Bio-sample sequencing device and method for controlling concentration of bio-sample library introduced thereto

Abstract

A method for controlling the concentration of a bio-sample library introduced into a bio-sample sequencing device, according to an embodiment of the present disclosure, may comprise the steps of: a) processing a bio-sample inside a sub-chamber by using nucleic acid analysis techniques; b) acquiring a signal from the processed bio-sample; c) measuring the concentration of the bio-sample inside the sub-chamber on the basis of the signal; d) determining, on the basis of the measured concentration, whether it is necessary to adjust the concentration of a bio-sample scheduled to be accommodated or already accommodated in a main chamber; and e) adjusting the concentration of the bio-sample scheduled to be accommodated or already accommodated in the main chamber on the basis of the determination as to whether it is necessary to adjust the concentration.

Description

Bio sample sequencing device and method for controlling the concentration of a bio sample library input thereto

[0001] The present disclosure relates to a bio-sample sequencing device and a method for controlling the concentration of a bio-sample library introduced therein. Specifically, the present disclosure relates to a sequencing device that automatically adjusts the concentration of a library to perform optimized sequencing during the process of sequencing bio-samples such as DNA and RNA, and a method for controlling the concentration of a bio-sample library introduced therein.

[0002] DNA and RNA sequencing technologies are continuously evolving. Generally, sequencing is the process of analyzing the base sequence of DNA or RNA, and methods such as NGS (Next Generation Sequencing) are used. In this specification, sequencing refers to the process of analyzing the base sequence of DNA or RNA (the sequence of bases adenine (A), guanine (G), cytosine (C), and thymine (T)), and is distinguished from PCR (Polymerase Chain Reaction) and POC (Point of Care).

[0003] The general sequencing process involves first mixing the biological sample and reagents and placing them inside a flow cell (microfluidic chamber); then, as the reagents move sequentially, biochemical reactions are induced and fluorescent signals are detected. Subsequently, the sequence of the biological sample is determined by analyzing the detected fluorescent signals.

[0004] During this process, the biosample and reagents can be mixed via a manifold and fluid system. Once placed in the flow cell, the biosample can undergo pretreatment during the biochemical reaction (e.g., DNA denaturation and amplification). Subsequently, the process of attaching and removing fluorescent substances can be repeated hundreds of times depending on the sequencing purpose.

[0005] Maintaining the appropriate concentration of the library during the sequencing process is a critical factor, as it directly impacts the accuracy and efficiency of the sequencing. In manual concentration adjustment methods, users can control library concentrations through dilution and formula calculations following the sequencing instrument manufacturer's guidelines. However, variations based on proficiency may occur during this process, and failure to accurately adjust the concentration can lead to sequencing failure. Furthermore, while the optimal concentration may vary depending on the sequencing instrument, manual adjustment methods have the difficulty of reflecting these variations.

[0006] Meanwhile, there are also methods to control library concentrations using automated equipment. Representative examples include using kits such as Nextera XT or Illumina DNA Prep, or preparing libraries at set concentrations using automated sequencing library preparation devices. However, using automated equipment presents challenges, such as the need for separate space and the potential inclusion of unnecessary processes like library cutting, making it difficult to perform concentration control independently. Furthermore, since automated equipment applies generalized concentrations based on specific chemical standards, there are limitations in achieving optimal concentrations tailored to individual libraries or specific sequencing instruments.

[0007] A method for controlling the concentration of a biosample library introduced into a biosample sequencing device, disclosed as a technical means for achieving a technical task, may include: a) processing a biosample inside a sub-chamber using Nucleic Acid Analysis Techniques; b) acquiring a signal from said processed biosample; c) measuring the concentration of said biosample inside the sub-chamber based on said signal; d) determining whether concentration control is required for a biosample that is scheduled to be received in a main chamber or has already been received based on said measured concentration; and e) controlling the concentration of said biosample that is scheduled to be received in the main chamber or has already been received based on said determination of whether concentration control is required.

[0008] A biosample sequencing device disclosed as a technical means for achieving a technical task may include one or more main chambers for receiving a first biosample library, a sub-chamber separated from the main chamber for receiving a second biosample library smaller than the first biosample library, a sensor unit for receiving a signal from the sub-chamber, a concentration control unit for controlling the concentration of a first biosample that is to be received or is already received in the main chamber, and a processor electrically connected to the sensor unit and the concentration control unit, wherein the processor processes the second biosample inside the sub-chamber using Nucleic Acid Analysis Techniques, and when the sensor unit receives a signal from the processed second biosample, measures the concentration of the second biosample inside the sub-chamber based on the signal, determines whether concentration control is required for the first biosample that is to be received or is already received in the main chamber based on the measured concentration, and controls the concentration control unit to control the concentration of the first biosample that is to be received or is already received in the main chamber based on the determination of whether concentration control is required. there is.

[0009] A computer-readable recording medium disclosed as a technical means for achieving a technical task has a program recorded thereon for performing a method to control the concentration of a bio-sample library introduced into the aforementioned bio-sample sequencing device on a computer, and the method can be performed on a computer.

[0010] FIG. 1 is a schematic diagram illustrating one side of a bio-sample sequencing device according to one embodiment of the present disclosure.

[0011] FIGS. 2a and FIGS. 2b are drawings for illustrating examples of the arrangement structure of the components forming the bio-sample sequencing device shown in FIGS. 1, respectively.

[0012] Figure 3 is a diagram illustrating the movement of a biosample or reagent inside the biosample sequencing device shown in Figure 1.

[0013] FIGS. 4a to 4e are drawings illustrating examples of mixing a bio sample or reagent through rotation inside the bio sample sequencing device shown in FIG. 1.

[0014] FIG. 5 is a diagram illustrating an example of mixing a bio sample or reagent through vibration inside the bio sample sequencing device shown in FIG. 1.

[0015] FIG. 6 is a diagram illustrating another example of mixing a bio sample or reagent through rotation inside the bio sample sequencing device shown in FIG. 1.

[0016] FIG. 7 is a schematic diagram illustrating another aspect of a bio-sample sequencing device according to one embodiment of the present disclosure.

[0017] FIG. 8 is a flowchart for explaining the operation of the bio-sample sequencing device illustrated in FIG. 7.

[0018] FIG. 9 is a flowchart illustrating the operation of controlling the concentration of a biosample in the biosample sequencing device illustrated in FIG. 7.

[0019] FIG. 10 is a flowchart illustrating an example of a series of operations for measuring the concentration of a biosample of the biosample sequencing device illustrated in FIG. 7.

[0020] FIG. 11 is a flowchart illustrating another example of a series of operations for measuring the concentration of a biosample of the biosample sequencing device illustrated in FIG. 7.

[0021] FIGS. 12a and FIGS. 12b are drawings illustrating examples of configurations used for diluting biosamples in the biosample sequencing device illustrated in FIG. 7.

[0022] In describing the present disclosure, technical details that are well known in the technical field to which the present disclosure belongs and are not directly related to the present disclosure are omitted. This is intended to convey the essence of the present disclosure more clearly without obscuring it by omitting unnecessary explanations. Furthermore, the terms described below are defined considering their functions within the present disclosure, and these definitions may vary depending on the intentions or practices of the user or operator. Therefore, their definitions should be based on the content throughout this specification.

[0023] For the same reason, some components in the attached drawings have been exaggerated, omitted, or schematically depicted. Additionally, the dimensions of each component do not entirely reflect their actual dimensions. Identical or corresponding components in each drawing have been assigned the same reference numbers.

[0024] The advantages and features of the present disclosure, and the methods for achieving them, will become clear by referring to the embodiments described below in detail together with the accompanying drawings. However, the present disclosure is not limited to the embodiments disclosed below but may be implemented in various different forms. The disclosed embodiments are provided to ensure that the disclosure of the present disclosure is complete and to fully inform those skilled in the art of the scope of the disclosure. An embodiment of the present disclosure may be defined according to the claims. Throughout the specification, the same reference numerals indicate the same components. Furthermore, in describing an embodiment of the present disclosure, if it is determined that a detailed description of a related function or configuration might unnecessarily obscure the essence of the present disclosure, such detailed description is omitted. Additionally, terms described below are defined considering their functions in the present disclosure, and these may vary depending on the intentions or conventions of the user or operator. Therefore, their definitions should be based on the content throughout the specification.

[0025] In one embodiment, each block of the flowcharts and combinations of the flowcharts may be executed by computer program instructions. Computer program instructions may be loaded onto a processor of a general-purpose computer, a computer for special purposes, or other programmable data processing equipment, and the instructions executed through the processor of the computer or other programmable data processing equipment may create means for performing the functions described in the flowchart block(s). Computer program instructions may also be stored in computer-available or computer-readable memory that can be directed toward the computer or other programmable data processing equipment to implement functions in a specific manner, and instructions stored in computer-available or computer-readable memory may produce a manufactured item containing instruction means for performing the functions described in the flowchart block(s). Computer program instructions may also be loaded onto a computer or other programmable data processing equipment.

[0026] Additionally, each block of the flowchart may represent a module, segment, or part of code containing one or more executable instructions for executing a specified logical function(s). In one embodiment, the functions mentioned in the blocks may occur out of order. For example, two blocks shown in succession may be executed substantially simultaneously or in reverse order depending on the function.

[0027] In one embodiment of the present disclosure, the term “part” used may refer to software or hardware components such as a Field Programmable Gate Array (FPGA) or an Application Specific Integrated Circuit (ASIC), and the “part” may perform a specific role. Meanwhile, the “part” is not limited to software or hardware. The “part” may be configured to reside in an addressable storage medium or may be configured to run one or more processors. In one embodiment, the “part” may include components such as software components, object-oriented software components, class components, and task components, as well as processes, functions, attributes, procedures, subroutines, segments of program code, drivers, firmware, microcode, circuits, data, databases, data structures, tables, arrays, and variables. Functions provided through a specific component or a specific “part” may be combined or separated into additional components to reduce their number. Additionally, in one embodiment, the “part” may include one or more processors.

[0028] Before describing specific embodiments of the present disclosure, the meanings of terms frequently used in this specification are defined.

[0029] A 'Bio Sample' may include a nucleic acid sequence composed of DNA (Deoxyribonucleic Acid) or RNA (Ribonucleic Acid). The bio sample covered in the present invention may undergo a preprocessing process before performing sequencing, and the process may include steps such as nucleic acid extraction, purification, fragmentation, reverse transcription, and adapter ligation.

[0030] A 'Bio Sample Library' refers to a collection of DNA or RNA fragments ready for sequencing. In other words, a Bio Sample Library loaded into a sequencing device is referred to as a 'Sequencing Library,' which can mean bio samples (DNA or RNA) that have undergone special processing (pretreatment) to enable sequencing. The library preparation process may include steps such as (i) fragmentation of the bio samples, (ii) attachment of adapters or barcodes, and (iii) PCR amplification or concentration adjustment. In the case of RNA sequencing, RNA samples are first converted into cDNA (complementary DNA) through a reverse transcription process, after which the library can be prepared in a manner similar to DNA sequencing. Finally, the completed library is loaded into the flow cell of the sequencing device to perform base sequence analysis.

[0031] Embodiments of the present disclosure are described below with reference to the attached drawings so that those skilled in the art can easily implement them. However, the present disclosure may be embodied in various different forms and is not limited to the embodiments described herein.

[0032] Embodiments of the present disclosure will be described in detail below with reference to the drawings.

[0033] In the following, we will describe one aspect of a bio-sample sequencing device capable of efficiently performing mixing of a DNA or RNA library (bio-sample) for sequencing with reagents, or between reagents.

[0034] FIG. 1 is a schematic diagram illustrating one side of a bio-sample sequencing device according to one embodiment of the present disclosure.

[0035] Referring to FIG. 1, a bio sample sequencing device (1) according to one embodiment may include a reaction platform (100), a cartridge array (200), a fluid system (300), a connection part (400), and a mixing promotion part (500).

[0036] The reaction platform (100) is where the bio sample library is mounted. When the bio sample library is mounted on the reaction platform (100), reactions between various substances, including the bio sample, can occur. Accordingly, base sequence analysis of the bio sample can be performed.

[0037] For example, the reaction platform (100) may include a flow cell. The flow cell is a core component of the reaction platform (100) and may be a structure in which a biosample library is mounted and reagents are supplied sequentially while base sequence analysis is performed.

[0038] The flow cell can be designed with a structure based on a microfluidic system and may include multiple reaction channels or microchannels that regulate fluid flow. The flow cell can be designed to precisely control the flow of reagents, induce biochemical reactions with biological samples, and ultimately detect and analyze fluorescent or electrical signals.

[0039] Generally, flow cells are fabricated from glass, silicon, or polymer materials, and their surfaces may be chemically coated to immobilize or amplify DNA or RNA libraries. Depending on the sequencing method, the role and structure of the flow cell can be designed differently.

