# US 10,308,977 B2 · Device and method for processing a biological sample and analysis system for analyzing a biological specimen > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,308,977 B2 - Document ID: US10308977B2 - Status: Granted - Kind: B2 - Application number: 15/311,142 - Filed: 2015-04-29 - Published: 2017-03-30 - Granted: 2019-06-04 - Earliest claimed: 2014-05-15 - Assignees: Robert Bosch GmbH - Applicants: Robert Bosch GmbH - Inventors: Thomas Brettschneider; Jochen Hoffmann; Karin Lemuth - Web page: https://patentgrep.com/patent/US10308977B2 ## CPC - C12Q 1/6806: Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay (C12Q1/6804 takes precedence) - B01L 3/502715: {characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces} - B01L 3/502753: {characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation} - C12N 1/066: by physical processes - C12N 13/00: Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves - C12N 15/1017: {by filtration, e.g. using filters, frits, membranes} - B01L 2200/0631: Purification arrangements, e.g. solid phase extraction [SPE] - B01L 2200/0647: Handling flowable solids, e.g. microscopic beads, cells, particles - B01L 2200/10: Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept - B01L 2300/0627: Sensor or part of a sensor is integrated - B01L 2300/0681: Filter - B01L 2300/087: Multiple sequential chambers - B01L 2300/0887: Laminated structure - B01L 2300/12: Specific details about materials - B01L 2400/0415: electrical forces, e.g. electrokinetic - G01N 2001/4088: {filtration} - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract A device for processing a biological sample includes a first substrate having a first cavity, a second substrate having a second cavity, a filter element having a plurality of perforations, and an electrically conductive structure. The first cavity forms a first chamber segment of a chamber for accommodating the biological sample. The second cavity forms a second chamber segment of the chamber for accommodating the biological sample. The filter element is formed between the first cavity and the second cavity in order to hold back a plurality of organic cells of the biological sample on the plurality of perforations when the biological sample moves between the first cavity and the second cavity through the filter element. The electrically conductive structure is arranged on the filter element and is configured to cause lysis of the organic cells and/or to duplicate and/or detect defined segments of exposed DNA. ## Claims ### Claim 1 An apparatus for processing a biological sample, the apparatus comprising: a first substrate having a first cavity forming a first chamber portion of a chamber, the chamber configured to receive the biological sample; a second substrate having a second cavity forming a second chamber portion of the chamber; a filter element having a plurality of perforations, the filter element arranged between the first cavity and the second cavity and configured to hold back a plurality of organic cells of the biological sample at the plurality of perforations when moving the biological sample from the first cavity to the second cavity through the filter element; and an electrically conductive structure arranged at the filter element and configured to bring about lysis of the plurality of organic cells as the plurality of organic cells are held back by the filter element and/or to duplicate and/or detect defined sections of exposed DNA, wherein the electrically conductive structure comprises a first conductor track between a first connection region of the electrically conductive structure and a second connection region of the electrically conductive structure, the first conductor track configured to apply a first voltage between the first connection region and the second connection region, and the electrically conductive structure comprises a second conductor track between a third connection region of the electrically conductive structure and a fourth connection region of the electrically conductive structure, the second conductor track configured to apply a second voltage between the third connection region and the fourth connection region. ### Claim 2 (depends on 1) The apparatus as claimed in claim 1, wherein the first substrate and the second substrate are at least partly formed from silicon. ### Claim 3 (depends on 1) The apparatus as claimed in claim 1, further comprising: a first fluid channel extending between a main side of the first substrate and the first cavity, the main side of the first substrate facing away from the first cavity; and a second fluid channel extending between the main side of the first substrate and the second cavity, wherein one of the first fluid channel and the second fluid channel is configured to admit the biological sample into the chamber and the other of the first fluid channel and the second fluid channel is configured to release the biological sample from the chamber. ### Claim 4 (depends on 3) The apparatus as claimed in claim 3, wherein, for electrically contacting the electrically conductive structure, the first substrate has a first feedthrough between the main side of the first substrate and the electrically conductive structure and/or the second substrate has a second feedthrough between a main side of the second substrate facing away from the second cavity and the electrically conductive structure. ### Claim 5 (depends on 3) The apparatus as claimed in claim 3, further comprising a detection region configured to receive a lysate obtained during lysis of the organic cells, the detection region arranged adjacent to at least one of the first fluid channel and the second fluid channel at the main side of the first substrate. ### Claim 6 (depends on 1) The apparatus as claimed in claim 1, wherein: the second substrate comprises a first substrate portion comprising the second cavity; the second substrate comprises a second substrate portion arranged adjacent to a base of the second cavity forming a wall of the chamber; and the first substrate portion is made of silicon and the second substrate portion is made of glass. ### Claim 7 (depends on 6) The apparatus as claimed in claim 6, further comprising a further conductive structure arranged at the base of the second cavity. ### Claim 8 (depends on 1) The apparatus as claimed in claim 1, wherein: the first conductor track has at least one first conductor track portion and the second conductor track has at least one second conductor track portion; the first conductor track portion extends to an edge of a perforation; and the second conductor track portion extends to a further edge of the perforation, the further edge lying opposite the edge. ### Claim 9 (depends on 1) The apparatus as claimed in claim 1, wherein: the first conductor track extends in a first meandering structure along the plurality of perforations of the filter element from the first connection region to the second connection region and the second conductor track extends in a second