Polymer test cartridge mixer for cell lysis

A technology for testing boxes, polymer layers, applied in the direction of fluid mixers, containers for laboratory use, mixers, etc.

Active Publication Date: 2014-10-29
HONEYWELL INT INC
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AI-Extracted Technical Summary

Problems solved by technology

Merely adding reagents to blood samples may not be sufficient, resulting in in...
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Method used

[0021] In some embodiments, the width of the channel structure is on the order of about 1 mm, resulting in a total sample size of about 5-8 μL to sufficiently lyse the sample and fill the tes...
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Abstract

A multiple polymer layer test cartridge (100, 300) includes an input (110, 310) to receive a sample containing cells, multiple lysing channel structures (130, 140, 330, 340, 350, 360) on alternate layers of the multiple layer test cartridge coupled to each other to pass the sample in sequence between the lysing channel structures, and a test chamber (370) to receive the sample from the multiple lysing channel structures.

Application Domain

Flow mixersTransportation and packaging +4

Technology Topic

PhysicsTest chamber +4

Image

  • Polymer test cartridge mixer for cell lysis
  • Polymer test cartridge mixer for cell lysis
  • Polymer test cartridge mixer for cell lysis

Examples

  • Experimental program(1)

Example Embodiment

[0010] In the following description, reference is made to the accompanying drawings, which constitute a part of this document, in which specific embodiments that can be implemented are shown by way of example. These embodiments are described in sufficient detail to enable those skilled in the art to implement the present invention, and it should be understood that other embodiments may be adopted and structural and logical arrangements may be made without departing from the scope of the present invention. And electrical changes. Therefore, the following description of exemplary embodiments does not have a limiting meaning, and the scope of the present invention is defined by the appended claims.
[0011] The multiple fluid structures formed in the polymer layer of the test cartridge are used to mix reagents with red blood cells. The mixing that occurs within these structures helps lysis of red blood cells to release heme into the solution to be measured. The unique shape of the channel allows the sample to be repeatedly separated and recombined on the lysing agent, so that each cell is exposed to the reagent and the sample is completely mixed at the measurement point. The channels are connected to form a chaotic horizontal convection micromixer to aid cell lysis. In different embodiments, the cells can be red blood cells or other cells, and can even work against bacteria. Some channels can also lyse red blood cells without the use of lysing agents.
[0012] Can use CO 2 The laser cuts out the structure from the layer of polymer material. The structure is formed in at least two different layers, which are laminated together to form a test box. The lysing agent is packed into the structure and dried. The sample is loaded into the box and drawn into the measurement area at a known rate. Then, in one embodiment, optical density measurements are performed at wavelengths of 570 nm and 880 nm. In other embodiments, the measured wavelength and the type of measurement can be changed.
[0013] figure 1 It is a top view of the test box 100. In some embodiments, the test card 100 includes multiple layers of transparent materials, such as PET or other acrylic resin materials or suitable materials, which can be patterned into various liquid fluid transport characteristics. In some embodiments, the card 100 can be used to perform one or more blood tests with a small amount of blood. The blood or other liquid to be tested can be transported through one or more layers of the test card and ready for analysis by the test instrument into which the card is inserted. Various sensors can be used to test the liquid, such as a combination of light emitting diodes, lasers, and photoreceptors.
[0014] The test cassette includes an input opening 110 where the sample enters the cassette 100 and is held in the sample well 115. The sample moves into the first optional channel 120, which in some embodiments is about 1 mm wide. The first channel 120 can be used to ensure that air bubbles are removed from the sample as the sample advances through the first channel 120. The first channel 120 may be serpentine to provide a desired length, and is coupled to the first fluid structure 130 at the end 125, which is formed on a separate layer and fluidly coupled to the first channel 120 端部125.