[0040] A cartridge array (200) refers to an array composed of multiple cartridges. Each cartridge included in the cartridge array (200) can accommodate a bio sample or a reagent required for the sequencing process. In this case, the bio sample may exist in a form mixed with a buffer solution. Hereinafter, the bio sample, buffer solution, and reagent required for the sequencing process may be collectively referred to as "various substances."

[0041] In the sequencing process, mixing libraries (bio-samples) with reagents, or mixing reagents among themselves, is essential. In particular, to enhance the accuracy and efficiency of the sequencing reaction, it is often necessary to optimize reaction conditions by pre-mixing specific combinations of substances.

[0042] Typical cases requiring mixing include, first, the need to mix the library with a denaturation reagent to convert it into single-stranded DNA before fixing the biosample (library) in a flow cell. Additionally, enzymes (e.g., DNA polymerase, ligase, etc.) are generally stored with high concentrations of salt or glycerol to maintain high stability, and since an appropriate buffer environment is required for the reaction to proceed, the process of mixing the enzymes with the reaction reagent is required before the reaction.

[0043] In the case of fluorescent reagents, they are stored separately to maintain the stability of the fluorescent substance, and prior to the reaction, they must be mixed with appropriate reaction reagents to create an environment optimized for fluorescent signal detection. Additionally, certain reagents, such as enzymes, are often provided in a lyophilized state to facilitate long-term storage and transportation; therefore, it is essential to dissolve and activate the reagent by mixing it with an appropriate buffer solution before the reaction.

[0044] In some reactions, it is necessary to mix reagents containing catalysts with enzymes. Since catalysts may be required only for specific reaction steps, a method is applied where enzymes and catalysts are stored separately according to the reaction stage and mixed when needed. Additionally, to reduce frozen shipping costs, a method is utilized where reagents are frozen and shipped at high concentrations, and then mixed with a buffer solution that can be shipped at room temperature prior to the reaction to achieve the final reaction conditions. In particular, in high-throughput sequencing environments, the mixing of frozen reagents and the separate shipping of buffer solutions are essential requirements.

[0045] Previously, mixing was generally performed by the user manually or by using a pump inside the sequencing instrument. In manual mixing methods, the user gathers reagents into a single container and mixes them using methods such as pipetting, vortex mixing, magnetic stirring, or shaking. However, these methods have the problem that mixing efficiency can vary depending on the operator's skill level and are difficult to apply in high-throughput sequencing processes.

[0046] The methods of using pumps within sequencing instruments can be broadly divided into mixing within the reagent tank and mixing along the flow path. Mixing within the reagent tank involves transferring the liquid to be mixed into a specific tank and then applying flow using a pump to perform the mixing; in this method, the inner diameter of the ejection needle is sometimes reduced to maximize the flow effect. On the other hand, mixing along the flow path involves alternately filling the fluids requiring mixing and then attempting to mix them using pump flow within a relatively large volume of the flow path.

[0047] However, these existing methods have limitations in effectively mixing large volumes of libraries and reagents. In particular, as sequencing instruments become larger, it is becoming difficult to guarantee uniform mixing using conventional methods. Furthermore, as the use of freeze-dried reagents for room-temperature storage increases, the process of mixing freeze-dried reagents with buffers becomes inevitably required; however, it is difficult to secure sufficient mixing efficiency with current methods. Therefore, there is a need to develop new methods and devices capable of rapidly and uniformly mixing large volumes of reagents and biological samples.

[0048] According to one embodiment, the cartridge array (200) may include a plurality of storage cartridges (210) and one or more mixed cartridges (2200).

[0049] The storage cartridge (210) is configured to store various substances. Multiple storage cartridges (210) may be arranged to store various substances individually, and each storage cartridge (210) may store only one type of substance. In this case, the one type of substance may be used as a concept including a 'bio sample mixed with a buffer solution'.

[0050] The mixing cartridge (220) is configured to provide a place where various substances are mixed. Various substances stored individually in the storage cartridge (210) are moved to the mixing cartridge (220) by the fluid adjustment unit (310) described later, and then can be mixed in the mixing cartridge (220) in a combination desired by the user.

[0051] According to one embodiment, since the cartridge array (200) is positioned outside the fluid system (300), the mixing cartridge (220) can be positioned outside the fluid adjustment unit (310). Accordingly, the degree of freedom to more flexibly adjust the position and capacity of the mixing cartridge (220) can be improved. When a large-capacity mixing cartridge (220) is positioned according to the user's needs, various substances can be introduced into the mixing cartridge (220) in large quantities. Accordingly, a large amount of substances can be mixed at once inside the mixing cartridge (220), so the time used to mix various substances inside the bio-sample sequencing device (1) can be effectively shortened.

[0052] The fluid system (300) is configured to be connected to the cartridge array (200) to control the flow of various substances. At this time, the various substances whose flow is controlled by the fluid system (300) may exist in the form of a fluid. For example, a bio sample may exist in the form of a fluid by being mixed with a buffer.

[0053] The fluid system (300) may include a fluid control unit (310) and a fluid transfer unit (320). The fluid control unit (310) and the fluid transfer unit (320) may cooperate with each other to effectively mix the bio sample and reagent and transfer them to the reaction platform (100).

[0054] The fluid control unit (310) can control the flow of various substances in relation to the cartridge array (200). For example, the fluid control unit (310) may include a manifold. The manifold is a structure containing multiple fluid paths and can be designed to guide multiple fluids individually or in combination to a specific path. Additionally, the manifold may include elements such as valves, flow regulators, and pumps, thereby controlling the flow rate of each fluid. Furthermore, the manifold can selectively open or close specific substances as needed to control the mixing of fluids at an appropriate timing.

[0055] According to this, the fluid control unit (310) can temporarily hold various substances or fluids, distribute them to other components inside the bio-sample sequencing device (1), and control them to be mixed at appropriate times and in appropriate proportions.

[0056] The fluid control unit (310) can control the flow to guide various fluids supplied from the storage cartridge (210) to the mixing cartridge (220). At this time, the fluid control unit (310) can precisely control the flow and movement path of various materials moving from multiple storage cartridges (210) to one or more mixing cartridges (220) through the fluid control unit (310).

[0057] Through this, the fluid control unit (310) can control the mixing of the bio sample and the denaturation reagent in a precise ratio, or allow the enzymes and reaction reagents to be combined under appropriate conditions. Additionally, the fluid control unit (310) can control the fluid flow so that the fluorescent reagent and the reaction reagent are mixed uniformly.

[0058] The fluid control unit (310) can perform functions such as temperature control, pressure control, and flow profiling to optimize reaction conditions, in addition to simple fluid flow control. Through this, the fluid control unit (310) can create a precise reaction environment required in the sequencing process and maintain optimal conditions in processes such as enzyme activation and fluorescent labeling reaction promotion.

[0059] Additionally, the fluid control unit (310) controls the flow rate so that various substances can be mixed in a constant ratio in the mixing cartridge (220), and may selectively supply a specific fluid as needed. For example, if a catalyst-containing reagent needs to be introduced only at a specific reaction step, the fluid control unit (310) can control the supply of the corresponding fluid to prevent unnecessary mixing.

[0060] The fluid transfer unit (320) can perform the function of transferring various materials mixed in the mixing cartridge (220) to the reaction platform (100). The fluid transfer unit (320) can generally be composed of a pump, a valve, and a flow path, and can operate by applying pressure or suction to move a specific fluid smoothly.

[0061] The fluid transfer unit (320) can fluidly connect the fluid control unit (310) and the reaction platform (100). In this case, 'fluid connection' may mean that elements are connected so that fluid can pass through and flow. The movement of material between each cartridge (210, 220) included in the cartridge array (200) and the fluid system (300) is controlled by the fluid control unit (310), and the movement of material between the fluid system (300) and the reaction platform (100) can be controlled by the fluid transfer unit (320). However, depending on the embodiment, the fluid transfer unit (320) may be involved in the movement of material between the cartridge array (200) and the fluid control unit (310).

[0062] According to one embodiment, the fluid system (300) can precisely control the flow of the fluid and selectively supply various substances to the mixing cartridge (220) according to reaction conditions so that various substances can be mixed at an optimal ratio. Accordingly, the fluid system (300) can supply the various substances mixed at an optimal ratio to the reaction platform (100) to maximize the reaction efficiency within the reaction platform (100).

[0063] Additionally, the fluid system (300) can mix a large amount of material at once in conjunction with a large-capacity mixing cartridge (220) placed outside the fluid control unit (310). With this in mind, the fluid system (300) can be designed to operate stably even in a sequencing environment that processes a large amount of bio samples.

[0064] The connecting portion (400) is configured to connect each cartridge (210, 220) included in the cartridge array (200) with the fluid adjustment portion (310). The connecting portion (400) has a tubular shape and may include a hollow so that various materials can pass through. The hollow formed in the connecting portion (400) may extend long along the longitudinal direction of the connecting portion (400) along the tubular connecting portion (400).

[0065] Various substances or fluids can move through the hollow formed in the connecting part (400). In one example, a substance stored in the storage cartridge (210) can move to the fluid adjustment part (310) through the connecting part (400). In another example, a substance temporarily present in the fluid adjustment part (310) can move to the mixing cartridge (220) through the connecting part (400).

[0066] Multiple connecting parts (400) may be arranged. Each of the multiple connecting parts (400) can connect each cartridge (210, 220) and the fluid adjustment part (310). Accordingly, the number of connecting parts (400) and the number of cartridges (210, 220) are the same, and each connecting part (400) can connect the cartridge (210, 220) and the fluid adjustment part (310) that correspond to it one-to-one.

[0067] The mixing promoter (500) is a component that assists in mixing so that various substances inside the mixing cartridge (220) are evenly mixed. That is, the mixing promoter (500) can induce the various substances contained inside the mixing cartridge (220) to be uniformly mixed. Accordingly, various substances present inside the bio sample sequencing device (1) can be uniformly mixed inside the mixing cartridge (220) by the mixing promoter (500).

[0068] Meanwhile, although not illustrated, a bio sample sequencing device (1) according to one embodiment may include a sensor unit (not illustrated) and a processor (not illustrated).

[0069] The sensor unit can perform the role of detecting signals generated from the reaction platform (100). As an example, in the case of fluorescence-based sequencing, the sensor unit can detect fluorescent signals associated with each base (A, T, G, C) using a fluorescence detector. As another example, in the case of electrical signal-based sequencing, the sensor unit can read base information by measuring changes in current of DNA or RNA passing through a specific channel. Signal data acquired from the sensor unit can be transmitted to a processor for analysis.

[0070] The processor can perform the role of extracting base sequence information based on data received from the sensor unit. The processor performs base calling to read specific bases by analyzing signal intensity and can improve sequencing accuracy by applying error correction algorithms. Data analyzed by the processor can be converted into a bioinformatics file format and stored or transmitted to a server.

[0071] The sensor unit and the processor can cooperate in real time to process data. This enables the sequencing reaction to proceed smoothly and allows for high-accuracy DNA sequencing analysis.

[0072] Below, the relative arrangement relationship between the cartridge array (200) and the fluid adjustment unit (310) inside the bio sample sequencing device (1) will be described.

[0073] FIGS. 2a and FIGS. 2b are drawings for illustrating examples of the arrangement structure of the components forming the bio-sample sequencing device shown in FIGS. 1, respectively.

[0074] Referring to FIGS. 2a and 2b, a bio sample sequencing device (1) according to one embodiment may include a reaction platform (100), a cartridge array (200), a fluid system (300), and a connection part (400). Regarding the configuration and effects of the bio sample sequencing device (1), detailed descriptions that overlap with those described in FIG. 1 will be omitted.

[0075] According to one embodiment, a plurality of storage cartridges (210) and one or more mixing cartridges (220) may be combined to form a cartridge array (200). However, for convenience of explanation, one storage cartridge (210) and one mixing cartridge (220) are each shown, and the embodiment is not limited to the number of storage cartridges (210) and mixing cartridges (220) shown in the drawing.

[0076] As illustrated, each cartridge (210, 220) included in the cartridge array (200) may be arranged in a line in one direction. However, the arrangement of the storage cartridge (210) and the mixing cartridge (220) is not limited to that illustrated, and each cartridge (210, 220) may form the cartridge array (200) in various arrangements.

[0077] Referring to FIG. 2a, a fluid control unit (310) may be positioned on the upper side of a cartridge array (200). In this case, each cartridge (210, 220) may include an open area (200a) that is open to the upper side. Accordingly, the open area (200a) of each cartridge (210, 220) is open toward the fluid control unit (310), and the fluid control unit (310) may come into contact with the material contained in each cartridge (210, 220) through the open area (200a).

[0078] Each connecting part (400) can extend from the fluid control part (310) into the interior of each cartridge (210, 220) through the open area (200a). Accordingly, the interior of each cartridge (210, 220) and the fluid control part (310) can be fluidly connected by each connecting part (400). Thus, various substances such as bio samples or reagents can move between each cartridge (210, 220) and the fluid control part (310) through the connecting part (400).

