US20120187021A1 - Sample carrier and sample carrier processing apparatus - Google Patents

Sample carrier and sample carrier processing apparatus Download PDF

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Publication number
US20120187021A1
US20120187021A1 US13/012,892 US201113012892A US2012187021A1 US 20120187021 A1 US20120187021 A1 US 20120187021A1 US 201113012892 A US201113012892 A US 201113012892A US 2012187021 A1 US2012187021 A1 US 2012187021A1
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United States
Prior art keywords
region
sample
fluid
sample carrier
vessel
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US13/012,892
Inventor
Gilbert W. McKenna
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Analogic Corp
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Analogic Corp
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Publication of US20120187021A1 publication Critical patent/US20120187021A1/en
Abandoned legal-status Critical Current

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0816Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0867Multiple inlets and one sample wells, e.g. mixing, dilution
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/12Specific details about materials
    • B01L2300/123Flexible; Elastomeric
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/505Containers for the purpose of retaining a material to be analysed, e.g. test tubes flexible containers not provided for above

Definitions

  • the following generally relates to a sample carrier and/or a sample carrier processing apparatus configured to process one or more samples carried by the sample carrier, and more particularly to moving a fluid (e.g., a sample, a processing material, etc.) through a channel of the sample carrier via direct displacement for processing the sample by the sample carrier processing apparatus.
  • a fluid e.g., a sample, a processing material, etc.
  • Micro channel devices include, but are not limited to, devices which carry one or more small samples for processing and/or analysis by a sample processing apparatus. Such devices have included, for each sample, a plurality of processing regions, processing material chambers, micro-fluidic channels, valves, etc., and such apparatuses have included a plurality of processing stations for processing samples. One or more samples carried by a micro channel device are moved through the micro channel device, in series or parallel, via the micro-fluidic channels of the device from processing station to processing station of the sample processing apparatus, where the one or more samples are processed, with each of the samples being sequentially processed by corresponding processing regions using the processing materials from the chambers.
  • One approach for moving the samples and/or the processing materials in a micro channel device includes using a pressurized gas.
  • a pressurized gas can be delivered by a compressor, a tank holding pressurized air, an air mover, and/or other source of pressurized gas through pneumatic valves sequenced by a controller or processor of the sample processing system.
  • a micro channel device can be highly complex.
  • a multi-channel micro channel device may require hundreds of valves, which need to be synchronized, and corresponding valve lines to open and close the valves.
  • the pressure applied actually moves a sample and/or processing material to its destination within the device.
  • a sample carrier for carrying one or more samples to be processed by a sample processing apparatus includes at least one sample processing channel, the channel including a first region configured to carry a first fluid and at least a second region, wherein the first fluid in the first region is moved to the second region via compression of the first region.
  • a sample processing apparatus for processing samples carried by sample carriers including at least one raised vessel carrying at least one a sample or a processing material includes a sample carrier receiving region configured to receive the sample carriers and a displacer configured to apply physical pressure to the raised vessel which causes compression of the raised vessel, thereby moving a fluid in the raised vessel to another region of the sample carrier for at least one of mixing or processing by the at least one processing component.
  • a method in another aspect, includes controllably moving a fluid in a sample carrier via compression during DNA analysis.
  • FIG. 1 schematically illustrates an example sample carrier that includes raised fluid vessels holding samples and/or processing materials, and a sample processing apparatus configured to process samples carried by such sample carriers;
  • FIGS. 2A , 2 B and 2 C schematically illustrate a sub-portion of a processing channel of the sample carrier in connection with a sub-portion of the sample processing apparatus in which the sample processing apparatus moves samples and/or processing materials in the vessels in the sample carrier;
  • FIGS. 3 and 4 schematically illustrate variations of the raised fluid vessel relative to a processing or mixing region internal to the sample carrier
  • FIG. 5 schematically illustrates an example in which a fluid in a raised vessel is moved to another raised vessel via a raised fluid channel of the sample carrier;
  • FIG. 6 schematically illustrates sequential movement of samples and/or processing materials in the raised vessels through a sub-portion of the sample carrier
  • FIG. 7 schematically illustrates an example sample carrier that includes raised vessels on multiple sides of the sample carrier
  • FIG. 8 schematically illustrates an example sample carrier that includes raised vessels that moves a fluid in the sample carrier.
  • FIG. 9 illustrates an example method for moving fluid in a sample carrier.
  • FIG. 1 illustrates a sample processing apparatus 100 for processing one or more samples carried on a micro-channel device, such as a sample carrier 102 , which is installed or inserted into a sample carrier receiving region 104 of the sample processing apparatus 100 .
  • a micro-channel device such as a sample carrier 102
  • FIG. 1 illustrates a sample processing apparatus 100 for processing one or more samples carried on a micro-channel device, such as a sample carrier 102 , which is installed or inserted into a sample carrier receiving region 104 of the sample processing apparatus 100 .
  • the processing apparatus 100 is configured for DNA, enzymatic, protein, and/or other processing and/or analysis of at least one or more bio-sample located on the sample carrier 102 .
  • the sample processing apparatus 100 is configured to process other bio-samples and/or non bio-samples on the sample carrier 102 .
  • An example of a suitable sample carrier 102 includes, but is not limited to, a biochip, a lab-on-a-chip, and/or other sample carrier.