[0015] The first fluid structure 130 (also referred to as a cracking channel structure) includes a substantially straight main channel having a base and a top, and two substantially parallel side channels of the same length extend substantially perpendicular to the top of the main channel. The second fluid structure 135 is coupled to the first fluid structure 130 and exists on a separate layer. The second fluid structure may have the same shape as the first fluid structure, but the side channels extend from the trunk in the opposite direction and are coupled to the lower part of the trunk of the first fluid structure to receive the sample. The channel structure is arranged such that the channel structure receives the sample at the ends of the two side channels away from its backbone. Additional fluid structures 140, 145 are similarly coupled to form multiple lysis channel structures on alternating layers of the multi-layer test cartridge, and the alternating layers are coupled to each other to sequentially transport samples between the lysis channel structures.
[0016] Although four cleavage channel structures are shown, in other embodiments as few as two, three, and more than four cleavage channel structures can be used. A typical embodiment includes 6, 7, 8 or more such structures to provide chaotic mixing of the sample and reagents, and the reagents may be provided in the first channel 120, in one or more lysis channel structures Or the dried reagent set in both. As mentioned above, in some embodiments, no reagent is needed to lyse some cells. If a reagent is used, the reagent can be placed anywhere along the channel or in the lysis channel structure. The cleavage structure causes the sample to make several 90-degree turns as the sample moves between structures successively formed on different layers of the test card, all in a single structure. The joined structures may be formed on adjacent layers, or in various embodiments may even be separated by one or more layers, which are designed to allow flow between the structures. Although some structures can be formed in the same layer, alternating layers seem to provide additional chaotic mixing by forcing the sample to make more turns as it advances through the structure.
[0017] Upon leaving the last lysis channel structure 145, the sample is sufficiently lysed and provided to a measurement chamber such as a test tube 150. The test tube 150 may also include a channel 155 that leads to an optional gas-permeable membrane 160 that stops the sample. In other embodiments, other devices for stopping the sample at a selected point can also be used. The membrane 160 is located between the layer where the channel 155 is located and the drain channel 165, which is discharged to the environment at 170. In order to move the sample through the fluid structure of the test card, positive or negative pressure can be applied between the end of the discharge channel 165 and the sample well. In one embodiment, a negative pressure is applied at 170, thereby causing the sample to move from the sample well toward the test tube 150.
[0018] figure 2 It is a top view and provides a larger view of an exemplary lysis channel structure 200. The structure 200 includes a substantially straight trunk portion 205 from which side channels 210 and 215 extend to form a structure called an "F" shaped structure. The structure 200 may include a diagonal portion 220 located between the bottom of the side channel 215 and the side of the trunk 205 closest to the base 222 of the trunk. When the sample moves through the channel structure, the diagonal portion 220 is adapted to reduce the formation of bubbles. In other embodiments, the diagonal portion 220 may be curved. In other embodiments, the side channel 210 may also include such a diagonal portion. In other embodiments, the diagonal portion 220 is optional, and the diagonal portion 220 may not be included.
[0019] In operation, when the sample enters the structure 200 at the ends 225, 230 of the side channels 210 and 215 away from the trunk, the sample is separated and then recombined in the lower portion 222 of the trunk 205. In one embodiment, the end of the lower portion 222 is coupled to the distal end 225 of the top channel 200 of the next lysis structure. For each successive lysis structure, the separation and recombination of the sample is repeated because the backbone of the upstream structure is connected to the distal end of the subsequent lysis structure. The additional layer changes between the cleavage structures further promote the chaotic mixing provided.
[0020] In other embodiments, other cleavage structures can be used. The "F" shape may have one or more additional side channels added. In other embodiments, an "X" shape may be used. Other embodiments may also adopt a microfluidic chaotic mixing structure, which provides separation, turning, and recombination of samples.
[0021] In some embodiments, the width of the channel structure is on the order of about 1 mm, resulting in a total sample size of about 5-8 μL, thereby sufficiently lysing the sample and filling the test chamber 150 before encountering the membrane 160. In different embodiments, the size of the channel can be varied according to the total available sample volume in order to optimize performance.
[0022] image 3 It is a top view of an alternative fluid cartridge 300 to help lyse red blood cells according to an exemplary embodiment. In some embodiments, the test card 300 includes multiple layers of transparent materials, such as PMMA, PET, or acrylic resin adhesives. Once cut out, they are assembled manually and squeezed to seal various microfluidic features (such as channels and test tubes). In some embodiments, the cartridge 300 can be used to perform one or more blood tests with a small amount of blood. The blood or other liquid to be tested can be transported through one or more layers of the test card and ready for analysis by the test instrument into which the card is inserted. Various sensors can be used to test the liquid, such as a combination of light emitting diodes, lasers, and photoreceptors.