[0079] Meanwhile, as the fluid control unit (310) is positioned on the upper side of the cartridge array (200), various substances temporarily contained in the fluid control unit (310) can move into the interior of each cartridge (210, 220) along with gravity. At this time, the fluid control unit (310) can control the movement of substances or fluids present inside the fluid control unit (310) to each cartridge (210, 220) using a valve. Accordingly, the fluid control unit (310) can prevent substances or fluids from flowing indiscriminately into the interior of each cartridge (210, 220) along with gravity.

[0080] On the other hand, the material contained in each cartridge (210, 220) cannot rise against gravity to the fluid control unit (310). In this case, the fluid control unit (310) can assist in the movement of the material or fluid using a pump. That is, the fluid control unit (310) can lift the material contained in each cartridge (210, 220).

[0081] Referring to FIG. 2b, the fluid control unit (310) may be positioned on the lower side of the cartridge array (200). In this case, each cartridge (210, 220) may include an outlet (200b) formed on the bottom surface. Accordingly, the outlet (200b) of each cartridge (210, 220) is open toward the fluid control unit (310), and the fluid control unit (310) may come into contact with the material contained in each cartridge (210, 220) through the outlet (200b).

[0082] Each connecting part (400) can connect the outlet (200b) and the fluid control part (310). Accordingly, the interior of each cartridge (210, 220) and the fluid control part (310) can be fluidly connected by each connecting part (400). Thus, various substances such as bio samples or reagents can move between each cartridge (210, 220) and the fluid control part (310) through the connecting part (400).

[0083] Meanwhile, as the fluid control unit (310) is positioned on the lower side of the cartridge array (200), various substances contained in each cartridge (210, 220) can move to the fluid control unit (310) by gravity. At this time, the fluid control unit (310) can control the movement of substances or fluids present inside each cartridge (210, 220) to the fluid control unit (310) by using a valve. Accordingly, the fluid control unit (310) can prevent substances or fluids from flowing indiscriminately into the fluid control unit (310) by gravity.

[0084] On the other hand, the material temporarily contained in the fluid control unit (310) cannot rise against gravity to each cartridge (210, 220). In this case, the fluid control unit (310) can use a pump to assist in the movement of the material or fluid. That is, the fluid control unit (310) can lift the material contained inside toward each cartridge (210, 220).

[0085] Meanwhile, according to the embodiment, not only the fluid adjustment unit (310) but also the fluid transfer unit (320) can control the movement of various substances between each cartridge (210, 220) and the fluid adjustment unit (310). That is, the fluid transfer unit (320) can control the movement of various substances moving through each connection unit (400) using a pump and a valve.

[0086] When multiple cartridges (210, 220) constituting the cartridge array (200) are arranged, it may be difficult for the fluid control unit (310) to control the flow of material or fluid for all cartridges (210, 220). In this case, the fluid transfer unit (320) assists the fluid control unit (310), so that the fluid system (300) can stably control the flow of material or fluid moving between each cartridge (210, 220) and the fluid control unit (310).

[0087] Below, we will explain the process of mixing various substances stored in the storage cartridge (210) in the mixing cartridge (220).

[0088] Figure 3 is a diagram illustrating the movement of a biosample or reagent inside the biosample sequencing device shown in Figure 1.

[0089] Referring to FIG. 3, a bio sample sequencing device (1) according to one embodiment may include a storage cartridge (210), a mixing cartridge (220), a fluid adjustment unit (310), and a connection unit (400). Regarding the configuration and effects of the bio sample sequencing device (1), detailed descriptions that overlap with the above descriptions will be omitted.

[0090] According to one embodiment, different substances may be stored in each of the plurality of storage cartridges (210). For example, a first substance may be contained in the first storage cartridge (211), a second substance may be contained in the second storage cartridge (212), and a third substance may be contained in the third storage cartridge (213).

[0091] At this time, since each storage cartridge (211, 212, 213) is not connected to each other, each material stored in each storage cartridge (211, 212, 213) may not mix with each other.

[0092] For example, if reagents or bio-samples are stored in a pre-mixed state, the likelihood of chemical degradation or non-specific side reactions occurring over time may increase. In particular, sensitive substances such as enzymes or fluorescent reagents require specific storage conditions, and if they react with other components prematurely, it may be difficult to maintain desired performance. According to one embodiment, since each substance is stored individually without mixing, the stability of the substance is maintained, and the accuracy and reproducibility of the reaction can be improved.

[0093] Furthermore, individual storage methods offer the flexibility to mix substances in desired combinations when needed and can be advantageous for optimizing reaction conditions. For example, storing catalysts or auxiliary reagents required only for specific reaction steps individually prevents unnecessary activation or consumption before the reaction occurs. This approach facilitates the long-term storage of reagents and allows the properties of each substance to be maintained until the moment of reaction, thereby enhancing the reliability and efficiency of sequencing.

[0094] Meanwhile, when a pretreatment process for sequencing or sequencing is in progress, the bio sample or reagent needs to be mixed and supplied to a reaction platform (e.g., reaction platform (100) of FIG. 1). Each material stored in each storage cartridge (211, 212, 213) can be moved to a mixing cartridge (220) via a fluid control unit (310) when mixing is required.

[0095] Each substance contained in each storage cartridge (211, 212, 213) can be moved to the fluid adjustment unit (310) through each connection part (400). At this time, the fluid adjustment unit (310) may include a mixing channel (315) connected to each connection part (400). Accordingly, the first substance, the second substance, and the third substance moved from each storage cartridge (211, 212, 213) to the fluid adjustment unit (310) can come into contact with each other on the mixing channel (315).

[0096] Each substance may simply be in contact with the mixing channel (315) and remain unmixed. That is, each substance may remain in a 'pre-mixing contact state'. Each substance in the pre-mixing contact state, temporarily accommodated in the fluid control unit (310), may be moved to the mixing cartridge (220) through the connection unit (400).

[0097] In the mixing cartridge (220), each substance can be mixed with each other. In this case, mixing may mean that two or more substances are uniformly mixed to form a single phase or uniform state. That is, mixing can be distinguished in meaning from simply the contact of each substance.

[0098] Inside the mixing cartridge (220), each substance can be mixed by being evenly mixed by a mixing promoter (e.g., the mixing promoter (500) of FIG. 1). When it is determined that each substance is sufficiently mixed after a predetermined time, the ‘mixed various substances’ contained in the mixing cartridge (220) can be moved back to the fluid adjustment unit (310) through the connection unit (400).

[0099] That is, the fluid control unit (310) can supply various materials to a mixing cartridge (220) located outside the fluid control unit (310) through each connecting unit (400), and can also recover various materials mixed in the mixing cartridge (220) through each connecting unit (400). The mixed materials can be transferred from the fluid control unit (310) to the reaction platform (100) through the fluid transfer unit (320).

[0100] Below, various examples of a mixing promotion unit (500) that induces the mixing of various substances contained within a mixing cartridge (220) will be described.

[0101] FIGS. 4a to 4e are drawings illustrating examples of mixing a bio sample or reagent through rotation inside the bio sample sequencing device shown in FIG. 1.

[0102] Referring to FIGS. 4a to 4e, a bio sample sequencing device (1) according to one embodiment may include a mixing cartridge (220), a fluid adjustment unit (310), a connection unit (400), and a mixing promotion unit (500). Regarding the configuration and effects of the bio sample sequencing device (1), detailed descriptions that overlap with the above descriptions will be omitted.

[0103] For the sake of simplification of the drawing, the storage cartridge (e.g., storage cartridge (210) of FIG. 1) of the cartridge array (e.g., cartridge array (200) of FIG. 1) is omitted, and only one mixing cartridge (220) is shown.

[0104] According to one embodiment, each cartridge (210, 220) may be opened in one direction (e.g., upward). For example, similar to the appearance shown in FIG. 2a, the fluid control unit (310) of FIG. 4a through 4e is positioned above the mixing cartridge (220), and the mixing cartridge (220) may include an open area that is opened upward.

[0105] According to one embodiment, each cartridge (210, 220) may include a sealing plug (200s) for closing an open area. Since the sealing plug (200s) covers each cartridge (210, 220), various materials contained inside each cartridge (210, 220) can be protected from contamination that may occur when exposed to the external environment.

[0106] Each connection (400) may be positioned to penetrate the sealing plug (200s). For example, the sealing plug (200s) may include a hole through which each connection (400) can penetrate. The connection (400) penetrating the sealing plug (200s) may extend from the fluid control unit (310) into the interior of each cartridge (210, 220).

[0107] According to an embodiment, when a component (e.g., a wing) of the mixing promotion unit (500) is mounted on each connecting part (400), the hole formed in the sealing plug (200s) may have a size large enough to allow not only the connecting part (400) but also a component of the mixing promotion unit (500) to pass through.

[0108] According to one embodiment, the mixing promotion unit (500) may include a mechanical rotary actuator (510) for rotating each connecting unit (400) around an axis (e.g., the longitudinal central axis of the mixing cartridge (220)) that extends in one direction (e.g., upward) where the mixing cartridge (220) is open. Unless otherwise noted below, the longitudinal central axis of the mixing cartridge (220) may mean the 'rotational central axis of the connecting unit (400)'.

[0109] A mechanical rotary actuator (510) is an actuator that mechanically generates rotational motion and can be classified into hydraulic, pneumatic, electric (motor-based), cam type, etc. depending on the operating method, but the embodiment is not limited to an actuator of a specific type.

[0110] The mechanical rotary actuator (510) may be placed inside the fluid control unit (310), but is not limited thereto and may be placed in various positions capable of rotating the connecting unit (400). The mechanical rotary actuator (510) can rotate various materials inside the mixing cartridge (220) by rotating the connecting unit (400). Thus, various materials can be mixed evenly.

[0111] In this case, each connecting part (400) not only serves as a passage for the movement of material or fluid connecting the fluid adjustment part (310) and the mixing cartridge (220), but also serves to mix the materials contained inside the mixing cartridge (220).

[0112] The mixing promotion section (500) may include a rotary link (520) connecting a mechanical rotary actuator (510) and a tubular connecting section (400). The rotary link (520) may correspond to a connecting structure that transmits the rotational motion of the mechanical rotary actuator (510) to the connecting section (400).

[0113] Referring to FIG. 4a, a mechanical rotary actuator (510) can rotate a connecting part (400a) connected via a rotary link (520) about the longitudinal central axis of the connecting part (400a). At this time, the longitudinal central axis of the connecting part (400a) may be the same as the longitudinal central axis of the mixing cartridge (220). Substances or fluids located around the connecting part (400a) can be evenly mixed by rotating along the connecting part (400a).

[0114] Meanwhile, the sealing plug (200s) illustrated in FIG. 4a may not include a separate hole. In this case, each connection (400a) may include a fine point portion formed at one end to puncture the sealing plug (200s). Each connection (400a) may extend through the sealing plug (200s) via the fine point portion into the interior of each cartridge (210, 220). According to this, until the sealing plug (200s) is punctured through the connection (400a), each cartridge (210, 220) can be completely sealed to prevent internal contamination.

[0115] Referring to FIG. 4b, each connecting part (400b) may be positioned to be inclined with respect to an axis extending in one direction (e.g., upward) where the mixing cartridge (220) is open (e.g., the longitudinal central axis of the mixing cartridge (220) shown by a dotted line in FIG. 4b).

[0116] At this time, the mechanical rotary actuator (510) can rotate the connecting part (400b) based on the ‘longitudinal central axis of the mixing cartridge (220)’ rather than the ‘longitudinal central axis of the connecting part (400b).’

[0117] As the connecting part (400b) is tilted, the distance from the longitudinal central axis of the mixing cartridge (220) to the end of the connecting part (400b) increases, thereby increasing the radius of rotation of the connecting part (400b). When the connecting part (400b) rotates while tilted, the trajectory (rotational trajectory) through which the end of the connecting part (400b) passes becomes larger, so the rotating connecting part (400b) can occupy a larger space.

[0118] That is, compared to the structure shown in FIG. 4a, the rotation radius of the connecting part (400b) is larger, so the material or fluid present inside the mixing cartridge (220) can be mixed more evenly by rotating more along the connecting part (400b).

[0119] According to one embodiment, the mixing promotion unit (500) may further include a wing (530) mounted on the outer surface of each connecting unit (400) to rotate around each connecting unit (400) as a central axis and mix various materials. By mounting the wing (530) on the connecting unit (400), a rotation radius equal to the 'distance from the rotational central axis of the connecting unit (400) to the end of the wing (530)' can be secured.

[0120] Referring to FIG. 4c, the wing (530a) may include a paddle shape that protrudes radially from the outer side of each connecting part (400c). By mounting the paddle-shaped wing (530a) on the connecting part (400c), a rotation radius can be secured to the extent that the wing (530a) protrudes radially from the rotation center axis of the connecting part (400c). Accordingly, the material or fluid present inside the mixing cartridge (220) can be mixed more evenly by rotating more significantly along the paddle-shaped wing (530a).

[0121] Meanwhile, as illustrated in FIG. 4c, the paddle-shaped wing (530a) is basically a flat structure, but may have a curved shape depending on the embodiment. For example, the wing (530) may include a propeller shape.

