Manually operated microtube automatic capper/decapper system for clinical laboratory and biological laboratory personnel

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PCR tests (from specimen collection to result acquisition) involve sample pretreatment, nucleic acid extraction, and PCR procedure. Automating the pretreatment process is crucial to mitigate the risk of infection for workers and to reduce the likelihood of sample contamination-triggered misdiagnosis, particularly when handling centrifuge tubes, cryopreservation tubes, and microtubes. Robotic systems have been engineered to automate cell culture and PCR-based diagnosis , predominantly designed for use with screw-capped containers. However, this leaves a notable gap in automation solutions for microtubes equipped with press-type caps. To address this gap, we developed a versatile microtube capper/decapper system. On the other hand, many tasks of manual operation using microtubes, which are routinely conducted in clinical tests and biological experiments, were performed. Despite the risks of contamination and infection derived from the manual handling of microtube caps, which can compromise diagnosis/experiment accuracy and worker safety, devices for manually opening and closing microtube caps without direct contact remain lacking. Therefore, leveraging the technology from the developed versatile microtube capper/decapper system for laboratory automation, we created a manually operated microtube equipped with an automatic capper/decapper system tailored for personnel in clinical and biological laboratories. In this study, we first examined the required specifications and prerequisites for a manual microtube capper/decapper and clarified the operating methods, operating procedures, operation environment, device size, accompanying functions, etc. Based on the required specifications and preconditions, we proceeded with the mechanical and control design of the conceptual model, manufactured a prototype, and confirmed its basic functions and performance. The compliant to the required specifications and preconditions and the usefulness of the proposed manual microtube capper/decapper were validated through various experiments and demonstrations. Because microtubes are used in various clinical tests and biological experiments, we believe that the proposed system can markedly reduce the workload for personnel across numerous clinical and biological laboratories. Laboratory automation Mechanism design Microtube Clinical examination Biological experiment Manual operation Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Introduction Polymerase chain reaction (PCR) is an effective method for diagnosing infectious diseases and has been the primary method throughout the novel coronavirus disease (COVID-19) pandemic [1]. To accommodate newly emerging viruses and the mutants in the future, it is crucial to establish an inspection system that offers flexibility and continuity in both inspection operations and information processing. PCR tests (from specimen collection to result acquisition) involve a sample pretreatment, nucleic acid extraction, and PCR procedure. Automating the pretreatment process is significant due to the risks of infection for workers and potential misdiagnosis caused by sample contamination, particularly when handling centrifuge tubes, cryopreservation tubes, and microtubes. Robotic systems for automating cell culture [2]-[4] and PCR-based diagnosis [5]-[8] have been developed, but these primarily cater to containers with screw caps, leaving a gap for systems compatible with microtubes with press-type caps. According to our knowledge, there are limited examples of automated systems incorporating microtubes with press-type caps [9]-[11]. Although capper/decapper systems for press-type caps exist [12]-[14], there is a notable lack of compact microtube cappers/decappers that accommodate a wide array of microtubes. Addressing this gap, we developed a versatile microtube capper/decapper system [15]. Moreover, in clinical tests and biological experiments, numerous tasks like centrifugation, vortexing, spinning down, and pipetting are conducted manually. Operations such as centrifugation, vortexing, and spinning down require closed microtube caps, while pipetting requires open caps. Manual handling of microtube caps poses a contamination and infection risk, compromising both test/experiment accuracy and worker safety. Despite the existence of compact, manually operated devices for pipetting [16], [17], vortex mixing [18], [19], and spinning down [20], [21] that can be utilized within a biological safety cabinet, a device for manually opening and closing microtube caps without direct contact is absent. This underscores the need for a microtube capper/decapper capable of safely handling caps without direct contact. In this paper, we first examine the required specifications and prerequisites for a manual microtube capper/decapper. We then proceed to design the mechanism and control of a conceptual model, followed by prototyping this model to confirm its basic functions and performance. The utility of the proposed manual