  • the illustrated sample carrier 102 includes one or more sample regions 106 for carrying a sample to be processed, and one or more processing regions 108 for processing the one or more samples in the one or more sample regions 106 .
  • the sample carrier 102 further includes one or more processing agent regions 110 which carry one or more processing materials or agents 112 used to facilitate processing samples.
  • the sample carrier 102 further includes one or more mixing regions 114 and/or one or moving regions 116 respectively for mixing a sample and an agent and/or one or more agents, and moving a sample, an agent, or a combination thereof in the sample carrier 102 .
  • At least one of the regions 106 , 108 , 110 , 114 , or 116 is configured as a raised vessel that is at least partially raised above a surface of the sample carrier 102 .
  • a fluid in such a vessel can be displaced or moved out of the vessel and to another portion of the sample carrier 102 by applying a suitable pressure, generally in a direction toward the sample carrier 102 , to the raised portion of the vessel, which causes the vessel to compress and/or collapse towards the sample carrier 102 , pushing the fluid out of an opposing side of the vessel, which is in fluid communication with other portions of the sample carrier 102 such that the fluid can move to the other portions of the sample carrier 102 .
  • the vessel With a moving vessel, the vessel is similarly compressed; however, the fluid remains therein and is solely used to move fluid out of another region.
  • the sample apparatus 100 includes one or more processing stations 120 . Where configured for DNA analysis, such the processing stations 120 are configured to process one or more DNA samples in different lanes or channels of the sample carrier 102 . In this instance, the processing stations 120 are configured to perform at least such functions as extract and purify DNA fragments, replicate and label the fragments with fluorescent dyes having known emission spectrums (or colors), separate the labeled fragments based on fragment size, for example, via electrophoresis, scan the fragments, and determine allele numbers for the DNA samples.
  • the processing stations 120 are configured to process one or more DNA samples in different lanes or channels of the sample carrier 102 .
  • the processing stations 120 are configured to perform at least such functions as extract and purify DNA fragments, replicate and label the fragments with fluorescent dyes having known emission spectrums (or colors), separate the labeled fragments based on fragment size, for example, via electrophoresis, scan the fragments, and determine allele numbers for the DNA samples.
  • the sample processing apparatus 100 also includes a fluid displacer 122 .
  • the fluid displacer 122 is configured to controllably apply suitable pressure to the raised vessel of at least one of the regions 106 , 108 , 110 , 114 , or 116 for moving the fluid held therein. This allows for moving samples and/or processing materials in the sample carrier 102 without using external pneumatics and/or external pneumatic valves, which may simplify the sample carrier 102 and reduce the cost thereof.
  • a drive system 124 drives the fluid displacer 122 .
  • the drive system 124 may include an AC or DC motor (e.g., linear, stepper, etc.), a drive (e.g., a ball screw, a lead screw, gears, a belt, a chain, a piston, etc.), and an encoder for tracking the position of the drive and/or the fluid displacer 122 , directly and/or via the motor.
  • an AC or DC motor e.g., linear, stepper, etc.
  • a drive e.g., a ball screw, a lead screw, gears, a belt, a chain, a piston, etc.
  • an encoder for tracking the position of the drive and/or the fluid displacer 122 , directly and/or via the motor.
  • a controller 126 controls the drive system 124 and the one or more processing components 120 .
  • the illustrated controller 126 includes one or more processors that execute one or more computer readable instructions encoded on computer readable storage medium such as physical memory. Additionally or alternatively, at least one of the instructions can be carried by a carrier wave or signal.
  • a user interface 128 provides an interactive user interface for presenting information to and/or receiving commands from a user of the sample processing apparatus 100 via buttons, knobs, a stylist, a digital pen, a mouse, a keypad, a keyboard, an audible command, etc.
  • the one or more vessels include fluid to be mixed, moved, combined, processed, etc. and can be thought of as formable blisters or bubbles of plastic or the like that stick above the surface of the sample carrier 102 and can be compressed to move fluid by direct displacement.
  • the fluid displacer 122 comes along with sufficient force to compress and squash the one or more vessels, for example, in a linear fashion, to displace the fluid therein.
  • the location of the fluid can be determined based on the position of the fluid displacer 122 , and the fluid can be mixed or combined with other fluids and/or unknowns to complete an experiment and quantify results.
  • the controller 126 can accurately synchronize the sequence (e.g., the timing and logical flow) of fluid flow, and execution and lack of complex control elements renders a reliable and robust system.
  • the processing apparatus 100 is configured to be a hand-held, portable apparatus that can be readily carried by an operator. In this configuration, the processing apparatus 100 can be carried and employed at the location where the sample is collected, if desired, or elsewhere. In this configuration, the processing apparatus 100 may also be configured such the operator can operate it with one hand. In another embodiment, the processing apparatus 100 is configured to be a stationary apparatus mounted to or placed on a table, the floor, etc. in a laboratory, office, or the like. In such a configuration, the processing apparatus 100 may be configured to remain at a particular location and process sample carriers 102 loaded therein.
  • FIGS. 2A , 2 B and 2 C schematically illustrate an example raised vessel 200 of the sample carrier 102 in connection with an example fluid displacer 212 .
  • the illustrated raised vessel 200 includes a first or raised sub-portion 202 , which extends from a major surface 204 of the sample carrier 102 above the major surface 204 , forming a cavity 206 there between, and a second or fluid releasing sub-portion 208 that is attached to the first sub-portion 202 so as to close and seal the vessel 200 .