[0122] A curved wing can improve mixing performance by inducing a more efficient flow during the mixing process of a substance or fluid. Specifically, the curved wing can increase mixing efficiency by effectively forming vortices while smoothly controlling the flow of the substance or fluid, and can facilitate smooth flow, especially when mixing high-viscosity fluids or slurries (solid + liquid).

[0123] Furthermore, curved blades disperse the fluid over a wider area to promote uniform mixing and minimize localized stagnation, thereby reducing mixing time. In addition, they can efficiently transfer energy while maintaining balance during rotation, which is expected to reduce power consumption. Therefore, curved blades offer the advantage of simultaneously improving mixing uniformity and energy efficiency in fluid mixing devices.

[0124] Referring to FIG. 4d, the wing (530b) may include a helical shape that wraps around each connection (400d) along the longitudinal direction of each connection (400d). The helical structure can move a material or fluid simultaneously in the axial and radial directions when rotated.

[0125] By mounting a helical wing (530b) on the connecting part (400d), the mixing area can be expanded and the mixing uniformity can be improved. In addition, by inducing the fluid flow in a spiral to form a strong vortex, the mixing of high-viscosity fluids or heterogeneous materials can be made smoother.

[0126] Compared to flat wings, helical wings (530b) can reduce the residence time of the fluid and induce efficient flow, thereby shortening the mixing time. Furthermore, the helical shape can effectively disperse resistance within the fluid to increase energy efficiency, while also preventing the accumulation of sediment. Due to these characteristics, the connecting part (400d) equipped with helical wings (530b) can enable more uniform and efficient fluid mixing.

[0127] Meanwhile, according to an embodiment, the wing (530) may include a downward-facing blade portion to puncture the sealing plug (200s). The wing (530), mounted on the outer surface of each connection (400), can penetrate the sealing plug (200s) through the blade portion. Accordingly, the connection (400) and the wing (530) can extend into the interior of each cartridge (210, 220). According to this, until the sealing plug (200s) is punctured through the wing (530), each cartridge (210, 220) can be completely sealed to prevent internal contamination.

[0128] Referring to FIG. 4e, each connecting part (400e) may be positioned at a predetermined distance from the longitudinal center axis of the mixing cartridge (220) shown by a dotted line. At this time, two mechanical rotary actuators (510) of the mixing promotion part (500) may be positioned.

[0129] The first mechanical rotary actuator (511) can rotate the connecting part (400e) based on the 'longitudinal central axis of the connecting part (400e)' which is spaced a predetermined distance from the longitudinal central axis of the mixing cartridge (220). At this time, the first mechanical rotary actuator (511) can be connected to the connecting part (400e) through a rotary link (520).

[0130] The second mechanical rotary actuator (512) can rotate the connecting part (400e), the rotary link (520), and the first mechanical rotary actuator (511) based on the longitudinal central axis of the mixing cartridge (220).

[0131] The connecting part (400e) and the helical wing (530b) mounted thereon are primarily rotated by the first mechanical rotary actuator (511) to mix surrounding material or fluid, and are secondarily rotated by the second mechanical rotary actuator (512) to mix the material or fluid being mixed once more. According to this structure, the mixing of material or fluid inside the mixing cartridge (220) can be maximized.

[0132] FIG. 5 is a diagram illustrating an example of mixing a bio sample or reagent through vibration inside the bio sample sequencing device shown in FIG. 1.

[0133] Referring to FIG. 5, a bio sample sequencing device (1) according to one embodiment may include a mixing cartridge (220), a fluid adjustment unit (310), a connection unit (400), and a mixing promotion unit (500). Regarding the configuration and effects of the bio sample sequencing device (1), detailed descriptions that overlap with the above descriptions will be omitted.

[0134] For the sake of simplification of the drawing, the storage cartridge (e.g., storage cartridge (210) of FIG. 1) of the cartridge array (e.g., cartridge array (200) of FIG. 1) is omitted, and only one mixing cartridge (220) is shown.

[0135] According to one embodiment, the mixing promoter (500) may include a vibration actuator (540) for vibrating the mixing cartridge (220). The vibration actuator (540) is an actuator that generates vibration and may be classified according to the operating method as an eccentric mass (ERM), linear resonance (LRA), piezoelectric method, magnetofluid method, etc., but the embodiment is not limited to an actuator of a specific type.

[0136] The vibration actuator (540) can rotate various materials inside the mixing cartridge (220) by transmitting vibrations into the interior of the mixing cartridge (220). Thus, various materials can be mixed evenly. In addition, even when the mixing cartridge (220) is sealed, vibrations transmitted from the outside can mix the materials contained inside the mixing cartridge (220), thereby protecting the internal materials or fluids from contamination caused by external exposure as much as possible.

[0137] As described, the vibration actuator (540) may be placed inside the fluid control unit (310), but is not limited thereto and may be placed at various locations within the mixing cartridge (220) capable of transmitting vibration. Additionally, the fluid control unit (310) is placed above the mixing cartridge (220), but the arrangement between the two components is not limited thereto, and as long as the vibration actuator (540) can transmit vibration within the mixing cartridge (220), the arrangement between the two components can be made in various ways.

[0138] The mixing promotion unit (500) may include a contact member (550) connecting the vibration actuator (540) and the mixing cartridge (220). For example, the contact member (550) may be made of a spring, an elastic body, a damping layer, etc.

[0139] One end of the contact member (550) contacts the vibration actuator (540), and the other end of the contact member (550) can contact a part of the mixing cartridge (220). Thus, vibrations generated from the vibration actuator (540) can be transmitted to the mixing cartridge (220) through the contact member (550).

[0140] According to one embodiment, since the vibration is transmitted indirectly by placing a contact member (550) between the vibration actuator (540) and the mixing cartridge (220) without direct contact, various advantages can be obtained.

[0141] First, by utilizing the contact member (550) to adjust the intensity and frequency of the vibration, the vibration optimized for the mixing cartridge (220) can be transmitted, thereby preventing unnecessary excessive vibration and efficiently transmitting the vibration.

[0142] Additionally, the contact member (550) can mitigate mechanical shock caused by vibration, thereby improving the durability of the mixing cartridge (220) and the vibration actuator (540) and reducing wear caused by repetitive vibration.

[0143] In addition, the contact member (550) can perform a vibration damping function to reduce noise and minimize vibration interference with surrounding parts. Furthermore, the contact member (550) can adjust the vibration transmission path to ensure that vibrations are uniformly dispersed during fluid mixing, thereby providing a more stable mixing effect and maximizing mixing efficiency.

[0144] Meanwhile, when the vibration actuator (540) is positioned inside the fluid adjustment unit (310), the mixing promotion unit (500) may include a buffer member (560) connecting the fluid adjustment unit (310) and the mixing cartridge (220). The buffer member (560) may be made of a spring, an elastic body, a damping layer, etc., similar to the contact member (550).

[0145] According to one embodiment, a vibration actuator (540) disposed inside a fluid adjustment unit (310) transmits vibration by contacting a mixing cartridge (220) through a contact member (550), but vibration transmission can be optimized by placing a separate cushioning member between the fluid adjustment unit (310) and the mixing cartridge (220).

[0146] The damping member (560) can prevent excessive concentration of vibration in the mixing cartridge (220) and distribute it evenly to provide a more stable vibration effect. Additionally, the damping member (560) prevents unnecessary resonance to regulate the transmission of optimal vibration in the desired frequency band, and can improve structural stability by reducing mechanical interference between the fluid adjustment unit (310) and the mixing cartridge (220).

[0147] Furthermore, the buffer member (560) helps the fluid adjustment unit (310) and the mixing cartridge (220) operate independently, enabling smooth assembly and separation between components even in a replaceable structure.

[0148] FIG. 6 is a diagram illustrating another example of mixing a bio sample or reagent through rotation inside the bio sample sequencing device shown in FIG. 1.

[0149] Referring to FIG. 6, a bio sample sequencing device (1) according to one embodiment may include a mixing cartridge (220), a fluid adjustment unit (310), a connection unit (400), and a mixing promotion unit (500). Regarding the configuration and effects of the bio sample sequencing device (1), detailed descriptions that overlap with the above descriptions will be omitted.

[0150] For the sake of simplification of the drawing, the storage cartridge (e.g., storage cartridge (210) of FIG. 1) of the cartridge array (e.g., cartridge array (200) of FIG. 1) is omitted, and only one mixing cartridge (220) is shown.

[0151] As illustrated, each cartridge (210, 220) may be opened downward. For example, similar to the configuration shown in FIG. 2b, the fluid control unit (310) of FIG. 6 may be positioned below the mixing cartridge (220), and the mixing cartridge (220) may include an outlet formed on the bottom surface. However, the embodiment is not limited to an embodiment in which each cartridge (210, 220) is opened downward. Depending on the embodiment, each cartridge (210, 220) may be opened upward.

[0152] According to one embodiment, the mixing promotion unit (500) may include a rotatable stirring element (570) disposed inside the mixing cartridge (220) and a non-contact rotary actuator (580) disposed outside the mixing cartridge (220) to rotate the stirring element (570).

[0153] A rotatable stirring element (570) can perform mixing and stirring of a material or fluid contained within a mixing cartridge (220). A non-contact rotary actuator (580) can operate by transmitting rotational force without being directly mechanically connected to the stirring element (570).

[0154] The operating principle of the non-contact rotary actuator (580) may utilize methods such as magnetic coupling, inductive rotation, or electrostatic actuation. As an example, when the magnetic coupling method is used, the non-contact rotary actuator (580) includes a magnet, and a corresponding magnet is also placed in the stirring element (570), so that the stirring element (570) can rotate through the interaction of the magnetic field. As another example, when the inductive rotation method is used, the alternating magnetic field generated by the non-contact rotary actuator (580) can induce an electromagnetic rotational force in the stirring element (570) to rotate the stirring element (570).

[0155] According to one embodiment, a non-contact driving method can provide various advantages. First, since no separate mechanical connection is required to transmit rotational motion, friction and wear are minimized, which can improve the durability of the device. In addition, maintenance cycles can be reduced, making long-term operation easier, and since there is no mechanical contact, it can operate at a low noise level.

[0156] In particular, the stirring element (570) can rotate even if the housing of the mixing cartridge (220) is present between the stirring element (570) and the non-contact rotary actuator (580). That is, even when the mixing cartridge (220) is sealed, the stirring element (570) placed inside the mixing cartridge (220) can mix the material or fluid, thereby protecting the material or fluid inside the mixing cartridge (220) from contact with the external environment. Accordingly, the stirring element (570) and the non-contact rotary actuator (580) can be usefully employed in sequencing processes where precise mixing and prevention of contamination are important.

[0157] Additionally, the non-contact rotary actuator (580) can provide optimized vibration and rotation effects in a specific frequency band by applying a uniform rotational force to the stirring element (570) using a magnetic field or electromagnetic induction. This enables more uniform mixing within the fluid and is effective for stirring high-viscosity fluids or multiphase fluids.

[0158] Furthermore, the non-contact rotary actuator (580) can be designed to be applicable even in high temperature and high pressure environments, and can provide a stable driving system that is protected from external shock or structural deformation.

[0159] According to the embodiments described above, a large amount of bio-sample or reagent can be mixed in a mixing cartridge (220) placed inside the bio-sample sequencing device (1). Accordingly, user convenience during the mixing process of the reagent can be improved, and the quality of the reagent can be maintained at its highest level in terms of storage. Meanwhile, since a separate microchannel is not required for mixing, the fluid system inside the bio-sample sequencing device (1) can be simplified. Accordingly, the maintenance burden of the bio-sample sequencing device (1) can be reduced, and the reliability of the fluid system can be improved.

[0160] A bio-sample sequencing device according to one embodiment may include: a reaction platform in which a reaction between various substances including bio-samples takes place and a bio-sample library is mounted; a cartridge array comprising a plurality of storage cartridges for individually storing various substances and one or more mixing cartridges for providing a place where various substances are mixed; a fluid system comprising a fluid control unit disposed outside the cartridge array and controlling the flow of various substances in relation to the cartridge array, and a fluid transfer unit for transferring various substances mixed in the mixing cartridge to the reaction platform; a plurality of tubular connecting parts connecting each cartridge included in the cartridge array and the fluid control unit and including a hollow through which various substances pass; and a mixing promotion unit that induces various substances contained inside the mixing cartridge to be uniformly mixed.

[0161] According to one embodiment, the fluid adjustment unit may be positioned above the cartridge array, and each cartridge may include an open area that is open to the upper side, and each connection unit may extend from the fluid adjustment unit through the open area into the interior of each cartridge.

[0162] According to one embodiment, each cartridge may include a sealing plug for closing the open area, and each connection may be positioned to penetrate the sealing plug.

[0163] According to one embodiment, each connection may include a tip portion formed at one end to puncture the sealing plug.

[0164] According to one embodiment, the mixing promoter may include a wing mounted on the outer surface of each connecting part, and the wing may include a downward-facing blade portion to puncture the sealing plug.

