TWI910071B - Vertical cassette and sample processing system - Google Patents

Abstract

Disclosed herein is a vertical cassette and a sample processing system comprising the same. The vertical cassette includes a body having an inlet channel, a receiving chamber, a plurality of reaction chambers, a plurality of drainage channels, a plurality of air channels, and a plate. The inlet channel is located at the upper portion of the body, the receiving chamber is disposed below the inlet channel, and the reaction chambers are arranged downstream of the receiving chamber. Each drainage channel is in fluid communication with the receiving chamber and a corresponding reaction chamber. Each air channel has one end in fluid communication with a reaction chamber and the other end extending upward to merge with the inlet channel. The plate is disposed in the receiving chamber and located between the inlet channel and the drainage channels.

Description

Vertical cassette and sample handling system

This invention relates to an upright cartridge, and more particularly to a microchannel cartridge that can complete the detection response without external power.

Micro-volume diagnostic reagents offer several advantages, enabling various clinical tests to be performed with minimal sample volume. Furthermore, these reagents can be developed to be combined with various immunoassay methods (e.g., direct detection, sandwich assay, or competitive assay) to complete a wide range of tests. For medical testing, micro-volume diagnostic reagents offer numerous advantages, including convenience, speed, and safety.

However, in the detection of microchannels for meristem analysis, external power is required to drive the sample fluid flow through pressure difference using a micro-pump, and microfluidic valves are used to control the flow direction of the sample fluid in the microchannel. Furthermore, the development of vertical cartridges still has limitations in the design of the flow channels, such as uneven fluid distribution or bubble accumulation. Therefore, it is evident that prior art microchannel cartridges still have many shortcomings in practical use and require further improvement.

In view of this, in order to improve the shortcomings of the prior art, there is an urgent need in this field for an improved upright cartridge to improve the deficiencies of the prior art.

This invention is intended to provide a simplified summary of the disclosure to enable the reader to have a basic understanding of it. This invention is not a complete overview of the disclosure and is not intended to identify important/key elements of the embodiments of the invention or to define the scope of the invention.

To overcome the shortcomings of prior art, this invention proposes a novel upright cartridge and a sample processing system comprising the upright cartridge. The upright cartridge of this invention, through its unique fluid and gas channel design, enables automatic splitting and detection of fluid samples without the need for external pressurization or driving devices, making it particularly suitable for trace nucleic acid or immunoassay detection, but this invention is not limited thereto.

One aspect of this invention relates to a vertical cartridge for processing fluid samples. The vertical cartridge comprises a main body, which has an inlet channel, a receiving slot, a plurality of reaction slots, a plurality of drainage channels, a plurality of venting channels, and a crossbar. The inlet channel is located above the main body for receiving fluid samples; the receiving slot is located below the inlet channel and communicates with the fluid inlet channel; the plurality of reaction slots are located downstream of the receiving slots; each drainage channel has one end connected to the fluid in the receiving slot and the other end connected to the fluid in each reaction slot; each venting channel has one end connected to a reaction slot and the other end extending above the main body and converging into the inlet channel, communicating with the fluid in the inlet channel. The crossbar is located within the receiving slot, below the inlet channel, and positioned between the inlet channel and each drainage channel.

According to one embodiment of the present invention, the receiving slot in the upright cartridge of the present invention further includes a guide channel in its structure. The guide channel has an inclined surface, such that the depth of the guide channel gradually decreases along a first direction, and the upper side of the guide channel is located below the inlet channel, while the lower side of the guide channel is connected to the horizontal plate. Furthermore, the guide channel may be further provided with a recessed portion, which is also provided along the first direction and gradually tapers into a cone shape, the recessed portion extending from below the inlet channel to the horizontal plate.

According to one embodiment of the present invention, each of the plurality of reaction tanks includes a receiving ring and a buffer channel, wherein the buffer channel is disposed around the receiving ring and communicates with any of the flow channels to regulate the flow velocity and direction of the fluid sample entering the reaction tank. Furthermore, in one embodiment, each flow channel has a ramp located near any of the buffer channels. Additionally, in a non-limiting embodiment, the plurality of reaction tanks are symmetrically arranged downstream of the receiving tank.