  • the content in a vessel 200 can be contained and isolated, which may facilitate mitigating contamination and/or cross contamination in the sample carrier 102 .
  • the illustrated vessel 200 is filled with a fluid 210 such as a sample, a processing agent, or a combination thereof.
  • the vessel 200 can be pre-loaded. Alternatively, such fluids can be added to the vessel 200 .
  • the illustrated vessel 200 can represent any of the regions 106 , 108 , 110 , or 114 .
  • the vessel may include an ingress port for loading the sample in the vessel 200 .
  • the illustrated vessel 200 is disposed on the sample carrier 102 such that the second or fluid releasing sub-portion 208 of the vessel 200 is next to and/or is a side covering an opening of the region 106 , 108 , 110 , or 114 .
  • the raised vessel 200 can be part of a separate layer (in roll form) attached to the sample carrier 102 or part of the same layer as the regions the region 106 , 108 , 110 , or 114 .
  • the sample carrier 102 can be composed of one or more layers, with via or the like providing pathways between the one or more layers.
  • the raised sub-portion 202 is generally compressible and collapsible under first predetermined pressure by the fluid displacer 122 .
  • the fluid releasing sub-portion 208 is generally breakable, tearable or otherwise openable such that the fluid 210 in the raised vessel 200 can be displaced and egress out of the raised vessel 200 .
  • the fluid 210 is displaced out of the raised vessel 200 and into the region 108 , 110 , or 114 .
  • displacing fluid out of the raised vessel 200 removes the fluid from the sample carrier 102 .
  • the raised vessel 200 has a hemisphere shape and the region 108 , 110 , or 114 has parallelepiped shape.
  • the illustrated shapes (and relative sizes) are provided for explanatory purposes and are not limiting. As such, other three dimensional shape are contemplated herein.
  • the raised vessel 200 can have parallelepiped shape and the region 108 , 110 , or 114 can have a hemisphere shape, the shapes of both the raised vessel 200 and the regions 108 , 110 , or 114 can be the same, etc.
  • the illustrated fluid displacer 122 includes a roller or rotatable drum 212 that is moved via a ball screw 214 driven by a linear stepper motor 230 . More particularly, in the illustrated example, a first end region 218 of a support member 220 is affixed at a side 222 of the drum 212 at a rotational axis 224 that extends along a longitudinal axis of the drum 212 . An opposing end region 226 of the support member 220 is affixed to a threaded ball screw nut 228 of the ball screw 214 .
  • the motor 230 is configured to rotate a threaded shaft 232 of the ball screw 214 , which in turns translates ball screw nut 228 , and hence the drum 214 along the a direction of the shaft 232 .
  • the drum 212 is in physical contact with the surface 204 of the sample carrier 102 and moves across the surface 204 .
  • the motor 230 drives the shaft 232 , under control of the controller 126 , such that a force exerted by the drum 212 when the drum 212 physically contacts the raised sub-portion 202 of the raised vessel 200 the drum compresses and collapses the raised sub-portion 202 , collapsing it towards the surface 204 , pushing the fluid in the raised vessel 202 into the region 108 , 110 , or 114 .
  • the collapsed sub-portion 202 remains in a substantially collapsed position after the cylindrical drum 210 passes the raised vessel 202 .
  • the displacer 122 illustrated and discussed in this example is not limiting and is provided for explanatory purposes.
  • FIGS. 2A , 2 B and 2 C show an example of rolling the drum 212 from one side of the raised vessel 200 to the other side of the raised vessel 200 .
  • the drum 212 has not physically contacted the raised vessel 200 , which is filled with the fluid 210 .
  • the drum 212 has physically contacted and collapsed a portion of the raised vessel 200 .
  • a portion of the fluid 210 has been displaced from the raised vessel 200 to the region 108 , 110 , or 114 .
  • FIG. 3B the drum 212 has collapsed the entire raised vessel 200 , and the fluid 210 in the raised vessel 200 is in the region 108 , 110 , or 114 .
  • FIGS. 2A , 2 B and 2 C show a single drum 212 that moves in one direction to collapse the raised vessel 200 .
  • the more than one drum 212 can utilized and/or at least one of those drums 212 may move in the same or another direction, including multiple different directions (e.g., opposing directions, diagonal, zig zag, etc.) for collapsing the raised vessel 200 and/or other vessels and/or other structure.
  • the fluid releasing side 208 of the raised vessel 200 has the same or about the same dimensions as the opening in the region 108 , 110 , or 114 .
  • the opening in the region 108 , 110 , or 114 can be larger then the fluid releasing side 208
  • the opening in the region 108 , 110 , or 114 can be smaller then the fluid releasing side 208 .
  • portions of the fluid releasing side 208 are disposed against the surface 204 of the sample carrier 102 and thus the fluid 210 does not flow through these portions.
  • FIG. 5 schematically illustrates an example configuration in which a first fluid in a first vessel 200 1 is to be moved to a second vessel 200 2 .
  • sides 502 and 504 of the raised vessel 200 1 are generally compressible and collapsible sides (similar to side 202 of FIGS. 2-4 ) and a side 506 of the raised vessel 200 1 is a fluid releasing side (similar to side 208 of FIGS. 2-4 ).
