Reagent delivery system with fluidic device and sensor

Abstract

Systems and devices for reagent delivery are described herein. In one example, a disclosed fluidic device includes: a plurality of first inlet ports; a first common channel; a plurality of first valves, each associated with one of the first inlet ports; a plurality of second inlet ports; a second common channel; a plurality of second valves, each associated with one of the second inlet ports; a plurality of outlet ports; a third common channel; a plurality of third valves, each associated with one outlet port; a first shut-off valve fluidly coupled between the first common passage and the third common passage; and a second shut-off valve fluidly coupled between the second common passage and the third common passage. Each first or second valve is fluidly coupled between one of the first or second inlet ports and the first or second common passage. Each third valve is fluidly coupled between one outlet port and a third common passage.

Description

Priority Claims and Cross-References

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 409,251, filed on September 23, 2022, the entire content of which is hereby incorporated by reference in its entirety. Technical Field

[0002] This disclosure generally relates to fluid reagent delivery, and more particularly to systems, devices, and methods for delivering fluid reagents with fill control via sensors. Background Art

[0003] Microfluidic technology is considered a group of technologies capable of manipulating small amounts of fluid in chemical biology, chemical synthesis, and lab-on-a-chip devices. The challenge of moving small amounts of fluid from point A to point B lies in minimizing the swept volume and dead volume, which will reduce reagent usage and cross-contamination. Fluid movement has received extensive attention in the range of cross-sectional area of approximately 10 to 1000 μm 2 and volume of approximately 1 to 1000 μL. However, in the slightly larger range of cross-sectional area of 0.1 to 10 mm 2 and reagent volume of 1 to 100 mL, dispensing manifold technology is still lacking.

[0004] Mechanical movement is used in some large-scale delivery applications. Mechanical pipettes are easy to implement, but have problems such as low speed, atmospheric contamination, and large volumes required for fluid connections. Smaller-scale microfluidic devices have been developed for spraying / inkjet printing small droplets onto a substrate surface. This method can achieve high resolution and small reaction droplets, but is not suitable for closed reaction chambers. Microfluidic valve / manifold systems with zero dead volume have been developed on a smaller scale. The valves and manifolds must be tightly integrated, so there is a lack of application flexibility and expansion space.

[0005] Syringe pumps have traditionally been the main instrument for delivering small amounts of liquid to the desired location. However, they are limited in terms of volume capacity, chemical compatibility, pressure fluctuations, and vibrations. Measures to expand their capabilities involve sucking the medium from the outlet, using a permeable membrane to seal the reservoir, and optimizing operating conditions. Pressure-driven flow is an alternative that limits dynamic forces, is pulse-free, and has a faster response time. The disadvantage is that additional components are required to regulate the dispensed volume. Summary of the Invention

[0006] Exemplary embodiments disclosed herein are directed to solving problems related to one or more of the problems presented in the prior art and to providing additional features that will become readily apparent by reference to the following detailed description when taken in conjunction with the accompanying drawings. According to various embodiments, exemplary systems, methods, apparatuses, and computer program products are disclosed herein. However, it is to be understood that these embodiments are presented by way of example and not limitation, and that various modifications to the disclosed embodiments can be made by those of ordinary skill in the art upon reading this disclosure while remaining within the scope of this disclosure.

[0007] In one embodiment, a fluid device is disclosed. The fluid device includes: a plurality of first inlet ports; a first common channel; a plurality of first valves, each of the plurality of first valves being associated with one of the plurality of first inlet ports; a plurality of second inlet ports; a second common channel; a plurality of second valves, each of the plurality of second valves being associated with one of the plurality of second inlet ports; a plurality of outlet ports; a third common channel; a plurality of third valves, each of the plurality of third valves being associated with one of the plurality of outlet ports; a first shut-off valve fluidly coupled between the first common channel and the third common channel; and a second shut-off valve fluidly coupled between the second common channel and the third common channel. Each first valve is fluidly coupled between the associated first inlet port and the first common channel. Each second valve is fluidly coupled between the associated second inlet port and the second common channel. Each third valve is fluidly coupled between the associated outlet port and the third common channel.

[0008] In another embodiment, a reagent delivery system is disclosed. The reagent delivery system includes: a plurality of first reagent containers, each of the plurality of first reagent containers containing a respective first liquid reagent selected from a first group; a plurality of second reagent containers, each of the plurality of second reagent containers containing a respective second liquid reagent selected from a second group; a fluid device including a plurality of first inlet ports, a plurality of second inlet ports, and a plurality of outlet ports; and a plurality of chambers, each of the plurality of chambers including a first chamber port and a second chamber port. Each of the plurality of first reagent containers is fluidly coupled to one of the plurality of first inlet ports. Each of the plurality of second reagent containers is fluidly coupled to one of the plurality of second inlet ports. The first chamber port of each chamber is fluidly coupled to one of the plurality of outlet ports.

[0009] In yet another embodiment, a non-transitory computer-readable medium is disclosed having stored thereon computer-executable instructions for performing the disclosed methods performed by the disclosed devices or systems in some embodiments. Description of the Drawings

[0010] The various exemplary embodiments of the present disclosure are described in detail below with reference to the following drawings. The drawings are provided for illustrative purposes only and depict only the exemplary embodiments of the present disclosure to assist the reader in understanding the present disclosure. Therefore, the drawings should not be considered as limiting the breadth, scope, or applicability of the present disclosure. It should be noted that these drawings are not necessarily drawn to scale for clarity and ease of illustration.

[0011] Figure 1A An exemplary perspective view of an exemplary fluid handling device according to some embodiments of the present disclosure is shown.

[0012] Figure 1B Shown are some embodiments of the present disclosure Figure 1A Another exemplary perspective view of the fluid handling device.

[0013] Figure 2A Shown are some embodiments of the present disclosure Figure 1A An exemplary bottom cross-sectional view of the fluid handling device.

[0014] Figure 2B Shown are some embodiments of the present disclosure Figure 1A An exemplary side cross-sectional view of the fluid handling device.

[0015] Figure 2C Shown are some embodiments of the present disclosure Figure 1A Another exemplary side cross-sectional view of the fluid handling device.

[0016] Figure 3A An exemplary perspective view of an exemplary valve in a fluid handling device according to some embodiments of the present disclosure is shown.

[0017] Figure 3B Shown are some embodiments of the present disclosure as Figure 3A An exemplary side cross-sectional view of the valve in the fluid handling device.

[0018] Figure 4 A schematic diagram of an exemplary fluid handling device according to some embodiments of the present disclosure is shown.

[0019] Figure 5 An example diagram of an exemplary reagent delivery system according to some embodiments of the present disclosure is shown.

[0020] Figure 6A Shown are some embodiments of the present disclosure during Figure 5 The actuation fluid path during the first operation of the cleaning fluid in the reagent delivery system of A.

[0021] Figure 6B Shows the actuation fluid path during the second operation of the cleaning fluid in the reagent delivery system of Figure 5 A.

[0022] Figure 7 Shows the actuation fluid path during the rinsing operation of the cleaning fluid in the reagent delivery system of Figure 5 A.

[0023] Figure 8 Shows the actuation fluid path during the purging operation of the inert gas in the reagent delivery system of Figure 5 A.

[0024] Figure 9A Shows the actuation fluid path during the prime operation of the dry reagent in the reagent delivery system of Figure 5 A.

[0025] Figure 9B Shows the actuation fluid path during the operation of filling the dry reagent into the Figure 5 chamber in the reagent delivery system of A.

[0026] Figure 9C Shows the actuation fluid path during the purging operation of the chamber filled with the dry reagent in the reagent delivery system of Figure 5 A.

[0027] Figure 10A Shows the actuation fluid path during the prime operation of the wet reagent in the reagent delivery system of Figure 5 A.

[0028] Figure 10B Shows the actuation fluid path during the operation of filling the wet reagent into the Figure 5 chamber in the reagent delivery system of A.

[0029] Figure 10C Shows the actuation fluid path during the purging operation of the chamber filled with the wet reagent in the reagent delivery system of Figure 5 A.

[0030] Figures 11A to 11B Shows a fluid handling device for testing the manifold function according to some embodiments. Figure 11A Is an exemplary cross-sectional side view of the fluid handling device, and Figure 11BIt is an exemplary cross-sectional bottom view of a fluid handling device. Detailed Description

[0031] The following describes various exemplary embodiments of the present disclosure with reference to the accompanying drawings so that those of ordinary skill in the art can make and use the present disclosure. As will be apparent to those of ordinary skill in the art, after reading the present disclosure, various changes or modifications can be made to the examples described herein without departing from the scope of the present disclosure. Therefore, the present disclosure is not limited to the exemplary embodiments and applications described and shown herein. Additionally, the specific order and / or hierarchy of steps in the methods disclosed herein are merely exemplary methods. Based on design preferences, the specific order or hierarchy of steps of the disclosed methods or processes can be rearranged while remaining within the scope of the present disclosure. Thus, those of ordinary skill in the art will understand that the methods and techniques disclosed herein present various steps or acts in a sample order, and unless otherwise expressly stated, the present disclosure is not limited to the specific order or hierarchy presented.

[0032] This description of the exemplary embodiments is intended to be read in conjunction with the accompanying drawings, which are considered to be a part of the entire written description. In the description, relative terms (such as "lower", "upper", "horizontal", "vertical", "above", "below", "on", "under", "top", and "bottom") and their derivatives (e.g., "horizontally", "downwardly", "upwardly", etc.) should be interpreted as referring to the orientation shown in the drawings being described or discussed at that time. These relative terms are for ease of description and do not require the device to be constructed or operated in a particular orientation. Unless otherwise clearly described, terms regarding attachment, coupling, etc. (such as "connected", "coupled", and "interconnected") refer to a relationship in which structures are directly or indirectly fixed or attached to each other through intervening structures, as well as movable or rigid attachments or relationships.

[0033] For the purposes of the description below, it should be understood that the embodiments described below can take alternative variations and embodiments. It should also be understood that the specific articles, compositions, and / or processes described herein are exemplary and should not be considered limiting.

[0034] In the present disclosure, unless the context clearly indicates otherwise, the singular forms "a", "an", and "the" include plural references, and references to a particular numerical value include at least that particular value. When a value is expressed as an approximation using the antecedent "about", it will be understood that the particular value forms another embodiment. As used herein, "about X" (where X is a numerical value) preferably refers to a value that is ±10% (inclusive of the endpoints) of the stated value. For example, the phrase "about 8" preferably refers to a value from 7.2 to 8.8 (inclusive of the endpoints). The term "substantially the same" will be understood to allow variations such as ±10% or 5%.

[0035] The present disclosure provides a reagent dispensing system that utilizes available valves and integrates them into a modular manifold. Actuation of the corresponding valves will allow selected reagents to flow from their corresponding inlets to selected outlets. In some embodiments, the reagents that can flow through the reagent dispensing system are divided into two groups: a dry group and a wet group. The reagents in the dry group are substantially free of water or anhydrous, while the reagents in the wet group can contain water. The reagents in the dry group can also be referred to as anhydrous, and the moisture content can be less than 100 ppm by weight. In some embodiments, the "dry" reagents contain a moisture content of less than 10 ppm. The water contained in the reagents in the wet group can be higher than 0.1% by weight of the reagent. In some embodiments, water is the solvent in the reagents in the wet group. In some embodiments, these reagents are used for the synthesis of biochemical substances such as DNA, RNA, and peptides, and the reactions are carried out in microfluidic devices such as microarray synthesis chips. For example, suitable examples of the reagents in the dry group can include, but are not limited to, amidides, activators, and inert gases. Suitable examples of the reagents in the wet group can include, but are not limited to, oxidants (OX), CapA solution (CapA), CapB solution (CapB), and electrochemical reaction medium (Echem). CapA and CapB are the first and second capping reagents for DNA synthesis. This separate arrangement further reduces cross-contamination between the dry and wet reagent groups and can be achieved by built-in shut-off valves, thereby greatly reducing the internal volume of the fluid manifold.

[0036] In some embodiments, the fluid system is isolated from the atmosphere and free of such contamination and is driven by a pressurized inert gas. The pressure-driven reagent delivery system can utilize an inert gas to prevent atmospheric contamination. The pressurized inert gas can push the required reagent through the delivery manifold into the target chamber. When the chamber outlet of the target chamber reaches atmospheric pressure, the target chamber is filled. When the bubble sensor located at the chamber outlet detects the transition from gas to liquid, the process stops. In some embodiments, the bubble sensor can be an ultrasonic bubble sensor capable of monitoring fluid flow in a non-invasive manner. In certain discontinuous applications, a reagent delivery system is required to fill and empty a chamber of a fixed volume. Therefore, using a bubble sensor at the chamber outlet will indicate whether the meniscus of the liquid plug has crossed the chamber, thus indicating that the chamber is full when no additional bubbles are present.

[0037] In some embodiments, a pressure sensor is located on the pressurized gas side to monitor the pressure, so that a consistent and stable pressure difference can be achieved for flow rate and software control.