According to another embodiment of the present invention, the upright cartridge further includes at least one sealing film for covering the front and/or rear sides of the body to seal the cartridge and prevent contamination or liquid leakage.

In one specific embodiment, the reaction tank is a through hole penetrating the body and is covered by the sealing membrane.

According to another embodiment of the present invention, the rear side of the body corresponding to the reaction tank area is a flat area.

In another embodiment, the upright cartridge further includes at least one microbead disposed in any reaction tank.

In another specific embodiment, the end of the diversion channel that connects to the receiving tank fluid extends downward along the first direction of the body, then extends to one side of the body and then upward, and then connects to each of the plurality of reaction tank fluids.

Another embodiment of the present invention is a sample processing system comprising a vertical cartridge, a heating module, and an optical detection module as shown in any of the foregoing embodiments. The heating module is disposed on one side of the vertical cartridge and is used to heat the reaction tank in the cartridge, while the optical detection module is used to detect the reaction result of the fluid sample in the reaction tank.

After referring to the embodiments described below, those skilled in the art to which this invention pertains will be able to easily understand the basic spirit and other purposes of this invention, as well as the technical means and embodiments adopted by this invention.

To make the description of this disclosure more detailed and complete, the following illustrative descriptions of the embodiments and specific examples of the invention are provided; however, these are not the only forms of implementing or using the specific examples of the invention. The embodiments cover the features of multiple specific examples and the method steps and their order for constructing and operating these specific examples. However, other specific examples can also be used to achieve the same or equivalent functions and step sequences.

All numerical ranges and parameters disclosed herein (including but not limited to percentages, numerical values, ratios, etc.) should be understood to encompass all endpoints and subranges contained within that range. For example, when a range is described as "1 to 10", it should be considered to include 1 and 10 themselves, as well as any subranges of 1 to 10, and all integer values within that range (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10). Unless otherwise defined, such numerical ranges and their variations should be considered within the scope of this invention.

Although the numerical ranges and parameters used to define the broader scope of this invention are approximate, the relevant values in specific embodiments have been presented as precisely as possible. However, due to differences in experimental measurement methods, each value may inherently contain a certain degree of standard error or measurement bias. The term "approximately" as used herein generally means that the value falls within ±10%, 5%, 1%, or 0.5% of the stated value or range, or it may refer to a standard error range recognized by those skilled in the art. Unless otherwise expressly stated, all values used herein, except in specific embodiments, should be considered as "approximate" and are subject to the specific application.

The term "fluid sample" as used herein refers to a sample suitable for use with the upright cartridge 100 of the present invention, preferably a biological sample, such as a liquid sample containing biological samples. In one alternative embodiment, the biological sample may be blood, bodily fluids, saliva, or other secretions. In another alternative embodiment, the biological sample may be a treated biological sample, such as a biological sample pretreated with a buffer. In a specific embodiment, the fluid sample is a sample containing nucleic acids.

The "heating module" or "optical detection module" referred to herein is a mechanical device used to heat or detect the reaction results of the vertical cassette of the present invention within the system. The heating module and optical detection module can also be used in conjunction with a moving module to move laterally and/or longitudinally in three-dimensional space. The moving module can be composed of mechanical arms, slide rails, gears, or other related components.

Unless otherwise defined in this specification, the scientific and technical terms used herein have the same meaning as understood and commonly used by one of ordinary skill in the art to which this invention pertains. Furthermore, unless conflicting with the context, the singular nouns used herein include their plural forms, and vice versa.

This invention proposes a novel upright cartridge, a microchannel detection cartridge. Through its channel design, sample processing and/or detection reactions can be completed within the upright cartridge without the need for external pressure (e.g., fluid pressurization) from other devices. In a non-limiting embodiment, the upright cartridge of this invention can complete sample processing and/or detection reactions at atmospheric pressure. Furthermore, by integrating the inlet channel, sample channel, and venting channel, the upright cartridge of this invention effectively reduces the risk of bubble formation during sample loading while maintaining stable fluid sample flow within the channel, thus improving the smoothness and reliability of fluid sample flow within the upright cartridge. Furthermore, by integrating the ventilation channel into the inlet channel, this invention allows sample addition and exhaust to share the same channel, which can also reduce contamination during the testing process.