  • the fluid releasing side 506 is disposed against a raised hollow channel 508 , which is raised above the surface 204 of the sample carrier 102 similar to that of the raised vessel 200 1 .
  • the raised hollow channel 508 provides a fluid pathway to the second raised vessel 200 2 .
  • the vessel 200 2 is open to the channel 508 .
  • the channel 508 and the vessel 200 2 may be separate component or parts of the same component.
  • a fluid releasing side (like sides 208 and 506 ) is disposed between the channel 508 and the vessel 200 2 .
  • the drum 212 physically contacts and collapses the raised vessel 200 1 , displacing the fluid therein into the channel 508 .
  • the drum 212 continues by collapsing the channel 508 , displacing the fluid therein into the raised vessel 200 2 .
  • the drum 212 can be used to collapse the raised vessel 200 2 , displacing the fluid therein into another channel or vessel (not shown).
  • FIG. 6 schematically illustrates a top down view of a portion of the sample carrier 102 .
  • the portion includes a plurality of raised vessels 200 fluidly connected via various channels 508 such that fluid can flow from vessel to vessel.
  • the drum 212 FIG. 2
  • the drum 212 can be used to sequentially move one or more fluids across a lane or channel of the sample carrier 102 , from raised vessel (region 106 , 108 , 110 , or 114 ) to vessel (region 108 , 110 , or 114 ).
  • One or more back check valves or flappers can be used to ensure the fluid only flows in a predetermined direction of interest.
  • the sample carrier 102 includes raised vessels 200 located on opposing sides of the sample carrier 102 .
  • the same or different drums 212 are used to collapse the raised vessels 200 and displace the fluid therein to the region 108 , 110 , or 114 .
  • both vessels are compressed at the same time, for example, when mixing the fluids therein in the region 108 , 110 or 114 .
  • the vessels are compressed at different times. For example, in one instance, one of the fluids is moved to the region 108 , 110 or 114 where it is processed. Afterwards, the other fluid is moved to the region 108 , 110 or 114 to be mixed with the processed fluid.
  • FIG. 8 illustrates an embodiment in which the first vessel 200 1 is as described in connection with FIG. 5 , and the second the first vessel 200 2 is a moving region 116 utilized to move the fluid out of the region 108 , 110 , or 114 .
  • the vessel 200 2 Before the drum 212 collapses the vessel 200 2 , the vessel 200 2 includes a fully distended raised sub-portion 202 A and a flexible or elastic second portion 802 A , which is disposed against the opening the region 114 or 110 as described in connection with the fluid releasing side 208 of FIG. 2 .
  • the flexible or elastic second portion 802 A expands under the pressure from drum 212 but does not open like the side 208 . Instead, in response to the drum 212 collapsing the vessel 200 2 , the fluid in the vessel 200 2 moves the flexible or elastic second portion 802 A into the region 108 , 110 , or 114 , displacing the fluid there from. This is shown in FIG. 8 through the partially collapsed raised sub-portion 202 B and the partially expended flexible or elastic second portion 802 B . Note also in this embodiment that the channels 508 are not raised from (i.e., they are internal to) the sample carrier 102 .
  • FIG. 9 illustrates a method for moving fluid in a sample carrier.
  • pressure is applied to a raised vessel of a sample carrier.
  • the pressure causes the raise vessel to compress towards the sample carrier.
  • a side of the vessel facing a mixing or processing region 114 or 108 in response to the pressure, opens, allowing fluid in the vessel to egress therefrom.
  • a fluid in the vessel in response to the pressure, is displaced from the vessel and into the mixing or processing region 114 or 108 .
  • the above acts are repeated one or more times to move the fluid to another region of the sample carrier.

Abstract

A sample carrier for carrying one or more samples to be processed by a sample processing apparatus includes at least one sample processing channel, the channel including a first region configured to carry a first fluid and at least a second region, wherein the first fluid in the first region is moved to the second region via compression of the first region. A sample processing apparatus for processing samples carried by sample carriers including at least one raised vessel carrying at least one a sample or a processing material includes a sample carrier receiving region configured to receive one of the sample carriers and a displacer configured to apply physical pressure to the raised vessel which causes compression of the raised vessel, thereby moving a fluid in the raised vessel to another region of the sample carrier for at least one of mixing or processing by the at least one processing component.

Description

    TECHNICAL FIELD
  • The following generally relates to a sample carrier and/or a sample carrier processing apparatus configured to process one or more samples carried by the sample carrier, and more particularly to moving a fluid (e.g., a sample, a processing material, etc.) through a channel of the sample carrier via direct displacement for processing the sample by the sample carrier processing apparatus.
  • BACKGROUND
  • Micro channel devices include, but are not limited to, devices which carry one or more small samples for processing and/or analysis by a sample processing apparatus. Such devices have included, for each sample, a plurality of processing regions, processing material chambers, micro-fluidic channels, valves, etc., and such apparatuses have included a plurality of processing stations for processing samples. One or more samples carried by a micro channel device are moved through the micro channel device, in series or parallel, via the micro-fluidic channels of the device from processing station to processing station of the sample processing apparatus, where the one or more samples are processed, with each of the samples being sequentially processed by corresponding processing regions using the processing materials from the chambers.
