1 .mu.l or 0.2 .mu.l, particularly
preferably greater than 0.5 .mu.l or 1 .mu.l, in particular greater
than 2 .mu.l, and/or less than 10 .mu.l or 8 .mu.l, particularly
preferably less than 6 .mu.l or 3 .mu.l.
[0182] The sensor arrangement, in particular the sensor apparatus
113 and the sensor cover 117, is/are preferably planar and/or
plate-shaped. Preferably, the surface area of a flat side of the
sensor apparatus 113 and/or sensor cover 117 is less than 400
mm.sup.2 or 300 mm.sup.2, particularly preferably less than 250
mm.sup.2 or 150 mm.sup.2, in particular less than 100 mm.sup.2 or
50 mm.sup.2, and/or greater than 0.01 mm.sup.2 or 0.25 mm.sup.2,
particularly preferably greater than 1 mm.sup.2 or 4 mm.sup.2.
[0183] The sensor apparatus 113 preferably has a front side or
measuring side and a rear side or connection side, the measuring
side and the connection side each preferably forming one flat side
of the in particular planar and/or plate-shaped sensor apparatus
113.
[0184] The measuring side is preferably the side of the sensor
apparatus 113 facing the fluid, the sample P, the analytes A and/or
the sensor compartment 118.
[0185] The connection side is preferably opposite the measuring
side and/or is the side of the sensor apparatus 113 that faces away
from the fluid, the sample P, the analytes A and/or the sensor
compartment 118.
[0186] The sensor apparatus 113 preferably comprises a sensor array
113A on the measuring side, having a plurality of sensor cavities
and/or sensor fields 113B, the sensor fields 113B preferably being
circular, in a plan view of the sensor array 113A and/or being
arranged so as to be directly next to one another.
[0187] Preferably, the sensor arrangement or sensor apparatus 113
or the sensor array 113A comprises more than 10 or 20, particularly
preferably more than 50 or 80, in particular more than 100 or 120
and/or less than 1000 or 800 sensor fields 113B.
[0188] Preferably, the sensor fields 113B are separated or spaced
apart from one another, in particular by less than 100 .mu.m or 10
.mu.m and/or more than 10 nm or 100 nm. Particularly preferably,
all the sensor fields 113B are arranged on a surface area of less
than 100 mm.sup.2 and/or greater than 1 mm.sup.2 and/or the sensor
array 113A has a surface area of less than 100 mm.sup.2 and/or
greater than 1 mm.sup.2.
[0189] Preferably, the sensor arrangement or sensor apparatus 113
or the sensor array 113A comprises a plurality of electrodes 113C.
At least two electrodes 113C are preferably arranged in each sensor
field 113B. In particular, at least two electrodes 113C in each
case form a sensor field 113B.
[0190] The electrodes 113C are preferably made of metal, in
particular of noble metal, such as platinum or gold, and/or said
electrodes are coated, in particular with thiols.
[0191] Preferably, the electrodes 113C are finger-like and/or
engage in one another, as can be seen from the enlarged detail of a
sensor field 113B according to FIG. 4. However, other structural
solutions or arrangements are also possible.
[0192] The sensor apparatus 113 preferably comprises a support
113D, in particular a chip, the electrodes 113C preferably being
arranged on the support 113D and/or being integrated in the support
113D.
[0193] The chip or support 113D preferably contains electrical
circuits or an integrated circuit, to which the electrodes 113C
and/or electronic contacts 113E are connected.
[0194] Preferably, the sensor apparatus 113 comprises a housing
113G that surrounds the chip or support 113D at least in part
and/or in which said chip or support is integrally cast. The
housing 113G and/or the chip or the support 113D preferably
supports the contacts 113E, optionally by means of a connection
layer or intermediate layer.
[0195] The housing 113G leaves the sensor array 113A of the chip or
support 113D free of the housing on the measuring side as can be
seen, e.g., in FIGS. 9 & 10.
[0196] The housing 113G is in particular made of an insulating
and/or hard plastics material or other material.
[0197] In the example shown, the contacts 113E, optionally together
with the optional intermediate layer or a very thin portion of the
housing 113G, project laterally beyond the housing 113G in part.
However, if required, the housing 113G can also extend as far as
the edge of the contacts 113E and/or support said contacts over the
entire surface thereof or completely.
[0198] The sensor apparatus 113 or the support 113D and/or the
housing 113G is/are preferably resistant to bending and/or
rigid.
[0199] The sensor apparatus 113 is in particular card-like and/or
designed at least substantially as a planar plate part.
[0200] The sensor apparatus 113, in particular the support 113D,
preferably comprises a plurality of, in this case eight, electrical
contacts or contact surfaces 113E, the contacts 113E preferably
being arranged on the connection side and/or forming the connection
side, as shown in FIGS. 5 and 8.
[0201] Preferably, the sensor apparatus 113 can be electrically
contacted on the connection side and/or by means of the contacts
113E and/or can be electrically connected to the analysis device
200. In particular, an electrical connection can be established
between the cartridge 100, in particular the sensor apparatus 113,
and the analysis device 200, in particular the control apparatus
207, by electrically connecting the contacts 113E to the contact
elements 203A.
[0202] Preferably, the contacts 113E are arranged laterally, in the
edge region and/or in a plan view or projection around the
electrodes 113C and/or the sensor array 113A, and/or the contacts
113E extend as far as the edge region of the sensor apparatus 113,
in particular such that the sensor apparatus 113 can be
electrically contacted, preferably by means of the connection
apparatus 203 or the contact elements 203A, laterally, in the edge
region and/or around the sensor temperature-control apparatus 204C,
which can preferably be positioned centrally or in the middle on
the support 113D, as already explained.
[0203] In particular, the sensor apparatus 113 comprises barriers
or partitions between each of the sensor fields 113B, which are
preferably formed by an in particular hydrophobic layer 113F having
corresponding recesses for the sensor fields 113B. However, other
structural solutions are also possible.
[0204] As already explained, the sensor compartment 118 is
preferably arranged between the sensor apparatus 113 and the sensor
cover 117, the measurement side and/or the sensor array 113A of the
sensor apparatus 113 preferably defining or delimiting the sensor
compartment 118.