[0038] Figure 1AShows an exemplary perspective view of a fluid handling device 100 according to some embodiments of the present disclosure. The fluid handling device described herein is also referred to as a fluid device or a fluid delivery device, and is a fluid device for delivering one or more different fluids or chemicals. In some embodiments, the fluid device is a microfluidic device. The term "handling" can be understood to cover the precise control of delivering different chemicals, for example, delivering dry chemicals and wet chemicals using the same device structure while keeping them separate without any contamination. Such a device can have a suitable size, for example, in the millimeter or centimeter range. Such a device can be an independent unit device, or its components can be in a panel or a block. The device can be used to move and deliver fluids with a suitable cross-sectional area (e.g., in some embodiments, in the range from 0.1 square millimeters to 10 square millimeters). As Figure 1A shown, the exemplary fluid handling device 100 includes a plastic base 101 and a plurality of valves 102. In this example, the plastic base 101 includes five blocks, forming three segments: a first input segment 110, a second input segment 120, and an output segment 130. The five blocks 105-1, 105-2, 105-3, 105-4, 105-5 ( Figure 1B ) are connected and integrated together in a straight line using fasteners 104 located on both sides of the fluid handling device 100. The number of valves and ports described herein is for illustrative purposes only and can be any suitable number.

[0039] Figure 1B Shows another exemplary perspective view of the fluid handling device 100 according to some embodiments of the present disclosure. Figure 1B The perspective view in Figure 1B shows the bottom of the fluid handling device 100. As

[0040] shown, there are many ports on the bottom of the fluid handling device 100. In this example, the first input segment 110 of the fluid handling device 100 has a suitable first number (such as seven) of first inlet ports 111, while the second input segment 120 of the fluid handling device 100 has a suitable second number (such as ten) of second inlet ports 121. Additionally, the output segment 130 of the fluid handling device 100 has six outlet ports 131. The valves 102 are integrated into different segments of the plastic base 101 and include: a plurality of first valves 102-1, a plurality of second valves 102-2, a plurality of third valves 102-3, a first stop valve 102-4, and a second stop valve 102-5.

[0040] As Figure 1BAs shown, the first input section 110 of the fluid handling device 100 is formed by two integrated plastic blocks: a plastic block 105-1 having five inlet ports and another plastic block 105-2 having two inlet ports. The second input section 120 of the fluid handling device 100 is formed by two integrated plastic blocks: a plastic block 105-4 having five inlet ports and another plastic block 105-5 also having five inlet ports. The output section 130 of the first input section 110 is formed by a single plastic block 105-3 including six outlet ports.

[0041] As Figure 1A and Figure 1B shown, each inlet port and outlet port is associated with a corresponding valve 102, which is integrated onto the plastic base 101 and disposed on top of the port. Each first valve 102-1 is associated with one of the first inlet ports 111 in the first input section 110; each second valve 102-2 is associated with one of the second inlet ports 121 in the second input section 120; each third valve 102-3 is associated with one of the outlet ports 131 in the output section 130. The term "associated with" as used herein will also be understood to mean "coupled to" or "corresponding to". The term "coupled" means connected to each other directly or indirectly. In this example, there are a total of 23 ports and a total of 25 valves. This is because there are two dedicated valves: a first shut-off valve 102-4, which is disposed in the first input section 110 and is closer (or adjacent) to the output section 130 than all other valves in the first input section 110; and a second shut-off valve 102-5, which is disposed in the second input section 120 and is closer (adjacent) to the output section 130 than all other valves in the second input section 120. For each of the two shut-off valves 102-4, 102-5, there is no associated port at the bottom of the first input section 110.

[0042] In some embodiments, the 25 valves 102 in the fluid handling device 100 are arranged in a row, with each two adjacent valves being disposed close to each other with a negligible gap therebetween. Along the Y direction, the distance between each two adjacent first inlet ports 111 is a first distance; the distance between each two adjacent second inlet ports 121 is a second distance; the distance between each two adjacent outlet ports 131 is a third distance. In some embodiments, all of the first distance, second distance, and third distance are the same as each other and are substantially the same as the width of each valve 102 along the Y direction. This compact design of the fluid handling device 100 can reduce the internal volume of the fluid handling device 100. As Figures 1A to 1BAs shown, the X direction and the Y direction are the width direction and the longitudinal direction of the device respectively, and the Z direction is the height direction of the device. These three directions are perpendicular to each other.

[0043] In some embodiments, the length of the fluid handling device 100 in the Y direction is about 20 cm, the width in the X direction is about 2 to 3 cm, and the height in the Z direction is about 5 cm.

[0044] As Figure 1A and Figure 1B shown, all valves including the first valve 102-1, the second valve 102-2, the third valve 102-3, the first stop valve 102-4, and the second stop valve 102-5 are arranged in parallel on the same first side (i.e., the top side) of the fluid handling device 100. All ports including the first inlet port 111, the second inlet port 121, and the outlet port 131 are arranged on the same second side (i.e., the bottom side) of the fluid handling device 100. In some embodiments, the outlet port 131 may be located on the side opposite to the side where the first inlet port 111 and the second inlet port 121 are located. Correspondingly, the third valve 102-3 may be located on the side opposite to the side where the other valves are located.

[0045] As Figure 1B shown, the first inlet port 111 in the first input section 110 and the second inlet port 121 in the second input section 120 are both aligned and arranged in a straight line in the Y direction. Additionally, the outlet ports 131 in the output section 130 are both aligned and arranged in another straight line in the Y direction. This will be better shown in Figure 2A below.

[0046] Figure 2A FIG. 200-1 shows an exemplary cross-sectional bottom view of a fluid handling device (e.g., the fluid handling device 100 in Figure 1A and Figure 1B ) according to some embodiments of the present disclosure. In some embodiments, the cross-sectional bottom view 200-1 can be obtained by cutting the fluid handling device 100 in Figure 1A along the plane P-P' and observing from the bottom upward in the Z direction. Figure 2B FIG. 200-2 shows an exemplary cross-sectional side view of a fluid handling device (e.g., the fluid handling device 100 in Figure 1A and Figure 1B ) according to some embodiments of the present disclosure. In some embodiments, the cross-sectional side view 200-2 can be obtained by cutting the fluid handling device 100 along the line A-A' shown in Figure 2A without cutting the bottom of the fluid handling device 100 and observing from the side of the fluid handling device 100 in the X direction (i.e., observing downward in Figure 2A ). Figure 2CShows another exemplary cross-sectional side view 200-3 of a fluid handling device (e.g., the fluid handling device 100 in Figure 1A and Figure 1B ) according to some embodiments of the present disclosure. In some embodiments, without cutting through the bottom of the fluid handling device 100, by cutting through the fluid handling device 100 along the line B-B' shown in Figure 2A and observing from the side of the fluid handling device 100 in the X direction (i.e., looking down in Figure 2A ), the cross-sectional side view 200-3 can be obtained. In some embodiments, without cutting through the side of the fluid handling device 100, by cutting through the fluid handling device 100 along the line C-C' in Figure 2B or Figure 2C and observing from the bottom upwards in the Z direction, a cross-sectional bottom view 200-1 can also be obtained.

[0047] As Figure 2A shown, the first input section 110 may include a first common channel 212 extending horizontally in the Y direction; the second input section 120 may include a second common channel 222 extending horizontally in the Y direction. Further, the output section 130 may also include a third common channel 232 extending horizontally in the Y direction. The term "common channel" as used herein should be understood to include a channel that belongs to or is shared by two or more ports or valves.

[0048] As Figure 2A and Figure 2C shown, the first input section 110 includes a plurality of first inlet channels 211, each of which corresponds to and is connected to one of the first inlet ports 111 in the first inlet port. Each first inlet channel 211 extends vertically in the Z direction in the fluid handling device 100 and is fluidly coupled between the corresponding first inlet port 111 and an associated first valve 102-1 disposed directly above the first inlet channel 211 in the Z direction. Each first valve 102-1 is fluidly coupled between the associated first inlet port 111 and the first common channel 212 through the corresponding first inlet channel 211. In some embodiments, each first inlet port 111 is configured to receive a wet liquid reagent containing water. When the first valve 102-1 is opened, due to, for example, a pressure difference driven by a pressurized inert gas, the wet liquid reagent is allowed to flow from the corresponding first inlet port 111 located directly below the first valve 102-1 in the Z direction through the corresponding first inlet channel 211 located directly above the first inlet port 111 and directly below the first valve 102-1 in the Z direction to the first common channel 212. As Figures 2A to 2C shown, the first common channel 212 is shared by all the first inlet ports in the first input section 110.

[0049] As Figure 2A and Figure 2C shown, the second input section 120 includes a plurality of second inlet channels 221, each of which corresponds to and is connected to one of the second inlet ports 121 in the second inlet port. Each second inlet channel 221 extends vertically in the Z direction in the fluid handling device 100 and is fluidly coupled between the corresponding second inlet port 121 and the associated second valve 102-2 disposed directly above the second inlet channel 221 in the Z direction. Each second valve 102-2 is fluidly coupled between the associated second inlet port 121 and the second common channel 222 through the corresponding second inlet channel 221. In some embodiments, each second inlet port 121 is configured to receive a dry liquid reagent. When the second valve 102-2 is open, due to a pressure difference driven, for example, by a pressurized inert gas, the dry liquid reagent is allowed to flow from the corresponding second inlet port 121 located directly below the second valve 102-2 in the Z direction through the corresponding second inlet channel 221 located directly above the second inlet port 121 and directly below the second valve 102-2 in the Z direction to the second common channel 222. As Figures 2A to 2C shown, the second common channel 222 is shared by all the second inlet ports in the second input section 120. For ease of description, the first input section 110 and the second input section 120 are used for wet and dry reagents, respectively. However, this does not limit the scope of use of these two sections. These two sections 110 and 120 can be used for reagents of different natures that cannot be mixed during the delivery stage and before being delivered to the reaction chamber. For example, the first input section 110 and the second input section 120 are used for dry and wet reagents, respectively.

[0050] As Figure 2A and Figure 2B shown, the output section 130 includes a plurality of outlet channels 231, each of which corresponds to and is connected to one of the outlet ports 131 in the outlet port. Each outlet channel 231 extends vertically in the Z direction in the fluid handling device 100 and is fluidly coupled between the corresponding outlet port 131 and the associated third valve 102-3 disposed directly above the outlet channel 231 in the Z direction. Each third valve 102-3 is fluidly coupled between the associated outlet port 131 and the third common channel 232 through the corresponding outlet channel 231. When the third valve 102-3 is open, due to a pressure difference driven, for example, by a pressurized inert gas, the liquid reagent is allowed to flow from the third common channel 232 through the corresponding outlet channel 231 located directly below the third valve 102-3 in the Z direction to the corresponding outlet port 131 located directly below the outlet channel 231 in the Z direction. As Figures 2A to 2C shown, the third common channel 232 is shared by all the outlet ports in the output section 130.

[0051] As Figures 2A to 2CAs shown, although the first common channel 212 is a single continuous straight pipe extending through two blocks 105-1 and 105-2 in the first input section 110 ( Figure 1B ), the two blocks 105-1 and 105-2 in the first input section 110 are connected and integrated using fasteners 104 and flange seals 204. Although the second common channel 222 is a single continuous straight pipe extending through two blocks 105-4 and 105-5 in the second input section 120 ( Figure 1B ), the two blocks 105-4 and 105-5 in the second input section 120 are connected and integrated using fasteners 104 and flange seals 204. Similarly, the first input section 110 is connected and integrated to the output section 130 using fasteners 104 and flange seals 204; and the second input section 120 is also connected and integrated to the output section 130 using fasteners 104 and flange seals 204.

[0052] In some embodiments, all channels including the first inlet channel 211, the second inlet channel 221, the third inlet channel 231, the first common channel 212, the second common channel 222, and the third common channel 232 have the same cross-sectional area (e.g., between 0.1 square millimeters and 10 square millimeters) and the same inner diameter. In some embodiments, the liquid flowing in each of the first inlet channel 211, the second inlet channel 221, the third inlet channel 231, the first common channel 212, the second common channel 222, and the third common channel 232 is isolated from the atmosphere and driven by a pressurized inert gas.

[0053] The first shut-off valve 102-4 is fluidly coupled between the first common channel 212 and the third common channel 232. When the first shut-off valve 102-4 is open, it allows the wet fluid reagent to flow from the first common channel 212 to the third common channel 232. The second shut-off valve 102-5 is fluidly coupled between the second common channel 222 and the third common channel 232. When the second shut-off valve 102-5 is open, it allows the dry fluid reagent to flow from the second common channel 222 to the third common channel 232.

[0054] In some embodiments, the wet liquid is selected from the wet group consisting of: oxidant (OX), CapA, Cap B, and electrochemical reaction medium (Echem); the dry liquid is selected from the dry group consisting of: amide compound, activator, and inert gas.

[0055] As Figures 2A to 2CAs shown, the first inlet port 111, the first inlet channel 211, the first common channel 212, the first valve 102-1, and the first check valve 102-4 are integrated in the first input section 110 of the fluid handling device 100; the second inlet port 121, the second inlet channel 221, the second common channel 222, the second valve 102-2, and the second check valve 102-5 are integrated in the second input section 120 of the fluid handling device 100; the outlet port 131, the outlet channel 231, the third common channel 232, and the third valve 102-3 are integrated in the output section 130 of the fluid handling device 100. The output section 130 is physically connected between the first input section 110 and the second input section 120. The first input section 110 and the second input section 120 are separated from each other. In some embodiments, as Figure 1A and Figure 1B and Figures 2A to 2C shown, the device 100 further includes a controller (not shown), such as a control panel, configured to connect to a computer by wire or wirelessly, or configured as a controller (such as a control panel or a computer).