[0023] The test cassette includes an input opening 310 at which the sample enters the cassette 300 and is held in the sample well 315. The sample moves into the first channel 320, which in some embodiments is approximately 1 mm wide. The first channel 320 may be used to ensure that air bubbles are removed from the sample as the sample advances through the first channel 320. The first channel 320 may be serpentine to provide a desired length. The first channel 320 is coupled to the first fluid structure 330, which is formed on a separate layer and is fluidly coupled to the first channel 320.
[0024] The first fluid structure 330 (also referred to as a cracking channel structure) includes a substantially straight main channel having a base and a top, and two substantially parallel side channels of the same length extend substantially perpendicular to the top of the main channel. The second fluid structure 335 is coupled to the first fluid structure 330 and exists on a separate layer. The second fluid structure may have the same shape as the first fluid structure, but the side channels extend from the trunk in the opposite direction and are coupled to the lower part of the trunk of the first fluid structure to receive the sample. The channel structure is arranged such that the channel structure receives the sample at the end away from the backbone of the side channel and provides the sample to the backbone of the next channel structure away from the side channel. Additional fluid structures 340 are similarly coupled to form multiple lysis channel structures on the alternating layers of the multi-layer test cartridge, and the alternating layers are coupled to each other to sequentially transport samples between the lysis channel structures. In one embodiment, one or more of the channels and channel mechanisms 330, 335, 340 contain a lysing agent mixed with the sample. The loop 345 extends the reaction time between the reagent and the blood, resulting in a more homogeneous sample being provided to the measurement area.
[0025] In one embodiment, three additional fluid structures 350, 355, 360 are provided after the loop 345. One or more of these structures may also contain a lysing agent. Although six lysis channel structures are shown, as few as two and more than six lysis channel structures can be used in other embodiments. A typical embodiment includes 6, 7, 8 or more such structures to provide chaotic mixing of the sample and reagents, and the reagents may be provided in the first channel 320, in one or more lysis channel structures Or the dried reagent set in both. The cleavage structure causes the sample to make several 90-degree turns as the sample moves between structures successively formed on different layers of the test card, all in a single structure. The joined structures may be formed on adjacent layers, or in various embodiments may even be separated by one or more layers, which are designed to allow flow between the structures. Although some structures can be formed in the same layer, alternating layers seem to provide additional chaotic mixing by forcing the sample to make more turns as it advances through the structure.
[0026] Upon leaving the last lysis channel structure 360, the sample is sufficiently lysed and is provided to a measurement chamber such as a test tube 370 via the channel 365. In one embodiment, the test tube 370 may also include a channel 375 that leads to an optional gas-permeable membrane 380 that stops the sample. Other devices can also be used to stop the sample so that the measurement chamber contains enough sample. The optional membrane 380 is located between the layer where the channel 375 is located and the drain channel 385, which is discharged to the environment at 390. In order to move the sample through the fluid structure of the test card, positive or negative pressure can be applied between the end of the discharge channel 375 and the sample well 370. In one embodiment, a negative pressure is applied at 390, causing the sample to move from the sample well toward the membrane 380.
[0027] Figure 4 It is a top view of an exemplary cracked "F"-shaped structure 400 according to an exemplary embodiment, and the exemplary size unit is μm.
[0028] Figure 5 Is according to an exemplary embodiment image 3 An exploded view of the cartridge 300 showing the individual layers 510, 520, 530, 540, 550, 560, and 570. Used with image 3 The same reference numerals are used to denote the features formed in these layers.
[0029] Example:
[0030] 1. A test box including:
[0031] The input part is used to receive a sample containing cells;
[0032] A plurality of lysis channel structures on alternating polymer layers of the multi-layer test cartridge, the alternating polymer layers being coupled to each other to sequentially transport the sample between the lysis channel structures; and
[0033] The test chamber is used to receive the sample from the multiple lysis channel structures.