microtube capper/decapper is demonstrated through various tests and demonstrations. Methods This section delineates the essential specifications and prerequisites for the manual microtube capper/decapper, followed by the mechanism and control design of a conceptual model, taking into account the needs of workers and researchers in biological experiments and clinical tests. Conceptual design/basic design process Required specifications and preconditions of conceptual design To facilitate the conceptual design of the manual microtube capper/decapper, we established the following specifications and preconditions, reflecting the requirements of biological experiment and clinical test personnel: Operators must manually insert and remove microtubes from the capper/decapper. The device should accommodate the opening and closing of caps on both 1.5 mL and 2 mL microtubes. It should allow for the insertion of microtubes with the cap in both open and closed states, as well as the removal. The size, weight, and power source of the device should be compatible with use within a biological safety cabinet, and the device should be easy to carry (easy to put in and take out of the cabinet) The operating procedures must be straightforward and simple. It must have a function to emergency stop the device when operators feel danger. The device should permit visual inspection of the microtube’s interior when the cap is in open and closed positions. The device should be operable with a mobile battery. It should be cleanable with alcohol or similar disinfectants. The device with a cooling function for specimens and reagents within the microtube is preferable. It should minimize the risk of contamination from specimen scattering, exposure to microorganisms, and aerosol generation during cap manipulation. Taking these requirements and conditions into account, we designed a manual microtube capper/decapper. Basic design of manual microtube capper/decapper body Figures 1 and 2 illustrate the manual microtube capper/decapper body and the microtube holder, respectively. The cap opening and closing mechanism is fundamentally similar to that of the automated microtube capper/decapper previously developed [15]. For manual operation, a switch box has been incorporated into the main body’s front. The subsequent section will detail the control system and operating procedures, while this section focuses on the mechanism’s structure. The microtube is secured by a C-shaped holder near the top and a stopper near the bottom, allowing for external observation of the microtube. This dual-point securing method ensures stability during cap manipulation. Additionally, this setup facilitates precise pipetting, as the operator can visually assess the spatial relationship between the pipette tip and the sample within the microtube. The stopper components are interchangeable, accommodating both 1.5 mL and 2 mL microtubes, as depicted in Figure 2 (3) and (4). While the main body is not airtight, all electrical components, including the drive motor and sensors, are encased and can be cleaned with alcohol. The cap is opened by elevating the lower surface of the cap’s front protrusion using the opening arm. This action, synchronized with specific movements, facilitates a smooth cap opening process. A push pin is positioned inside the C-shaped holder’s side. The inner surface of the closure arm features two levels with a slope in between. As the closure arm rotates forward, the push pin transitions from the lower level, up the slope, to the higher level, exerting pressure on the microtube’s upper side (Figure 2 (2)). Moreover, during cap opening, the closing arm’s tip gently presses the cap’s top while the opening arm operates, preventing the cap from dislodging abruptly. This mechanism significantly reduces the risk of contamination through specimen or virus dispersal and aerosol generation during cap manipulation. Figure 1 Conceptual design of a manual microtube capper/decapper Figure 2 Microtube holding mechanism and visibility Figure 3 depicts the cooling function, which comprises a cooling box and a cooling material. The front side of the cooling box was designed to be open, allowing visibility into the microtube. Ice or frozen gel was used for the cooling material. Depending on the required cooling duration, a large or small cooling box may be selected. Although integrating a Peltier element-based cooling device was considered, to minimize the system’s size and reduce power consumption, the cooling box and cooling material were synergized for the cooling function. This approach requires precooling the cooling material, but it allows for use only as needed, contributing to the system’s compactness. Fig. 3 Cooling function Control system design Figure 4 illustrates the control system. The microtube capper/decapper is governed by a mini box PC running Windows 11, paired with a motor position control system (Maxon EPOS2 24/2), both located at the device’s base. The motor position control system receives operation signals for the opening, closing, and stop buttons through an interface circuit board. The device can be powered by a 100 V AC supply