[0056] As Figure 2A shown, the first common channel 212, the second common channel 222, and all the outlet channels 231 (and thus all the outlet ports 131) are aligned along the line A-A'; while the third common channel 232, all the first inlet channels 211, and all the second inlet channels 221 (and thus all the first inlet ports 111 and all the second inlet ports 121) are aligned along the line B-B'. The offset between the line A-A' and the line B-B' corresponds to the connection part of the first port and the second port, as Figure 3B described.

[0057] In some embodiments, all the valves 102, including multiple first valves 102-1, multiple second valves 102-2, multiple third valves 102-3, the first check valve 102-4, and the second check valve 102-5, have the same structure and the same orifice diameter. Each valve can be implemented as any valve that is chemically compatible with the target reagent and has sufficient dynamic response to fluid reagent delivery.

[0058] Figure 3A Shows an exemplary perspective view of an exemplary valve in the fluid handling device 100 according to some embodiments of the present disclosure. Figure 3B Shows according to some embodiments of the present disclosure Figure 3A shown exemplary side cross-sectional views of the valve. In some embodiments, Figure 3A and Figure 3B shown valves can be used as any of the valves 102 in FIGS. 1 to 2.

[0059] As Figure 3AAs shown, the valve 102 includes a valve body 310, a coil housing 320 located on the valve body 310, and a connector 330 located on the coil housing 320. The valve body 310 may include a plastic material with high chemical resistance. The coil housing 320 may include a coil for generating magnetic force and / or some circuit structures. The connector 330 may include pins for connecting the valve 102 to a control panel using wires or other connection methods. In some embodiments, the control panel may be connected to all the valves 102 of the fluid control device 100 and also to a control computer. Therefore, the operation of the fluid control device 100 can be controlled based on the firmware or software running on the control computer.

[0060] In some embodiments, by cutting through the valve body 310 of the valve 102 in a plane Q along the Z direction and observing from the side of the valve 102 along the Y direction, Figure 3A a side cross-sectional view as shown in Figure 3B can be obtained. As shown in Figure 3B , the valve body 310 includes: a first port 301 including a vertical channel, a second port 302 including an inclined channel, and a movable membrane 305 disposed above both the first port 301 and the second port 302. The valve body 310 further includes a metal weight 306 located on the movable membrane 305. In some embodiments, each valve 102 is integrated onto a plastic base 101 using flange seals 304 and some fasteners on both sides of the valve 102 along the X direction.

[0061] According to an embodiment, either the first port 301 or the second port 302 can be an input port, and the other can be an output port accordingly. In the Figures 2A to 2C example shown, all the first ports 301 of the valve 102 are aligned along the Figure 2A line B - B' in Figure 2A ; and all the second ports 302 of the valve 102 are aligned along the

[0062] Similarly, in the second input section 120, the first port 301 of each second valve 102-2 is the input port of the second valve 102-2 because the first port 301 is directly connected or integrated (e.g., using fasteners and flange seals) to the second inlet channel 221 of the corresponding second inlet port 121. Accordingly, the second port 302 of each second valve 102-2 in the second input section 120 is the output port of the second valve 102-2 because the second port 302 is fluidly connected or integrated to the second common channel 222 in the second input section 120.

[0063] In the output section 130, the first port 301 of each third valve 102-3 is the input port of the third valve 102-3 because the first port 301 is fluidly connected or integrated to the third common channel 232 in the output section 130. Accordingly, the second port 302 of each third valve 102-3 in the output section 130 is the output port of the third valve 102-3 because the second port 302 is directly connected or integrated (e.g., using fasteners and flange seals) to the outlet channel 231 of the corresponding outlet port 131.

[0064] Specifically, the first port 301 of the first shut-off valve 102-4 ( Figure 2B and Figure 2C ) is the output port of the first shut-off valve 102-4 because the first port 301 is fluidly connected or integrated to the third common channel 232. Accordingly, the second port 302 of the first shut-off valve 102-4 is the input port of the first shut-off valve 102-4 because the second port 302 is fluidly connected or integrated to the first common channel 212.

[0065] Similarly, the first port 301 of the second shut-off valve 102-5 is the output port of the second shut-off valve 102-5 because the first port 301 is fluidly connected or integrated to the third common channel 232. Accordingly, the second port 302 of the second shut-off valve 102-5 is the input port of the second shut-off valve 102-5 because the second port 302 is fluidly connected or integrated to the second common channel 222.

[0066] Figure 3B Shows the closed state of the valve 102, where the pressure generated by the coil in the coil housing 320 and / or by the weight of the metal counterweight 306 itself is applied to the movable membrane 305. Accordingly, the movable membrane 305 is pushed downward to cover the first port 301 and the second port 302, such that the first port 301 and the second port 302 are not fluidly coupled to each other. That is, the liquid in the input ports of the first port 301 and the second port 302 cannot flow into the output ports of the first port 301 and the second port 302.

[0067] When the valve 102 (e.g., based on a control signal sent by a control computer via a control panel) is switched to the open state, no pressure is applied to the metal counterweight 306 (or there is even an attractive force that lifts the metal counterweight 306). Then, the fluid in the input port exerts pressure from the bottom of the movable membrane 305 to push the movable membrane 305 and the metal counterweight 306 upward, allowing the fluid to flow from the input port to the output port.

[0068] In one example, one of the first valves 102-1, when open, allows wet liquid to flow from the associated first inlet port 111 through the corresponding first inlet channel 211, through the first valve 102-1, to the first common channel 212. The first shut-off valve 102-4, when open, allows wet liquid to flow from the first common channel 212 through the first shut-off valve 102-4 to the third common channel 232. Then, one of the third valves 102-3, when open, allows wet liquid to flow from the third common channel 232 through the third valve 102-3, through the corresponding outlet channel 231, to the associated outlet port 131. Then, the wet liquid is delivered to the target chamber connected to the associated outlet port 131.

[0069] In another example, one of the second valves 102-2, when open, allows dry liquid to flow from the associated second inlet port 121 through the corresponding second inlet channel 221, through the second valve 102-2, to the second common channel 222. The second shut-off valve 102-5, when open, allows dry liquid to flow from the second common channel 222 through the second shut-off valve 102-5 to the third common channel 232. Then, one of the third valves 102-3, when open, allows dry liquid to flow from the third common channel 232 through the third valve 102-3, through the corresponding outlet channel 231, to the associated outlet port 131. Then, the dry liquid is delivered to the target chamber connected to the associated outlet port 131.

[0070] In some embodiments, the cross-sectional area of the fluid flow path remains uniform within the manufacturing capabilities. Specifically, the inner diameters of all the inlet / outlet channels 211, 221, 231, the inner diameters of all the common channels 212, 222, 232, the orifice diameters of all the valves 102, and the interconnect hole diameters of the fluid handling device 100 are closely matched. Thus, sudden expansions or contractions that cause pressure and flow rate variations rarely occur in the fluid path.

[0071] In some embodiments, the internal reagent volume of the fluid handling device 100 is between 1 and 100 milliliters (mL), where the cross-sectional area of the channels in the fluid handling device 100 is between 0.1 and 10 square millimeters (mm 2) between. The channels in the fluid handling device 100 (such as the first common channel 212, the second common channel 222, or the third common channel 232) can be formed by drilling holes from opposite sides of a plastic block. The channels do not collapse during the drilling process. The holes on both sides (for example, with a diameter of 1 mm) need to be aligned with each other.

[0072] Merely reducing the scale of the device for large-scale fluid dispensing does not work. Because a fluid device with a large internal volume (such as 1 to 100 L) does not need to care about a small amount (such as 100 mL) of dead reagent or waste during dispensing. Using the same design as the large-scale fluid device (for example, connecting metal tubes with inner diameters of 3 / 8 inch and 1 / 2 inch by connectors or welding) will result in a large unacceptable percentage of dead reagent, for example, 100 mL of dead reagent per 300 mL of transferred reagent. In addition, for the scale of the fluid handling device 100 (1 to 100 mL internal volume and 0.1 to 10 mm 2 ), it is very difficult or even impossible to connect or weld together the relatively close side metal channels (for example, 7.5 mm between two adjacent side channels).

[0073] Merely increasing the scale of the device for small-scale fluid dispensing also does not work. The small-scale fluid device has channels with an inner diameter of 10 to 100 μm, and these channels are connected by pouring polydimethylsiloxane silicone into a mold (such as 4 to 5 inches). However, it is very difficult or even impossible to pour polydimethylsiloxane silicone resin into a large (such as >10 inches) mold because the relatively large-sized channels constructed in this way are prone to collapse.

[0074] In some embodiments, the orifice diameter of each valve is 0.7 to 1 mm (such as 0.8 mm); and the station width is approximately 7 to 8 mm (such as 7.2 mm), which is the minimum allowable station spacing (center spacing). The flange interface for the fluid handling device 100 can be designed according to the manufacturer's recommendations.

[0075] In some embodiments, a simple implementation of the common channel connecting all the outputs of these valves 102 is to make the common channel about 166 mm long, resulting in an aspect ratio (channel length: channel inner diameter) of approximately 150:1 to 200:1. Drilling holes at this scale cannot achieve accuracy without channel collapse. For the required accuracy, the maximum drilling depth for a 1.0 mm hole is determined to be 40 mm. Therefore, the fluid handling device 100 includes five blocks: a 3-station block and a 5-station block forming the first input section 110; a 5-station block and a 6-station block forming the second input section 120; and a 6-station block forming the output section 130.

[0076] Each pair of adjacent manifold blocks is sealed with an O-ring having high temperature resistance and extreme chemical resistance. In some embodiments, the inner diameter of each O-ring is about 1 mm (e.g., 1.07 mm). In some embodiments, there is no additional retention structure inside the O-ring, allowing the O-ring to form a long channel with an almost constant cross-section. In some embodiments, the operating compression of the O-ring is about 24%.

[0077] Two shut-off valves 102-4, 102-5 are integrated into the fluid handling device 100 to separate the inputs and prevent one set of reagents from contaminating the other. For example, when wet reagents flow towards the outlet, the reagents do not flow through the dry-side shut-off valve and thus do not contaminate the dry reagent inlet. Additionally, integrating the shut-off valves into the fluid handling device 100 as described above can significantly reduce the internal volume of the fluid handling device 100 while maintaining a low percentage of dead reagent.

[0078] The embodiments shown in FIGS. 1 to 3 use at least 23 valve stations. In other embodiments, the number of blocks can be easily increased. For example, the 2 blocks in the first input section 110 and the second input section 120 can be easily expanded to 3 or more blocks. In some embodiments, due to the manufacturing limitations described, the maximum number of stations per block is 6 stations.

[0079] Generally, the fluid handling device 100 is a reagent distribution manifold that can be used for any fluid distribution application having multiple inlets and multiple outlets, such as bioreactors, chemical synthesis, or other microfluidic chips.

[0080] Figure 4 A schematic diagram of a fluid handling manifold 400 according to some embodiments of the present disclosure is shown. In some embodiments, the manifold 400 can have the structure of the fluid handling device 100 as in Figure 1A and Figure 1B As shown in Figure 4 , the manifold 400 includes a wet-side input section 410 configured to receive wet fluid via an inlet port, an inlet valve 402-1, and a wet-side common channel 412. The manifold 400 also includes a dry-side input section 420 configured to receive dry fluid via an inlet port, an inlet valve 402-2, and a dry-side common channel 422. Additionally, the manifold 400 further includes an output section 430 configured to receive wet fluid from the wet-side input section 410 via a shut-off valve 402-4, receive dry fluid from the dry-side input section 420 via a shut-off valve 402-5, and output each received fluid to a target chamber via a corresponding outlet through an outlet common channel 432 and an outlet valve 402-3. In some embodiments, Figure 4 the sections 410 and 420 in

[0081] Figure 4 It also shows an exemplary fluid path when one of the inlets 421 in the dry-side input section 420 is enabled and one of the outlets 431 in the output section 430 is enabled. In some embodiments, it is expected that all the valves on the fluid path are open while all the other valves are closed. For example, regarding Figure 4 the fluid path in (see the thick line), the inlet valve 402-2, the shut-off valve 402-5, and the outlet valve 402-3 through which the fluid path passes are all open, while all the other valves including the shut-off valve 402-4 are closed.

[0082] According to Figure 4 the fluid path in (see the thick line), the dry fluid flows into the fluid manifold through the enabled inlet 421, thus flowing to the dry-side common channel 422 through the open inlet valve 402-2, then flowing to the outlet common channel 432 through the open shut-off valve 402-5, and then flowing to the enabled outlet 431 through the open outlet valve 402-3. Then, the dry fluid can flow to a certain target chamber via the enabled outlet 431. Since the shut-off valve 402-4 is closed, the dry fluid can only flow to the end of the outlet common channel 432 and cannot flow into the wet-side common channel 412.

