# US 12,005,450 B2 · Method and apparatus for the reduction of the volume of a sample > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,005,450 B2 - Document ID: US12005450B2 - Status: Granted - Kind: B2 - Application number: 16/648,634 - Filed: 2018-09-21 - Published: 2020-09-10 - Granted: 2024-06-11 - Earliest claimed: 2017-09-21 - Assignees: Menarini Silicon Biosystems S.p.A. - Applicants: Menarini Silicon Biosystems S.p.A. - Inventors: Gianni Medoro; Alex Calanca; Fabrizio Alberti - Web page: https://patentgrep.com/patent/US12005450B2 ## CPC - B01L 3/502753: {characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation} - B01L 3/5021: {Test tubes specially adapted for centrifugation purposes} - G01N 1/4077: {by other techniques involving separation of suspended solids} - B01L 2200/0652: Sorting or classification of particles or molecules - G01N 2001/4088: {filtration} - B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE - 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 Method and apparatus for the reduction of the volume of a sample; the method comprises an acceleration step, during which a container containing the sample is accelerated so that a part of a liquid component of the sample flows out of an opening of one end of the container; according to some embodiments, the container is made to rotate around a rotation axis passing through the container; the container is orientated radially relative to the rotation axis with its opening facing outwards. ## Claims ### Claim 1 A method for the reduction of the volume of a sample comprising at least one at least partially liquid component and having a volume up to 10 mL using at least one container having an inner space, a first closed end, a second end provided with an opening, which establishes a connection between the inner space and the outside, and at least one side wall, the method comprising: an acceleration step, during which a manipulation assembly moves the container containing the sample subjecting the container to an acceleration which has at least one component that is orientated from the second end towards the first closed end and is transverse to said opening, so that a first part of said at least partially liquid component flows out of the container flowing through said opening and a second part of said at least partially liquid component with a substantially defined volume remains in the container, in particular at said first closed end; wherein the manipulation assembly comprises a moving device, which, during the acceleration step, rotates the container around a rotation axis so that the centrifugal force causes said first part of said at least partially liquid component to flow out of the container going through said opening; and wherein, during the acceleration step, the rotation axis extends through the container between the first closed end and the second end. ### Claim 2 (depends on 1) The method according to claim 1, wherein the sample comprises at least one microparticle; during the acceleration step, the manipulation assembly subjects the container to the acceleration so that the at least one microparticle remains in the container. ### Claim 3 (depends on 2) The method according to claim 2, further comprising a pre-treatment step, which is prior to the acceleration step and during which the container containing the sample is subjected to a further acceleration having at least one component that is orientated from the first closed end towards the second end and is transverse to said opening, so that the microparticle is arranged in the area of the first closed end. ### Claim 4 (depends on 1) The method according to claim 1, wherein, during the acceleration step, as a consequence of the acceleration applied to the container, at least one first inertial force is exerted upon the first part of the sample and at least one second inertial force is exerted upon the second part of the sample; the first and the second inertial forces are orientated from the first closed end towards the second end transversely to said opening; during the acceleration step, the first inertial force is greater than a first retaining force exerted between the first part of the sample and the container, and the second inertial force is smaller than a second retaining force exerted between the second part of the sample and the container. ### Claim 5 (depends on 1) The method according to claim 1, further comprising an adjustment step, which is prior to the acceleration step and during which a calculated acceleration and/or a calculated angular speed are determined based on the substantially defined volume to be obtained; during the acceleration step, the acceleration to which the manipulation assembly subjects the container is the calculated acceleration and/or the angular speed to which the manipulation assembly subjects the container is the calculated angular speed. ### Claim 6 (depends on 1) The method according to claim 1, wherein the manipulation assembly, during the acceleration step, simultaneously subjects a plurality of containers to said acceleration; in particular, the manipulation assembly comprises a plurality of seats, each housing a respective container. ### Claim 7 (depends on 2) The method according to claim 2, wherein the at least one microparticle is selected from the group consisting of: cells, cellular debris, cellular aggregates, bacteria, lipo-beads, microbeads, nano-beads, assemblies formed by micro-beads bound to cells, circulating tumour cells bound to ferrofluid, exosomes, colloidal suspension, liposomes, nuclei, spores, and combinations thereof. ### Claim 8 (depends on 1) The method according to claim 1, further comprising an insertion step, during which the sample is inserted into the container; and a treatment step, which is subsequent to the insertion step and prior to the acceleration step and during which the sample is treated with a further substance. ### Claim 9 (depends on 8) The method according to claim 8, wherein the treatment step comprises a first addition sub-step, during which a reactant is inserted into the container containing the sample; and a second addition sub-step, which is subsequent to the first addition sub-step and during which a washing liquid is inserted into the container containing the sample. ### Claim 10 (depends on 1) The method according to claim 1, wherein, during the acceleration step, a collecting device, which collects the first part of said at least partially liquid component, is arranged in the area of the opening out of the container. ### Claim 11 (depends on 10) The method according to claim 10, wherein the collecting device comprises a retaining system to hold back at least a fraction of the first part of said at least partially liquid component. ### Claim 12 (depends on 1) The method according to claim 1, wherein, during the acceleration step, the temperature of the container is kept within a predefined temperature interval. ### Claim 13 (depends on 1) The method according to claim 1 and comprising an insertion step, during which the sample is inserted into the container by an instrument selected from the group consisting of: microfluidic devices, pipetting instruments, flow cytometers, micromanipulators, and optical tweezers. ### Claim 14 (depends on 1) The method according to claim 1, wherein the sample comprises at least one microparticle provided with at least one magnetic component; during the acceleration step, a magnetic force is exerted upon the at least one microparticle towards the side wall and/or the closed end. ### Claim 15 (depends on 1) The method according to claim 1, wherein, during the acceleration step, a magnetic force is exerted towards the opening so as to remove undesired material from the container. ### Claim 16 (depends on 2) The method of claim 2, wherein the at least one particle remains in the area of said first closed end. ### Claim 17 (depends on 7) The method of claim 7, wherein the at least one microparticle is selected from the group consisting of stem cells, erythroblasts, trophoblasts, neuronal cells, epithelial cells, tumour cells, white blood cells (WBC), stromal cells, sperm cells, circulating tumour cells (CTC), fetal cells, micro-beads, colloidal suspension, assemblies formed by micro-beads bound with cells, erythrocytes, circulating tumour cells bound with ferrofluid, and combinations thereof. ### Claim 18 (depends on 9) The method of claim 9, wherein the treatment step comprises an incubation sub-step, which is subsequent to the first addition sub-step and prior to the second addition sub-step and during which the reactant is left with the sample. ### Claim 19 (depends on 11) The method of claim 11, wherein the retaining system comprises an element selected from the group consisting of: absorbing material, capillary trap, liquid trap, and a combination thereof; the capillary trap comprising a plurality of grooves having a width that is smaller than 2.0 mm, wherein the liquid trap comprising a collecting chamber, which is provided with an inlet, and at least one movable wall, which is movable between a closing position, in which it prevents liquid from flowing through the inlet, and an opening position, in which the liquid can flow through the inlet; during the acceleration step, said acceleration moves the movable wall to the opening position; once the acceleration is no longer applied to the container. ### Claim 20 (depends on 1) The method of claim 1, wherein a magnet is arranged in the area of the first closed end.