[0205] Preferably, the sensor fields 113B and/or the electrodes
113C are fluidically interconnected by the sensor compartment 118,
in particular such that the sensor fields 113B and/or electrodes
113C can come into contact with a fluid, the sample P and/or the
analytes A via the sensor compartment 118.
[0206] The sensor cover 117 can preferably be moved relative to the
sensor apparatus 113. In particular, the sensor cover 117 can be
lowered onto the sensor apparatus 113, in particular the sensor
array 113A and/or the layer 113F, preferably such that the sensor
fields 113B are closed and/or fluidically separated from one
another.
[0207] In particular, the fluid in the sensor compartment 118 can
be displaced onto the sensor apparatus 113 by means of the sensor
cover 117, and/or by lowering the sensor cover 117.
[0208] The sensor cover 117 is therefore designed to seal and/or
fluidically separate the individual sensor fields 113B from one
another for the actual measurement, preferably such that fluid
cannot be exchanged between the sensor fields 113B.
[0209] FIG. 6 is a schematic section through the sensor arrangement
with the sensor cover 117 moved away. FIG. 7 is a schematic section
through the sensor arrangement with the sensor cover 117 lowered
onto the layer 113F. The construction and the mode of operation of
the sensor cover 117 are explained in greater detail in the
following, with reference to FIGS. 8 to 10.
[0210] At least when the sensor cover 117 is moved away, the sensor
apparatus 113 and/or the sensor compartment 118 is fluidically
linked to the fluid system 103, preferably by the inlet 119 and the
outlet 120, in particular such that fluids, in particular the
(pretreated) sample P or the analytes A and/or reagents, can be
admitted to the measurement side of the sensor apparatus 113 or
sensor array 113A.
[0211] The sensor compartment 118 can thus be loaded with fluids
and/or said fluids can flow therethrough, at least when the sensor
cover 117 is raised or moved away from the sensor apparatus 113
and/or the sensor array 113A.
[0212] The sensor apparatus 113 preferably comprises a plurality of
in particular different capture molecules M for bonding the
analytes A, different capture molecules M preferably being arranged
and/or immobilized in or on different sensor fields 113B and/or
being assigned to different sensor fields 113B.
[0213] The capture molecules M are in particular oligonucleotide
probes.
[0214] Preferably, the capture molecules M are immobilized on the
sensor apparatus 113 or the sensor array 113A or electrodes 113C by
a bond and/or what is known as a spacer, in particular a C6 spacer.
The formation of structures that disrupt hybridization, e.g.
hairpin structures, can be prevented by the preferred bonding of
the capture molecules M by the bond B.
[0215] Particularly preferably, the electrodes 113C are provided
with the capture molecules M, in this case via bonds B, in
particular thiol bonds, in particular in order to bond and/or
detect or identify suitable analytes A.
[0216] Different capture molecules M1 to M3 are preferably provided
for the different sensor fields 113B and/or the different electrode
pairs and/or electrodes 113C, in order to specifically bond
different analytes A, in FIGS. 6 and 7 the analytes A1 to A3, in
the sensor fields 113B.
[0217] Particularly preferably, the sensor apparatus 113 or sensor
array 113A allows the analytes A bonded in each sensor field 113B
to be qualitatively or quantitatively determined.
[0218] Optionally, the sensor apparatus 113 comprises capture
molecules M having different hybridization temperatures, preferably
in order to bond the analytes A to the corresponding capture
molecules M at different hybridization temperatures.
[0219] The hybridization temperature is preferably the (average)
temperature at which an (amplified) analyte A or an amplification
product is bonded to a corresponding capture molecule M and/or is
hybridized to a corresponding capture molecule M.
[0220] The optimal hybridization temperature is preferably the
temperature at which the number of analytes A or amplification
products bonded to corresponding capture molecules M is maximized
and/or the number of analytes A or amplification products bonded to
one another is minimized
[0221] Preferably, the (optimal) hybridization temperature varies
for different analytes A or amplification products.
[0222] In particular, in order to achieve hybridization at the
different hybridization temperatures, the temperature of the sensor
apparatus 113, in particular of the electrodes 113C, the support
113D, the sensor compartment 118 and/or the cover 117, can be
controlled or set, at least indirectly, preferably by means of the
analysis device 200, in particular the temperature-control
apparatus 204B and/or 204C, as already explained.
[0223] Preferably, the sensor temperature-control apparatus 204C is
used to temperature-control the sensor compartment 118, in this
case by being in contact with the connection side, in particular
such that the desired or required or optimal hybridization
temperature is reached or set on the measuring side and/or in the
sensor compartment 118.
[0224] Preferably, in the operating state, the sensor
temperature-control apparatus 204C rests on the support 113D in a
planar manner and/or centrally and/or so as to be opposite the
sensor array 113A and/or rests on one or more contacts 113E at
least in part. This makes it possible to particularly rapidly and
efficiently temperature-control the sensor compartment 118 and/or
the capture molecules M and analytes A.
[0225] The sensor apparatus 113, in particular the chip or support
113D, preferably comprises at least one, preferably a plurality of,
electronic or integrated circuits, the circuits in particular being
designed to detect electrical currents or voltages that are
preferably generated at the sensor fields 113B in accordance with
the redox cycling principle.
[0226] Particularly preferably, the measurement signals from the
different sensor fields 113B are separately collected and/or
measured by the sensor apparatus 113 and/or the circuits.
[0227] Particularly preferably, the sensor apparatus 113 or the
integrated circuits directly convert the measurement signals into
digital signals or data, which can in particular be read out by the
analysis device 200.
[0228] Particularly preferably, the sensor apparatus 113, the chip
and/or the support 113D is constructed as described in EP 1 636 599
B1.
[0229] The construction and the mode of operation of the sensor
cover 117 according to a preferred embodiment are explained in
greater detail in the following, with reference to FIGS. 8 to
10.
[0230] FIG. 8 shows the back 100B of the cartridge 100 in the
region of the sensor arrangement, the sensor cover 117 being
indicated by dashed lines. FIG. 9 is a schematic sectional view of
the cartridge 100 in the region of the sensor arrangement, along
the sectional line IX-IX according to FIG. 8, in which the sensor
cover 117 is not lowered. FIG. 10 is a schematic sectional view of
the cartridge 100 along the sectional line X-X according to FIG. 8,
in which the sensor cover 117 is lowered.