[0083] Figure 5 shows an example diagram of a reagent delivery system 500 including a fluid manifold 400 as shown in Figure 4 according to some embodiments of the present disclosure. The reagent delivery system 500 is a pressure-driven reagent delivery system that uses an inert gas to prevent atmospheric contamination. In some embodiments, the pressurized inert gas pushes the reagent through the fluid manifold 400 into the target chamber. When the chamber outlet reaches atmospheric pressure, the target chamber is completely filled. When the bubble sensor located at the chamber outlet detects the transition from gas to liquid, the process stops. The pressure sensor is located on the pressurized gas side to monitor the gas pressure, so that a consistent and stable pressure difference can be achieved for flow rate and software control.

[0084] As Figure 5As shown, the reagent delivery system 500 includes: a plurality of wet reagent containers 541, each of the plurality of wet reagent containers containing a corresponding wet liquid reagent containing water; a plurality of dry reagent containers 542, each of the plurality of dry reagent containers containing a corresponding dry liquid reagent that does not contain water or contains only trace amounts of water; an inert gas source 510 configured to provide pressurized inert gas; and an inert gas manifold 520 coupled to the inert gas source 510. In this example, the inert gas is argon; the inert gas source 510 is an argon gas cylinder; and the inert gas manifold 520 is an argon gas manifold. In other examples, the pressurized inert gas can be any other inert gas, such as nitrogen, helium, etc.; the inert gas source 510 can be a source or container for any inert gas; and the inert gas manifold 520 can be a manifold for the inert gas provided by the inert gas source 510. The inert gas manifold 520 is configured to distribute the pressurized inert gas to the plurality of wet reagent containers 541 and the plurality of dry reagent containers 542.

[0085] As Figure 5 shown, the reagent delivery system 500 further includes a fluid handling manifold 400. In some embodiments, Figure 5 the fluid handling manifold 400 in is a fluid device having the same structure as the fluid handling device 100 described with respect to FIGS. 1 - 3. For example, the fluid handling manifold 400 can include a plurality of first inlet ports, a plurality of second inlet ports, and a plurality of outlet ports. Each of the plurality of wet reagent containers 541 is fluidly coupled to one of the plurality of first inlet ports; each of the plurality of dry reagent containers 542 is fluidly coupled to one of the plurality of second inlet ports. For example, in the wet reagent containers 541, the wet reagent containers containing CapA and CapB are fluidly coupled to the first inlet ports 463, 464 of the fluid handling manifold 400, respectively. For example, in the dry reagent container 542, the dry reagent container containing the activator (ACT) is fluidly coupled to the second inlet port 453 of the fluid handling manifold 400.

[0086] As Figure 5 shown, the reagent delivery system 500 further includes a plurality of bubble sensors 590, 591......596; and a plurality of chambers: chamber 0, chamber 1, chamber 2, chamber 3. Each chamber includes two chamber ports: a first chamber port and a second chamber port. The first chamber port of each chamber is fluidly coupled to one of the plurality of outlet ports of the manifold 400; the second chamber port of each chamber is fluidly coupled to one of the plurality of bubble sensors 590, 591......596. For example, chamber 2 has a first chamber port 481 and a second chamber port 482. When the first chamber port 481 is fluidly coupled to the outlet port 474 of the fluid handling manifold 400, the second chamber port 482 is fluidly coupled to the bubble sensor 592.

[0087] As Figure 5 shown, the inlet of the inert gas manifold 520 is connected to an inert gas source 510 via a first plastic tube 515; the inert gas manifold 520 has a plurality of outlets. The reagent delivery system 500 further includes a plurality of pressure regulators PR0, PR1... PR5, each of which is fluidly connected to one of the plurality of outlets of the inert gas manifold 520 via a second plastic tube. The inner diameter of the first plastic tube 515 is greater than the inner diameter of the second plastic tube. For example, the outlet 524 of the inert gas manifold 520 is fluidly connected to the pressure regulator PR4 via a second plastic tube 525, where the inner diameter of the first plastic tube 515 is greater than the inner diameter of the second plastic tube 525. In some embodiments, the inner diameter of the first plastic tube 515 is about 1 / 4 inch; and the inner diameter of each second plastic tube is about 1 / 8 inch.

[0088] In some embodiments, the reagent delivery system 500 includes: at least one dry-side manifold fluidly connected between at least one of the plurality of outlets of the inert gas manifold 520 and a plurality of dry reagent containers 542 via a third plastic tube; and at least one wet-side manifold fluidly connected between at least one of the plurality of outlets of the inert gas manifold 520 and a plurality of wet reagent containers 541 via a third plastic tube. In some embodiments, the inner diameter of each third plastic tube is the same as the inner diameter of the second plastic tube. In Figure 5 the example shown, the reagent delivery system 500 includes: a first wet-side manifold 531, a second wet-side manifold 532, and a dry-side manifold 533. The dry-side manifold 533 is fluidly connected between one of the plurality of outlets of the inert gas manifold 520 and all of the dry reagent containers 542 via a third plastic tube 535 and a pressure regulator PR0. The dry-side manifold 533 is configured to receive pressurized inert gas from the inert gas manifold 520 via the pressure regulator PR0 and distribute the received pressurized inert gas to all of the dry reagent containers 542 to push the dry reagents in the dry reagent containers 542 into the corresponding inlet ports of the manifold 400. In some embodiments, the inner diameter of each third plastic tube 535 is 1 / 8 inch, the same as the inner diameter of the second plastic tube 525.

[0089] Similarly, the first wet-side manifold 531 is fluidly coupled between one of the plurality of outlets of the inert gas manifold 520 and two wet reagent containers respectively containing CapA and CapB via a third plastic tube. The second wet-side manifold 532 is fluidly coupled between one of the plurality of outlets of the inert gas manifold 520 and three wet reagent containers respectively containing Echem, OX, and trichloroacetic acid deprotecting agent (DB) via a third plastic tube. Each of the first wet-side manifold 531 and the second wet-side manifold 532 is configured to receive pressurized inert gas from the inert gas manifold 520 and distribute the received pressurized inert gas to the corresponding wet reagent container 541 to push the wet reagent in the wet reagent container 541 to the corresponding inlet port of the manifold 400.

[0090] In some embodiments, each of the plurality of dry reagent containers 542 is fluidly coupled to a corresponding second inlet port of the manifold 400 via a fourth plastic tube; each of the plurality of wet reagent containers 541 is fluidly coupled to a corresponding first inlet port of the manifold 400 via a fifth plastic tube. The inner diameter of the fourth plastic tube is the same as the inner diameter of the fifth plastic tube. In one example, the dry reagent container ACT containing the activator is fluidly coupled to the corresponding second inlet port 453 of the manifold 400 via the fourth plastic tube 555. In another example, the wet reagent container CapA containing CapA is fluidly coupled to the corresponding first inlet port 463 of the manifold 400 via the fifth plastic tube 556. In some embodiments, both the fourth plastic tube 555 and the fifth plastic tube 556 have the same inner diameter of 1 / 8 inch. In other embodiments, both the fourth plastic tube 555 and the fifth plastic tube 556 have the same inner diameter of 1 / 16 inch. In other embodiments, the inner diameters of the fourth plastic tube 555 and the fifth plastic tube 556 both vary from 1 / 8 inch at the portion near the reagent container to 1 / 16 inch at the portion near the corresponding inlet port of the manifold 400. In Figure 5 the example shown, the dry reagent containers 542 further include containers respectively containing: amidide X (X), universal linker (UL), amidide T (T), amidide C (C), amidide G (G), amidide A (A).

[0091] For each reagent container in the wet reagent containers 541 and the dry reagent containers 542, the pressure of the inert gas can force the fluid reagent in the reagent container to flow to the manifold 400. The chamber outlet is brought to atmospheric pressure during the filling process to create the pressure difference required for flow. The flow rate can be determined by the pressure of the inert gas, the pressure of the chamber outlet of the target chamber (during the filling process), and the fluid resistance experienced by the fluid reagent as it flows through the tubes and channels in the reagent delivery system 500.

[0092] As Figure 5As shown, the reagent delivery system 500 further includes a plurality of dry flow sensors 553. Each of the plurality of dry flow sensors is coupled to a fourth plastic tube that connects the dry reagent container 542 to a corresponding second inlet port of the manifold 400, and is configured to monitor the flow rate of the corresponding dry liquid reagent flowing from the dry reagent container 542 to the corresponding second inlet port. For example, the dry flow sensor ACT’553 is coupled to a fourth plastic tube 555 that connects the dry reagent container ACT 542 to the corresponding second inlet port 453 of the manifold 400. In some embodiments, the dry flow sensor ACT’553 can be coupled to the fourth plastic tube 555 in a non-invasive manner without affecting the flow of fluid in the fourth plastic tube 555. Thus, the dry flow sensor ACT’553 can monitor the flow rate of the activator flowing from the dry reagent container ACT 542 to the corresponding second inlet port 453.

[0093] The reagent delivery system 500 further includes a plurality of wet flow sensors 551, 552. Each of the plurality of wet flow sensors is coupled to a fifth plastic tube that connects the wet reagent container 541 to a corresponding first inlet port of the manifold 400, and is configured to monitor the flow rate of the corresponding wet liquid reagent flowing from the wet reagent container 541 to the corresponding first inlet port. For example, the wet flow sensor CapA’551 is coupled to a fifth plastic tube 556 that connects the wet reagent container CapA 541 to the corresponding first inlet port 463 of the manifold 400. In some embodiments, the wet flow sensor CapA’551 can be coupled to the fifth plastic tube 556 in a non-invasive manner without affecting the flow of fluid in the fifth plastic tube 556. Thus, the wet flow sensor CapA’551 can monitor the flow rate of Cap A flowing from the wet reagent container CapA 541 to the corresponding first inlet port 463. In some embodiments, all containers containing reagents that may need to be mixed with another reagent should be coupled to a flow sensor via a corresponding plastic tube. Thus, it can be monitored whether the mixing conforms to a predetermined ratio, such as 1:1 or 50%:50%. For example, each amidate can be mixed with an activator (ACT); the CapA solution and the CapB solution can be mixed together. In some embodiments, due to volume and tubing size limitations, the containers of the universal joint (UL) are not coupled to any flow sensors.

[0094] In some embodiments, the outlet ports of the manifold 400 are arranged in a row on one side of the manifold 400. As Figure 5As shown, a first outlet port 471 disposed at one end of the row is directly connected to a bubble sensor 595, and no chamber is provided between the first outlet port and the bubble sensor; a second outlet port 476 disposed at the other end of the row is directly connected to a bubble sensor, and no chamber is provided between the second outlet port and the bubble sensor. Both the bubble sensor 595 and the bubble sensor 596 are configured to monitor the fluid flow in the outlet common channel 432 of the manifold 400. In one example, when the shut-off valve 402-5 is open and the shut-off valve 402-4 is closed, the bubble sensor 596 can indicate whether the outlet common channel 432 is filled with dry fluid, wherein when there are no additional bubbles at the bubble sensor 596, the outlet common channel 432 is filled. In another example, when the shut-off valve 402-5 is closed and the shut-off valve 402-4 is open, the bubble sensor 595 can indicate whether the outlet common channel 432 is filled with wet fluid, wherein when there are no additional bubbles at the bubble sensor 595, the outlet common channel 432 is filled.

[0095] As Figure 5 shown, the reagent delivery system 500 further includes: a first waste container 581 coupled to the bubble sensor 595; and a second waste container 582 coupled to the bubble sensor 596. The reagent flowing from the outlet port 471 to the bubble sensor 595 is treated as waste and collected by the first waste container 581. Similarly, the reagent flowing from the outlet port 476 to the bubble sensor 596 is treated as waste and collected by the second waste container 582. In some embodiments, the pressures of the first waste container 581 and the second waste container 582 are always at atmospheric pressure.

[0096] As Figure 5As shown, the reagent delivery system 500 further includes: a plurality of first two-way valves 560, 561, each of the plurality of first two-way valves being coupled between a respective one of the bubble sensors 590, 591 and the first waste container 581; and a plurality of second two-way valves 562, 563, each of the plurality of second two-way valves being coupled between a respective one of the bubble sensors 592, 593 and the second waste container 582. In addition, the reagent delivery system 500 further includes: a plurality of first three-way valves 570, 571; and a plurality of second three-way valves 572, 573. A first end of the three-way valve 570 is coupled to the two-way valve 560, and a second end is switchable between the first waste container 581 and a pressure regulator PR5 that is fluidly coupled to one of a plurality of outlets of the inert gas manifold 520. A first end of the three-way valve 571 is coupled to the two-way valve 561, and a second end is switchable between the first waste container 581 and a pressure regulator PR5 that is fluidly coupled to one of a plurality of outlets of the inert gas manifold 520. A first end of the three-way valve 572 is coupled to the two-way valve 562, and a second end is switchable between the second waste container 582 and a pressure regulator PR5 that is fluidly coupled to one of a plurality of outlets of the inert gas manifold 520. A first end of the three-way valve 573 is coupled to the two-way valve 563, and a second end is switchable between the second waste container 582 and a pressure regulator PR5 that is fluidly coupled to one of a plurality of outlets of the inert gas manifold 520.