In addition, in a non-limiting embodiment, the fluid sample suitable for use in the vertical cartridge of the present invention is a liquid sample containing biological samples. In one embodiment, the amount of liquid sample added to the vertical cartridge of the present invention is at least about 500 μL, 600 μL, 700 μL, 800 μL, 900 μL, or 1000 μL. According to a specific embodiment of the present invention, the amount of liquid sample added to the vertical cartridge of the present invention is about 1000 to 1500 μL. In an alternative embodiment, the reaction volume in each reaction vessel is about 5 to 100 μL, preferably about 20 to 90 μL, and more preferably about 20 to 30 μL.

Figure 1A is a front schematic diagram of an upright cartridge 100 according to an embodiment of the present invention. As shown in Figure 1A, the upright cartridge 100 of the present invention is used to process a fluid sample and structurally includes a main body 110, an inlet channel 120, a receiving slot 130, a plurality of reaction slots 140, a plurality of drainage channels 150, a plurality of venting channels 160, and a cross plate 170. The upright cartridge 100 of the present invention adopts an upright design, that is, the cartridge of the present invention is used in an upright manner during operation and testing. This usage can reduce the volume occupied by the testing device and is helpful for places that require rapid testing or where the testing environment is limited. The inlet channel 120 is located above the main body 110, and the receiving slot 130 is located below the inlet channel 120 and is in fluid communication with the inlet channel 120. A plurality of reaction tanks 140 are disposed downstream of the receiving tank 130, and the receiving tank 130 and the reaction tank 140 are fluidly connected through a plurality of flow channels 150. Specifically, in the configuration of the receiving tank 130 and each flow channel 150, the lower edge of the receiving tank 130 is provided with an arc shape, one end of each flow channel 150 is connected to the fluid of the receiving tank 130, and the other end is connected to the fluid of each reaction tank 140, so as to guide the fluid sample from the receiving tank 130 to the reaction tank 140. The horizontal plate 170 is disposed below the inlet channel 120, particularly between the inlet channel 120 and the plurality of drainage channels 150. This allows the horizontal plate 170 to act as a buffer structure when fluid samples are added to the upright cartridge 100 from above the inlet channel 120, ensuring that the fluid sample is first guided through the horizontal plate 170 before entering each drainage channel 150. Furthermore, the horizontal plate 170 can also serve as an indicator line for the amount of fluid sample injected into the upright cartridge 100.

Furthermore, according to one embodiment of the present invention, the receiving groove 130 is further provided with a flow guide groove 131, which is located above the inlet channel 120 and connected to the horizontal plate 170 on its lower side. The flow guide groove 131 has an inclined surface 132, so that the depth of the flow guide groove 131 gradually decreases along the first direction A. Furthermore, the flow guide groove 131 may be further provided with a recessed portion 133, which can assist in the sample addition process when the fluid sample is added to the upright cartridge 100 through the sample dropper tip or pipette tip, providing a sample positioning effect and guiding the flow of the fluid sample to be concentrated on the horizontal plate 170 as much as possible. The recess 133 is structurally located at the inclined surface 132 and extends from below the inlet channel 120 to the horizontal plate 170, and is arranged along the first direction A and gradually tapers into a cone shape. Furthermore, please refer to Figure 1B, which is a cross-sectional view of the upright cartridge 100 shown in Figure 1A, to clearly show the arrangement of the guide channel 131 in the receiving slot 130 and the horizontal plate 170. The leading edges of the horizontal plate 170 and the receiving slot 130 are at the same level; that is, in Figure 1B, the horizontal plate 170 and the receiving slot 130 are at the same height, while the guide channel 131 is slightly lower than the horizontal plate 170. During the actual sample loading process, the fluid sample passes through the inlet channel 120, through the recess 133 and inclined surface 132 of the guide channel 131 of the receiving tank 130, and then through the horizontal plate 170 as a buffer. It flows out from the guide channel 131 from both sides of the horizontal plate 170, and then through the arc-shaped lower edge of the receiving tank 130 to each drainage channel 150, and then flows into the reaction tank 140. The overall structural design enables the fluid sample to be dispersed and reduces the risk of stagnation in specific areas of the receiving tank 130.