[0165] According to one embodiment, the fluid adjustment unit may be positioned on the lower side of the cartridge array, and each cartridge may include an outlet formed on the bottom surface, and each connection unit may connect the outlet and the fluid adjustment unit.

[0166] According to one embodiment, the mixing cartridge may be opened in one direction, and the mixing promoting member may include a mechanical rotary actuator for rotating each connecting member around an axis extended in the one direction.

[0167] According to one embodiment, each connecting member may be arranged to be inclined with respect to the axis extending in one direction.

[0168] According to one embodiment, the mixing promoter may further include a wing mounted on the outer surface of each connecting part to rotate around each connecting part as a central axis and mix various materials.

[0169] According to one embodiment, the wing may include a paddle shape protruding radially from the outer side of each connecting part.

[0170] According to one embodiment, the wing may include a helical shape that wraps around each connection along the longitudinal direction of each connection.

[0171] According to one embodiment, the mixing cartridge may be open in the longitudinal direction of the mixing cartridge, and each connecting part may be spaced apart from the central axis in the longitudinal direction of the mixing cartridge at a predetermined distance, and the mixing promoting part may include a first mechanical rotary actuator for rotating each connecting part around the central axis in the longitudinal direction of the mixing cartridge, and a second mechanical rotary actuator for rotating each connecting part and the first mechanical rotary actuator around the central axis in the longitudinal direction of each connecting part.

[0172] According to one embodiment, the mixing promoting unit may include a vibration actuator for vibrating each cartridge.

[0173] According to one embodiment, the mixing promoter may include a rotatable stirring element disposed inside the mixing cartridge and a non-contact rotary actuator disposed outside the mixing cartridge to rotate the stirring element.

[0174] According to one embodiment, the fluid control unit can supply various substances to the mixing cartridge disposed outside the fluid control unit through each connection unit, and can recover various substances mixed in the mixing cartridge through each connection unit.

[0175] Below, we will describe another aspect of a bio-sample sequencing device capable of performing optimized sequencing by automatically adjusting the concentration of the library during the sequencing process of bio-samples such as DNA and RNA.

[0176] FIG. 7 is a schematic diagram illustrating another aspect of a bio-sample sequencing device according to one embodiment of the present disclosure.

[0177] Referring to FIG. 7, a bio sample sequencing device (1) according to one embodiment may include a reaction platform (100), a sensor unit (600), a concentration control unit (700), and a processor (900). Regarding the configuration and effects of the bio sample sequencing device (1), detailed descriptions that overlap with the above descriptions will be omitted.

[0178] According to one embodiment, the reaction platform (100) may include a main chamber (110) and a sub-chamber (120) for accommodating different bio-sample libraries. For example, the main chamber (110) may accommodate a first bio-sample library, and the sub-chamber (120) may accommodate a second bio-sample library. The main chamber (110) and the sub-chamber (120) may be separated from each other. Accordingly, the first bio-sample library accommodated in the main chamber (110) and the second bio-sample library accommodated in the sub-chamber (120) may not be mixed with each other.

[0179] The main chamber (110) may be a part of the flow cell where main sequencing takes place. In this case, main sequencing may refer to sequencing of a bio sample performed by the user to analyze the base sequence according to the original purpose. That is, the user may build a first bio sample library with a bio sample whose base sequence they wish to analyze, and install it in the main chamber (110) to perform main sequencing. The term main sequencing may be used with the same meaning below.

[0180] One or more main chambers (110) may be provided. When multiple main chambers (110) are provided, sequencing of bio samples may be performed in each of the multiple main chambers (110). Accordingly, the user can perform sequencing of multiple bio samples simultaneously through the multiple main chambers (110). As a result, the user can analyze base sequences more quickly and accurately.

[0181] Meanwhile, before proceeding with main sequencing in the main chamber (110), it may be necessary to optimize the concentration of the first bio-sample library that is scheduled to be received or has already been received in the main chamber (110). This may be a very important factor as it directly affects the accuracy and efficiency of sequencing.

[0182] In this case, 'concentration of the bio sample library' may refer to the amount of the bio sample relative to the buffer solution. According to one embodiment, the surface density of the library may be measured to calculate the concentration of the bio sample library. The concentration of the bio sample library may be estimated through the measured surface density of the library. In the following, the meaning of 'measuring the concentration of the bio sample library' may include the meaning of measuring the surface density of the library and estimating the concentration of the bio sample library based thereon.

[0183] A bio sample sequencing device (1) according to one embodiment can automatically measure the concentration of a bio sample library within the device, determine whether the concentration of the library needs to be adjusted, and then adjust the concentration of the bio sample library. Unlike conventional methods that require the use of separate equipment, this concentration adjustment process can be performed within the bio sample sequencing device (1).

[0184] According to this, the concentration of the bio sample library within the bio sample sequencing device (1) can be optimized, thereby improving ease of use. Additionally, as the concentration of the bio sample library is optimized, the likelihood of sequencing failure can be reduced and the accuracy of the sequencing results can be improved. Furthermore, the time required to prepare for sequencing can be reduced compared to conventional methods that involve manually adjusting the library concentration or using separate equipment.

[0185] According to one embodiment, in order to optimize the concentration of a first bio sample library that is to be accommodated in or has already been accommodated in a main chamber (110), the concentration of a second bio sample library accommodated in a sub-chamber (120) may be measured.

[0186] The sub-chamber (120) is a chamber for measuring the concentration of a bio sample and may be part of a flow cell. The bio sample sequencing device (1) measures the concentration of a second bio sample library contained in the sub-chamber (120) and, based on this, can estimate the concentration of a first bio sample library that is scheduled to be contained in or has already been contained in the main chamber (110). For example, the concentration of the first bio sample library may be estimated to be substantially the same as the concentration of the second bio sample library.

[0187] Based on at least one of the measured concentration of the second biosample library and the concentration of the first biosample library estimated therefrom, it can be determined whether concentration adjustment of the first biosample library is necessary. For example, if it is determined that dilution of the first biosample library is necessary, the first biosample library may be mixed with a buffer.

[0188] If the first bio sample library is not mounted on the reaction platform (100), the first bio sample and buffer may be mixed in a mixing cartridge (e.g., the mixing cartridge (220) of FIG. 1) and then transferred to the main chamber (110) of the reaction platform (100). If the first bio sample library is already contained in the main chamber (110), the buffer may be introduced into the main chamber (110). Accordingly, the concentration of the first bio sample library may be adjusted to a concentration set by the user.

[0189] Meanwhile, according to the embodiment, the process of estimating the concentration of the first bio sample library that is scheduled to be received or has already been received in the main chamber (110) may be omitted. Accordingly, the bio sample sequencing device (1) can measure the concentration of the second bio sample library received in the sub-chamber (120) and determine whether the concentration of the first bio sample library needs to be adjusted based on the measured concentration value.

[0190] The second bio-sample library contained in the sub-chamber (120) may be used solely for concentration control of the first bio-sample library that is scheduled to be contained in the main chamber (110) or has already been contained therein. That is, main sequencing may not be performed on the second bio-sample library contained in the sub-chamber (120). Accordingly, the second bio-sample library may be constructed to be relatively smaller than the first bio-sample library. Additionally, the sub-chamber (120) may have a relatively smaller size compared to the main chamber (110).

[0191] The main chamber (110) and the sub-chamber (120) can accommodate microfluidics. That is, a microfluidic system can be used in the flow cell. The reasons for using a microfluidic system are precise control of reagent flow, improvement of reaction efficiency, improvement of sequencing accuracy, minimization of sample and reagent consumption, and securing efficiency of mass processing.

[0192] First, the microfluidic system can perform the function of supplying and removing reagents (e.g., fluorescently labeled nucleotides, wash solutions, etc.) at a constant rate within the flow cell. This allows the reagents to be uniformly distributed to DNA clusters, thereby increasing the precision of base sequence reading. Additionally, utilizing the microfluidic system allows for the efficient removal of unnecessary reagents or fluorescent substances, which minimizes signal fluctuations and improves the accuracy of the reaction.

[0193] Furthermore, by applying microfluidic systems, sequencing is possible with very small amounts of sample and reagent, allowing for reduced sample usage while maximizing reaction efficiency. In particular, when combined with an automated system utilizing multiple channels, high-speed mass processing is possible, thereby improving sequencing productivity.

[0194] Therefore, microfluidic systems can be utilized as a key technology to precisely control reagent flow in flow cells, optimize the reaction environment, and maximize the accuracy and efficiency of sequencing.

[0195] The sensor unit (600) is configured to measure the concentration of a bio sample library. The sensor unit (600) can be used to quantitatively analyze the concentration of a bio sample library mounted on a reaction platform (100). The sensor unit (600) can be used to measure the concentration of a second bio sample library contained in a sub-chamber (120).

[0196] The sensor unit (600) can be configured in various ways depending on the measurement method. For example, the sensor unit (600) may include an optical sensor, an electrochemical sensor, or a microfluidic sensor.

[0197] An optical sensor can detect changes in fluorescence, absorbance, scattered light, etc., and transmit the corresponding signals to a processor (900). An electrochemical sensor can detect changes in electrical signals (e.g., electrical conductivity, potential difference) using electrodes and transmit them to a processor (900). A microfluidic-based sensor can detect changes in the concentration of a sample within a microchannel and provide the corresponding data to a processor (900).

[0198] The sensor unit (600) can acquire a signal from the sub-chamber (120). Specifically, the sensor unit (600) can detect a signal from a second bio-sample library contained in the sub-chamber (120) and transmit the signal to the processor (900). The processor (900) can analyze the received signal to calculate the concentration of the second bio-sample library.

[0199] The calculated concentration can be used to determine whether it is necessary to adjust the concentration of the first bio sample library that is scheduled to be received in the main chamber (110) or has already been received. Through this, the concentration of the first bio sample library can be optimized, so that the bio sample sequencing device (1) can maintain the optimal bio sample library concentration during the main sequencing process.

[0200] The concentration control unit (700) is configured to control the concentration of a bio sample library that is to be installed on or is already installed on the reaction platform (100). Specifically, the concentration control unit (700) can control the concentration of a first bio sample library that is to be installed on or is already installed in the main chamber (110). For example, by mixing the first bio sample with a buffer solution, the concentration can be controlled in a way that dilutes the first bio sample library.

[0201] If the first bio sample library is not yet mounted on the reaction platform (100), the dilution of the first bio sample library may be carried out in a mixing cartridge (220). In this case, the mixing cartridge (220), a fluid control unit (e.g., the fluid control unit (310) of FIG. 1), a connection unit (e.g., the connection unit (400) of FIG. 1), and a mixing promoter (e.g., the mixing promoter (500) of FIG. 1) may function as a concentration control unit (700).

[0202] When the first bio sample library is mounted in the main chamber (110) of the reaction platform (100), the dilution of the first bio sample library can be performed in the main chamber (110). In this case, a separate concentration control unit (700) placed inside the bio sample sequencing device (1) can dilute the first bio sample library.

[0203] The concentration control unit (700) can perform an appropriate dilution or concentration process based on the concentration value measured through the sensor unit (600) to ensure that the first bio sample library maintains an optimal concentration.

[0204] The concentration control unit (700) may control the concentration in a manner such as dilution through the injection of a reagent or buffer solution, concentration using centrifugation or microfiltration, or selective removal of specific components (purification).

[0205] In the present disclosure, the concentration control of the concentration control unit (700) will be described with a focus on 'dilution'. However, the concentration control of the concentration control unit (700) is not limited to an embodiment of diluting a bio sample library.

[0206] The concentration control unit (700) can be implemented in various ways. As one example, the concentration control unit (700) may include a liquid handling module that controls the concentration of a bio-sample library through precise liquid transfer. As another example, the concentration control unit (700) may include a microfluidic system that performs automated concentration control using microchannels. As yet another example, the concentration control unit (700) may include a temperature and reaction time control module that controls the concentration by changing the physical and chemical properties of the bio-sample under specific conditions.

[0207] The concentration control unit (700) can control the concentration of a first bio sample library that is scheduled to be contained in the main chamber (110) or is already contained inside the main chamber (110) through the control of the processor (900). For example, if the processor (900) determines that the concentration of the first bio sample library needs to be controlled, the concentration control unit (700) can control the concentration of the first bio sample library according to the command of the processor (900).

[0208] Meanwhile, the concentration control unit (700) may optimize the concentration of the bio sample library in real time in conjunction with the processor (900). This can improve the accuracy and reproducibility of the main sequencing process.

[0209] The processor (900) is configured to be electrically connected to the sensor unit (600) and the concentration control unit (700). The processor (900) is a computing device that processes a signal received from the sensor unit (600) to calculate the concentration of the bio sample library and outputs a control command to the concentration control unit (700). The processor (900) is a central control unit that manages the overall operation of the sequencing device and can perform functions such as signal analysis, generation of control commands, data storage and output, and automatic correction.