[0097] Each of the bubble sensors 590, 591, 592, 593 is configured to monitor the liquid fluid in the correspondingly connected chamber and indicate when the connected chamber is full. The fluid flowing from the connected chamber to the corresponding bubble sensor is treated as waste and collected by the corresponding waste container. In one example, the bubble sensor 592 can indicate whether the liquid fluid in chamber 2 is full, where when there are no additional bubbles at the bubble sensor 592, chamber 2 is completely filled with liquid fluid. The liquid fluid flowing from chamber 2 to the bubble sensor 592 is treated as waste and collected by the waste container 582 via the two-way valve 562 and the three-way valve 572.

[0098] As Figure 5 shown, the reagent delivery system 500 further includes a cleaning liquid container 543 that houses a cleaning liquid configured to clean the channels, valves, and ports of the manifold 400. The cleaning liquid container 543 is coupled between a pressure regulator PR2 and a second common channel 422 of the manifold 400. In Figure 5 the example shown, the cleaning liquid is acetonitrile (ACN). In other examples, the cleaning liquid in the cleaning liquid container 543 can be water, ethanol, methanol, acetone, hexane, benzene, and / or acetic acid. The cleaning liquid is a solvent or a solvent mixture. Acetonitrile (ACN) is herein and Figure 5to the exemplary cleaning solution described with reference to FIGS. 1-10.

[0099] As Figure 5 shown, the reagent delivery system 500 further includes: a two-way valve 565 coupled between the cleaning solution container 543 and the second common channel 422; and a three-way valve 575 having a first end coupled to the two-way valve 565 and a second end switchable between a first waste container 581 and the cleaning solution container 543.

[0100] As Figure 5 shown, the reagent delivery system 500 further includes: a bubble sensor 594 coupled between the first common channel 412 and the second waste container 582; and a two-way valve 564 coupled between the bubble sensor 594 and the second waste container 582.

[0101] In some embodiments, the reagent delivery system 500 further includes pressure sensors 585, 586, 587, 588. As Figure 5 shown, a gas tube 526 is coupled between a pressure regulator PR1 and a second inlet port 450 located at an end of the manifold 400. The gas tube 526 is configured to transport pressurized inert gas from the pressure regulator PR1 to the second inlet port 450 to purge the manifold 400. In this example, the inert gas is argon, and in other examples, the inert gas may be nitrogen or helium. In some embodiments, the pressure sensor 587 is coupled to the gas tube 526 and is configured to monitor the pressure of the gas blown into the manifold 400.

[0102] As Figure 5 shown, the reagent delivery system 500 further includes gas tubes 528 coupled between a pressure regulator PR5 and each of the three-way valves 570, 571, 572, 573. The gas tubes 528 are configured to transport pressurized inert gas from the pressure regulator PR5 to at least one of a plurality of chambers (chambers 0 to 3) to purge the at least one chamber. In some embodiments, the pressure sensor 588 is coupled to the gas tube 528 and is configured to monitor the pressure of the gas blown into the at least one chamber.

[0103] In some embodiments, the pressure sensor 585 is directly coupled to one of a plurality of outlets of the inert gas manifold 520 and is configured to monitor the pressure of the gas blown from the inert gas source 510 and / or the inert gas manifold 520, with no pressure regulator disposed between the pressure sensor and the outlet. In some embodiments, a fourth pressure sensor 586 is coupled between a pressure regulator PR0 and a dry-side manifold 533 fluidly coupled to a plurality of dry reagent containers 542 and is configured to monitor the pressure of the gas blown into the plurality of dry reagent containers 542.

[0104] In some embodiments, each of the plurality of pressure sensors 585, 586, 587, 588 is configured to use a program to control the pressure of the pressurized inert gas and / or the blowing rate based on feedback information from at least one of the plurality of bubble sensors 590, 591......596. In some embodiments, the pressure of the inert gas entering the reagent containers 541, 542 is higher than atmospheric pressure, for example 8 psi. In some embodiments, the feedback information is also used to control at least one valve in the reagent delivery system 500.

[0105] Figure 6A Shows the actuation fluid path during the first operation of the cleaning fluid (e.g., ACN) in a reagent delivery system (e.g., reagent delivery system 500) according to some embodiments of the present disclosure. Figure 6A The thick lines therein represent the fluid paths that traverse all the regions through which the ACN passes during the first operation. Before the first operation, all the valves in the reagent delivery system 500 are closed. At the start of the first operation, Figure 6A all the valves on the fluid path therein are opened in the order from the downstream to the upstream of the fluid path. That is, the outlet valve 476-1 of the outlet port 476 in the control manifold 400 is opened first. Then, the shut-off valve 402-5 is opened to fluidly connect the dry-side common channel 422 and the outlet common channel 432. Then, the two-way valve 565 is opened to allow the ACN to flow into the dry-side common channel 422. Here, it is assumed that the three-way valve 575 has been switched to the ACN container 543 before the first operation. In some embodiments, after the two-way valve 565 is opened, the three-way valve 575 can be switched to the ACN container 543 to push the ACN into the dry-side common channel 422.

[0106] During the first operation, the ACN flows from the ACN container 543 through the three-way valve 575 and the two-way valve 565 into the dry-side common channel 422, and then through the shut-off valve 402-5 into the outlet common channel 432. Since the shut-off valve 402-4 is closed, the ACN cannot flow into the wet-side common channel 412. The ACN will flow out of the manifold 400 through the outlet valve 476-1 and the outlet port 476 and be collected by the second waste container 582 for waste treatment. The bubble sensor 596 can monitor the state of the ACN flow and indicate whether the outlet common channel 432 has been completely filled with the ACN. One purpose of the first operation is to use the ACN to fill and / or clean the dry-side common channel 422 and the outlet common channel 432, for example, to prepare for later filling and / or cleaning the chamber.

[0107] At the end of the first operation, Figure 6AAll valves on the fluid path in [the system] are closed in order from the upstream to the downstream of the fluid path. That is, the two-way valve 565 is first closed to prevent ACN from flowing into the dry-side common channel 422. In some embodiments, the three-way valve 575 may remain as it is. In other embodiments, the three-way valve 575 may be switched from the ACN container 543 to the first waste container 581. Then, the shut-off valve 402-5 is closed to fluidly disconnect the dry-side common channel 422 and the outlet common channel 432. Then, the outlet valve 476-1 that controls the outlet port 476 is closed.

[0108] Figure 6B Shows the actuation fluid path during the second operation of the cleaning fluid (e.g., ACN) in a reagent delivery system (e.g., reagent delivery system 500) according to some embodiments of the present disclosure. Figure 6B The thick lines in [the figure] represent the fluid path that traverses all the areas through which ACN passes during the second operation. In some embodiments, the second operation is performed immediately after the first operation. Before the second operation, all valves in the reagent delivery system 500 are closed. At the start of the second operation, Figure 6B All valves on the fluid path in [the system] are opened in order from the downstream to the upstream of the fluid path. That is, the two-way valve 562 is first opened to allow fluid to flow from chamber 2 to the second waste container 582. Here, it is assumed that the three-way valve 572 has been switched to the second waste container 582 before the second operation. In some embodiments, the three-way valve 572 may be switched to the second waste container 582 before the two-way valve 562 is opened. Then, the outlet valve 474-1 that controls the outlet port 474 in the manifold 400 is opened. Then, the shut-off valve 402-5 is opened to fluidly connect the dry-side common channel 422 and the outlet common channel 432. Then, the two-way valve 565 is opened, and the three-way valve 575 is switched to the ACN container 543 (if not already switched), as described above for the first operation.

[0109] During the second operation, ACN flows from the ACN container 543 through the three-way valve 575 and the two-way valve 565 into the dry-side common passage 422, and then through the shut-off valve 402-5 into the outlet common passage 432. Then, the ACN will flow out of the manifold 400 through the outlet valve 474-1 and the outlet port 474, and into the chamber 2. Since the ACN has filled the outlet common passage 432 during the first operation, the chamber 2 can directly receive the ACN at the start of the second operation without receiving impurities or residues from the outlet common passage 432. The bubble sensor 592 can monitor the state of the ACN flow entering the chamber 2 and indicate whether the chamber 2 has been completely filled with ACN. (After the chamber 2 is filled), the ACN flowing out of the chamber 2 flows through the two-way valve 562 and the three-way valve 572, and is collected by the second waste container 582 for waste treatment. One purpose of the second operation is to fill and / or clean the chamber 2 with ACN.

[0110] At the end of the second operation, Figure 6B all the valves on the fluid path in are closed in order from the upstream to the downstream of the fluid path. That is, the two-way valve 565 is first closed to block the inflow of ACN into the dry-side common passage 422. In some embodiments, the three-way valve 575 can remain as it is. In other embodiments, the three-way valve 575 can be switched from the ACN container 543 to the first waste container 581. Then, the shut-off valve 402-5 is closed to fluidly disconnect the dry-side common passage 422 and the outlet common passage 432. Then, the outlet valve 474-1 controlling the outlet port 474 is closed. Subsequently, the two-way valve 562 will be closed.

[0111] Figure 7 shows the actuation fluid path during the flushing operation of the cleaning fluid, such as ACN (acetonitrile), in a reagent delivery system (e.g., the reagent delivery system 500) according to some embodiments of the present disclosure. Figure 7 The thick lines in represent the fluid path, which traverses all the areas that the ACN passes through during the flushing operation. Before the flushing operation, all the valves in the reagent delivery system 500 are closed. At the start of the flushing operation, Figure 7 all the valves on the fluid path in are opened in order from the downstream to the upstream of the fluid path. That is, the two-way valve 564 is first opened to allow the fluid in the wet-side common passage 412 to flow into the second waste container 582. Then, the shut-off valve 402-4 is opened to fluidly connect the wet-side common passage 412 and the outlet common passage 432. Then, the shut-off valve 402-5 is opened to fluidly connect the dry-side common passage 422 and the outlet common passage 432. Then, the two-way valve 565 is opened, and the three-way valve 575 is switched to the ACN container 543 (if not already switched), as described above for the first operation.

[0112] During the flushing operation, ACN flows from the ACN container 543 through the three-way valve 575 and the two-way valve 565 into the dry-side common channel 422, then through the shut-off valve 402-5 into the outlet common channel 432, and then through the shut-off valve 402-4 into the wet-side common channel 412. The bubble sensor 594 can monitor the state of the ACN flow and indicate whether the wet-side common channel 412 has been completely filled with ACN. Excess ACN flowing out of the wet-side common channel 412 is collected by the second waste container 582 for waste treatment. One purpose of the flushing operation is to use ACN to clean the wet-side common channel 412, the dry-side common channel 422, and the outlet common channel 432 after, for example, fluid manipulation and transportation using the manifold 400.

[0113] At the end of the flushing operation, Figure 7 all valves on the fluid path in are closed in order from the upstream to the downstream of the fluid path. That is, the two-way valve 565 is first closed to block the inflow of ACN into the dry-side common channel 422. In some embodiments, the three-way valve 575 can remain as it is. In other embodiments, the three-way valve 575 can be switched from the ACN container 543 to the first waste container 581. Then, the shut-off valve 402-5 is closed to fluidly disconnect the dry-side common channel 422 and the outlet common channel 432. Then, the shut-off valve 402-4 is closed to fluidly disconnect the wet-side common channel 412 and the outlet common channel 432. Then, the two-way valve 564 is closed.

[0114] Figure 8 Shows the actuation fluid path during the purging operation of an inert gas (such as argon) in a reagent delivery system (such as the reagent delivery system 500) according to some embodiments of the present disclosure. Figure 8 The thick lines in represent the fluid path, which traverses all the areas through which argon passes during the purging operation. In some embodiments, the purging operation of the inert gas can be performed immediately after the flushing operation of the cleaning liquid.

[0115] Before the purging operation, all valves in the reagent delivery system 500 are closed. At the start of the purging operation, Figure 8 all valves on the fluid path in are opened in order from the downstream to the upstream of the fluid path. That is, the two-way valve 564 is first opened to allow the gas fluid in the wet-side common channel 412 to flow into or be blown into the second waste container 582. Then, the shut-off valve 402-4 is opened to fluidly connect the wet-side common channel 412 and the outlet common channel 432. Then, the shut-off valve 402-5 is opened to fluidly connect the dry-side common channel 422 and the outlet common channel 432. Then, the inlet valve 450-1 of the inlet port 450 in the control manifold 400 is opened to allow argon to flow into the dry-side common channel 422.

[0116] During the purge operation, argon flows from the inert gas manifold 520 through the pressure regulator PR1, through the inlet valve 450-1 and the inlet port 450 into the dry-side common channel 422, then through the shut-off valve 402-5 into the outlet common channel 432, and then through the shut-off valve 402-4 into the wet-side common channel 412. The bubble sensor 594 can monitor the state of the argon flow and indicate whether the wet-side common channel 412 has been fully filled with argon. The excess argon flowing out of the wet-side common channel 412 is collected as waste by the second waste container 582. One purpose of the purge operation is to use argon or another inert gas to purge the wet-side common channel 412, the dry-side common channel 422, and the outlet common channel 432, for example, after fluid manipulation at the manifold 400 and flushing the manifold 400.