[0231] The cartridge 100, in particular the main body 101,
preferably comprises a depression or receptacle 101B for the sensor
arrangement, sensor apparatus 113 and/or the sensor cover 117, as
shown in particular in FIG. 9 and FIG. 10. In the embodiment shown,
the receptacle 101 extends from the back 100B to the front 100A of
the cartridge 100. In particular, the receptacle 101B is formed by
an opening in the cartridge 100 and/or the main body 101. However,
other solutions are also possible here.
[0232] The sensor cover 117 and/or the sensor apparatus 113 is/are
inserted or installed or introduced into the depression or
receptacle 101B in the main body 101, the sensor apparatus 113
preferably closing the receptacle 101B to the outside or on the
back 100B of the cartridge 100.
[0233] Preferably, the sensor apparatus 113 and/or the sensor cover
117 is/are held in the receptacle 101B in a form-fit or
interlocking manner, in particular in the edge region.
[0234] Preferably, the cartridge 100 and/or the main body 101
comprises a mount 127, the sensor apparatus 113 and/or the sensor
cover 117 preferably being held in the receptacle 101B in a
form-fit manner and/or being prevented from falling out by means of
the mount 127.
[0235] In the embodiment shown, the mount 127 comprises a plurality
of, in this case four, projections 127A or the mount 127 is formed
by a plurality of projections 127A, the projections 127A preferably
being deformed, in particular by heat staking, and/or holding the
sensor apparatus 113 and/or the sensor cover 117 in the receptacle
101B in a form-fit manner However, other solutions are also
possible here, for example in which the projections 127A are formed
as detents or locking pins or the like.
[0236] Preferably, the mount 127 further comprises retaining
elements 127B, in this case two retaining elements 127B which are
opposite to each other and are integrally formed on the mount 127.
The retaining elements 127B retain the sensor apparatus 113 and/or
the sensor cover 117 in the desired position and/or delimit the
receptacle 101B.
[0237] The sensor cover 117 is preferably formed in one piece or
forms a unit and/or membrane. In particular, the sensor cover 117
is made of and/or injection-molded from plastics material, in
particular an elastomer, for example silicone.
[0238] Preferably, the sensor cover 117 is flexible and/or
extensible and/or elastically deformable at least in part, in
particular in order to lower the sensor cover 117 onto the sensor
apparatus 113.
[0239] The sensor cover 117 is preferably designed as a planar
unit, the main plane of extension of the sensor cover 117
preferably extending, in the installed state, at least
substantially in parallel with the main plane of extension of the
sensor apparatus 113 and/or of the main body 101.
[0240] The sensor cover 117 preferably comprises a cover part 117A,
a side part 117B and/or a connecting part 117C, the cover part 117A
preferably being held and/or connected to the side part 117B by
means of the connecting part 117C.
[0241] The side part 117B and/or the connecting part 117C
preferably surrounds the cover part 117A laterally, peripherally,
in a frame-like manner and/or in a collar-like manner In
particular, the cover part 117A is arranged centrally and the side
part 117B is arranged at the edge.
[0242] The sensor cover 117 and/or the side part 117B thereof is
preferably supported, mounted and/or rests on a stop or bearing
101C, and/or is held in or on the receptacle 101B. Particularly
preferably, the bearing 101C is formed by the main body 101.
[0243] Preferably, the bearing 101C is designed in the manner of a
shoulder or arm and/or forms a base in a rear depression in the
main body 101, the base preferably comprising a central recess for
forming the pressure chamber 128 that adjoins the sensor cover 117
towards the front 100A.
[0244] Preferably, the receptacle 101B in the main body 101 forms
the above-mentioned bearing 101C and/or the wall for the pressure
chamber 128.
[0245] The cartridge 100, the main body 101 and/or the sensor
arrangement and/or sensor apparatus 113 preferably further
comprises a stop 101D which is in particular peripheral or on
opposite sides for supporting or mounting the sensor apparatus 113,
as shown schematically in FIG. 10. In the example shown, the stop
101D engages in particular laterally overhanging regions of the
contacts 113E of the sensor apparatus 113 from below. Alternatively
or additionally, however, the stop 101D can for example also
support the sensor apparatus 113 on the housing 113G, for example
by means of a corresponding shoulder and a corresponding opening in
the side part 117B of the sensor cover 117.
[0246] The cover part 117A is preferably designed to cover the
sensor apparatus 113, in particular the sensor array 113A.
[0247] Particularly preferably, the cover part 117A is designed to
completely cover all the sensor fields 113B and/or all of the
sensor array 113A. In particular, the cover part 117A comprises a
covering surface that is larger than the surface area of the sensor
array 113A, in particular such that the entire sensor array 113A
and/or all the sensor fields 113B can be covered and/or closed by
means of the cover part 117A.
[0248] Preferably, the cover part 117A can be moved relative to the
sensor apparatus 113, in particular relative to the sensor array
113A, in particular in order to close and/or fluidically separate
the sensor fields 113B from one another and/or to displace the
fluid in the sensor compartment 118 and/or between the cover part
117A and the layer 113F, as already explained at the outset.
[0249] The cover part 117A can preferably be lowered onto the
sensor apparatus 113 in a planar manner and/or so as to have a flat
side facing the sensor apparatus 113.
[0250] Preferably, the cover part 117A is at least substantially
planar, flat and/or straight also in the lowered state. In
particular, the cover part 117A can be lowered evenly and/or such
that the cover part 117A does not curve or bend or at least
substantially does not curve or bend.
[0251] In particular, in order to achieve and/or ensure an even or
smooth lowering of the sensor cover 117 and/or the cover part 117A,
the sensor cover 117 is preferably centrally reinforced, in
particular stiffened, thickened and/or has a raised portion. This
achieves and/or allows planar and/or simultaneous covering of all
the sensor fields 113B, in particular the sensor fields 113B in the
edge region of the sensor array 113A.
[0252] In particular, the cover part 117A is thicker and/or more
rigid than the connecting part 117C and/or the side part 117B.
Preferably, the thickness or material thickness of the cover part
117A is at least 1.5 times or twice the material thickness or
thickness of the connecting part 117C and/or side part 117B.
Preferably, the cover part 117A has a thickness or material
thickness of more than 10 .mu.m or 50 .mu.m, particularly
preferably more than 100 .mu.m or 200 .mu.m and/or less than 1000
.mu.m or 500 .mu.m.