  • One approach for moving the samples and/or the processing materials in a micro channel device includes using a pressurized gas. Such a gas can be delivered by a compressor, a tank holding pressurized air, an air mover, and/or other source of pressurized gas through pneumatic valves sequenced by a controller or processor of the sample processing system. Unfortunately, such a micro channel device can be highly complex. For example, with such an approach, a multi-channel micro channel device may require hundreds of valves, which need to be synchronized, and corresponding valve lines to open and close the valves. Furthermore, there is no guarantee that the pressure applied actually moves a sample and/or processing material to its destination within the device. Moreover, there is no easy way to accurately track the movement and location of a sample and/or processing material as it moves though the device.
  • SUMMARY
  • Aspects of the application address the above matters, and others.
  • In one aspect, a sample carrier for carrying one or more samples to be processed by a sample processing apparatus includes at least one sample processing channel, the channel including a first region configured to carry a first fluid and at least a second region, wherein the first fluid in the first region is moved to the second region via compression of the first region.
  • In another aspect, a sample processing apparatus for processing samples carried by sample carriers including at least one raised vessel carrying at least one a sample or a processing material includes a sample carrier receiving region configured to receive the sample carriers and a displacer configured to apply physical pressure to the raised vessel which causes compression of the raised vessel, thereby moving a fluid in the raised vessel to another region of the sample carrier for at least one of mixing or processing by the at least one processing component.
  • In another aspect, a method includes controllably moving a fluid in a sample carrier via compression during DNA analysis.
  • Those skilled in the art will recognize still other aspects of the present application upon reading and understanding the attached description.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • The application is illustrated by way of example and not limitation in the figures of the accompanying drawings, in which like references indicate similar elements and in which:
  • FIG. 1 schematically illustrates an example sample carrier that includes raised fluid vessels holding samples and/or processing materials, and a sample processing apparatus configured to process samples carried by such sample carriers;
  • FIGS. 2A, 2B and 2C schematically illustrate a sub-portion of a processing channel of the sample carrier in connection with a sub-portion of the sample processing apparatus in which the sample processing apparatus moves samples and/or processing materials in the vessels in the sample carrier;
  • FIGS. 3 and 4 schematically illustrate variations of the raised fluid vessel relative to a processing or mixing region internal to the sample carrier;
  • FIG. 5 schematically illustrates an example in which a fluid in a raised vessel is moved to another raised vessel via a raised fluid channel of the sample carrier;
  • FIG. 6 schematically illustrates sequential movement of samples and/or processing materials in the raised vessels through a sub-portion of the sample carrier;
  • FIG. 7 schematically illustrates an example sample carrier that includes raised vessels on multiple sides of the sample carrier;
  • FIG. 8 schematically illustrates an example sample carrier that includes raised vessels that moves a fluid in the sample carrier; and
  • FIG. 9 illustrates an example method for moving fluid in a sample carrier.
  • DETAILED DESCRIPTION
  • FIG. 1 illustrates a sample processing apparatus 100 for processing one or more samples carried on a micro-channel device, such as a sample carrier 102, which is installed or inserted into a sample carrier receiving region 104 of the sample processing apparatus 100.
  • In the illustrated embodiment, the processing apparatus 100 is configured for DNA, enzymatic, protein, and/or other processing and/or analysis of at least one or more bio-sample located on the sample carrier 102. In another embodiment, the sample processing apparatus 100 is configured to process other bio-samples and/or non bio-samples on the sample carrier 102. An example of a suitable sample carrier 102 includes, but is not limited to, a biochip, a lab-on-a-chip, and/or other sample carrier.
  • The illustrated sample carrier 102 includes one or more sample regions 106 for carrying a sample to be processed, and one or more processing regions 108 for processing the one or more samples in the one or more sample regions 106. The sample carrier 102 further includes one or more processing agent regions 110 which carry one or more processing materials or agents 112 used to facilitate processing samples. The sample carrier 102 further includes one or more mixing regions 114 and/or one or moving regions 116 respectively for mixing a sample and an agent and/or one or more agents, and moving a sample, an agent, or a combination thereof in the sample carrier 102.
  • As described in greater detail below, at least one of the regions 106, 108, 110, 114, or 116 is configured as a raised vessel that is at least partially raised above a surface of the sample carrier 102. A fluid in such a vessel can be displaced or moved out of the vessel and to another portion of the sample carrier 102 by applying a suitable pressure, generally in a direction toward the sample carrier 102, to the raised portion of the vessel, which causes the vessel to compress and/or collapse towards the sample carrier 102, pushing the fluid out of an opposing side of the vessel, which is in fluid communication with other portions of the sample carrier 102 such that the fluid can move to the other portions of the sample carrier 102. With a moving vessel, the vessel is similarly compressed; however, the fluid remains therein and is solely used to move fluid out of another region.
  • The sample apparatus 100 includes one or more processing stations 120. Where configured for DNA analysis, such the processing stations 120 are configured to process one or more DNA samples in different lanes or channels of the sample carrier 102. In this instance, the processing stations 120 are configured to perform at least such functions as extract and purify DNA fragments, replicate and label the fragments with fluorescent dyes having known emission spectrums (or colors), separate the labeled fragments based on fragment size, for example, via electrophoresis, scan the fragments, and determine allele numbers for the DNA samples.