[0117] At the end of the purge operation, Figure 8 all the valves on the fluid path in are closed in order from the upstream to the downstream of the fluid path. That is, the inlet valve 450-1 controlling the inlet port 450 is first closed to prevent argon from flowing into the dry-side common channel 422. Then, the shut-off valve 402-5 is closed to fluidly disconnect the dry-side common channel 422 and the outlet common channel 432. Then, the shut-off valve 402-4 is closed to fluidly disconnect the wet-side common channel 412 and the outlet common channel 432. Then, the two-way valve 564 is closed.

[0118] Figure 9A Shows the actuation fluid path during the priming operation of the dry reagent (e.g., ACT) in a reagent delivery system (e.g., reagent delivery system 500) according to some embodiments of the present disclosure. The ACT including the activator is an exemplary dry reagent for describing the operation applicable to all other dry reagents. Figure 9A The thick lines in represent the fluid path that traverses all the areas through which the ACT passes during the priming operation. Before the priming operation, all the valves in the reagent delivery system 500 are closed. At the start of the priming operation, Figure 9A all the valves on the fluid path in are opened in order from the downstream to the upstream of the fluid path. That is, the outlet valve 476-1 controlling the outlet port 476 in the manifold 400 is first opened. Then, the shut-off valve 402-5 is opened to fluidly connect the dry-side common channel 422 and the outlet common channel 432. Then, the inlet valve 453-1 controlling the inlet port 453 is opened to allow the ACT to flow into the dry-side common channel 422. Here, the two-way valve 565 is closed so that the ACT cannot flow out of the left end of the manifold 400 from the dry-side common channel 422.

[0119] During the perfusion operation, the ACT flows from the ACT container 542 through the inlet valve 453-1 and the inlet port 453 into the dry-side common channel 422, and then through the shut-off valve 402-5 into the outlet common channel 432. Since the shut-off valve 402-4 is closed, the ACT cannot flow into the wet-side common channel 412. The ACT will flow out of the manifold 400 through the outlet valve 476-1 and the outlet port 476, and be collected by the second waste container 582 for waste disposal. The bubble sensor 596 can monitor the status of the ACT flow and indicate whether the outlet common channel 432 has been completely filled with the ACT. One purpose of the perfusion operation is to use the ACT to fill the dry-side common channel 422 and the outlet common channel 432, for example, to prepare for filling the chambers with the ACT later.

[0120] At the end of the perfusion operation, Figure 9A all the valves on the fluid path in

[0121] Figure 9B shows the actuation fluid path during the operation of filling a dry reagent (such as the ACT) into a chamber in a reagent delivery system (such as the reagent delivery system 500) according to some embodiments of the present disclosure. Figure 9B The thick lines in Figure 9B represent the fluid path, which traverses all the areas that the ACT passes through during the filling operation. In some embodiments, Figure 9A the filling operation in Figure 9B is performed immediately after the perfusion operation in

[0122] During the filling operation, the ACT flows from the ACT container 542 through the inlet valve 453-1 and the inlet port 453 into the dry-side common channel 422, and then through the shut-off valve 402-5 into the outlet common channel 432. Then, the ACT will flow out of the manifold 400 through the outlet valve 474-1 and the outlet port 474, and into the chamber 2, for example, for use in a deoxyribonucleic acid (DNA) synthesizer, chromatography, or other chemical reactions or biotechnological operations. Since the ACT has filled the outlet common channel 432 during the perfusion operation, the chamber 2 can directly receive the ACT at the start of the filling operation without receiving impurities or residues from the outlet common channel 432. The bubble sensor 592 can monitor the status of the ACT flow in the chamber 2 and indicate whether the chamber 2 has been completely filled with the ACT. (After the chamber 2 is filled) the ACT flowing out of the chamber 2 flows through the two-way valve 562 and the three-way valve 572, and is collected by the second waste container 582 for waste disposal. During the filling operation, the ACT flows into the chamber 2 via the port 481 and out of the chamber 2 via the port 482. One purpose of the filling operation is to transport the ACT into the chamber 2 for some biotechnological and / or chemical operations.

[0123] At the end of the filling operation, Figure 9B all the valves on the fluid path in are closed in order from the upstream to the downstream of the fluid path. That is, the inlet valve 453-1 controlling the inlet port 453 is first closed to block the inflow of the ACT into the dry-side common channel 422. Then, the shut-off valve 402-5 is closed to fluidly disconnect the dry-side common channel 422 and the outlet common channel 432. Then, the outlet valve 474-1 controlling the outlet port 474 is closed. Subsequently, the two-way valve 562 will be closed.

[0124] Figure 9C Shows the actuation fluid path during the purging operation of a chamber filled with a dry reagent (such as ACT) in a reagent delivery system (such as the reagent delivery system 500) according to some embodiments of the present disclosure. Figure 9C The thick lines in represent the fluid path, which traverses all the areas that the ACT passes through during the purging operation. In some embodiments, Figure 9C the purging operation in is performed immediately after Figure 9B the filling operation in. Before the purging operation, all the valves in the reagent delivery system 500 are closed. At the start of the purging operation, Figure 9CAll valves on the fluid path therein are opened in the order from the downstream to the upstream of the fluid path. That is, the outlet valve 476-1 of the outlet port 476 in the control manifold 400 is opened first. Then, the outlet valve 474-1 that controls the outlet port 474 in the manifold 400 is opened. Then, the two-way valve 562 is opened, and the three-way valve 572 is switched to the pressure regulator PR5 to receive pressurized inert gas from the inert gas manifold 520.

[0125] During the purge operation, an inert gas (such as argon) flows from the inert gas manifold 520 through the three-way valve 572 and the two-way valve 562 into the chamber 2 via the pressure regulator PR5. The inert gas flows into the chamber 2 via the port 482, and pushes out the ACT (and any other liquid) remaining in the chamber 2 via the port 481. Therefore, the ACT (and any other liquid) flows out of the chamber 2 via the port 481, into the outlet common channel 432 through the outlet valve 474-1 and the outlet port 474. The ACT (and any other liquid) will flow out of the manifold 400 through the outlet valve 476-1 and the outlet port 476, and is collected by the second waste container 582 for waste treatment. The bubble sensor 596 can monitor the state of the ACT flow and indicate whether there is any ACT remaining in the outlet common channel 432. Therefore, the flow direction of the ACT in the purge operation is opposite to that in the filling operation. One purpose of the purge operation is to purge the chamber 2 with argon or another inert gas, for example, after the fluid is delivered to the chamber 2 and operations are performed in the chamber.

[0126] In some embodiments, the chamber 2 (and all other chambers in the reagent delivery system 500) has a window-like shape, with a small thickness value, a regular length value, and a large height value. In some embodiments, the first chamber port 481 is located at the lower part or bottom of the window, while the second chamber port 482 is located at the upper part or top of the window. Although the liquid reagent can easily enter the chamber 2 via the first chamber port 481 to push the air or gas in the chamber 2 upward during the filling process, it is preferably to make the inert gas enter the chamber 2 via the second chamber port 482 to push the liquid reagent in the chamber 2 downward during the purge process. Therefore, the flow direction of the liquid reagent in the chamber 2 (and all other chambers in the reagent delivery system 500) is different during the filling process and the purge process.

[0127] At the end of the purge operation, Figure 9CAll valves on the fluid path in [the system] are closed in order from the upstream to the downstream of the fluid path. That is, the three-way valve 572 is first switched to the second waste container 582 to stop receiving pressurized inert gas from the inert gas manifold 520. Then, the two-way valve 562 is closed. Then, the outlet valve 474-1 that controls the outlet port 474 in the manifold 400 is closed. Then, the outlet valve 476-1 that controls the outlet port 476 in the manifold 400 is closed.

[0128] Figure 10A Shows the actuation fluid path during the priming operation of a wet reagent (e.g., OX) in a reagent delivery system (e.g., reagent delivery system 500) according to some embodiments of the present disclosure. OX, which represents an oxidant, is an exemplary wet reagent used to describe the operation applicable to all other wet reagents. Figure 10A The thick lines in [the figure] represent the fluid path that traverses all the areas through which OX passes during the priming operation. Before the priming operation, all valves in the reagent delivery system 500 are closed. At the start of the priming operation, Figure 10A all valves on the fluid path in [the system] are opened in order from the downstream to the upstream of the fluid path. That is, the outlet valve 471-1 that controls the outlet port 471 in the manifold 400 is first opened. Then, the shut-off valve 402-4 is opened to fluidly connect the wet-side common channel 412 and the outlet common channel 432. Then, the inlet valve 462-1 that controls the inlet port 462 is opened to allow OX to flow into the wet-side common channel 412. Here, the two-way valve 564 is closed so that OX cannot flow out of the wet-side common channel 412 from the right end of the manifold 400.

[0129] During the priming operation, OX flows from the OX container 541 through the inlet valve 462-1 and the inlet port 462 into the dry-side common channel 422, and then through the shut-off valve 402-4 into the outlet common channel 432. When the shut-off valve 402-5 is closed, OX cannot flow into the dry-side common channel 422. OX will flow out of the manifold 400 through the outlet valve 471-1 and the outlet port 471, and be collected as waste by the first waste container 581. The bubble sensor 595 can monitor the state of the OX flow and indicate whether the outlet common channel 432 has been completely filled with OX. One purpose of the priming operation is to use OX to fill the wet-side common channel 412 and the outlet common channel 432, for example, to prepare for filling the chamber with OX later.

[0130] At the end of the priming operation, Figure 10AAll valves on the fluid path in [the system] are closed in order from the upstream to the downstream of the fluid path. That is, the inlet valve 462-1 that controls the inlet port 462 is first closed to prevent OX from flowing into the wet-side common channel 412. Then, the shut-off valve 402-4 is closed to fluidly disconnect the wet-side common channel 412 and the outlet common channel 432. Then, the outlet valve 471-1 that controls the outlet port 471 is closed.

[0131] Figure 10B Shows the actuation fluid path during the operation of filling a wet reagent (such as OX) into a chamber in a reagent delivery system (such as the reagent delivery system 500) according to some embodiments of the present disclosure. Figure 10B The thick lines in [the figure] represent the fluid path, which traverses all the regions that OX passes through during the filling operation. In some embodiments, Figure 10B the filling operation in [the figure] is performed Figure 10A immediately after the perfusion operation. Before the filling operation, all valves in the reagent delivery system 500 are closed. At the start of the filling operation, Figure 10B all valves on the fluid path in [the system] are opened in order from the downstream to the upstream of the fluid path. That is, the two-way valve 562 is first opened to allow fluid to flow from chamber 2 to the second waste container 582. Here, it is assumed that the three-way valve 572 has been switched to the second waste container 582 before the filling operation. In some embodiments, the three-way valve 572 may be switched to the second waste container 582 before the two-way valve 562 is opened. Then, the outlet valve 474-1 that controls the outlet port 474 in the manifold 400 is opened. Then, the shut-off valve 402-4 is opened to fluidly connect the wet-side common channel 412 and the outlet common channel 432. Then, the inlet valve 462-1 that controls the inlet port 462 is opened to allow OX to flow into the wet-side common channel 412.

[0132] During the filling operation, OX flows from the OX container 541 through the inlet valve 462-1 and the inlet port 462 into the wet-side common channel 412, and then through the shut-off valve 402-4 into the outlet common channel 432. Then, OX will flow out of the manifold 400 through the outlet valve 474-1 and the outlet port 474, and into the chamber 2, for example, for a DNA synthesizer, chromatography, or other chemical reactions or biotechnological operations. Since OX has filled the outlet common channel 432 during the perfusion operation, chamber 2 can directly receive OX at the start of the filling operation without receiving impurities or residues from the outlet common channel 432. The bubble sensor 592 can monitor the state of the OX flow in chamber 2 and indicate whether chamber 2 has been completely filled with OX. (After chamber 2 is filled) The OX flowing out of chamber 2 flows through the two-way valve 562 and the three-way valve 572, and is collected by the second waste container 582 for waste treatment. During the filling operation, OX flows into chamber 2 via port 481 and out of chamber 2 via port 482. One purpose of the filling operation is to transport OX into chamber 2 for some biotechnological and / or chemical operations.

[0133] At the end of the filling operation, Figure 10B all the valves on the fluid path in are closed in order from the upstream to the downstream of the fluid path. That is, the inlet valve 462-1 controlling the inlet port 462 is first closed to prevent OX from flowing into the wet-side common channel 412. Then, the shut-off valve 402-4 is closed to fluidly disconnect the wet-side common channel 412 and the outlet common channel 432. Then, the outlet valve 474-1 controlling the outlet port 474 is closed. Subsequently, the two-way valve 562 will be closed.