[0253] In the example shown, the side part 117B is preferably
thinner than the cover part 117A.
[0254] The connecting part 117C is preferably thinner than the side
part 117B. In particular, a depression or groove 117D is formed on
the side remote from the sensor compartment 118, as shown
schematically in FIGS. 9 and 10. This depression or groove 117D is
preferably formed peripherally around the (central) cover part
117A, such that the connecting part 117C can be very flexibly, in
particular elastically, deformed in order to allow the desired
placement of the cover part 117A on the sensor apparatus 113, the
sensor array 113A thereof and/or the layer 113F thereof when the
sensor cover 117 is actuated and/or lowered.
[0255] Preferably, the sensor cover 117 and/or the connecting part
117C has a sufficiently high restoring force to allow, if required,
a return movement of the sensor cover 117 and/or the cover part
117A into the unactuated initial position shown in FIG. 9, in which
position the cover part 117A is moved away from the sensor
apparatus 113 and/or the sensor array 113A.
[0256] In the embodiment shown, in the unactuated state the sensor
cover 117 is at least substantially planar or flat on the side
facing the sensor apparatus 113 and is raised or has a raised
portion in the center, at least compared with the side part 117B
and/or connecting part 117C, on the side remote from the sensor
apparatus 113. Particularly preferably, the flat sides of the cover
part 117A, side part 117B and/or connecting part 117C, and/or the
sides thereof facing the sensor apparatus 113, lie in or form a
common plane at least when the sensor cover 117 is in the initial
position unactuated and/or moved away. However, other solutions are
also possible, in which the cover part 117A is reinforced in
another manner, for example by means of a core and/or a coating
(not shown).
[0257] Preferably, the sensor cover 117 and/or the side part 117B
is held and/or clamped in the edge region in a stationary manner,
in particular between the sensor apparatus 113 or the housing
thereof 113G on one side, and the main body 101 or the bearing 101C
on the other side, in particular such that the cover part 117A is
moved and/or lowered relative to the (stationary) side part 117B
when the sensor cover 117 is actuated.
[0258] Preferably, the connecting part 117C is considerably thinner
than the side part 117B and/or is flexible and/or extensible and/or
elastically deformable at least in part, in particular such that
the connecting part 117C allows a relative movement between the
cover part 117A and the side part 117B.
[0259] The sensor cover 117, in particular the side part 117B,
preferably seals the sensor apparatus 113 and/or the sensor
compartment 118 laterally and/or at the edge.
[0260] In particular, the sensor apparatus 113 and/or the housing
113G thereof is sealingly mounted on the sensor cover 117 and/or on
the side part 117B in the edge region, preferably such that no
fluid can escape from the cartridge 100 and/or the receptacle 101B,
in particular also when the sensor cover 117 is moved away from the
sensor apparatus 113.
[0261] In the normal operating position of the cartridge 100, fluid
can flow through the sensor arrangement and/or the sensor
compartment 118 at least substantially vertically and/or from the
top to the bottom, or vice versa. In particular, in the normal
operating position of the cartridge 100, the preferably elongate
sensor compartment 118 has a vertical longitudinal extension, as
shown in particular in FIG. 8.
[0262] Preferably, fluid can flow through the sensor compartment
118 by means of the inlet 119 and the outlet 120. In particular, a
fluid can flow into the sensor compartment 118 via the inlet 119
and can flow out of the sensor compartment 118 via the outlet 120;
however, the flow direction can also be reversed. In particular,
the inlet 119 can be designed or used as the outlet, at least
temporarily, and the outlet 120 can be designed or used as the
inlet, at least temporarily.
[0263] The inlet 119 and/or the outlet 120 is/are preferably formed
by cut-outs, holes, openings, channels or the like in the main body
101, the sensor cover 117 and/or the sensor apparatus 113.
[0264] The inlet 119 and/or outlet 120 preferably comprises a
plurality of portions. In the embodiment shown, the inlet 119
and/or outlet 120 comprise a first portion 119A and/or 120A,
respectively, a second portion 119B or 120B, respectively, and a
third portion 119C or 120C, respectively.
[0265] Preferably, the first portion 119A or 120A extends at least
substantially in the main body 101 and/or orthogonally to the main
plane of extension of the cartridge 100, and/or from the front 100A
to the back 100B, in particular in order to transport the fluid
and/or the sample P from the front 100A to the back 100B and/or to
the sensor cover 117 or the side part 117B or vice versa.
[0266] Preferably, the second portions 119B or 120B, respectively,
are connected to the first portions 119A or 120A, respectively.
[0267] The second portion 119B or 120B preferably extends at least
substantially in parallel with the main plane of extension of the
main body 101 and/or obliquely, transversely or at least
substantially perpendicularly to the longitudinal extension of the
sensor compartment 118 and/or the main flow direction in the sensor
compartment 118, as shown, in particular, in FIG. 8.
[0268] Preferably, the third portions 119C or 120C, respectively,
are connected to the second portions 119B or 120B, respectively,
the third portions 119C or 120C, respectively, preferably directly
adjoining and/or opening into the sensor compartment 118.
[0269] Preferably, the third portion 119C or 120C extends at least
substantially in parallel with the main plane of extension of the
cartridge 100 and/or of the main body 101 and/or substantially
between the sensor cover 117 or the side part 117B on one side and
the sensor apparatus 113 or the housing 113G on the other side.
[0270] Preferably, the inlet 119, in particular the third portion
119C, and/or the outlet 120, in particular the third portion 120C,
is/are elongate and/or slot-like in cross section, and/or the inlet
119, in particular the third portion 119C, and/or the outlet 120,
in particular the third portion 120C, diverges/diverge towards the
sensor compartment 118, in particular in order to conduct the fluid
and/or the sample P evenly into the sensor compartment 118.
[0271] Preferably, the inlet 119, in particular the second portion
119B, and/or the outlet 120, in particular the second portion 120B,
extends/extend through the sensor cover 117, in particular the side
part 117B. In particular, the sensor cover 117 forms and/or defines
or delimits the inlet 119, in particular the second portion 119B,
and/or the outlet 120, in particular the second portion 120B, at
least in part and/or laterally. This ensures that the transition
into the sensor compartment 118 and/or from the first portion 119A
or 120A, respectively, to the third portion 119C or 120C,
respectively, is sealed.