Referring again to Figure 1A, in this embodiment, the plurality of reaction tanks 140 have the same height. Furthermore, in terms of configuration, the plurality of reaction tanks 140 are not located directly below the receiving tank 130, but rather below the receiving tank 130 and located on both sides. In a non-limiting embodiment, the plurality of reaction tanks 140 is an even number, and is equally distributed on both sides of the receiving tank 130. In this embodiment, there are six plurality of reaction tanks 140, with three reaction tanks 140 on each of the two sides below the receiving tank 130. The number of flow channels 150 corresponds to the number of reaction tanks 140; six flow channels 150 are provided to guide the fluid sample from the receiving tank 130 into the reaction tank 140. As shown in the figure, the end of each of the drainage channels 150 that is connected to the fluid in the receiving tank 130 extends downward along the first direction A of the body 110, then extends to both sides of the body 110 and upward, and then connects to the fluid in each of the plurality of reaction tanks 140.

In an alternative embodiment, the plurality of reaction tanks 140 can simultaneously detect different or the same test items.

Furthermore, to enable the vertical cartridge 100 to flow fluid samples without external force, the vertical cartridge 100 of this invention is provided with a plurality of venting channels 160. One end of each venting channel 160 is connected to the fluid in the reaction tank 140, and the other end extends upward toward the body 110 and converges to the inlet channel 120, and is connected to the fluid in the inlet channel 120. Specifically, the vertical cartridge 100 of this invention has a hole 122 at the connection between the inlet channel 120 and the venting channel 160, so that the venting channel 160 is connected to the fluid in the inlet channel 120. Thus, during the fluid sample injection process, air is vented through the venting channel 160 and then through the inlet channel 120, so as to facilitate the smooth addition of the fluid sample into the vertical cartridge 100. Furthermore, the vertical cartridge 100 of this invention integrates the vent 160 and the inlet channel 120, so that the end of the vent 160 (i.e., the hole 122) is located on the inlet channel 120, thereby eliminating the need to open vent holes on the front or rear side of the cartridge 100. This design makes the vertical cartridge 100 use the inlet channel 120 as the only open opening, which not only simplifies the overall structure but also helps to reduce the risk of detection contamination and ensures the cleanliness and accuracy of the detection process. At the same time, through this configuration, the vertical cartridge 100 of this invention ensures that the fluid sample is unidirectionally arranged within the vertical cartridge 100, and the velocity of the fluid sample flowing from the receiving tank 130 to each reaction tank 140 is as close to uniform as possible.

In an alternative embodiment, the upright cartridge 100 can be sealed with a plastic cap or a film to prevent leakage of the fluid sample. In a specific embodiment, it can be a reaction tank 140 with a bottom, or a through hole penetrating the body 110, and then sealed with a sealing film.

Figures 2 and 3 illustrate reaction tank 140 according to different embodiments of the present invention. Specifically, the reaction tank 140 of the present invention is structurally provided with a receiving ring 142 and a buffer channel 144, wherein the buffer channel 144 is disposed around the receiving ring 142 and is fluid-connected to any of the guide channels 150. Furthermore, in order to regulate the flow rate of the fluid sample entering the reaction tank 140, improve the uniformity of the fluid sample entering the reaction tank 140, and avoid the generation or accumulation of bubbles, a ramp 146 is provided near the buffer channel 144 in any guide channel 150 of the vertical cartridge 100. In a non-limiting embodiment, the receiving ring 142 is a non-closed annular structure, and the opening size of each receiving ring 142 can be the same or different. The reaction tank 140 shown in FIG3 has the same structure as the reaction tank 140 in FIG2 in principle, so the same structure will not be described again. The vertical cartridge 100 of the present invention further includes at least one microbead 148 disposed in any reaction tank 140. In one embodiment, each reaction tank 140 is provided with one microbead 148. Those skilled in the art to which the present invention pertains should understand that the microbead 148 can be a magnetic microbead, a polymer microbead, or a glass microbead, and its surface can be modified to capture target molecules (e.g., antigens, antibodies, oligonucleotide probes, or other biometric elements) for detection within the reaction tank 140. For example, in nucleic acid detection applications, the microbeads 148 can also carry specific nucleic acid probes to capture target sequences and perform amplification or labeling reactions. Through the microbeads 148 inside the reaction tank 140, the reaction efficiency and sensitivity can be effectively improved, and various tests can be supported according to actual needs.