[0034] 2. The test cartridge according to Example 1, wherein the lysis channel structure has the shape of the letter "F".
[0035] 3. The test box according to example 2, wherein the lysis channel structure includes a substantially straight main channel, the main channel has a base and a top, and two substantially parallel side channels of the same length are substantially perpendicular to the backbone The top of the channel extends.
[0036] 4. The test cartridge according to example 3, wherein the channel structure is arranged such that the first lysis channel structure receives the sample at the ends of the two side channels away from its backbone.
[0037] 5. The test cartridge according to example 4, wherein the second lysis channel structure is located on a different layer from the first lysis channel structure, and the ends of the two side channels of the second lysis channel structure are connected to The base of the backbone of the first channel structure receives samples.
[0038] 6. The test cartridge as described in Example 5, further comprising a plurality of additional sequential lysis channel structures, each of which has the same shape and is connected to the previous channel structure.
[0039] 7. The test cartridge of example 6, wherein at least two channel structures are separated by a loop channel configured to promote mixing of the reagent and the fluid.
[0040] 8. The test cartridge according to example 5, wherein the lysis channel structure has a diagonal portion located at the bottom of the side channel and one of the trunk closest to the base of the trunk between.
[0041] 9. The test box of example 8, wherein the diagonal portion is adapted to reduce the formation of bubbles when the sample moves through the channel structure.
[0042] 10. The test cartridge of any one of examples 1-9, further comprising a drain channel located on a different polymer layer from the test chamber, the drain channel being coupled to the environment.
[0043] 11. The test cartridge according to any one of examples 1-10, further comprising a reagent located in at least one of the input part and the selected lysis channel.
[0044] 12. The test box of any of examples 1-11, wherein the alternating layers are adjacent layers.
[0045] 13. The test cartridge of any of examples 1-12, wherein at least some of the alternating layers are separated by at least one layer.
[0046] 14. A multi-layer test box, including:
[0047] An input part for receiving a sample, the sample containing red blood cells and having reagents to mix with the sample;
[0048] A plurality of sequential "F"-shaped lysis channel structures on alternating layers of the multi-layer test cartridge, the alternating layers stacked on top of each other to sequentially transport the sample between the lysis channel structures and from the Said red blood cells release heme; and
[0049] The test chamber is used to receive the sample with the released heme from the plurality of lysis channel structures.
[0050] 15. The test box according to example 14, wherein the channel structure includes a substantially straight main channel having a base and a top, and two substantially parallel side channels of the same length are substantially perpendicular to the main channel The top extends.
[0051] 16. The test cartridge according to example 15, wherein the channel structure is arranged such that the first channel structure receives samples at the ends of two side channels away from its backbone, wherein the second channel structure is located at the same The first channel structure is on a different layer, and the ends of the two side channels of the second channel structure are coupled to receive samples from the base of the backbone of the first channel structure.
[0052] 17. A method including:
[0053] Receive blood samples;
[0054] Moving the blood sample through the first "F"-shaped fluid structure on the first polymer layer of the stacked multi-layer test box;
[0055] Moving the blood sample from the first "F"-shaped fluid structure to a second "F"-shaped fluid structure formed on the second layer of the multi-layer test cartridge; and
[0056] The blood sample is provided from the first and second fluid structures to a sampling test tube.
[0057] 18. The method of example 17, further comprising: moving the blood sample through a plurality of additional sequentially arranged "F"-shaped fluid structures on different layers of the test cartridge.
[0058] 19. The method of any of examples 17-18, further comprising: adding reagents to the blood sample before moving the blood sample through the "F"-shaped fluid structure.
[0059] 20. The method of example 19, wherein the reagent is added to the blood sample in one of the "F"-shaped fluid structures and is located between two of the "F"-shaped fluid structures The loop channel is mixed with the blood sample.
[0060] Although some embodiments have been described in detail above, other modifications are also possible. For example, the logic flow shown in the figure does not require the specific order or sequence shown to achieve the desired result. Other steps may be provided, or some steps may be removed from the described process, other components may be added to or removed from the described system. Other embodiments may be within the scope of the appended claims.

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