through an AC-DC converter ranging from 15 to 24 V DC, or by a mobile battery designed for laptop PCs. Within the device, a 12 V DC supply powers the mini box PC, the EPOS2, and the interface circuit board via a DC-DC converter. Next, we will explain a series of operations. To commence operation, the power switch located at the rear of the microtube capper/decapper is activated, followed by the powering on of the mini box PC at the front. Subsequently, the capper/decapper’s operating software initiates automatically, performs a homing sequence, and enters standby mode. An LED indicator near the operation buttons illuminates to signal readiness for operation. Figure 4 Control system configuration Figure 5 illustrates the state transition diagram following the standby state, highlighting the relationship between switch operations and cap opening/closing actions. The operation follows a structured flow, with three distinct procedures aligned with the established specifications: (1) Procedure A involves placing a microtube with a closed cap in the standby state. By pressing the opening button (blue button), the cap is opened, transitioning the tube to an opened state. Subsequent pipetting actions are followed by pressing the closing button (blue button) to seal the cap, reverting the system to the standby state for microtube retrieval. This sequence represents the standard operation. (2) Procedure B is initiated after opening the cap via Procedure A. Pressing the opening button again maintains the open cap state without transitioning to closure, effectively entering standby mode. This procedure is optimal for removing the microtube while keeping the cap open. (3) Procedure C caters to situations where a microtube with an open cap is set in the standby state. Pressing the closing button seals the cap, returning the system to standby, allowing for the microtube’s removal. This procedure is dedicated to executing cap closure operations exclusively. Regarding the described state transition, should you inadvertently activate an unintended operation, you can rectify this by subsequently pressing the appropriate button for your desired action, based on the current state of the system. This allows you to ultimately execute the intended operation. If it becomes necessary to halt the operation immediately, you can employ the stop button (red button) for this purpose. However, be advised that using the stop button will necessitate a system restart. Figure 5 State transition and operation procedure This conceptual and basic design framework enables the realization of a manually operated microtube automatic capper/decapper system that meets the specified requirements and conditions. Results and discussion This segment will detail the prototyping of a microtube capper derived from the aforementioned design, alongside evaluations of mechanical functionality and usability, ensuring compliance with the specified requirements and conditions. Prototype model Figure 6 presents a prototype of the proposed manually operated microtube automatic capper/decapper system, conforming to the mechanical design outlined earlier. The front panel hosts the mini box PC switch, with the power supply connector and switch positioned at the rear. The stopper for a 2 mL microtube is placed on the back side. The prototype’s total weight is approximately 1,330 g, underscoring its compact and lightweight nature for facile transportation within a biological safety cabinet. It facilitates direct visual inspection of the microtube’s interior, whether the cap is open or closed. The exposed metal parts are primarily constructed from anodized aluminum alloy or stainless steel, and the covers are 3D-printed parts (printed by Stratasys F170, 333-60300 ABS-M30 (Ivory)). Particular damage was not observed after wiping and spraying with disinfectant alcohol. Figure 6 Overview of a prototype of the proposed manually operated microtube automatic capper/decapper system Evaluation of opening and closing cap function The function of the opening and closing cap of the microtube was evaluated. The microtubes used this time were Thermo Fisher #3448 (1.5 ml) and Greiner 623201 (2 ml). We verified that when the microtube capper/decapper was powered by a 15 to 24 V DC supply, connected through an AC–DC converter from a 100 V AC source, and linked to a mini box PC, the device’s operating program for manual capping and decapping automatically initiated. It executed a return-to-origin operation and then entered a standby state. It took about 30 s from powering on the mini box PC to the standby state. Furthermore, we confirmed that a series of operations, such as Procedures A–C, can be performed by pressing the open and close buttons as appropriate after setting the microtube in the standby state. Figure 7 shows a series of opening and closing operations using the manual microtube capper (Procedure A). We also confirmed smooth opening and closing operations. The time from pressing the button to completing the opening and closing operations were 5.4 and 4.9 s each. The operation could be stopped immediately by pressing the stop button. Furthermore, it was driven in