[0210] The processor (900) can be implemented as a central processing unit (CPU), a microcontroller unit (MCU), a digital signal processor (DSP), an application-specific integrated circuit (ASIC), etc., and can receive data such as optical signals and electrical signals collected from the sensor unit (600) and perform normalization and analysis.

[0211] The processor (900) can calculate the concentration of the bio sample library based on the analyzed data and, if necessary, output control commands such as dilution or concentration to the concentration control unit (700). For example, the processor (900) can calculate the concentration of the second bio sample library contained in the sub-chamber (120), and based on this, calculate the concentration of the first bio sample library that is scheduled to be contained in the main chamber (110) or has already been contained therein, and can control the concentration control unit (700) to control the concentration of the first bio sample library.

[0212] Additionally, the processor (900) can store data measured in real time and provide information by linking with the display of the sequencing device or an external data processing system. Furthermore, the processor (900) can perform a correction function to minimize concentration errors through repetitive measurements and execute an algorithm to maintain an optimal concentration during the sequencing process. Through this, the processor (900) can precisely control the concentration of the bio sample library to improve the accuracy and efficiency of sequencing.

[0213] The operation of the overall bio-sample sequencing device will be explained below.

[0214] FIG. 8 is a flowchart for explaining the operation of the bio-sample sequencing device illustrated in FIG. 7.

[0215] In describing the operation of the bio sample sequencing device of FIG. 8 below, reference will be made to the components of the bio sample sequencing device (1) shown in FIG. 7.

[0216] Referring to FIG. 8, the operation of the bio sample sequencing device (1) can be started with the bio sample library introduced. At this time, the bio sample library may be mounted in each of the main chamber (110) and sub chamber (120) of the reaction platform (100), but may not be mounted in the reaction platform (100) before the main sequencing proceeds and may be stored in a storage cartridge (e.g., the storage cartridge (210) of FIG. 1).

[0217] At this time, the bio sample constituting the bio sample library to be mounted in the main chamber (110) (e.g., the first bio sample library of FIG. 7) may be called the 'main sample', and the bio sample constituting the bio sample library to be mounted in the sub chamber (120) (e.g., the second bio sample library of FIG. 7) may be called the 'test sample'.

[0218] The terms "main sample" and "test sample" may be used interchangeably with the same meaning below. Additionally, the terms "main sample library" and "first bio sample library" may be used interchangeably with the same meaning below, and the terms "test sample library" and "second bio sample library" may be used interchangeably with the same meaning.

[0219] In step S110, the bio-sample sequencing device (1) can process the test sample. Specifically, processing the test sample may mean processing the test sample using Nucleic Acid Analysis Techniques. Processing the test sample may be performed to measure the concentration of the test sample library.

[0220] In step S120, the bio sample sequencing device (1) calculates the concentration of the bio sample library introduced into the bio sample sequencing device (1) and can determine whether the concentration of the introduced library is an optimal concentration in terms of sequencing accuracy and efficiency.

[0221] Regarding the calculation of concentration, the bio sample sequencing device (1) can calculate the concentration of the test sample library through the processing of the test sample. In addition, the bio sample sequencing device (1) can calculate the concentration of the main sample library by estimating the concentration of the main sample library through the concentration of the test sample library.

[0222] Determining whether the concentration of the library is at an optimal concentration can effectively have the same meaning as determining whether there is a need to adjust the concentration of the library. That is, the bio sample sequencing device (1) can determine whether there is a need to adjust the concentration of the introduced bio sample library.

[0223] At this point, the library subject to judgment regarding whether the concentration is optimal or if adjustment is necessary may be the main sample library. In the case of the test sample library, such judgment may not be required because sequencing is not performed in subsequent steps.

[0224] If the bio sample sequencing device (1) determines that the concentration of the main sample library is optimal, in other words, if the bio sample sequencing device (1) determines that there is no need to adjust the concentration of the main sample library, step S130 can be performed.

[0225] In step S130, the bio sample sequencing device (1) can perform sequencing on the main sample. At this time, sequencing on the main sample may refer to main sequencing. The user can analyze the base sequence of the main sample through main sequencing. When main sequencing is completed, the operation of the bio sample sequencing device (1) may be terminated.

[0226] Meanwhile, if the bio sample sequencing device (1) determines that the concentration of the main sample library is not optimal, in other words, if the bio sample sequencing device (1) determines that it is necessary to adjust the concentration of the main sample library, step S140 may be performed.

[0227] In step S140, the bio sample sequencing device (1) can adjust the concentration of the main sample library to a target concentration. At this time, the target concentration may correspond to the previously mentioned optimal concentration. The target concentration may be pre-set by the user, or it may be automatically set by the processor (900) considering the amount of the main sample.

[0228] Step S140 can be performed automatically inside the bio sample sequencing device (1). That is, if the bio sample sequencing device (1) determines that it needs to adjust the concentration of the library, Step S140 can be performed automatically.

[0229] Once the concentration of the main sample library is adjusted to the target concentration through step S140, step S130 can be performed to proceed with main sequencing of the main sample library.

[0230] According to one embodiment, before main sequencing is performed on a main sample library housed in a main chamber (110), nucleic acid analysis technology processing can be performed first on a test sample library housed in a sub-chamber (120).

[0231] When processing a bio sample library using nucleic acid analysis technology, since it is difficult to reuse the surface of the bio sample library, a bio sample sequencing device (1) according to one embodiment can process a test sample library in a small sub-chamber (120) that is smaller in size than the main chamber (110). Accordingly, the bio sample sequencing device (1) can quickly estimate the concentration of the main sample library while reducing loss of bio samples and quickly determine whether it is necessary to adjust the concentration.

[0232] In addition, according to one embodiment, since main sequencing for the main sample library is not performed until the main sample library has an optimal concentration, the main sample library can maintain a state where no reaction occurs until main sequencing is performed, and accordingly, main sequencing can proceed in an optimal state.

[0233] Meanwhile, although not explicitly stated, after step S130 is completed and sequencing is finished, post-sequencing of the main sample library may be performed before the operation of the bio sample sequencing device (1) is terminated. The post-sequencing process is a process of evaluating the quality of sequencing data, processing it into an analyzable form, and performing biological interpretation. The post-sequencing process may largely consist of steps such as data cleaning, alignment and assembly, mutation analysis, and functional interpretation.

[0234] First, the bio sample sequencing device (1) or processor (900) can improve the reliability of the data by evaluating the quality of raw data generated from the bio sample sequencing device (1) and then purifying base sequences that contain errors. Subsequently, the processor (900) can align the purified sequencing data to a reference genome or reconstruct the base sequence by performing a de novel assembly without a reference genome.

[0235] Subsequently, the processor (900) can analyze the aligned data for mutations to detect genetic mutations such as single nucleotide substitutions (SNPs) and insertions / deletions (InDels). In the case of RNA sequencing, the processor (900) can analyze the gene expression levels in the same data to evaluate differences in expression.

[0236] Finally, the processor (900) interprets gene functions based on the analyzed results to assign biological significance, and can utilize this for disease-related mutation prediction or personalized genomic research.

[0237] Therefore, the post-processing process can play a role in improving data accuracy and converting it into biologically meaningful information, rather than simply storing sequencing results.

[0238] Meanwhile, the post-processing process may be performed outside the bio sample sequencing device (1). In this case, after step S130 is performed, the operation of the bio sample sequencing device (1) is terminated, and the post-processing process may be performed through another analysis system (e.g., cloud server, external analysis device, etc.).

[0239] Below, the process of measuring the concentration of the test sample library and adjusting the concentration of the main sample library inside the bio sample sequencing device (1) will be explained in more detail.

[0240] FIG. 9 is a flowchart illustrating the operation of controlling the concentration of a biosample in the biosample sequencing device illustrated in FIG. 7.

[0241] In describing the control operation of FIG. 9 below, reference will be made to the components of the bio-sample sequencing device (1) illustrated in FIG. 7.

[0242] Referring to FIG. 9, as described above, the operation of the bio sample sequencing device (1) can be started with a bio sample library introduced into the bio sample sequencing device (1). The operation described below can be performed automatically inside the bio sample sequencing device (1). Although not illustrated, the main sequencing to be performed thereafter can also be performed automatically.

[0243] Prior to performing step S210, microfluid can be applied to the bio samples. Since the main chamber (110) and the sub-chamber (120) can accommodate microfluid, when microfluid is applied to the main sample library accommodated in the main chamber (110) and the test sample library accommodated in the sub-chamber (120), the bio samples constituting each library can remain in contact with the microfluid.

[0244] However, according to the embodiment, while microfluid is contained in the main chamber (110) and the sub-chamber (120), a bio sample library may be introduced into each chamber. Even in this case, the bio samples constituting each library may remain in contact with the microfluid.

[0245] In step S210, the bio sample sequencing device (1) can process a bio sample (e.g., a test sample) inside a sub-chamber (120) using nucleic acid analysis technology. Although not shown in FIG. 7, the bio sample sequencing device (1) may include one or more components capable of performing nucleic acid analysis technology used to process the test sample. Such components may be controlled by a processor (900).

[0246] As described above, processing of the test sample can be performed to measure the concentration of the test sample library. Accordingly, processing of the test sample using nucleic acid analysis technology can be performed sufficiently to measure the concentration of the test sample library. When the processor (900) determines that the processing of the test sample is finished, it can control the sensor unit (600) to measure the concentration of the test sample library.

[0247] In step S220, the bio sample sequencing device (1) can acquire a signal from the bio sample (e.g., test sample) processed in step S210 through the sensor unit (600). At this time, the signal may vary depending on the concentration of the bio sample or library inside the sub-chamber (120). That is, the signal acquired by the sensor unit (600) may also vary in correspondence with the concentration of the test sample library. The sensor unit (600) can transmit the signal acquired from the test sample to the processor (900). In this case, the sensor unit (600) may generate a signal separate from the signal acquired from the test sample and transmit it to the processor (900).

[0248] In step S230, the bio sample sequencing device (1) can measure the concentration of a bio sample (e.g., test sample) or library inside the sub-chamber (120) through the processor (900) based on the signal obtained through the sensor unit (600) in step S220. At this time, the processor (900), having received the signal from the sensor unit (600), can analyze the signal corresponding to the concentration of the test sample library and calculate the concentration of the test sample or library.

[0249] At this time, the processor (900) can estimate the concentration of a bio sample (e.g., main sample) that is scheduled to be received or has already been received in the main chamber (110) based on the concentration of the calculated test sample or library. That is, the processor (900) can measure the concentration of the test sample or library and estimate the concentration of the main sample or library.

[0250] For example, the processor (900) may estimate the concentration of the main sample library by assuming that the concentration of the test sample library and the concentration of the main sample library are substantially the same, but the embodiments are not limited thereto. As another example, an algorithm used to estimate the concentration of the main sample library from the concentration of the test sample library may be installed in the bio-sample sequencing device (1), and the processor (900) may estimate the concentration of the main sample library using this. Meanwhile, the operation of estimating the concentration of the main sample library may be omitted.

[0251] In step S240, the bio sample sequencing device (1) can determine through the processor (900) whether concentration adjustment is needed for a bio sample (e.g., main sample) that is scheduled to be received in the main chamber (110) or has already been received. For example, the processor (900) can determine whether the concentration of the main sample library that is scheduled to be received in the main chamber (110) or has already been received is an optimal concentration and, based on this, determine whether concentration adjustment is needed.

[0252] Specifically, if the concentration of the main sample library is at an optimal concentration, the processor (900) may determine that no concentration adjustment of the main sample library is necessary. If the concentration of the main sample library is not at an optimal concentration, the processor (900) may determine that concentration adjustment of the main sample library is necessary.

[0253] However, as mentioned earlier, determining whether the concentration of the main sample library is optimal and determining whether concentration adjustment for the main sample library is necessary can practically have the same meaning.

[0254] When the processor (900) determines that the concentration of the main sample library is at an optimal concentration or that the concentration control of the main sample library is not necessary, the concentration control operation of the bio sample sequencing device (1) may be terminated.

[0255] On the other hand, if the processor (900) determines that the concentration of the main sample library is not optimal or that the concentration of the main sample library needs to be adjusted, step S250 may be performed. At this time, the processor (900) can control the concentration control unit (700) to adjust the concentration of the main sample library.

[0256] Step S250 may be the same step as Step S140 described in FIG. 8. In Step S250, the bio sample sequencing device (1) can control the concentration of a bio sample (e.g., main sample) that is to be received or has already been received in the main chamber (110) through the concentration control unit (700). At this time, the concentration control unit (700) can control the concentration of the main sample library to a target concentration under the control of the processor (900).

[0257] For example, if the processor (900) determines in step S240 that dilution is required for a bio sample (e.g., main sample) that is scheduled to be received in or has already been received in the main chamber (110), the processor (900) may control the concentration control unit (700) in step S250 to dilute the bio sample that is scheduled to be received in or has already been received in the main chamber (110). The concentration control unit (700) may mix the bio sample that is scheduled to be received in or has already been received in the main chamber (110) with a buffer to lower the concentration of the main sample or library to a target concentration.