[0272] As already explained at the outset, the sensor cover 117, in
particular the cover part 117A, can be actuated and/or lowered
pneumatically and/or by means of pressurized air.
[0273] Preferably, the cartridge 100 and/or the sensor arrangement
comprises the pressure chamber 128, the pressure chamber 128
preferably being delimited or defined by the main body 101, the
sensor cover 117 and the cover or film 102.
[0274] Particularly preferably, the pressure chamber 128 is formed
by the depression or receptacle 101B or a part thereof, and/or is
sealed off from the sensor apparatus 113 by means of the sensor
cover 117.
[0275] In particular, the sensor cover 117 is arranged between the
pressure chamber 128 and the sensor compartment 118 and/or the
sensor cover 117 separates the pressure chamber 128 from the sensor
compartment 118.
[0276] Preferably, the sensor cover 117, in particular the cover
part 117A, projects into the pressure chamber 128 at least in part,
at least in the unactuated state of the sensor cover 117, as shown
in particular in FIG. 9 and FIG. 10.
[0277] Preferably, the sensor cover 117 can be actuated and/or
lowered by supplying the working medium, in particular air, to the
cartridge 100, in particular the pressure chamber 128. Particularly
preferably, the sensor cover 117 is actuated and/or lowered at a
pressure in the pressure chamber 128 of more than 100 kPa,
particularly preferably more than 150 kPa or 250 kPa, in particular
more than 300 kPa or 350 kPa, and/or of less than 1 MPa,
particularly preferably less than 900 kPa or 800 kPa, in particular
less than 700 kPa.
[0278] The cartridge 100 preferably comprises a pneumatic
connection 129, the cartridge 100, in particular the pressure
chamber 128, preferably being able to be supplied with the working
medium by means of the connection 129, as shown in FIGS. 2, 11 and
12.
[0279] As shown in particular in FIG. 11 and FIG. 12, the
connection 129 preferably comprises a connection opening 129A and a
connection channel 129B, the connection opening 129A preferably
being arranged on the back 100B of the cartridge 100 and/or being
integrated in the surface of the main body 101. However, other
solutions are also possible here.
[0280] Preferably, the connection channel 129B connects the
connection opening 129A fluidically, in particular pneumatically,
to the pressure chamber 128, as shown by the dashed lines in FIG.
10.
[0281] As already explained, the analysis device 200 can preferably
be pneumatically connected to the cartridge 100, in particular the
sensor arrangement, in particular by means of the connection 129,
preferably in order to actuate the sensor cover 117.
[0282] In particular, the connection element 214A of the
pressurized gas supply 214 can be fluidically, in particular
pneumatically, connected or coupled to the connection 129.
[0283] FIG. 11 is a schematic section through the cartridge 100 in
the region of the connection 129, together with the connection
element 214A of which a detail is shown and which is moved away
and/or not connected. FIG. 12 is a schematic section through the
cartridge 100 in the region of the connection 129, together with
the connection element 214A in the pressed against and/or coupled
state.
[0284] Particularly preferably, the analysis device 200, in
particular the pressurized gas supply 214 and/or the connection
element 214A, can be positioned against the cartridge 100 and/or
the connection 129 and/or coupled to the cartridge 100 and/or the
connection 129 in a sealing manner, in particular in order to
supply the working medium to the pressure chamber 128 and/or to
actuate and/or lower the sensor cover 117.
[0285] Preferably, the cartridge 100, in particular the connection
129, and/or the connection element 214A comprises a seal 129C, the
seal 129C preferably being able to establish a preferably sealed
connection between the analysis device 200, in particular the
pressurized gas supply 214, and the cartridge 100, in particular
the pressure chamber 128.
[0286] In particular, the pressurized gas supply 214 and/or the
connection element 214A can be sealingly connected to the cartridge
100 and/or the connection 129 by means of the seal 129C, in
particular such that the working medium can be fed from the
analysis device 200 to the cartridge 100 and/or to the pressure
chamber 128.
[0287] The seal 129C is preferably arranged in the region of the
connection opening 129A and/or is formed around the connection
opening 129A.
[0288] In the embodiment shown, the seal 129C is preferably planar
and/or is formed as a film, layer or cover. Particularly
preferably, the seal 129C has a sealing surface area of more than 1
mm.sup.2 or 4 mm.sup.2, in particular more than 9 mm.sup.2 or 25
mm.sup.2, and/or less than 200 cm.sup.2 or 180 cm.sup.2, in
particular less than 150 cm.sup.2 or 120 cm.sup.2.
[0289] Preferably, the seal 129C is arranged on or attached to the
main body 101, in particular the back 100B of the cartridge 100,
and/or is connected to the main body 101, preferably in a bonded
manner, in particular by adhesion, and/or over the entire surface
thereof.
[0290] In the embodiment shown, the seal 129C is assigned to the
cartridge 100 and/or the cartridge 100 comprises or forms the seal
129C, preferably on the back 100B and/or on a side facing the
connection element 214A. In this way, each new cartridge 100 also
provides a new seal 129C and/or the cartridge 100 can be disposed
of together with the seal 129C. This is conducive to hygienic
testing of the sample P. However, other solutions are also possible
here, in particular in which the analysis device 200, in particular
the connection element 214A, comprises or forms the seal 129C,
preferably on a side facing the cartridge 100.
[0291] The seal 129C is preferably made of and/or injection-molded
from foamed plastics material, in particular foamed
polyethylene.
[0292] Preferably, the cartridge 100 can be moved, in particular
displaced, towards the pressurized gas supply 214 and/or the
connection element 214A, or vice versa, in particular in order to
connect or couple the analysis device 200 to the cartridge 100
fluidically, in particular pneumatically, and/or electrically
and/or thermally.
[0293] Preferably, the cartridge 100 is moved away from the
connection element 214A in a first position, as shown in FIG. 11,
and is positioned and/or pressed against the connection element
214A in a second position, as shown in FIG. 12.
[0294] The connection element 214A is preferably cylindrical,
tubular and/or dome-like.
[0295] Particularly preferably, the connection element 214A can be
pressed against the connection 129 and/or the seal 129C, preferably
such that the connection element 214A and the connection 129 are
interconnected or coupled together pneumatically, in particular in
a gas-tight manner
[0296] Particularly preferably, the connection element 214A, in
particular the end face thereof, is positioned on the cartridge
100, in particular the connection 129 and/or the seal 129C, in the
second position.