Figures 4A and 4B show an upright cartridge 200 according to another embodiment of the present invention. Specifically, the upright cartridge 200 is composed of a body 210 and two sealing films 215A and 215B. The body 210 is a single-layer sheet body, and its specific structure is generally the same as that of the upright cartridge 100 shown in Figure 1A. Therefore, the same components will not be described again. The difference is that the reaction groove 240 of the upright cartridge 200 is a through hole penetrating the body 210, and the area on the rear side of the upright cartridge 200 corresponding to the reaction groove 240 is a flat area 243. This design facilitates processing and heating. In one embodiment, the flat area 243 of the upright cartridge 200 is designed to facilitate use with the heating module or optical detection module of the sample processing system for bonding to those modules.

Referring again to Figure 4A, the front and rear sides of the body 210 of the upright cartridge 200 are sealed with sealing films 215A and 215B, respectively. In one embodiment, the sealing film is an optical film suitable for optical detection, which is generally composed of a substrate layer and an optical adhesive layer. The substrate layer includes, but is not limited to, polyethylene terephthalate, polycarbonate, or cycloolefin polymers, while the optical adhesive layer can be a pressure-sensitive adhesive (PSA) or a UV-curable optical adhesive.

Furthermore, referring to Figure 4C, after sealing, the vertical cartridge 200 of this invention has at least a transparent portion T on its front and/or rear sides for observing the sample volume and performing testing, particularly at the positions corresponding to the receiving slot 230 and the plurality of reaction slots 240. In actual use, the amount (e.g., volume) of the added fluid sample injected can be observed through the receiving slot 230 to determine if it is sufficient. In addition, the reaction slots 240 of the vertical cartridge 200 of this invention can be used with prior art optical detection equipment to detect the reaction results in the reaction slots 240.

Figure 5 is a schematic diagram of the configuration of a sample processing system 201 according to an embodiment of the present invention. The sample processing system 201 includes a vertical cartridge 200, a heating module 265, and an optical detection module 275 as shown in any of the above embodiments. In this embodiment, the component configuration of the vertical cartridge 200 is the same as that shown in Figures 4A to 4C, and therefore will not be described again here. Those skilled in the art will understand that the sample processing system 201 is electrically driven, and therefore a power supply module is electrically coupled to the heating module 265 and the optical detection module 275, although this is not shown in Figure 5. The heating module 265 and the optical detection module 275 are used to heat the fluid sample on the upright cartridge 200 and detect the reaction results in the upright cartridge 200, respectively.

In a preferred embodiment, the heating module 265 is a heating plate, and is actually configured to be located on one side of the upright cartridge 200 to heat the reaction tank 240 of the upright cartridge 200. In a specific embodiment, the heating module 265 is attached to one side of the upright cartridge 200, preferably the rear side, so that the heating area corresponds to the reaction tank 240 of the upright cartridge 200 to provide the temperature required for the reaction, for example, for a polymerase chain reaction. The optical detection module 275 is used to detect the fluid sample in the reaction tank 240 of the upright cartridge 200, and can be used to detect test results. For example, the optical detection module 275 can generate excitation light and perform detection to produce sample analysis results. Those skilled in the art will understand that the optical detection module 275 is a known optical detection module used for detecting immunoassays, molecular biological analyses, biochemical analyses, etc., and a suitable optical detection module can be selected according to the actual needs of use.

Therefore, the novel configuration of the upright cartridge and sample processing system proposed in this invention can reduce the volume occupied by biological samples during testing, and the detection reaction can be completed through a single cartridge, thus efficiently completing biomedical testing and analysis.