the same way by a mobile battery designed for notebook PCs (SANWA SUPPLY INC., 700-BTL033BK, DC12 V, 16 V, 19 V (3.6A) 17400mAh, 62.64Wh, and 700-BTL049 DC12 V (3.6A) 17400mAh, 62.64Wh). Figure 7 Opening and closing cap motion (Procedure A) Evaluation of the operation time of pipetting tasks The working times were compared between the full manual operation and the manual operation using the microtube capper/decapper. The comparison tasks were determined with reference to the procedures performed in the sample pretreatment process of the PCR-based diagnosis. Figure 8 shows the pipetting task sequences of full manual operation and manual operation using the microtube capper/decapper. The evaluation pipetting task involves dispensing 150 μL from a cryopreservation tube (SARSTEDT 72. 694. 100. 02) containing 1,000 μL of tap water to a microtube: Thermo Fisher #3448 (1.5 ml) containing 600 μL of tap water. One lot is 12 pieces. Figure 9 shows the arrangement of cryopreservation tubes and microtubes and opening/closing cap and aspiration/dispensing position. The tubes before aspiration/dispensing are arranged on the right side, and the tubes after aspiration/dispensing are arranged on the left side. The experimental setup is shown in Figure 10 . Before starting the experiment, a subject (right-handed, nonprofessional), one of the authors, was required to familiarize himself with the pipetting task. The subject ran four trials (12 pieces × 4 lots) for each condition, each of which was video-recorded. Each operation time shown in Fig. 8 (handling and opening cap time, pipetting time and closing cap and the handling time) was retrieved based on the video. Figure 8 Pipetting task sequences of full manual operation and manual operation using the microtube capper/decapper Figure 9 Arrangement of cryopreservation tubes and microtubes and opening/closing cap and aspiration/dispensing position Figure 10 Experimental setup for evaluation of operating time of pipetting tasks Figure 11 shows the experimental results of handling and opening cap time, pipetting time and closing cap and handling time by box plots, and the average operation time of one piece by bar graph. Due to some operational sequence errors in the first trial, the box plot data excluded the operation times affected by these errors. However, it was included in the average working time per piece. The first trial had a large variation, but the second to fourth trials had a smaller variation by learning curve. The time required to open and close the cap, including tube handling, was approximately 1–2 s longer when using the microtube capper/decapper relative to the full manual operation. No significant difference existed in dispensing time. The time taken to open and close the cap using the microtube capper was about 5 s each, but if parallel operations are possible during the opening and closing operations, the impact on the overall operation time is small, so the opening and closing time of the cap using the microtube capper is acceptable. Furthermore, the capper can markedly reduce the burden on the operator when opening and closing the microtube cap. Figure 11 Experimental results of h andling and opening cap time, p ipetting time, closing cap and handling time and average operation time of one piece. Evaluation of the cooling function The cooling function using the cooling boxes was evaluated. The cooling box was prototyped by a 3D printer (printed by Formlabs Form 3, Resin Rigid 4000 V1). The capacities of the small and large cooling boxes were 32.3 mL and 55.5 mL, respectively. Figure 12 shows the experimental conditions for the cooling function. The experiments were conducted under four conditions: (1) No-cooling box sample, (2) Small cooling box sample (Tap water ice), (3) Small cooling box sample (frozen gel), and (4) Large cooling box sample (Tap water ice). Furthermore, under all experimental conditions, room temperature and left indoor samples were simultaneously measured. The temperature was measured by K-Thermocouple (HIOKI 9810) in the microtube bottom and middle position and recorded by a data logger (HIOKI LR8431). An hour of data was acquired. Tap water ice or frozen gel was used as the cooling material. After putting tap water or gel (Contents of Snow Pack R-20 by MIE Chemical Industry) in the cooling box and cooling it in a freezer (−17℃) to freeze, experiments of the cooling functions were conducted. A 1,000 μL of tap water in the microtube: Thermo Fisher #3448 (1.5 ml) was cooled to approximately 0°C–4°C with crushed ice. Figure 13 shows the experimental setup for the cooling functions. Figure 14 shows the experimental results of the cooling functions as the average value of time series data acquired three times under the same conditions. The room temperatures were 22°C −23°C in all cases, and the experiments were conducted in almost the same temperature environment. In the case of the no-cooling function, the temperature rises after the measurement starts, rising to about 35℃ in 20–30 min, and then remaining almost constant. The heat sources are thought to be the mini box PC and motor position control system (Maxon EPOS2 