[0297] Preferably, the connection element 214A can be positioned so
as to be at least substantially coaxial with the connection 129
and/or the connection opening 129A thereof.
[0298] Preferably, the internal cross-sectional area and/or
external cross-sectional area of the connection element 214A is
greater than the internal cross-sectional area of the connection
129 and/or the cross-sectional area of the connection opening
129A.
[0299] In particular, the end face of the connection element 214A
can be connected to the cartridge 100 and/or the seal 129C in a
region around the connection 129 and/or the connection opening
129A. However, other structural solutions are also possible in
which the connection 129 can be plugged into the connection element
214A. In particular, other structural solutions are also possible
in which the connection element 214A is designed as a hollow needle
and/or can be plugged into the connection 129 and/or the connection
opening 129A at least in part.
[0300] Optionally, the connection element 214A and/or the
connection 129 and/or the connection opening 129A is/are conical,
preferably such that the connection element 214A and/or the
connection 129 center one another (not shown). In this way, any
manufacturing tolerances can be compensated.
[0301] In another embodiment (not shown), preferably prior to the
first use of the cartridge 100, the connection 129 and/or the
connection opening 129A is closed or sealed, and/or the cartridge
100 comprises a sealing means, such as a film, the sealing means
and/or the seal 129C preferably covering and/or sealing the
connection 129 and/or the connection opening 129A.
[0302] In an embodiment of this kind, in particular for a first
use, the seal 129C and/or the sealing means can preferably be
severed, pierced, broken and/or destroyed by means of the
connection element 214A in order to produce a pneumatic connection
between the analysis device 200 and the cartridge 100, and/or the
connection element 214A can be pushed through the seal 129C and/or
the sealing means and into the connection 129 and/or the connection
opening 129A. This ensures that the cartridge 100, in particular
the connection 129, is not contaminated prior to the first use.
[0303] In the following, a preferred sequence of a test or analysis
using the proposed analysis system 1 and/or analysis device 200
and/or the proposed cartridge 100 and/or in accordance with the
proposed method is explained in greater detail by way of
example.
[0304] The analysis system 1, the cartridge 100 and/or the analysis
device 200 is preferably designed to carry out the proposed
method.
[0305] Within the context of the method according to the invention,
a sample P having at least one analyte A on the basis of a fluid or
a liquid from the human or animal body, in particular blood, saliva
or urine, is usually first introduced into the receiving cavity 104
via the connection 104A, in order to detect diseases and/or
pathogens, it being possible for the sample P to be pretreated, in
particular filtered.
[0306] Once the sample P has been received, the receiving cavity
104 and/or the connection 104A thereof is fluidically closed, in
particular in a liquid-tight and/or gas-tight manner.
[0307] Preferably, the cartridge 100 together with the sample P is
then linked or corrected to the analysis device 200, in particular
is inserted or slid into the analysis device 200.
[0308] The method sequence, in particular the flow and conveying of
the fluids, the mixing and the like, is controlled by the analysis
device 200 or the control apparatus 207, in particular by
accordingly activating and actuating the pump drive 202 or the pump
apparatus 112 and/or the actuators 205 or valves 115.
[0309] During the nucleic-acid assay, a desired volume of the
sample P that is mixed and/or pretreated in the mixing cavity 107
is subsequently preferably fed to one or more reaction cavities
109, particularly preferably via (respectively) one of the
upstream, optional intermediate cavities 106A to 106C and/or with
different reagents or primers, in this case dry reagents S4 to S6,
being added or dissolved.
[0310] In the reaction cavities 109, the amplification reactions or
PCRs are carried out to copy/amplify the analytes A. This is
carried out in particular by means of the assigned, preferably
common, reaction temperature-control apparatus(es) 204A and/or
preferably simultaneously for all the reaction cavities 109, i.e.
in particular using the same cycles and/or temperature
(curves/profiles).
[0311] During the nucleic-acid assay, a label L is in particular
produced directly and/or during the amplification reaction(s) (in
each case) and/or is attached to the analytes A and/or
amplification products. This is in particular achieved by using
corresponding, preferably biotinylated, primers. However, the label
L can also be produced and/or bonded to the analytes A and/or
amplification products V separately or later, optionally also only
in the sensor compartment 118 and/or after hybridization. In
particular, during the protein assay, a label L is only bonded to
analytes A after hybridization of the analytes A to the capture
molecules M.
[0312] The label L is used in particular for detecting bonded
analytes A and/or amplification products. In particular, the label
L can be detected or the label L can be identified in a detection
process, as explained in greater detail in the following.
[0313] After carrying out the amplification reaction(s),
corresponding fluid volumes and/or amplification products are
conducted out of the reaction cavities 109 in succession to the
sensor arrangement, in particular the sensor apparatus 113 and/or
the sensor compartment 118, in particular via a group-specific
and/or separate intermediate cavity 106E, 106F or 106G
(respectively) and/or via the optional (common) intermediate
temperature-control cavity 110.
[0314] After the sample P and/or the analytes A and/or
amplification products are fed to the sensor apparatus 113, the
analytes A and/or amplification products are hybridized to the
capture molecules M, preferably by (actively)
temperature-controlling, in particular heating, the sensor
arrangement or sensor apparatus 113, in particular by means of the
sensor temperature-control apparatus 204C.
[0315] When carrying out the protein assay, the sample P and/or the
analytes A is/are preferably fed directly from the mixing cavity
107 to the sensor arrangement or sensor apparatus 113 and/or is/are
guided past the intermediate cavity/cavities 106, reaction
cavity/cavities 109 and/or the intermediate temperature-control
cavity 110 via the bypass 114A.
[0316] Once the sample P, analytes A and/or amplification products
are hybridized and/or bonded to the capture molecules M, detection
follows, in particular by means of the preferably provided label L,
or in another manner.
[0317] In the following, a particularly preferred variant of the
detection is described in greater detail, specifically
electrochemical detection, but other types of detection, for
example optical detection, capacitive detection or the like, may
also be carried out.
[0318] Following the respective bondings/hybridizations, preferably
an optional washing process takes place and/or additional reagents
or liquids, in particular from the storage cavities 108B to 108E,
are optionally fed in.