  • The sample processing apparatus 100 also includes a fluid displacer 122. As described in greater detail below, the fluid displacer 122 is configured to controllably apply suitable pressure to the raised vessel of at least one of the regions 106, 108, 110, 114, or 116 for moving the fluid held therein. This allows for moving samples and/or processing materials in the sample carrier 102 without using external pneumatics and/or external pneumatic valves, which may simplify the sample carrier 102 and reduce the cost thereof. In the illustrated embodiment, a drive system 124 drives the fluid displacer 122. The drive system 124 may include an AC or DC motor (e.g., linear, stepper, etc.), a drive (e.g., a ball screw, a lead screw, gears, a belt, a chain, a piston, etc.), and an encoder for tracking the position of the drive and/or the fluid displacer 122, directly and/or via the motor.
  • A controller 126 controls the drive system 124 and the one or more processing components 120. The illustrated controller 126 includes one or more processors that execute one or more computer readable instructions encoded on computer readable storage medium such as physical memory. Additionally or alternatively, at least one of the instructions can be carried by a carrier wave or signal. A user interface 128 provides an interactive user interface for presenting information to and/or receiving commands from a user of the sample processing apparatus 100 via buttons, knobs, a stylist, a digital pen, a mouse, a keypad, a keyboard, an audible command, etc.
  • Generally, the one or more vessels include fluid to be mixed, moved, combined, processed, etc. and can be thought of as formable blisters or bubbles of plastic or the like that stick above the surface of the sample carrier 102 and can be compressed to move fluid by direct displacement. In operation, the fluid displacer 122 comes along with sufficient force to compress and squash the one or more vessels, for example, in a linear fashion, to displace the fluid therein. As the fluid moves in the carrier 102, the location of the fluid can be determined based on the position of the fluid displacer 122, and the fluid can be mixed or combined with other fluids and/or unknowns to complete an experiment and quantify results. The controller 126 can accurately synchronize the sequence (e.g., the timing and logical flow) of fluid flow, and execution and lack of complex control elements renders a reliable and robust system.
  • In the illustrated embodiment, the processing apparatus 100 is configured to be a hand-held, portable apparatus that can be readily carried by an operator. In this configuration, the processing apparatus 100 can be carried and employed at the location where the sample is collected, if desired, or elsewhere. In this configuration, the processing apparatus 100 may also be configured such the operator can operate it with one hand. In another embodiment, the processing apparatus 100 is configured to be a stationary apparatus mounted to or placed on a table, the floor, etc. in a laboratory, office, or the like. In such a configuration, the processing apparatus 100 may be configured to remain at a particular location and process sample carriers 102 loaded therein.
  • FIGS. 2A, 2B and 2C schematically illustrate an example raised vessel 200 of the sample carrier 102 in connection with an example fluid displacer 212.
  • Initially referring to FIG. 2A, the illustrated raised vessel 200 includes a first or raised sub-portion 202, which extends from a major surface 204 of the sample carrier 102 above the major surface 204, forming a cavity 206 there between, and a second or fluid releasing sub-portion 208 that is attached to the first sub-portion 202 so as to close and seal the vessel 200. As such, the content in a vessel 200 can be contained and isolated, which may facilitate mitigating contamination and/or cross contamination in the sample carrier 102. The illustrated vessel 200 is filled with a fluid 210 such as a sample, a processing agent, or a combination thereof. For fluids other than the sample, the vessel 200 can be pre-loaded. Alternatively, such fluids can be added to the vessel 200.
  • The illustrated vessel 200 can represent any of the regions 106, 108, 110, or 114. Where the vessel 200 is a sample region 106, the vessel may include an ingress port for loading the sample in the vessel 200. Furthermore, the illustrated vessel 200 is disposed on the sample carrier 102 such that the second or fluid releasing sub-portion 208 of the vessel 200 is next to and/or is a side covering an opening of the region 106, 108, 110, or 114. The raised vessel 200 can be part of a separate layer (in roll form) attached to the sample carrier 102 or part of the same layer as the regions the region 106, 108, 110, or 114. Generally, the sample carrier 102 can be composed of one or more layers, with via or the like providing pathways between the one or more layers.
  • The raised sub-portion 202 is generally compressible and collapsible under first predetermined pressure by the fluid displacer 122. Under the same pressure, the fluid releasing sub-portion 208 is generally breakable, tearable or otherwise openable such that the fluid 210 in the raised vessel 200 can be displaced and egress out of the raised vessel 200. In the illustrated configuration, the fluid 210 is displaced out of the raised vessel 200 and into the region 108, 110, or 114. In another instance, displacing fluid out of the raised vessel 200 removes the fluid from the sample carrier 102.
  • In the illustrated embodiment, the raised vessel 200 has a hemisphere shape and the region 108, 110, or 114 has parallelepiped shape. However, the illustrated shapes (and relative sizes) are provided for explanatory purposes and are not limiting. As such, other three dimensional shape are contemplated herein. By way of non-limiting example, the raised vessel 200 can have parallelepiped shape and the region 108, 110, or 114 can have a hemisphere shape, the shapes of both the raised vessel 200 and the regions 108, 110, or 114 can be the same, etc.
  • The illustrated fluid displacer 122 includes a roller or rotatable drum 212 that is moved via a ball screw 214 driven by a linear stepper motor 230. More particularly, in the illustrated example, a first end region 218 of a support member 220 is affixed at a side 222 of the drum 212 at a rotational axis 224 that extends along a longitudinal axis of the drum 212. An opposing end region 226 of the support member 220 is affixed to a threaded ball screw nut 228 of the ball screw 214. The motor 230 is configured to rotate a threaded shaft 232 of the ball screw 214, which in turns translates ball screw nut 228, and hence the drum 214 along the a direction of the shaft 232.