24/2). In contrast, using the cooling box caused the temperature of the tap water in the microtube to be maintained at about 5℃ or less for about 20–40 min. Although no noticeable difference was observed between the tap water ice and the frozen gel, the cooling function was maintained for a long time, depending on the difference in capacity between large and small boxes. While precise temperature control over long periods proved challenging with a cooling box–based cooling function, it effectively sustained the coolness of the microtube contents for short durations. The cooling performance is expected to improve through methods such as inserting a heat-insulating material between heat sources (the mini box PC and the Maxon EPOS2 24/2) and placing cooling material under the microtube. Figure 12 Experimental conditions for cooling function Figure 13 Experimental setup for cooling function Figure 14 Experimental results of the cooling functions. Discussion on required specifications and preconditions The considerations for the abovementioned requirement specifications and preconditions are summarized below. (1) Operators can manually insert and remove microtubes from the capper/decapper. (2) The device accommodates the opening and closing of caps on both 1.5 mL and 2 mL microtubes. (3) Using procedures A, B, and C, microtubes can be inserted and removed with their caps in both the open and closed states. (4) The size, weight, and power source of the device are compatible for use within a biological safety cabinet, and the device is easy to carry (easy to put in and take out of the cabinet) (5) The operating procedures are straightforward and simple, with only pushing buttons. (6) This device allows visual observation of the microtube’s interior when the cap is in open and closed positions. (7) The device is operable with a mobile battery. (8) It is cleanable with alcohol or similar disinfectants. (9) The device has a cooling function for specimens and reagents within the microtube. (10) Quantitative evaluations of the risk of contamination from specimen scattering, virus exposure, and aerosol generation during cap manipulation are currently being conducted and will be reported separately. Conclusion Manual handling of microtube caps poses a contamination and infection risk, compromising both diagnosis/experiment accuracy and worker safety. However, a device for manually opening and closing microtube caps without direct contact is absent. Therefore, leveraging the technology of our initially developed versatile microtube capper/decapper system for laboratory automation, we have developed a manually operated microtube equipped with an automatic capper/decapper system for clinical and biological laboratory personnel. The suit to the required specifications and preconditions and the usefulness of the proposed manual microtube capper/decapper were validated through various experiments and demonstrations. In the future, we plan to perform quantitative evaluations of contamination risk using the proposed microtube capper/decapper system. Furthermore, we plan to proceed with the social implementation of the proposed system. Given the extensive use of microtubes in diverse clinical and biological experiments, we believe that the proposed system can markedly reduce the workload of personnel across numerous clinical and biological laboratories. Abbreviations PCR Polymerase chain reaction LED Light-Emitting Diode Declarations Author contributions M.J. spearheaded the conceptual planning and design, the mechanical design, and the verification experiments for evaluations, in addition to drafting the initial manuscript. R.N. was instrumental in developing the control system, along with the design and implementation of the control software. Y.S., R.Y., T.K., and J.Y. were pivotal in defining the specifications and prerequisites for the conceptual design and carried out usability evaluations of the prototype for the proposed manually operated microtube automatic capper/decapper system. All authors have reviewed and endorsed the final manuscript. Acknowledgments The authors would like to thank Kawasaki City Institute for Public Health, Yamaguchi Prefectural Institute of Public Health and Environment, Hirakata City Public Health Center, National Mie Hospital, H.U. Group Research Institute G.K., and Laboratory Automation Supplier's Association for their comments and suggestions with required specifications and usability of the manually operated microtube automatic capper/decapper system. The authors wish to express their gratitude to the CREST, Japan Science and Technology Agency, for their support. 