[0319] Subsequently and/or after the washing process, in accordance
with a preferred variant of the method, detection of the analytes A
and/or amplification products bonded to the capture molecules M
takes place.
[0320] If the bonded analytes A and/or amplification products are
still not marked and/or provided with a label L, in particular
during the protein assay, the labels L are then fed to the sensor
arrangement or the sensor compartment 118, preferably from the
storage cavity 108E, particularly preferably in the form of a
liquid reagent F5. Optionally, there is then another washing
process.
[0321] In order to detect the analytes A or amplification products
bonded to the capture molecules M, a reagent F4 and/or detector
molecules D, in particular alkaline phosphatase/streptavidin,
is/are fed to the sensor apparatus 113, preferably from the storage
cavity 108D.
[0322] Within the meaning of the present invention, the term
"detector molecules" is preferably understood to mean molecules
that bond specifically to the marker or label L of the (bonded)
analytes A or amplification products and thus allow the detection
thereof.
[0323] In particular, the detector molecules D may be enzyme
conjugates and/or immunoconjugates, which bond specifically to the
marker or label L, in particular biotin, and comprise a reporter
enzyme for converting a substrate.
[0324] In the context of the present invention, the detector
molecules D preferably are based on streptavidin, which has a high
affinity for biotin, and/or alkaline phosphatase, which can convert
non-reactive phosphate monoesters to electrochemically active
molecules and phosphate.
[0325] Preferably, a detection system is used, where the label L is
based on biotin and where the detector molecules D are based on
streptavidin/alkaline phosphatase. However, other detector
molecules D can also be used.
[0326] The reagents F4 and/or detector molecules D can bond to the
bonded analytes A or amplification products, in particular to the
label L of the bonded analytes A or amplification products,
particularly preferably to the biotin marker, as shown in FIG.
6.
[0327] Optionally, subsequently or after the reagents F4 and/or
detector molecules D have bonded to the analytes A and/or
amplification products or the labels L, an (additional) washing
process and/or flushing takes place, preferably by means of the
fluid or reagent F3 or wash buffer, in particular in order to
remove unbonded reagents F4 and/or detector molecules D from the
sensor apparatus 113.
[0328] Preferably, a reagent S7 and/or S8 and/or substrate SU for
the detection, in particular from the storage cavity 106D, is
lastly fed to the sensor arrangement or sensor apparatus 113,
preferably together with a fluid or reagent F2 (in particular a
buffer), which is suitable for the substrate SU, particularly
preferably for dissolving the reagent S7 and/or S8 and/or substrate
SU, the fluid or reagent F2 in particular taken from the storage
cavity 108B. In particular, the reagent S7 and/or S8 can form or
can comprise the substrate SU.
[0329] Preferably, p-aminophenyl phosphate (pAPP) is used as the
substrate SU.
[0330] The substrate SU preferably reacts on and/or with the bonded
analytes A and/or amplification products and/or detector molecules
D and/or allows these to be electrochemically measured.
[0331] In order to carry out the detection and/or electrochemical
measurement of the bonded analytes A or amplification products
and/or after adding the substrate SU, the sensor cover 117 is
preferably pneumatically actuated and/or lowered onto the sensor
apparatus 113, in particular in order to fluidically separate the
(individual) sensor fields 113B from one another, and/or to prevent
or minimize the exchange of substances between the sensor fields
113B.
[0332] Preferably, the working medium, which is in particular
pressurized by the analysis device 200 and/or the pressurized gas
supply 214, is supplied to the cartridge 100, in particular the
pressure chamber 128, in particular such that the pressure in the
pressure chamber 128 increases and/or the sensor cover 117, in
particular the cover part 117A, is lowered and/or moved towards the
sensor apparatus 113 and/or seals the sensor array 113A and/or the
sensor fields 113B, as already explained at the outset.
[0333] By actuating and/or lowering the sensor cover 117, chemical
exchange between the sensor fields 113B is prevented. Moreover, a
reaction and/or detection is prevented from being assigned to an
incorrect sensor field 113B, and in this way measurement
inaccuracies or errors are prevented from occurring. In particular,
the sensor cover 117 increases the measurement accuracy of the
proposed method.
[0334] The pneumatic actuation of the sensor cover 117 makes it
possible to close the sensor fields 113B particularly rapidly and
reliably.
[0335] As shown in particular in FIG. 7, the substrate SU is
preferably split by the bonded detector molecules D, in particular
the alkaline phosphatase of the bonded detector molecules D,
preferably into a first substance SA, such as p-aminophenol, which
is in particular electrochemically active and/or redox active, and
a second substance SP, such as phosphate.
[0336] Preferably, the first or electrochemically active substance
SA is detected in the sensor apparatus 113 or in the individual
sensor fields 113B by electrochemical measurement and/or redox
cycling.
[0337] Particularly preferably, by means of the first substance SA,
specifically a redox reaction takes place at the electrodes 113C,
the first substance SA preferably discharging electrons to or
receiving electrons from the electrodes 113C.
[0338] In particular, the presence of the first substance SA and/or
the respective amounts in the respective sensor fields 113B is
detected by the associated redox reactions. In this way, it can be
determined qualitatively and in particular also quantitatively
whether and how many analytes A and/or amplification products are
bonded to the capture molecules M in the respective sensor fields
113B. This accordingly gives information on which analytes A are or
were present in the sample P, and in particular also gives
information on the quantity of said analytes.
[0339] In particular, by means of the redox reaction with the first
substance SA, an electrical current or power signal is generated at
the assigned electrodes 113C, the current or power signal
preferably being detected by means of an assigned electronic
circuit.
[0340] Depending on the current or power signal from the electrodes
113C that is generated in this way, it is determined whether and/or
where hybridization to the capture molecules M has occurred.
[0341] The measurement is preferably taken just once and/or for the
entire sensor array 113A and/or for all the sensor fields 113B, in
particular simultaneously or in parallel. In particular, the bonded
analytes A and/or amplification products are detected, identified
or determined simultaneously or in parallel in a single or common
detection process.
[0342] However, in principle, it is also possible to measure a
plurality of sample portions in the sensor apparatus 113 or in a
plurality of sensor apparatuses 113 in succession or
separately.
[0343] The test results or measurement results are in particular
electrically transmitted to the analysis device 200 or the control
apparatus 207 thereof, preferably by means of the electrical
connection apparatus 203, and are accordingly prepared, analyzed,
stored, displayed and/or output, in particular by the display
apparatus 209 and/or interface 210.