[0134] Figure 10C Shows the actuation fluid path during the purging operation of a chamber filled with a wet reagent (e.g., OX) in a reagent delivery system (e.g., reagent delivery system 500) according to some embodiments of the present disclosure. Figure 10C The thick lines in represent the fluid path, which traverses all the areas that OX passes through during the purging operation. In some embodiments, Figure 10C the purging operation in is performed immediately after Figure 10B the filling operation in. Before the purging operation, all the valves in the reagent delivery system 500 are closed. At the start of the purging operation, Figure 10C all the valves on the fluid path in are opened in order from the downstream to the upstream of the fluid path. That is, the outlet valve 471-1 controlling the outlet port 471 in the manifold 400 is first opened. Then, the outlet valve 474-1 controlling the outlet port 474 in the manifold 400 is opened. Then, the two-way valve 562 is opened, and the three-way valve 572 is switched to the pressure regulator PR5 to receive pressurized inert gas from the inert gas manifold 520.

[0135] During the purge operation, an inert gas (e.g., argon) flows from the inert gas manifold 520 into the chamber 2 via the pressure regulator PR5, through the three-way valve 572 and the two-way valve 562. The inert gas flows into the chamber 2 via the port 482, and pushes out the OX (and any other liquid) remaining in the chamber 2 via the port 481. Thus, the OX (and any other liquid) flows out of the chamber 2 via the port 481, through the outlet valve 474-1 and the outlet port 474 into the outlet common channel 432. The OX (and any other liquid) will flow out of the manifold 400 through the outlet valve 471-1 and the outlet port 471, and is collected by the first waste container 581 for waste treatment. The bubble sensor 595 can monitor the state of the OX flow and indicate whether there is any OX remaining in the outlet common channel 432. Therefore, the flow direction of the OX during the purge operation is opposite to that during the filling operation. One purpose of the purge operation is to purge the chamber 2 with argon or another inert gas, for example, after the fluid is delivered to the chamber 2 and operations are performed in the chamber.

[0136] At the end of the purge operation, Figure 10C all the valves on the fluid path in are closed in order from the upstream to the downstream of the fluid path. That is, the three-way valve 572 is first switched to the second waste container 582 to stop receiving the pressurized inert gas from the inert gas manifold 520. Then, the two-way valve 562 is closed. Then, the outlet valve 474-1 that controls the outlet port 474 in the manifold 400 is closed. Then, the outlet valve 471-1 that controls the outlet port 471 in the manifold 400 is closed.

[0137] Each inlet and outlet of the manifold 400 can be enabled separately. In some embodiments, two reagents in two respective reagent containers can be pushed into the manifold 400 together through two corresponding inlet ports. For example, when one outlet port 474 and two inlet ports 463, 464 are all opened simultaneously, CapA and Cap B in the wet reagent containers CapA and CapB respectively can be delivered to the chamber 2 in equal amounts together to be mixed with each other for some electrochemical reactions.

[0138] Referring to Figures 11A to 11B , the fluid handling device is tested for manifold functions according to some embodiments. The fluid handling device is the same as the fluid handling device described in FIGS. 1 to 3, except that the bottom port is used for gas outlet during the test. Similar to Figures 2B to 2C Similar to Figure 11A is an exemplary cross-sectional side view of the fluid handling device 100. Similar to Figure 2A Similar to Figure 11BIt is an exemplary cross-sectional bottom view of the fluid control device 100. Based on position and function, these blocks are labeled "LH", "CTL", "CH", "CTR", and "RT". The codes "LH", "CTL", "CH", "CTR", and "RT" represent left hand, center left, chamber, center, and right respectively.

[0139] The test medium used is compressed air with a pressure in the range of 0.0827 MPa to 0.331 MPa (from 12 psi to 48 psi). The volume flow rate of the air used is in the range of 4 L / minute (min.) to 40 L / min.

[0140] For the external leakage test, all ports are pressurized, and each valve is actuated to test the valve mounting seals, O-rings at the manifold connection points, and the flatness of the 10-32 seal surfaces. For the valve seat leakage test, the near inlet is pressurized and the valve is tested in the NC state (not actuated) to test the valve seat. During the external leakage test, each valve is open. During the valve seat leakage test, each valve is closed.

[0141] The duration of the leakage test lasts for 10 seconds. The passing criterion for the leakage test is that the pressure drop is less than 1 / 1000 of the inlet pressure.

[0142] For the functional flow test, the near inlet is pressurized and each valve is tested individually to ensure that each valve operates normally and there is no blockage in the flow path. The flow rate of the air used is tested. Such results indicate that the device can be used for reagents with good fluidity.

[0143] The following four groups of tests were conducted.

[0144] 1. As Figures 11A to 11B shown, the first group of tests on the valves (V1 to V5) in the LH manifold.

[0145] 1-1. External leakage test: The inlet 1 ( Figure 11A ) and the outlet are pressurized. Actuate (open) the five valves (LH: V1 to V5). Then cut off the pressurized gas. Measure the pressure drop after the leakage test duration ends.

[0146] 1-2. Valve seat leakage test: The inlet 1 ( Figure 11A ) is pressurized. Close the five valves (LH: V1 to V5). Then cut off the pressurized gas. Measure the pressure drop after the leakage test duration ends.

[0147] 1-3. Functional flow test: The inlet 1 ( Figure 11A ) is pressurized. The five valves (LH: V1 to V5) are tested individually. Once a stable flow rate is reached, record the individual flow rates.

[0148] 2. As Figures 11A to 11B shown, a second set of tests was performed on the valves in the CTL manifold (CTL: V1 to V5) and one valve in the CH manifold. Actuate valve 6 in the CTL manifold (CTL: V6) to detect the flow rate through CH.

[0149] 2-1. External leakage test: Pressurize the inlet 1 ( Figure 11A ) and the outlet ( Figure 11B ). Actuate (open) the first five valves in the CTL manifold and the first valve in the CH manifold (CTL: V1 to V5; CH: V1). Then cut off the pressurized gas. Measure the pressure drop after the end of the leakage test duration.

[0150] 2-2. Valve seat leakage test: Pressurize the inlet 1 ( Figure 11A ). Close the first five valves in the CTL manifold and the first valve in the CH manifold (CTL: V1 to V5; CH: V1). Then cut off the pressurized gas. Measure the pressure drop after the end of the leakage test duration.

[0151] 2-3. Functional flow test: Pressurize the inlet 1 ( Figure 11A ). Test the first five valves in the CTL manifold and the first valve in the CH manifold (CTL: V1 to V5; CH: V1) individually. Once a stable flow rate is reached, record the individual flow rates.

[0152] 3. As Figures 11A to 11B shown, a third set of tests was performed on the second to sixth valves in the CH manifold (CH: V2 to V6) through CTR. Actuate the first valve in the CTR manifold (CTR: V1) to detect the flow rate through CH.

[0153] 3-1. External leakage test: Pressurize the inlet 2 ( Figure 11A ) and the outlet. Actuate (open) the valves (CH: V2 to V6). Then cut off the pressurized gas. Measure the pressure drop after the end of the leakage test duration.

[0154] 3-2. Valve seat leakage test: Pressurize the inlet 2 ( Figure 11A ). Close the valves (CH: V2 to V6). Then cut off the pressurized gas. Measure the pressure drop after the end of the leakage test duration.

[0155] 3-2. Functional flow test: Pressurize the inlet 2 ( Figure 11A ). Test each valve (CH: V2 to V6) individually. Once a stable flow rate is reached, detect the individual flow rates.

[0156] 4. Fourth set of tests on two valves (CTR: V2 to V3) in the CTR manifold and five valves (RT: V1 to V5) in the RT manifold:

[0157] 4-1. External leakage test: Pressurize inlet 2 ( Figure 11A ) and the outlet. Actuate (open) the valves (CTR: V2 to V3; RT: V1 to V5). Then cut off the pressurized gas. Measure the pressure drop after the end of the leakage test duration.

[0158] 4-2. Valve seat leakage test: Pressurize inlet 2. Close the valves (CTR: V2 to V3; RT: V1 to V5). Then cut off the pressurized gas. Measure the pressure drop after the end of the leakage test duration.

[0159] 4-3. Functional flow test: Pressurize inlet 2. Test each valve (CTR: V2 to V3; RT: V1 to V5) individually. Once a stable flow rate is reached, record the individual flow rate.

[0160] The test results are shown in Table 1. As shown in Table 1, all results including external leakage and valve seat leakage meet the pass criteria of a pressure drop less than 1 / 1000 of the inlet test pressure. The device including the valves and ports has good sealing and shows no or very little leakage. The functional flow test results also indicate that the device including these valves can operate normally and there is no blockage in the flow path. The devices and systems provided in this disclosure can be used with reagents having good fluidity.

[0161] Table 1

[0162] Although various embodiments of this disclosure have been described above, it should be understood that they are presented by way of example and not limitation. Similarly, the various figures may depict example architectures or configurations that are provided to enable those of ordinary skill in the art to understand the exemplary features and functions of this disclosure. However, such persons will understand that this disclosure is not limited to the example architectures or configurations shown, but rather can be implemented using various alternative architectures and configurations. Additionally, as will be understood by those of ordinary skill in the art, one or more features of one embodiment can be combined with one or more features of another embodiment described herein. Therefore, the breadth and scope of this disclosure should not be limited by any of the above exemplary embodiments.

[0163] It should also be understood that any reference in this document to elements using terms such as "first", "second", etc. generally does not limit the number or order of these elements. Rather, these terms can be used herein as a convenient means to distinguish between two or more elements or instances of an element. Thus, the reference to a first element and a second element does not mean that only two elements can be employed, or that the first element must precede the second element in some manner.

[0164] In addition, those of ordinary skill in the art will understand that any of a variety of different technologies and techniques can be used to represent information and signals. For example, data, instructions, commands, information, signals, bits, and symbols that may be referred to in the above description can be represented by voltages, currents, electromagnetic waves, magnetic fields or particles, optical fields or particles, or any combination thereof.

[0165] Those of ordinary skill in the art should also understand that any of the various illustrative logical blocks, modules, processors, devices, circuits, methods, and functions described in connection with the aspects disclosed herein can be implemented by electronic hardware (e.g., digital implementation, analog implementation, or a combination thereof), firmware, various forms of programs or design code containing instructions (which may be referred to herein for convenience as "software" or "software modules"), or any combination of these technologies.

[0166] To clearly illustrate this interchangeability of hardware, firmware, and software, the various illustrative components, blocks, modules, circuits, and steps have been described above in terms of their functional aspects. Whether this functionality is implemented as hardware, firmware, or software, or a combination of these technologies, depends on the specific application and design constraints imposed on the overall system. A person skilled in the art can implement the described functionality in various ways for each specific application, but such implementation decisions do not result in departing from the scope of this disclosure. According to the various embodiments, a processor, device, component, circuit, structure, machine, module, etc. can be configured to perform one or more of the functions described herein. The terms "configured to" or "configured for" used herein with respect to a specified operation or function refer to a processor, device, component, circuit, structure, machine, module, etc. that is physically constructed, programmed, and / or arranged to perform the specified operation or function.

[0167] In addition, those of ordinary skill in the art will understand that the various illustrative logical blocks, modules, devices, components, and circuits described herein can be implemented within or performed by an integrated circuit (IC), which can include a general-purpose processor, a digital signal processor (DSP), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA), or other programmable logic device, or any combination thereof. The logical blocks, modules, and circuits can further include an antenna and / or transceiver to communicate with various components within a network or within a device. The general-purpose processor can be a microprocessor, but in the alternative, the processor can be any conventional processor, controller, or state machine. The processor can also be implemented as a combination of computing devices, e.g., a combination of a DSP and a microprocessor, multiple microprocessors, one or more microprocessors in conjunction with a DSP core, or any other suitable configuration for performing the functions described herein.

[0168] If implemented in software, the functions can be stored as one or more instructions or code on a computer-readable medium. Accordingly, the steps of the methods or algorithms disclosed herein can be implemented as software stored on a computer-readable medium. A computer-readable medium includes both computer storage media and communication media, which includes any medium that can be enabled to transfer a computer program or code from one place to another. The storage media can be any available media that can be accessed by a computer. By way of example and not limitation, such computer-readable media can include RAM, ROM, EEPROM, CD-ROM or other optical disk storage, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to store the desired program code in the form of instructions or data structures and that can be accessed by a computer.

[0169] In this document, as used herein, the term "module" refers to software, firmware, hardware, and any combination of these elements for performing the associated functions described herein. Additionally, for purposes of discussion, the various modules are described as discrete modules; however, as will be apparent to those of ordinary skill in the art, two or more modules can be combined to form a single module that performs the associated functions in accordance with embodiments of the present disclosure.

[0170] Additionally, a memory or other storage device, as well as communication components, may be employed in embodiments of the present disclosure. It will be understood that, for purposes of clarity, the above description has been presented with reference to different functional units and processors in describing embodiments of the present disclosure. However, it will be apparent that any suitable distribution of functionality between different functional units, processing logic elements or domains may be used without departing from the present disclosure. For example, functions shown to be performed by separate processing logic elements or controllers may be performed by the same processing logic element or controller. Thus, the reference to specific functional units is only a reference to the appropriate means for providing the described functionality, rather than an indication of a strict logical or physical structure or organization.

[0171] Various modifications to the embodiments described in the present disclosure will be readily apparent to those skilled in the art, and the general principles defined herein may be applied to other embodiments without departing from the scope of the present disclosure. Thus, the present disclosure is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the novel features and principles disclosed herein, as recited in the appended claims.