[0258] In one example, when the main sample or library is not accommodated in the main chamber (110), a mixing cartridge (e.g., mixing cartridge (220) of FIG. 1), a fluid control unit (e.g., fluid control unit (310) of FIG. 1), a connection unit (e.g., connection unit (400) of FIG. 1), and a mixing promoter (e.g., mixing promoter (500) of FIG. 1) may serve as a concentration control unit (700). In this case, the main sample or library may be mixed with a buffer solution in the mixing cartridge (220), and the diluted main sample or library may be transferred to a reaction platform (100) and mounted in the main chamber (110).

[0259] In another example, when a main sample or library is contained in a main chamber (110), the concentration control unit (700) can lower the concentration of the main sample or library to a target concentration by introducing a buffer solution into the main chamber (1100).

[0260] When step S250 is performed and the concentration of the main sample library reaches the target concentration, the concentration control operation of the bio sample sequencing device (1) can be terminated.

[0261] Below, examples of a series of operations for processing test samples, acquiring signals, and measuring the concentration of a test sample library will be described.

[0262] FIG. 10 is a flowchart illustrating an example of a series of operations for measuring the concentration of a biosample of the biosample sequencing device illustrated in FIG. 7.

[0263] In describing the control operation of FIG. 10 below, reference will be made to the components of the bio-sample sequencing device (1) illustrated in FIG. 7.

[0264] Referring to FIG. 10, steps S310 to S330 described below may correspond to steps S210 and S230 described in FIG. 9.

[0265] In step S310, the bio sample sequencing device (1) can perform test sequencing on a bio sample (e.g., a test sample) inside the sub-chamber (120). That is, the nucleic acid analysis technique mentioned in step S210 of FIG. 9 may be test sequencing on the test sample.

[0266] Test sequencing of the test sample library inside the sub-chamber (120) can be distinguished from main sequencing of the main sample library inside the main chamber (110). Unlike main sequencing, which is performed to analyze base sequences according to the user's original purpose, test sequencing can be performed only to measure the concentration of the test sample library.

[0267] In other words, test sequencing may be a small-scale sequencing performed on a test sample library to adjust the concentration of the main sample library, which is the target of the main sequencing, to an optimal concentration before the main sequencing is performed.

[0268] According to this, the number of repetitions of the test sequencing may be less than 1 / 100 of the number of repetitions of the main sequencing. For example, while the main sequencing must be performed 300 times, the test sequencing may be performed only 1 to 2 times, and the bio sample sequencing device (1) can achieve the purpose of ‘measuring the concentration of the test sample’.

[0269] That is, test sequencing can be performed for a relatively significantly shorter time compared to main sequencing. Accordingly, the time required to measure the concentration of the test sample can be significantly shorter compared to the entire operation of the bio sample sequencing device (1).

[0270] In step S320, the bio sample sequencing device (1) can acquire an image from a bio sample (e.g., test sample) that has finished test sequencing through the sensor unit (600). At this time, the image may include both photographs and videos. That is, the signal mentioned in step S220 of FIG. 9 may be an image of a bio sample (e.g., test sample) inside the sub-chamber (120), and the sensor unit (600) can acquire an image of the test sample.

[0271] For example, the sensor unit (600) may include a light source for irradiating light onto a test sample and a light microscope for acquiring an image. When the light source irradiates light onto a test sample housed in a sub-chamber (120), the light microscope can acquire an image by magnifying the light reflected from the test sample with an optical lens and recording it with a detection device (e.g., camera, CCD, CMOS sensor).

[0272] At this time, with respect to the image of the test sample acquired by the sensor unit (600), the spectrum of light, the distribution of light, and the intensity of light detected in the image may vary in correspondence with the concentration of the test sample or library.

[0273] In step S330, the bio sample sequencing device (1) can measure the concentration of a bio sample (e.g., a test sample) inside a sub-chamber (120) through a processor (900) based on an image acquired by a sensor unit (600). At this time, the processor (900) can measure or calculate the concentration of the bio sample inside the sub-chamber (120) based on at least one of the spectrum of light, the distribution of light, and the intensity of light detected in the image.

[0274] According to an embodiment, the processor (900) can estimate the concentration of a bio sample (e.g., main sample) that is to be received or has already been received in the main chamber (110) based on the concentration of the calculated test sample or library.

[0275] Although not yet described, in the process of determining whether concentration adjustment of the main sample library to be performed later is necessary, the processor (900) can determine this by comparing the measured concentration of the test sample or the estimated concentration of the main sample with a reference (e.g., concentration data) for the optimal concentration stored in the memory of the bio sample sequencing device (1).

[0276] In another example, the processor (900) can determine this based on the aforementioned 'distribution of light and intensity of light detected in the image'. Specifically, a reference for the optimal concentration existing in the form of an image may be stored in the memory of the bio-sample sequencing device (1). The processor (900) can determine this by comparing the acquired image with the reference image.

[0277] FIG. 11 is a flowchart illustrating another example of a series of operations for measuring the concentration of a biosample sequencing biosample illustrated in FIG. 7.

[0278] In describing the control operation of FIG. 11 below, reference will be made to the components of the bio-sample sequencing device (1) illustrated in FIG. 7.

[0279] Referring to FIG. 11, steps S410 to S430 described below may correspond to steps S210 and S230 described in FIG. 9.

[0280] In step S410, the bio sample sequencing device (1) can perform real-time quantitative PCR (microfluidic qPCR) using a microfluidic system on a bio sample (e.g., a test sample) inside a sub-chamber (120). That is, the nucleic acid analysis technique mentioned in step S210 of FIG. 9 may be microfluidic qPCR for the test sample.

[0281] With the introduction of microfluidic technology, microfluidic qPCR can provide various advantages over conventional qPCR, such as faster reaction rates, savings in biosamples and reaction reagents, improved precision, and high-efficiency processing.

[0282] Microfluidic qPCR of test samples can be completed much faster than sequencing of main samples. Even when performing microfluidic qPCR and sequencing on the same sample, microfluidic qPCR generally yields faster results. Accordingly, the process of measuring the concentration of the test sample library to determine whether the concentration of the main sample library needs to be adjusted can be significantly shortened through microfluidic qPCR.

[0283] In step S420, the bio sample sequencing device (1) can acquire a fluorescent signal from a bio sample (e.g., a test sample) after microfluidic qPCR is completed through the sensor unit (600). That is, the signal mentioned in step S220 of FIG. 9 may be a fluorescent signal emitted by a fluorescent substance attached to a bio sample (e.g., a test sample) inside a sub-chamber (120) after absorbing light, and the sensor unit (600) can acquire a fluorescent signal from the test sample.

[0284] For example, the sensor unit (600) may include a light source for irradiating light onto a test sample and a photodetector for acquiring a fluorescent signal emitted from the test sample. When the light source irradiates light onto a fluorescent material attached to a test sample inside a sub-chamber (120), the photodetector can acquire a fluorescent signal emitted by the fluorescent material.

[0285] At this time, with respect to the fluorescent signal acquired by the sensor unit (600), the fluorescent spectrum, fluorescent intensity, and temporal change of the fluorescent signal may vary in correspondence with the concentration of the test sample or library.

[0286] In step S430, the bio sample sequencing device (1) can measure the concentration of a bio sample (e.g., a test sample) inside a sub-chamber (120) through a processor (900) based on a fluorescence signal acquired by a sensor unit (600). At this time, the processor (900) can measure or calculate the concentration of the bio sample inside the sub-chamber (120) based on at least one of the fluorescence spectrum, fluorescence intensity, and temporal change of the fluorescence signal.

[0287] According to an embodiment, the processor (900) can estimate the concentration of a bio sample (e.g., main sample) that is to be received or has already been received in the main chamber (110) based on the concentration of the calculated test sample or library.

[0288] Although not described, in the process of determining whether concentration adjustment of the main sample library to be performed later is necessary, the processor (900) can determine this based on the aforementioned 'fluorescence spectrum, fluorescence intensity, and temporal change of the fluorescence signal'. Specifically, a reference signal for the optimal concentration may be stored in the memory of the bio-sample sequencing device (1). The processor (900) can determine this by comparing the acquired fluorescence signal with the reference signal.

[0289] Meanwhile, the image analysis described through Fig. 10 and the fluorescence signal analysis described through Fig. 11 may be substantially the same. That is, the 'technique for calculating concentration based on light detected in an image' described through Fig. 10 may be the same as the 'technique for calculating concentration based on a fluorescence signal' described through Fig. 11.

[0290] According to this, steps S320 and S330 described in Fig. 10 can be applied after step S410, and similarly, steps S420 and S430 can be applied after step S310 described in Fig. 10.

[0291] Below, we will explain a configuration that facilitates smooth dilution during the process of diluting the main sample library, when it is determined that concentration control (e.g., dilution) is necessary.

[0292] FIGS. 12a and FIGS. 12b are drawings illustrating examples of configurations used for diluting biosamples in the biosample sequencing device illustrated in FIG. 7.

[0293] Referring to FIGS. 12a and 12b, a bio-sample sequencing device (1) according to one embodiment may include a reaction platform (100) and a mixing aid (800). For convenience of explanation, the sensor unit (600), concentration control unit (700), and processor (900) described in FIG. 7 have been omitted.

[0294] As described above, when the main sample or library is not contained in the main chamber (110), the main sample or library may be mixed with a buffer in a mixing cartridge (e.g., the mixing cartridge (220) of FIG. 1). In this case, a mixing promoter (e.g., the mixing promoter (500) of FIG. 1) may induce the main sample or library contained inside the mixing cartridge (220) to be uniformly mixed with the buffer.

[0295] According to one embodiment, when a main sample or library is contained in a main chamber (110), the main sample or library may be mixed with a buffer inside the main chamber (110). In this case, a mixing aid (800) may induce the main sample or library contained inside the main chamber (110) and the buffer to be uniformly mixed. That is, the mixing aid (800) is configured to assist in mixing so that the material contained inside the main chamber (110) (e.g., bio sample, buffer, and reagent, etc.) is evenly mixed.

[0296] Referring to FIG. 12a, the mixing aid (800) may be a vibrator (810). The vibrator (810) is configured to apply vibration to the main chamber (110) of the reaction platform (100). The vibrator (810) may correspond to a configuration functionally identical to the vibration actuator described in FIG. 5 (e.g., the vibration actuator (540) of FIG. 5). As illustrated, the vibrator (810) is placed in a region on the reaction platform (100), specifically adjacent to the main chamber (110).

[0297] The processor (900) can control the vibrator (810) to dilute a bio sample (e.g., main sample) inside the main chamber (110). The vibrator (810) can apply vibration to the main chamber (110) so that the buffer introduced into the main chamber (110) and the main sample or library inside the main chamber (110) are mixed.

[0298] The process of mixing the buffer solution and the bio sample inside the main chamber (110) by applying vibration to the main chamber (110) with the vibrator (810) may be included in the process of diluting the bio sample inside the main chamber (110).

[0299] By the vibration of the vibrator (810), the buffer solution and the main sample inside the main chamber (110) are mixed evenly, so that the dilution of the main sample library can be accelerated. That is, the vibrator (810) can help to facilitate the smooth dilution of the main sample library.

[0300] Referring to FIG. 12b, the mixing aid (800) may be a rotating bar (820). The rotating bar (820) is a configuration that rotates inside the main chamber (110) of the reaction platform (100). The rotating bar (820) may correspond to a configuration functionally identical to the rotatable stirring element (570) described in FIG. 6 (e.g., the stirring element (570) of FIG. 6). The rotating bar (820) rotates inside the main chamber (110) and can rotate the buffer introduced into the main chamber (110) and the bio sample (e.g., main sample) inside the main chamber (110).

[0301] The processor (900) can control the rotation bar (820) to rotate in order to dilute a bio sample (e.g., main sample) inside the main chamber (110). At this time, a configuration functionally identical to the non-contact rotation actuator (580) described in FIG. 6 (e.g., the non-contact rotation actuator (580) of FIG. 6) may be separately placed to rotate the rotation bar (820). The rotation bar (820) can rotate the buffer inside the main chamber (110) and the main sample or library so that the buffer introduced into the main chamber (110) and the main sample inside the main chamber (110) are mixed.

[0302] The process of the rotating bar (820) rotating inside the main chamber (110) to mix the buffer inside the main chamber (110) with the bio sample may be included in the process of diluting the bio sample inside the main chamber (110).

[0303] By rotating the rotating bar (820), the buffer solution and the main sample inside the main chamber (110) are rotated and mixed evenly, thereby accelerating the dilution of the main sample library. That is, the rotating bar (820) can help facilitate the smooth dilution of the main sample library.

[0304] According to the embodiments described above, the concentration of the bio sample library within the bio sample sequencing device (1) is optimized, thereby improving user convenience. Additionally, as the concentration of the bio sample library is optimized, the likelihood of sequencing failure is reduced, and the accuracy of the sequencing results is improved. Furthermore, compared to conventional methods that involve manually adjusting the library concentration or using separate equipment, the time required to prepare for sequencing is reduced.