[0344] After the test has been carried out, the cartridge 100 is
disconnected from the analysis device 200 and/or is released or
ejected therefrom, and is in particular disposed of.
[0345] Individual aspects and features of the present invention and
individual method steps and/or method variants may be implemented
independently from one another, but also in any desired combination
and/or order.
[0346] In particular, the present invention relates also to any one
of the following aspects which can be realized independently or in
any combination, also in combination with any aspects described
above.
[0347] 1. Analysis system 1, in particular cartridge 100, for
testing an in particular biological sample P, the analysis system 1
comprising a main body 101 having a plurality of channels 114, and
comprising a sensor arrangement for detecting an analyte A of the
sample P, the sensor arrangement comprising a sensor apparatus 113
having capture molecules M and a sensor cover 117 that is flexible
at least in part for covering the sensor apparatus 113, the sensor
cover 117 being able to be lowered onto the sensor apparatus 113 by
actuation, characterized [0348] in that the sensor cover 117 can be
actuated and/or lowered pneumatically, and/or [0349] in that, in
the unactuated state, the sensor cover 117 is at least
substantially planar on a side facing the sensor apparatus 113 and
is raised in the center on a side remote from the sensor apparatus
113, and/or [0350] in that the sensor apparatus 113 is pressed
against the sensor cover 117 in the edge region, and/or is
sealingly mounted on the sensor cover 117 in the edge region,
and/or [0351] in that the sensor arrangement comprises a sensor
compartment 118 between the sensor apparatus 113 and the sensor
cover 117, an inlet 119 into the sensor compartment 118 and an
outlet 120 out of the sensor compartment 118, the inlet 119 and/or
the outlet 120 extending through the sensor cover 117.
[0352] 2. Analysis system according to aspect 1, characterized in
that the analysis system 1 and/or the cartridge 100 comprises a
preferably pneumatic connection 129, by means of which the analysis
system 1 and/or the cartridge 100 and/or the sensor cover 117 can
be supplied with a working medium, in particular gas, and/or can be
pneumatically actuated.
[0353] 3. Analysis system according to aspect 1 or 2, characterized
in that the analysis system 1 and/or the cartridge 100 and/or the
sensor arrangement comprises a pressure chamber 128, the pressure
chamber 128 preferably being able to be supplied with the working
medium by means of the connection 129, and/or the sensor cover 117
being arranged between the pressure chamber 128 and the sensor
apparatus 113 and/or fluidically separating the pressure chamber
128 from the sensor compartment 118.
[0354] 4. Analysis system according to any one of the preceding
aspects, characterized in that the sensor cover 117 is centrally
reinforced and/or formed in one piece or forms a unit and/or is
made of and/or injection-molded from plastics material, in
particular an elastomer.
[0355] 5. Analysis system according to any one of the preceding
aspects, characterized in that the sensor cover 117 comprises a
cover part 117A that can be lowered onto the sensor apparatus 113,
a side part 117B and a connecting part 117C that is flexible and/or
extensible at least in part, the cover part 117A preferably being
connected to the side part 117B by means of the connecting part
117C.
[0356] 6. Analysis system according to aspect 5, characterized in
that the cover part 117A is thicker and/or more rigid than the
connecting part 117C and/or side part 117B, and/or in that the
connecting part 117C is thinner than the side part 117B.
[0357] 7. Analysis system according to aspect 5 or 6, characterized
in that the side part 117B surrounds the cover part 117A in a
collar-like manner, is held and/or clamped directly between the
sensor apparatus 113 and the main body 101, and/or forms a seal for
the sensor apparatus 113 and/or the sensor compartment 118 and/or
the pressure chamber 128.
[0358] 8. Analysis system according to any one of aspects 5 to 7,
characterized in that the inlet 119 and/or the outlet 120
extends/extend through the side part 117B and/or is/are formed by
the side part 117B at least in part.
[0359] 9. Analysis system according to any one of the preceding
aspects, characterized in that the inlet 119 and/or the outlet 120
is/are elongate and/or slot-like in cross section and/or
diverges/diverge towards the sensor compartment 118.
[0360] 10. Analysis system according to any one of the preceding
aspects, characterized in that the sensor compartment 118 is
delimited by the sensor cover 117 and the sensor apparatus 113 on
the flat side, and/or fluid can flow therethrough at least
substantially vertically in the normal operating position of the
cartridge 100.
[0361] 11. Analysis system according to any one of the preceding
aspects, characterized in that the sensor apparatus 113 and/or
sensor cover 117 is inserted into a depression or receptacle 101B
in the main body 101, the sensor apparatus 113 and/or the sensor
cover 117 preferably being held in a form-fit manner in the
depression or receptacle 101B, in particular by means of heat
staking the main body 101.
[0362] 12. Analysis system according to any one of the preceding
aspects, characterized in that the sensor apparatus 113 is designed
for in particular electrochemically detecting analytes A bonded to
the capture molecules M and/or comprises a sensor array 113A having
a plurality of sensor fields 113B, the sensor fields 113B
preferably being able to be fluidically separated from one another
by lowering the sensor cover 117.
[0363] 13. Analysis system according to any one of the preceding
aspects, characterized in that the sensor apparatus 113 can be
electrically contacted on a side remote from the sensor compartment
118 and/or comprises a plurality of electrical contacts.
[0364] 14. Method for testing an in particular biological sample P,
[0365] analytes A of the sample P being bonded to capture molecules
M of a sensor apparatus 113 and the bonded analytes A being
detected by the sensor apparatus 113, [0366] a sensor cover 117
that is flexible at least in part being lowered onto the sensor
apparatus 113 for the detection, [0367] characterized [0368] in
that the sensor cover 117 is pneumatically actuated.
[0369] 15. Method according to aspect 14, characterized in that the
sample P is placed into a cartridge 100, and the cartridge 100
containing the sample P is received by an analysis device 200 at
least in part, the analysis device 200 preferably being
pneumatically and/or electrically connected to the cartridge 100,
in particular to a sensor arrangement of the cartridge 100, and/or
a working medium, in particular gas, being pressurized by the
analysis device 200 and being fed to the cartridge 100 in order to
actuate the sensor cover 117.
* * * * *