Although specific embodiments of the present invention have been disclosed in the above embodiments, they are not intended to limit the present invention. Those skilled in the art to which the present invention pertains may make various modifications and alterations to it without departing from the principles and spirit of the present invention. Therefore, the scope of protection of the present invention shall be determined by the scope of the appended patent application.

The main component symbols of this invention are listed below: 100, 200: Upright cartridge; 110, 210: Body; 120, 220: Inlet channel; 130, 230: Receiving slot; 140, 240: Reaction tank; 150: Drainage channel; 160: Ventilation channel; 170: Horizontal plate; 122: Hole; 131: Guide channel; 132: Sloping surface; 133: Recess; 142: Receiving ring; 144: Buffer channel; 146: Ramp; 148: Microbeads; 201: Sample processing system; 215A, 215B: Sealing film; 243: Flat area; 265: Heating module; 275: Optical detection module; T: Transparent area; A: First direction.

To make the above and other objects, features, advantages and embodiments of the present invention more apparent, the accompanying drawings are described as follows: Figures 1A and 1B are schematic diagrams and cross-sectional views of an upright cartridge 100 according to one embodiment of the present invention, respectively; Figures 2 and 3 are schematic diagrams of a reaction tank 140 according to different embodiments of the present invention, respectively; Figures 4A to 4C are schematic diagrams of an upright cartridge 200 according to another embodiment of the present invention; and Figure 5 is a schematic diagram of the configuration of a sample processing system 201 according to one embodiment of the present invention.

As is customary, the various features and components in the drawings are not drawn to scale. The drawing method is to present the specific features and components related to the invention in the best possible way. In addition, similar components/parts are referred to by the same or similar component symbols in different drawings.

100: Vertical cassette

110: The Body

120: Entrance Channel

122: Hole

130: Receiver slot

131: Flow channel

132: Incline

140: Reaction Tank

146: Climbing Slope

150: Drainage channel

160: Airway

170: Horizontal Plate

A: First direction

Claims (11)

A vertical cartridge for processing a fluid sample includes: a body comprising: an inlet channel for receiving the fluid sample and disposed above the body; a receiving slot disposed below the inlet channel and communicating with the fluid inlet channel; a plurality of reaction slots disposed downstream of the receiving slot; a plurality of drainage channels, each drainage channel having one end communicating with the fluid in the receiving slot and the other end communicating with the fluid in each of the plurality of reaction slots; a plurality of venting channels, each venting channel having one end communicating with the fluid in the reaction slot and the other end extending upwards from the body and converging to the inlet channel and communicating with the fluid in the inlet channel; and a crossbar disposed within the receiving slot, located below the inlet channel and between the inlet channel and the plurality of drainage channels. The upright cartridge as described in claim 1, wherein the receiving slot includes: a flow channel having an inclined surface such that the depth of the flow channel gradually decreases along a first direction, and the upper side of the flow channel is disposed below the inlet channel, and the lower side of the flow channel is connected to the cross plate. The upright cartridge as described in claim 2, wherein the flow channel further includes: a recess disposed along the first direction and tapering into a cone shape, the recess extending from below the inlet channel to the cross plate. The upright cartridge as described in claim 1, wherein the reaction grooves each include: a receiving ring; and a buffer channel disposed around the receiving ring and in communication with any of the drainage channels. As described in claim 4, in an upright cartridge, any of the drainage channels is provided with a ramp near the buffer channel. The upright cartridge as described in claim 1 further includes at least one sealing film for covering the front and/or rear sides of the body. The upright cartridge as described in claim 6, wherein the reaction grooves are a plurality of through holes penetrating the body and then covered by the sealing film. The upright cartridge as described in claim 1, wherein the rear side of the body forms a flat area corresponding to the reaction grooves. The upright cartridge as described in claim 1 further includes at least one microbead disposed in any of the reaction tanks. As described in claim 1, in the upright cartridge, the end of each of the drainage channels that communicates with the receiving tank fluid extends downward along a first direction of the body, then extends to one side of the body and upward along the body, and then communicates with each of the plurality of reaction tank fluids. A sample processing system includes: an upright cartridge as described in claim 1; a heating module disposed on one side of the upright cartridge for heating the reaction chambers of the upright cartridge; and an optical detection module for detecting fluid samples in the reaction chambers.