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Additional Declarations No competing interests reported. Supplementary Files Additionalfile1.mp4 Cite Share Download PDF Status: Published Journal Publication published 27 Sep, 2024 Read the published version in ROBOMECH Journal → Version 1 posted Editorial decision: Revision requested 15 Jul, 2024 Reviews received at journal 15 Jul, 2024 Reviews received at journal 05 Jul, 2024 Reviewers agreed at journal 20 Jun, 2024 Reviewers agreed at journal 17 Jun, 2024 Reviewers agreed at journal 03 Jun, 2024 Reviewers invited by journal 09 May, 2024 Editor assigned by journal 23 Apr, 2024 Submission checks completed at journal 22 Apr, 2024 First submitted to journal 21 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Diseases (CCPID)","correspondingAuthor":false,"prefix":"","firstName":"Takaaki","middleName":"","lastName":"KINOSHITA","suffix":""},{"id":294561207,"identity":"2b70ef0f-4691-43a7-8130-13c6c10765ca","order_by":5,"name":"Jiro YASUDA","email":"","orcid":"","institution":"Nagasaki University, Institute of Tropical Medicine (NEKKEN)","correspondingAuthor":false,"prefix":"","firstName":"Jiro","middleName":"","lastName":"YASUDA","suffix":""}],"badges":[],"createdAt":"2024-04-21 12:00:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4300601/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4300601/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s40648-024-00281-3","type":"published","date":"2024-09-27T15:57:11+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":55326890,"identity":"27851d63-eea9-464a-ad0d-689f82cf2d49","added_by":"auto","created_at":"2024-04-25 17:35:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":231528,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eConceptual design of a manual microtube capper/decapper\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4300601/v1/f08d6728b02fd614c08d4495.png"},{"id":55326888,"identity":"753ac75c-4e18-47aa-b963-ce6e60eaaef7","added_by":"auto","created_at":"2024-04-25 17:35:20","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":196464,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMicrotube holding mechanism and visibility\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4300601/v1/5634d1628d35072f8b8506ae.png"},{"id":55326895,"identity":"b6098da4-c85d-4535-a207-2f8b891e7b06","added_by":"auto","created_at":"2024-04-25 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of full manual operation and manual operation using the microtube capper/decapper\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-4300601/v1/e2ae6c22aaca6ae3d906794d.png"},{"id":55327115,"identity":"3e2c6e42-6498-42cb-ada5-674d658aeb0b","added_by":"auto","created_at":"2024-04-25 17:43:20","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":84960,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eArrangement of cryopreservation tubes and microtubes and opening/closing cap and aspiration/dispensing position\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"9.png","url":"https://assets-eu.researchsquare.com/files/rs-4300601/v1/ef6709384b2f6541e6b2854a.png"},{"id":55326898,"identity":"5cb2dd48-1eb2-4cd8-a09e-15c40f2e840d","added_by":"auto","created_at":"2024-04-25 17:35:21","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":469909,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eExperimental setup for evaluation of operating time of pipetting tasks\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"10.png","url":"https://assets-eu.researchsquare.com/files/rs-4300601/v1/ed0db244ad49bc2b5d530787.png"},{"id":55326899,"identity":"33f1cff4-5828-4405-9d1b-207d777c778a","added_by":"auto","created_at":"2024-04-25 17:35:21","extension":"png","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":91798,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eExperimental results of handling and opening cap time, pipetting time, closing cap and handling time and average operation time of one 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for cooling function\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"13.png","url":"https://assets-eu.researchsquare.com/files/rs-4300601/v1/0d6a72fe403a4e868a7b296d.png"},{"id":55326889,"identity":"cb2e2c7e-8578-4a8e-999b-fc3e35e5e811","added_by":"auto","created_at":"2024-04-25 17:35:20","extension":"png","order_by":14,"title":"Figure 14","display":"","copyAsset":false,"role":"figure","size":5713,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eExperimental results of the cooling functions.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Placeholderimage.png","url":"https://assets-eu.researchsquare.com/files/rs-4300601/v1/476c4d108629eb76918baa8b.png"},{"id":65627131,"identity":"e4e92dec-8582-43ab-b286-718b2533b615","added_by":"auto","created_at":"2024-09-30 16:12:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5827008,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4300601/v1/c3944254-34de-4023-bc07-a3dbf482a02e.pdf"},{"id":55326900,"identity":"a88389c5-3dd9-477d-bb16-e2beacdf3835","added_by":"auto","created_at":"2024-04-25 17:35:21","extension":"mp4","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":19665218,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile1.mp4","url":"https://assets-eu.researchsquare.com/files/rs-4300601/v1/80ccecf89fc665cc5f627d36.mp4"}],"financialInterests":"No competing interests reported.","formattedTitle":"Manually operated microtube automatic capper/decapper system for clinical laboratory and biological laboratory personnel","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePolymerase chain reaction (PCR) is an effective method for diagnosing infectious diseases and has been the primary method throughout the novel coronavirus disease (COVID-19) pandemic [1]. To accommodate newly emerging viruses and the mutants in the future, it is crucial to establish an inspection system that offers flexibility and continuity in both inspection operations and information processing. PCR tests (from specimen collection to result acquisition) involve a sample pretreatment, nucleic acid extraction, and PCR procedure. Automating the pretreatment process is significant due to the risks of infection for workers and potential misdiagnosis caused by sample contamination, particularly when handling centrifuge tubes, cryopreservation tubes, and microtubes.