Claims

1. A fluid device, comprising: A plurality of first inlet ports; A first common channel; A plurality of first valves, each of the plurality of first valves being associated with one of the plurality of first inlet ports, wherein each first valve is fluidly coupled between the associated first inlet port and the first common channel; A plurality of second inlet ports; A second common channel; A plurality of second valves, each of the plurality of second valves being associated with one of the plurality of second inlet ports, wherein each second valve is fluidly coupled between the associated second inlet port and the second common channel; A plurality of outlet ports; A third common channel; A plurality of third valves, each of the plurality of third valves being associated with one of the plurality of outlet ports, wherein each third valve is fluidly coupled between the associated outlet port and the third common channel; A first shut-off valve fluidly coupled between the first common channel and the third common channel; and A second shut-off valve fluidly coupled between the second common channel and the third common channel.

2. The fluid device according to claim 1, wherein: The plurality of first inlet ports, the first common channel, the plurality of first valves, and the first shut-off valve are integrated in a first input section of the fluid device; The plurality of second inlet ports, the second common channel, the plurality of second valves, and the second shut-off valve are integrated in a second input section of the fluid device; The plurality of outlet ports, the third common channel, and the plurality of third valves are integrated in an output section of the fluid device; and The output section is physically coupled between the first input section and the second input section.

3. The fluid device according to claim 2, wherein: The first input section and the second input section are separated from each other.

4. The fluid device according to claim 1, wherein: All valves among the plurality of first valves, the plurality of second valves, the plurality of third valves, the first shut-off valve, and the second shut-off valve are arranged in parallel on the same first side of the fluid device.

5. The fluid device according to claim 4, wherein: All ports among the plurality of first inlet ports, the plurality of second inlet ports, and the plurality of outlet ports are arranged on the same second side of the fluid device; and The second side is opposite to the first side.

6. The fluid device according to claim 1, wherein: Each first inlet port is configured to receive a first liquid; and Each second inlet port is configured to receive a second liquid.

7. The fluid device according to claim 6, wherein: The first liquid is selected from a first group consisting of: an oxidant, a first capping reagent (A), a second capping reagent (B), and an electrochemical reaction medium; and The second liquid is selected from a second group consisting of: an amide compound, an activator, and an inert gas.

8. The fluid device according to claim 7, wherein: The separation between the first group and the second group minimizes cross-contamination between the first group and the second group toward the outlet port.

9. The fluid device according to claim 6, wherein: the plurality of first inlet ports includes a first number of first inlet ports; and the plurality of second inlet ports includes a second number of second inlet ports.

10. The fluid device according to claim 9, wherein: the first number is different from the second number.

11. The fluid device according to claim 10, wherein: the first number is less than the second number.

12. The fluid device according to claim 1, further comprising: a plurality of first inlet channels, each of the plurality of first inlet channels corresponding to one of the plurality of first inlet ports, wherein each first inlet channel is vertically disposed in the fluid device perpendicular to the longitudinal direction of the fluid device and is fluidly coupled between the corresponding first inlet port and the associated first valve; a plurality of second inlet channels, each of the plurality of second inlet channels corresponding to one of the plurality of second inlet ports, wherein each second inlet channel is vertically disposed in the fluid device and is fluidly coupled between the corresponding second inlet port and the associated second valve; and a plurality of outlet channels, each of the plurality of outlet channels corresponding to one of the plurality of outlet ports, wherein each outlet channel is vertically disposed in the fluid device and is fluidly coupled between the corresponding outlet port and the associated third valve.

13. The fluid device according to claim 12, wherein: the first common channel, the second common channel, and the third common channel are horizontally disposed in the fluid device along the longitudinal direction of the fluid device.

14. The fluid device according to claim 13, wherein: all channels among the plurality of first inlet channels, the plurality of second inlet channels, the plurality of third inlet channels, the first common channel, the second common channel, and the third common channel have the same cross-sectional area and the same inner diameter.

15. The fluid device according to claim 14, wherein: all valves among the plurality of first valves, the plurality of second valves, the plurality of third valves, the first stop valve, and the second stop valve have the same structure and the same orifice diameter.

16. The fluid device according to claim 15, wherein: the liquid flowing in each of the plurality of first inlet channels, the plurality of second inlet channels, the plurality of third inlet channels, the first common channel, the second common channel, and the third common channel is isolated from the atmosphere and is driven by a pressurized inert gas.

17. The fluid device according to claim 15, wherein: the same cross-sectional area is between 0.1 and 10 square millimeters; the internal volume of the fluid device is between 1 and 100 milliliters; and the same inner diameter is substantially the same as the same orifice diameter.

18. The fluid device according to claim 12, wherein: when the first valve is open, it allows the first liquid to flow from the associated first inlet port through the corresponding first inlet channel, through the first valve, to the first common channel; When the first shut-off valve is open, it allows the first liquid to flow from the first common passage through the first shut-off valve to the third common passage; and When the third valve is open, it allows the first liquid to flow from the third common passage through the third valve, through the corresponding outlet passage, to the associated outlet port.

19. The fluid device according to claim 12, wherein: When the second valve is open, it allows the second liquid to flow from the associated second inlet port, through the corresponding second inlet passage, through the second valve, to the second common passage; When the second shut-off valve is open, it allows the second liquid to flow from the second common passage through the second shut-off valve to the third common passage; and When the third valve is open, it allows the second liquid to flow from the third common passage through the third valve, through the corresponding outlet passage, to the associated outlet port.

20. A reagent delivery system, comprising: A plurality of first reagent containers, each of the plurality of first reagent containers containing a corresponding first liquid reagent selected from a first group; A plurality of second reagent containers, each of the plurality of second reagent containers containing a corresponding second liquid reagent selected from a second group; A fluid device, the fluid device including a plurality of first inlet ports, a plurality of second inlet ports, and a plurality of outlet ports, wherein, Each of the plurality of first reagent containers is fluidly connected to one of the plurality of first inlet ports, and Each of the plurality of second reagent containers is fluidly connected to one of the plurality of second inlet ports; and A plurality of chambers, each of the plurality of chambers including a first chamber port and a second chamber port, wherein the first chamber port of each chamber is fluidly connected to one of the plurality of outlet ports.

21. The reagent delivery system according to claim 20, further comprising: An inert gas source configured to provide pressurized inert gas; An inert gas manifold connected to the inert gas source and configured to distribute the pressurized inert gas to the plurality of first reagent containers and the plurality of second reagent containers; And A plurality of bubble sensors.

22. The reagent delivery system according to claim 21, wherein: The inert gas manifold has an inlet that is connected to the inert gas source via a first plastic tube; and The inert gas manifold has a plurality of outlets.

23. The reagent delivery system according to claim 22, further comprising: A plurality of pressure regulators, each of the pressure regulators being fluidly connected to one of the plurality of outlets of the inert gas manifold via a second plastic tube.

24. The reagent delivery system according to claim 23, further comprising: At least one first side manifold fluidly connected between at least one of the plurality of outlets of the inert gas manifold and the plurality of first reagent containers via a third plastic tube; And At least one second side manifold, the at least one second side manifold being fluidly coupled between at least one of the plurality of outlets of the inert gas manifold and the plurality of second reagent containers via a third plastic tube.

25. The reagent delivery system according to claim 24, wherein: the at least one second side manifold includes one manifold fluidly coupled to all of the plurality of second reagent containers; and the at least one first side manifold includes: a first manifold fluidly coupled to three of the plurality of first reagent containers; and a second manifold fluidly coupled to another two of the plurality of first reagent containers.

26. The reagent delivery system according to claim 24, wherein: each of the plurality of second reagent containers is fluidly coupled to a corresponding second inlet port of the fluid device via a fourth plastic tube; and each of the plurality of first reagent containers is fluidly coupled to a corresponding first inlet port of the fluid device via a fifth plastic tube.

27. The reagent delivery system according to claim 26, further comprising: a plurality of second side flow sensors, each of the plurality of second side flow sensors being coupled to the fourth plastic tube connecting the second reagent container to the corresponding second inlet port and configured to monitor the flow rate of a corresponding second liquid reagent flowing from the second reagent container to the corresponding second inlet port.

28. The reagent delivery system according to claim 26, further comprising: a plurality of first side flow sensors, each of the plurality of first side flow sensors being coupled to the fifth plastic tube connecting the first reagent container to the corresponding first inlet port and configured to monitor the flow rate of a corresponding first liquid reagent flowing from the first reagent container to the corresponding first inlet port.

29. The reagent delivery system according to claim 23, wherein: the second chamber port of each chamber is fluidly coupled to one of the plurality of bubble sensors.

30. The reagent delivery system according to claim 29, wherein: the plurality of outlet ports are arranged in a row on one side of the fluid device; a first outlet port arranged at one end of the row is directly coupled to a first bubble sensor, and no chamber is provided between the first outlet port and the first bubble sensor; and a second outlet port arranged at the other end of the row is directly coupled to a second bubble sensor, and no chamber is provided between the second outlet port and the second bubble sensor.

31. The reagent delivery system according to claim 30, further comprising: a plurality of first three-way valves, each of the plurality of first three-way valves having a first end and a second end; and a plurality of second three-way valves, each of the plurality of second three-way valves having a first end and a second end.

32. The reagent delivery system according to claim 31, further comprising: a plurality of first two-way valves, each of the plurality of first two-way valves being coupled between the second chamber port of one of the plurality of chambers and the first end of a corresponding first three-way valve; and A plurality of second two-way valves, each of the plurality of second two-way valves being coupled between a second chamber port of one of the plurality of chambers and a first end of a corresponding second three-way valve.

33. The reagent delivery system according to claim 32, wherein: The second end of each first three-way valve is switchable between the first waste container and a pressure regulator fluidly coupled to one of the plurality of outlets of the inert gas manifold; And The second end of each second three-way valve is switchable between the second waste container and the pressure regulator.

34. The reagent delivery system according to claim 33, wherein, The fluid device further includes: A first common channel; A plurality of first valves, each of the plurality of first valves being associated with one of the plurality of first inlet ports, wherein each first valve is fluidly coupled between the associated first inlet port and the first common channel; A second common channel; A plurality of second valves, each of the plurality of second valves being associated with one of the plurality of second inlet ports, wherein each second valve is fluidly coupled between the associated second inlet port and the second common channel; A third common channel; A plurality of third valves, each of the plurality of third valves being associated with one of the plurality of outlet ports, wherein each third valve is fluidly coupled between the associated outlet port and the third common channel; A first shut-off valve fluidly coupled between the first common channel and the third common channel; and A second shut-off valve fluidly coupled between the second common channel and the third common channel.

35. The reagent delivery system according to claim 34, further comprising: A cleaning liquid container containing a cleaning liquid configured to clean the channels, valves, and ports of the fluid device, wherein the cleaning liquid container is coupled between one of the plurality of pressure regulators and the second common channel.

36. The reagent delivery system according to claim 35, further comprising: A third two-way valve coupled between the cleaning liquid container and the second common channel; And A third three-way valve having a first end coupled to the third two-way valve and a second end switchable between the first waste container and the cleaning liquid container.

37. The reagent delivery system according to claim 36, further comprising: A third bubble sensor coupled between the first common channel and the second waste container; And A fourth two-way valve coupled between the third bubble sensor and the second waste container.

38. The reagent delivery system according to claim 37, further comprising: A first gas pipe coupled between a first pressure regulator and a second inlet port at an end of the fluid device and configured to transport the pressurized inert gas from the first pressure regulator to the second inlet port to purge the fluid device; And A first pressure sensor, the first pressure sensor being coupled to the first gas tube and configured to monitor the pressure of the gas blown into the fluid device.

39. The reagent delivery system according to claim 37, further comprising: A second gas tube, the second gas tube being coupled between a second pressure regulator and each of a first three-way valve and a second three-way valve, and configured to transport the pressurized inert gas from the second pressure regulator to at least one of the plurality of chambers to purge the at least one chamber; And A second pressure sensor, the second pressure sensor being coupled to the second gas tube and configured to monitor the pressure of the gas blown into the at least one chamber.

40. The reagent delivery system according to claim 37, further comprising: A third pressure sensor, the third pressure sensor being directly coupled to one of the plurality of outlets of the inert gas manifold and configured to monitor the pressure of the gas blown out of the inert gas manifold, with no pressure regulator provided between the third pressure sensor and the outlet.

41. The reagent delivery system according to claim 37, further comprising: A fourth pressure sensor, the fourth pressure sensor being coupled between a third pressure regulator and a second side manifold fluidly coupled to the plurality of second reagent containers, and configured to monitor the pressure of the gas blown into the plurality of second reagent containers.

42. The reagent delivery system according to claim 23, wherein: Each of the plurality of bubble sensors is configured to monitor the state of a corresponding chamber to determine whether the corresponding chamber is completely filled with liquid; and Each of the plurality of pressure regulators is configured to control the pressure and / or the blowing rate of the pressurized inert gas based on feedback information from at least one of the plurality of bubble sensors.

43. The reagent delivery system according to claim 42, wherein: The feedback information is further used to control at least one valve in the reagent delivery system.

44. The reagent delivery system according to claim 20, wherein: The pressurized inert gas includes at least one of the following: argon, nitrogen, and helium.

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