  • The drum 212 is in physical contact with the surface 204 of the sample carrier 102 and moves across the surface 204. The motor 230 drives the shaft 232, under control of the controller 126, such that a force exerted by the drum 212 when the drum 212 physically contacts the raised sub-portion 202 of the raised vessel 200 the drum compresses and collapses the raised sub-portion 202, collapsing it towards the surface 204, pushing the fluid in the raised vessel 202 into the region 108, 110, or 114. As shown, in this embodiment, the collapsed sub-portion 202 remains in a substantially collapsed position after the cylindrical drum 210 passes the raised vessel 202. It is to be understood that the displacer 122 illustrated and discussed in this example is not limiting and is provided for explanatory purposes.
  • The combination of FIGS. 2A, 2B and 2C show an example of rolling the drum 212 from one side of the raised vessel 200 to the other side of the raised vessel 200. In FIG. 2A, the drum 212 has not physically contacted the raised vessel 200, which is filled with the fluid 210. In FIG. 2B, the drum 212 has physically contacted and collapsed a portion of the raised vessel 200. As a result, a portion of the fluid 210 has been displaced from the raised vessel 200 to the region 108, 110, or 114. In FIG. 3B, the drum 212 has collapsed the entire raised vessel 200, and the fluid 210 in the raised vessel 200 is in the region 108, 110, or 114.
  • FIGS. 2A, 2B and 2C show a single drum 212 that moves in one direction to collapse the raised vessel 200. However, it is to be understood the more than one drum 212 can utilized and/or at least one of those drums 212 may move in the same or another direction, including multiple different directions (e.g., opposing directions, diagonal, zig zag, etc.) for collapsing the raised vessel 200 and/or other vessels and/or other structure.
  • In FIGS. 2A, 2B and 2C, the fluid releasing side 208 of the raised vessel 200 has the same or about the same dimensions as the opening in the region 108, 110, or 114. As shown in FIG. 3, the opening in the region 108, 110, or 114 can be larger then the fluid releasing side 208, and as shown in FIG. 4, the opening in the region 108, 110, or 114 can be smaller then the fluid releasing side 208. In the latter case, portions of the fluid releasing side 208 are disposed against the surface 204 of the sample carrier 102 and thus the fluid 210 does not flow through these portions.
  • FIG. 5 schematically illustrates an example configuration in which a first fluid in a first vessel 200 1 is to be moved to a second vessel 200 2.
  • In this example, sides 502 and 504 of the raised vessel 200 1 are generally compressible and collapsible sides (similar to side 202 of FIGS. 2-4) and a side 506 of the raised vessel 200 1 is a fluid releasing side (similar to side 208 of FIGS. 2-4). The fluid releasing side 506 is disposed against a raised hollow channel 508, which is raised above the surface 204 of the sample carrier 102 similar to that of the raised vessel 200 1.
  • The raised hollow channel 508 provides a fluid pathway to the second raised vessel 200 2. In the illustrated embodiment, the vessel 200 2 is open to the channel 508. With such an embodiment, the channel 508 and the vessel 200 2 may be separate component or parts of the same component. In another embodiment, a fluid releasing side (like sides 208 and 506) is disposed between the channel 508 and the vessel 200 2.
  • Similar to that of FIGS. 2A, 2B and 2C, the drum 212 physically contacts and collapses the raised vessel 200 1, displacing the fluid therein into the channel 508. The drum 212 continues by collapsing the channel 508, displacing the fluid therein into the raised vessel 200 2. Once the fluid in raised vessel 200 2 is mixed, combined, processed, etc., the drum 212 can be used to collapse the raised vessel 200 2, displacing the fluid therein into another channel or vessel (not shown).
  • FIG. 6 schematically illustrates a top down view of a portion of the sample carrier 102. In this example, the portion includes a plurality of raised vessels 200 fluidly connected via various channels 508 such that fluid can flow from vessel to vessel. With this example, the drum 212 (FIG. 2) can be used to sequentially move one or more fluids across a lane or channel of the sample carrier 102, from raised vessel ( region 106, 108, 110, or 114) to vessel ( region 108, 110, or 114). One or more back check valves or flappers can be used to ensure the fluid only flows in a predetermined direction of interest.
  • In FIG. 7, the sample carrier 102 includes raised vessels 200 located on opposing sides of the sample carrier 102. In this example, the same or different drums 212 are used to collapse the raised vessels 200 and displace the fluid therein to the region 108, 110, or 114. In one instance, both vessels are compressed at the same time, for example, when mixing the fluids therein in the region 108, 110 or 114. In another instance, the vessels are compressed at different times. For example, in one instance, one of the fluids is moved to the region 108, 110 or 114 where it is processed. Afterwards, the other fluid is moved to the region 108, 110 or 114 to be mixed with the processed fluid.
  • FIG. 8 illustrates an embodiment in which the first vessel 200 1 is as described in connection with FIG. 5, and the second the first vessel 200 2 is a moving region 116 utilized to move the fluid out of the region 108, 110, or 114. Before the drum 212 collapses the vessel 200 2, the vessel 200 2 includes a fully distended raised sub-portion 202 A and a flexible or elastic second portion 802 A, which is disposed against the opening the region 114 or 110 as described in connection with the fluid releasing side 208 of FIG. 2.