\u003c/p\u003e\n\u003cp\u003eRobotic systems for automating cell culture [2]-[4] and PCR-based diagnosis [5]-[8] have been developed, but these primarily cater to containers with screw caps, leaving a gap for systems compatible with microtubes with press-type caps. According to our knowledge, there are limited examples of automated systems incorporating microtubes with press-type caps [9]-[11]. Although capper/decapper systems for press-type caps exist [12]-[14], there is a notable lack of compact microtube cappers/decappers that accommodate a wide array of microtubes. Addressing this gap, we developed a versatile microtube capper/decapper system [15].\u003c/p\u003e\n\u003cp\u003eMoreover, in clinical tests and biological experiments, numerous tasks like centrifugation, vortexing, spinning down, and pipetting are conducted manually. Operations such as centrifugation, vortexing, and spinning down require closed microtube caps, while pipetting requires open caps. Manual handling of microtube caps poses a contamination and infection risk, compromising both test/experiment accuracy and worker safety. Despite the existence of compact, manually operated devices for pipetting [16], [17], vortex mixing [18], [19], and spinning down [20], [21] that can be utilized within a biological safety cabinet, a device for manually opening and closing microtube caps without direct contact is absent. This underscores the need for a microtube capper/decapper capable of safely handling caps without direct contact.\u003c/p\u003e\n\u003cp\u003eIn this paper, we first examine the required specifications and prerequisites for a manual microtube capper/decapper. We then proceed to design the mechanism and control of a conceptual model, followed by prototyping this model to confirm its basic functions and performance. The utility of the proposed manual microtube capper/decapper is demonstrated through various tests and demonstrations.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis section delineates the essential specifications and prerequisites for the manual microtube capper/decapper, followed by the mechanism and control design of a conceptual model, taking into account the needs of workers and researchers in biological experiments and clinical tests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConceptual design/basic design process\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRequired specifications and preconditions of conceptual design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo facilitate the conceptual design of the manual microtube capper/decapper, we established the following specifications and preconditions, reflecting the requirements of biological experiment and clinical test personnel:\u003c/p\u003e\n\u003col class=\"decimal_type\"\u003e\n \u003cli\u003eOperators must manually insert and remove microtubes from the capper/decapper.\u003c/li\u003e\n \u003cli\u003eThe device should accommodate the opening and closing of caps on both 1.5 mL and 2 mL microtubes.\u003c/li\u003e\n \u003cli\u003eIt should allow for the insertion of microtubes with the cap in both open and closed states, as well as the removal.\u003c/li\u003e\n \u003cli\u003eThe size, weight, and power source of the device should be compatible with use within a biological safety cabinet, and the device should be easy to carry (easy to put in and take out of the cabinet)\u003c/li\u003e\n \u003cli\u003eThe operating procedures must be straightforward and simple. It must have a function to emergency stop the device when operators feel danger.\u003c/li\u003e\n \u003cli\u003eThe device should permit visual inspection of the microtube\u0026rsquo;s interior when the cap is in open and closed positions.\u003c/li\u003e\n \u003cli\u003eThe device should be operable with a mobile battery.\u003c/li\u003e\n \u003cli\u003eIt should be cleanable with alcohol or similar disinfectants.\u003c/li\u003e\n \u003cli\u003eThe device with a cooling function for specimens and reagents within the microtube is preferable.\u003c/li\u003e\n \u003cli\u003eIt should minimize the risk of contamination from specimen scattering, exposure to microorganisms, and aerosol generation during cap manipulation.