[0305] A method for controlling the concentration of a bio sample library introduced into a bio sample sequencing device according to one embodiment may include: a) processing a bio sample inside a sub-chamber using Nucleic Acid Analysis Techniques; b) acquiring a signal from the processed bio sample; c) measuring the concentration of the bio sample inside the sub-chamber based on the signal; d) determining whether concentration control is required for a bio sample that is scheduled to be received in a main chamber or has already been received based on the measured concentration; and e) controlling the concentration of a bio sample that is scheduled to be received in a main chamber or has already been received based on the determination of whether concentration control is required.

[0306] According to one embodiment, prior to performing step a), the method may further include a step of treating the bio sample with microfluidics.

[0307] According to one embodiment, the nucleic acid analysis technique may be test sequencing of a bio sample inside the sub-chamber.

[0308] According to one embodiment, the number of repetitions of the test sequencing may be 1 / 100 or less compared to the number of repetitions of the main sequencing for a bio sample that is scheduled to be received or has already been received in the main chamber.

[0309] According to one embodiment, the nucleic acid analysis technique may be real-time quantitative PCR (microfluidic qPCR) using a microfluidic system for a bio sample inside the sub-chamber.

[0310] According to one embodiment, the signal is an image of a bio sample inside the sub-chamber, and step c) can be performed based on at least one of the spectrum of light, the distribution of light, and the intensity of light detected in the image.

[0311] According to one embodiment, the signal is a fluorescent signal emitted by a fluorescent material attached to a bio-sample inside the sub-chamber after absorbing light, and step c) can be performed based on at least one of the fluorescence spectrum, fluorescence intensity, and temporal change of the fluorescent signal.

[0312] According to one embodiment, if it is determined in step d) that dilution is necessary for a bio sample that is to be received or has already been received in the main chamber, in step e), the bio sample that is to be received or has already been received in the main chamber can be mixed with a buffer solution to dilute it to a target concentration.

[0313] According to one embodiment, in step e), the process of diluting the bio sample contained in the main chamber may include the process of introducing the buffer solution into the main chamber and applying vibration to the main chamber to mix the buffer solution with the bio sample inside the main chamber.

[0314] According to one embodiment, in step e), the process of diluting the bio sample inside the main chamber may include the process of mixing the bio sample inside the main chamber by introducing the buffer solution into the main chamber and rotating the buffer solution and the bio sample inside the main chamber.

[0315] A bio sample sequencing device according to one embodiment may include one or more main chambers for accommodating a first bio sample library, a sub chamber separated from the main chamber for accommodating a second bio sample library smaller than the first bio sample library, a sensor unit for acquiring a signal from the sub chamber, a concentration control unit for controlling the concentration of a first bio sample that is to be accommodated or is already accommodated in the main chamber, and a processor electrically connected to the sensor unit and the concentration control unit. The processor may process the second bio sample inside the sub chamber using Nucleic Acid Analysis Techniques, and when the sensor unit acquires a signal from the processed second bio sample, measure the concentration of the second bio sample inside the sub chamber based on the signal, determine whether concentration control is required for the first bio sample that is to be accommodated or is already accommodated in the main chamber based on the measured concentration, and control the concentration control unit to control the concentration of the first bio sample that is to be accommodated or is already accommodated in the main chamber based on the determination of whether concentration control is required.

[0316] According to one embodiment, the main chamber and the sub-chamber can accommodate microfluidics.

[0317] According to one embodiment, the nucleic acid analysis technique may be test sequencing of a second bio sample inside the sub-chamber.

[0318] According to one embodiment, the number of repetitions of the test sequencing may be 1 / 100 or less compared to the number of repetitions of the main sequencing for the first bio sample that is scheduled to be received or has already been received in the main chamber.

[0319] According to one embodiment, the nucleic acid analysis technique may be real-time quantitative PCR (microfluidic qPCR) using a microfluidic system for a bio sample inside the sub-chamber.

[0320] According to one embodiment, the signal is an image of a second bio sample inside the sub-chamber, and when the sensor unit acquires the image, the processor can measure the concentration of the second bio sample inside the sub-chamber based on at least one of the spectrum of light, the distribution of light, and the intensity of light detected in the image.

[0321] According to one embodiment, the signal is a fluorescent signal emitted by a fluorescent substance attached to a second bio sample inside the sub-chamber after absorbing light, and the sensor unit can acquire the fluorescent signal emitted by the fluorescent substance by irradiating light onto the fluorescent substance attached to the second bio sample inside the sub-chamber, and the processor can measure the concentration of the second bio sample inside the sub-chamber based on at least one of the fluorescence spectrum, fluorescence intensity, and temporal change of the fluorescent signal.

[0322] According to one embodiment, if the processor determines that dilution is required for a first bio sample that is to be received in or has already been received in the main chamber, it can control the concentration control unit to dilute the first bio sample that is to be received in or has already been received in the main chamber by mixing it with a buffer solution to a target concentration.

[0323] According to one embodiment, the apparatus may further include a vibrator for applying vibration to the main chamber, and the processor may control the vibrator to dilute a first bio sample contained in the main chamber, and the vibrator may apply vibration to the main chamber so as to mix the buffer introduced into the main chamber with the first bio sample inside the main chamber.

[0324] According to one embodiment, the apparatus may further include a rotating bar that rotates inside the main chamber, and the processor may control the rotating bar to rotate in order to dilute a first bio sample contained in the main chamber, and the rotating bar may rotate the buffer and the first bio sample inside the main chamber so as to mix the buffer introduced into the main chamber and the first bio sample inside the main chamber.

[0325] A computer-readable recording medium according to one embodiment has a program recorded thereon for performing a method to control the concentration of a bio-sample library introduced into a bio-sample sequencing device according to the above embodiment on a computer, so that the method can be performed on a computer.

[0326] Various embodiments of the present disclosure may be implemented or supported by one or more computer programs, and computer programs may be formed from computer-readable program code and stored on a computer-readable medium. In the present disclosure, “application” and “program” may represent one or more computer programs, software components, instruction sets, procedures, functions, objects, classes, instances, related data, or parts thereof suitable for implementation in computer-readable program code. “Computer-readable program code” may include various types of computer code, including source code, object code, and executable code. “Computer-readable medium” may include various types of media accessible by a computer, such as read-only memory (ROM), random access memory (RAM), hard disk drive (HDD), compact disc (CD), digital video disc (DVD), or various types of memory.

[0327] Additionally, a device-readable storage medium may be provided in the form of a non-transitory storage medium. Here, a 'non-transitory storage medium' is a tangible device and may exclude wired, wireless, optical, or other communication links that transmit transient electrical or other signals. Meanwhile, this 'non-transitory storage medium' does not distinguish between cases where data is stored semi-permanently and cases where it is stored temporarily. For example, a 'non-transitory storage medium' may include a buffer in which data is stored temporarily. A computer-readable medium may be any available medium accessible by a computer and may include both volatile and non-volatile media, as well as removable and non-removable media. A computer-readable medium includes media in which data can be stored permanently and media in which data can be stored and subsequently overwritten, such as rewritable optical discs or erasable memory devices.

[0328] According to one embodiment, the method according to the various embodiments disclosed herein may be provided by being included in a computer program product. The computer program product may be traded between a seller and a buyer as a product. The computer program product may be distributed in the form of a device-readable storage medium (e.g., compact disc read-only memory (CD-ROM)), or distributed online (e.g., download or upload) through an application store or directly between two user devices (e.g., smartphones). In the case of online distribution, at least a portion of the computer program product (e.g., a downloadable app) may be temporarily stored or temporarily created on a device-readable storage medium, such as the memory of a manufacturer's server, an application store's server, or a relay server.

[0329] The foregoing description of the present disclosure is for illustrative purposes only, and those skilled in the art will understand that modifications can be easily made to other specific forms without altering the technical spirit or essential features of the present disclosure. For example, suitable results may be achieved even if the described techniques are performed in a different order than described, and / or components such as systems, structures, devices, circuits, etc., described are combined or assembled in a form different from described, or replaced or substituted by other components or equivalents. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive. For example, each component described as a single unit may be implemented in a distributed manner, and components described as distributed may likewise be implemented in a combined form.

[0330] The scope of the present disclosure is defined by the claims set forth below rather than by the detailed description above, and all modifications or variations derived from the meaning and scope of the claims and equivalent concepts thereof should be interpreted as being included within the scope of the present disclosure.

Claims

1. A method for controlling the concentration of a biosample library introduced into a biosample sequencing device, a) A step of processing a biosample inside a subchamber using Nucleic Acid Analysis Techniques; b) a step of acquiring a signal from the above-mentioned processed bio-sample; c) a step of measuring the concentration of the bio sample inside the sub-chamber based on the above signal; d) a step of determining whether concentration adjustment is required for a bio sample that is scheduled to be received in or has already been received in the main chamber based on the measured concentration above; and e) a step of adjusting the concentration of a bio sample that is to be received or has already been received in the main chamber based on a judgment of whether the above concentration adjustment is necessary; comprising a method.

2. In Paragraph 1, The above nucleic acid analysis technique is a test sequencing of a biosample inside the sub-chamber, a method.

3. In Paragraph 2, A method in which the number of repetitions of the above test sequencing is 1 / 100 times or less compared to the number of repetitions of the main sequencing for a bio sample that is scheduled to be received or has already been received in the above main chamber.

4. In Paragraph 1, The above nucleic acid analysis technique is a method of real-time quantitative PCR (microfluidic qPCR) using a microfluidic system for a biosample inside the sub-chamber.

5. In any one of paragraphs 1 through 4, The above signal is an image of a bio sample inside the sub-chamber, and The above step c) is performed based on at least one of the spectrum of light, the distribution of light, and the intensity of light detected in the image.

6. In any one of paragraphs 1 through 4, The above signal is a fluorescent signal emitted by a fluorescent substance attached to a bio-sample inside the sub-chamber after absorbing light, and The above step c) is performed based on at least one of the fluorescence spectrum, fluorescence intensity, and temporal change of the fluorescence signal.

7. In any one of paragraphs 1 through 6, In step d) above, if it is determined that dilution is necessary for the bio sample that is scheduled to be received or has already been received in the main chamber, A method for, in step e) above, mixing a bio sample that is to be received in or has already been received in the main chamber with a buffer to dilute it to a target concentration.

8. One or more main chambers for accommodating the first bio-sample library; A sub-chamber separated from the main chamber above and for accommodating a second bio-sample library smaller than the first bio-sample library; A sensor unit for acquiring a signal from the above sub-chamber; A concentration control unit for controlling the concentration of a first bio sample that is scheduled to be received or has already been received in the main chamber; and A processor electrically connected to the sensor unit and the concentration control unit; The above processor is, A biosample sequencing device that processes a second biosample inside the sub-chamber using nucleic acid analysis techniques, measures the concentration of the second biosample inside the sub-chamber based on the signal when the sensor unit acquires a signal from the processed second biosample, determines whether concentration control is required for a first biosample that is scheduled to be received or is already received in the main chamber based on the measured concentration, and controls the concentration control unit to control the concentration of the first biosample that is scheduled to be received or is already received in the main chamber based on the determination of whether concentration control is required.

9. In Paragraph 8, The above nucleic acid analysis technique is a biosample sequencing device, which is a test sequencing of a second biosample inside the sub-chamber.

10. In Paragraph 9, A bio sample sequencing device in which the number of repetitions of the above test sequencing is 1 / 100 or less compared to the number of repetitions of the main sequencing for a first bio sample that is scheduled to be received or has already been received in the above main chamber.

11. In Paragraph 8, A biosample sequencing device in which the nucleic acid analysis technique is real-time quantitative PCR (microfluidic qPCR) using a microfluidic system for a second biosample inside the sub-chamber.

12. In any one of paragraphs 8 through 11, The above signal is an image of a second bio sample inside the sub-chamber, and A biosample sequencing device in which, when the sensor unit acquires the image, the processor measures the concentration of a second biosample inside the sub-chamber based on at least one of the spectrum of light, the distribution of light, and the intensity of light detected in the image.

13. In any one of paragraphs 8 through 11, The above signal is a fluorescent signal emitted by a fluorescent substance attached to a second bio-sample inside the sub-chamber after absorbing light, and The sensor unit irradiates light onto a fluorescent substance attached to a second bio sample inside the sub-chamber to acquire the fluorescent signal emitted by the fluorescent substance, and A biosample sequencing device in which the processor measures the concentration of a second biosample inside the sub-chamber based on at least one of the fluorescence spectrum, fluorescence intensity, and temporal change of the fluorescence signal.

14. In any one of paragraphs 8 through 13, A bio sample sequencing device, wherein the processor controls the concentration control unit to dilute the first bio sample to be received in the main chamber or already received to a target concentration by mixing the first bio sample to be received in the main chamber or already received with a buffer solution when it determines that dilution is necessary for the first bio sample to be received in the main chamber or already received.

15. A computer-readable recording medium having a program recorded thereon for performing the method of any one of paragraphs 1 through 7 on a computer.

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