  • The flexible or elastic second portion 802 A expands under the pressure from drum 212 but does not open like the side 208. Instead, in response to the drum 212 collapsing the vessel 200 2, the fluid in the vessel 200 2 moves the flexible or elastic second portion 802 A into the region 108, 110, or 114, displacing the fluid there from. This is shown in FIG. 8 through the partially collapsed raised sub-portion 202 B and the partially expended flexible or elastic second portion 802 B. Note also in this embodiment that the channels 508 are not raised from (i.e., they are internal to) the sample carrier 102.
  • FIG. 9 illustrates a method for moving fluid in a sample carrier.
  • At 902, pressure is applied to a raised vessel of a sample carrier.
  • At 904, the pressure causes the raise vessel to compress towards the sample carrier.
  • At 906, a side of the vessel facing a mixing or processing region 114 or 108, in response to the pressure, opens, allowing fluid in the vessel to egress therefrom.
  • At 908, a fluid in the vessel, in response to the pressure, is displaced from the vessel and into the mixing or processing region 114 or 108.
  • At 910, the above acts are repeated one or more times to move the fluid to another region of the sample carrier.
  • The application has been described with reference to various embodiments. Modifications and alterations will occur to others upon reading the application. It is intended that the invention be construed as including all such modifications and alterations, including insofar as they come within the scope of the appended claims and the equivalents thereof.

Claims (21)

1. A sample carrier for carrying one or more samples to be processed by a sample processing apparatus, the sample carrier comprising:
at least one sample processing channel, the channel including:
a first region configured to carry a first fluid; and
at least a second region, wherein the first fluid in the first region is moved to the second region via compression of the first region.
2. The sample carrier of claim 1, the sample carrier including a surface and the first region, comprising:
a first sub-portion extending from and raised above the surface, and enclosing a material free cavity; and
a second sub-portion that closes the first sub-portion, forming a close fluid vessel containing the first fluid.
3. The sample carrier of claim 2, wherein the first sub-portion is compressible and collapsible towards the surface in response to applying a predetermined force on the first sub-portion.
4. The sample carrier of claim 3, wherein the second sub-portion is configured to allow the first fluid to egress therefrom in response to applying the predetermined force on the first sub-portion.
5. The sample carrier of claim 4, wherein the second sub-portion is disposed next to the at least second region, and the first fluid is displaced from the first region to the second region in response to applying the predetermined force on the first sub-portion.
6. The sample carrier of claim 5, further comprising a plurality of serially linked additional regions, wherein the first fluid is sequentially moved from region to region in response to sequentially applying the predetermined force on the regions with the first fluid.
7. The sample carrier of claim 1, wherein the first second region includes one of a sample carrying region, a sample processing region, an agent region, or a fluid mixing region.
8. The sample carrier of claim 1, wherein the at least the second region includes a fluid mixing or a sample processing region.
9. The sample carrier of claim 1, wherein further comprising:
a third region configured to carry a third fluid, wherein the first and third fluids are concurrently moved to the second region via compression of the first and third regions.
10. The sample carrier of claim 1, further comprising:
a channel configured to route fluid from the first region to the at least second region, wherein the channel is raise above the surface.
11. The sample carrier of claim 1, the sample processing apparatus comprising:
a displacer; and
a controller, wherein the displacer, under control of the controller, applies pressure which causes the compression of the first region.
12. The sample carrier of claim 1, wherein the first region and the second region are different layers of the sample carrier, and the first region is affixed to the second region.
13. The sample carrier of claim 1, wherein the first region and the second region are part of a same layer of the sample carrier.
14. A sample processing apparatus for processing samples carried by sample carriers including at least one raised vessel carrying at least one a sample or a processing material, the sample processing apparatus, comprising:
a sample carrier receiving region configured to receive one of the sample carriers; and
a displacer configured to apply physical pressure to the raised vessel which causes compression of the raised vessel, thereby moving a fluid in the raised vessel to another region of the sample carrier for at least one of mixing or processing by the at least one processing component.
15. The sample processing apparatus of claim 14, further comprising:
a controller that controls the displacer to apply the pressure to the raised vessel.
16. The sample processing apparatus of claim 14, the displacer comprising:
a roller that rolls over the raised vessel, thereby compressing the raised vessel.
17. The sample processing apparatus of claim 14, wherein the roller sequentially rolls over a plurality of raised vessel, thereby moving the fluid from raise vessel to raised vessel.
18. The sample processing apparatus of claim 14, wherein the raised vessel includes a sample to be processed and the displacer moves the sample from the vessel to a mixing region or a processing region of the sample carrier.
19. The sample processing apparatus of claim 17, wherein the raised vessel includes a processing agent and the displacer moves the processing agent from the raised vessel to a mixing region or a processing region of the sample carrier.
20. The sample processing apparatus of claim 14, wherein the raised vessel includes a sample to be processed, and further comprising a second raised vessel including a processing agent, wherein the displacer moves the sample and the processing agent to a mixing region or a processing region of the sample carrier.
21. A method comprising:
controllably moving a fluid in a sample carrier via compression during DNA analysis.
US13/012,892 2011-01-25 2011-01-25 Sample carrier and sample carrier processing apparatus Abandoned US20120187021A1 (en)

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