meandering structure complementary to the first meandering structure along the plurality of perforations of the filter element from the third connection region to the fourth connection region. ### Claim 10 (depends on 1) The apparatus as claimed in claim 1, wherein the filter element is formed from at least one of the first substrate and the second substrate. ### Claim 11 (depends on 10) The apparatus as claimed in claim 10, wherein the electrically conductive structure is positioned between the first cavity and the second cavity. ### Claim 12 An analysis system for analyzing a biological sample, the analysis system comprising: an apparatus configured to process the biological sample of organic cells, the apparatus including: a first substrate having a first cavity forming a first chamber portion of a chamber, the chamber configured to receive the biological sample; a second substrate having a second cavity forming a second chamber portion of the chamber; a filter element having a plurality of perforations, the filter element arranged between the first cavity and the second cavity and configured to hold back a plurality of organic cells of the biological sample at the plurality of perforations when moving the biological sample from the first cavity to the second cavity through the filter element; an electrically conductive structure arranged at the filter element and configured to bring about lysis of the plurality of organic cells as the plurality of organic cells are held back by the filter element and/or to duplicate and/or detect defined sections of exposed DNA; a first fluid channel extending between a main side of the first substrate and the first cavity, the main side of the first substrate facing away from the first cavity, and a second fluid channel extending between the main side of the first substrate and the second cavity, wherein one of the first fluid channel and the second fluid channel is configured to admit the biological sample into the chamber and the other of the first fluid channel and the second fluid channel is configured to release the biological sample it from the chamber; a detection region configured to receive a lysate obtained during lysis of the organic cells, the detection region arranged adjacent to at least one of the first fluid channel and the second fluid channel at the main side of the first substrate; and a detection unit configured to detect a predetermined cell constituent of the biological sample extracted from the organic cells in the apparatus, wherein the electrically conductive structure comprises a first conductor track between a first connection region of the electrically conductive structure and a second connection region of the electrically conductive structure, the first conductor track configured to apply a first voltage between the first connection region and the second connection region, and the electrically conductive structure comprises a second conductor track between a third connection region of the electrically conductive structure and a fourth connection region of the electrically conductive structure, the second conductor track configured to apply a second voltage between the third connection region and the fourth connection region the detection unit fluidically coupled to the apparatus. ### Claim 13 (depends on 12) The analysis system as claimed in claim 12, wherein: the detection unit comprises: a layer structure made of: a first polymer substrate comprising a channel system; a second polymer substrate comprising a recess; and a microfluidic layer arranged between the first polymer substrate and the second polymer substrate and comprising a microfluidic network; and an analysis cavity, coupled to the channel system, for performing an analysis method on the lysate obtained in the apparatus, and the apparatus is arranged in the recess and adjacent to the microfluidic layer such that the detection region lies in the analysis cavity and at least one of the first fluid channel and the second fluid channel is fluidically coupled to the channel system. ### Claim 14 (depends on 12) The apparatus of claim 12, wherein the filter element is formed from at least one of the first substrate and the second substrate. ### Claim 15 A method for processing a biological sample, the method comprising: moving the biological sample between a first cavity and a second cavity through a filter element and an electrically conductive structure, the first cavity laid out in a first substrate and forming a first chamber portion of a chamber for receiving the biological sample, the second cavity laid out in a second substrate and forming a second chamber portion of the chamber, the filter element comprising a plurality of perforations embodied between the first cavity and the second cavity in order to hold back a plurality of organic cells of the biological sample at the plurality of perforations, the electrically conductive structure arranged at the filter element; and applying at least one electric voltage to the electrically conductive structure in the presence of a lysing agent flushed into the chamber by applying a first electric voltage via a first conductor track connecting a first connection region of the electrically conductive structure with a second connection region of the electrically conductive structure, and by applying a second electric voltage via a second conductor track connecting a thud connection region of the electrically conductive structure to a fourth connection region of the electrically conductive structure, thereby lysing the plurality of organic cells held back at the plurality of perforations. ### Claim 16 (depends on 15) The method as claimed in claim 15, wherein: applying the at least one electric voltage includes thermally lysing the plurality of organic cells held back at the plurality of perforations by Joule heating of the filter element. ### Claim 17 (depends on 15) The method as claimed in claim 15, wherein: applying the at least one electric voltage includes electrically lysing the plurality of organic cells held back at the plurality of perforations by generating an electric field between the first conductor track and the second conductor track while the plurality of organic cells are held back at the plurality of perforations. ### Claim 18 (depends on 15) The method as claimed in claim 15, further comprising: re-applying the at least one electric voltage to the electrically conductive structure to duplicate a plurality of cell constituents released from the plurality of organic cells during lysis when a reaction agent is present in the chamber. ### Claim 19 (depends on 15) The method of claim 15, wherein moving the biological sample between a first cavity and a second cavity through a filter element and an electrically conductive structure comprises: moving the biological sample between the first cavity and the second cavity through a filter element formed from at least one of the first substrate and the second substrate, and through an electrically conductive structure.