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eTaking these requirements and conditions into account, we designed a manual microtube capper/decapper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBasic design of manual microtube capper/decapper body\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigures\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;1\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;and 2\u003c/strong\u003e illustrate the manual microtube capper/decapper body and the microtube holder, respectively. The cap opening and closing mechanism is fundamentally similar to that of the automated microtube capper/decapper previously developed [15]. For manual operation, a switch box has been incorporated into the main body\u0026rsquo;s front. The subsequent section will detail the control system and operating procedures, while this section focuses on the mechanism\u0026rsquo;s structure.\u003c/p\u003e\n\u003cp\u003eThe microtube is secured by a C-shaped holder near the top and a stopper near the bottom, allowing for external observation of the microtube. This dual-point securing method ensures stability during cap manipulation. Additionally, this setup facilitates precise pipetting, as the operator can visually assess the spatial relationship between the pipette tip and the sample within the microtube. The stopper components are interchangeable, accommodating both 1.5 mL and 2 mL microtubes, as depicted in Figure 2 (3) and (4).\u003c/p\u003e\n\u003cp\u003eWhile the main body is not airtight, all electrical components, including the drive motor and sensors, are encased and can be cleaned with alcohol.\u003c/p\u003e\n\u003cp\u003eThe cap is opened by elevating the lower surface of the cap\u0026rsquo;s front protrusion using the opening arm. This action, synchronized with specific movements, facilitates a smooth cap opening process. A push pin is positioned inside the C-shaped holder\u0026rsquo;s side. The inner surface of the closure arm features two levels with a slope in between. As the closure arm rotates forward, the push pin transitions from the lower level, up the slope, to the higher level, exerting pressure on the microtube\u0026rsquo;s upper side (Figure 2 (2)). Moreover, during cap opening, the closing arm\u0026rsquo;s tip gently presses the cap\u0026rsquo;s top while the opening arm operates, preventing the cap from dislodging abruptly. This mechanism significantly reduces the risk of contamination through specimen or virus dispersal and aerosol generation during cap manipulation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 1 Conceptual design of a manual microtube capper/decapper\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 2 Microtube holding mechanism and visibility\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 3\u003c/strong\u003e depicts the cooling function, which comprises a cooling box and a cooling material. The front side of the cooling box was designed to be open, allowing visibility into the microtube. Ice or frozen gel was used for the cooling material. Depending on the required cooling duration, a large or small cooling box may be selected. Although integrating a Peltier element-based cooling device was considered, to minimize the system\u0026rsquo;s size and reduce power consumption, the cooling box and cooling material were synergized for the cooling function. This approach requires precooling the cooling material, but it allows for use only as needed, contributing to the system\u0026rsquo;s compactness.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFig. 3 Cooling function\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eControl system design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 4\u003c/strong\u003eillustrates the control system. The microtube capper/decapper is governed by a mini box PC running Windows 11, paired with a motor position control system (Maxon EPOS2 24/2), both located at the device\u0026rsquo;s base. The motor position control system receives operation signals for the opening, closing, and stop buttons through an interface circuit board. The device can be powered by a 100 V AC supply through an AC-DC converter ranging from 15 to 24 V DC, or by a mobile battery designed for laptop PCs. Within the device, a 12 V DC supply powers the mini box PC, the EPOS2, and the interface circuit board via a DC-DC converter.\u003c/p\u003e\n\u003cp\u003eNext, we will explain a series of operations. To commence operation, the power switch located at the rear of the microtube capper/decapper is activated, followed by the powering on of the mini box PC at the front. Subsequently, the capper/decapper\u0026rsquo;s operating software initiates automatically, performs a homing sequence, and enters standby mode. An LED indicator near the operation buttons illuminates to signal readiness for operation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 4 Control system configuration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 5\u0026nbsp;\u003c/strong\u003eillustrates the state transition diagram following the standby state, highlighting the relationship between switch operations and cap opening/closing actions. The operation follows a structured flow, with three distinct procedures aligned with the established specifications:\u003c/p\u003e\n\u003cp\u003e(1) Procedure A involves placing a microtube with a closed cap in the standby state. By pressing the opening button (blue button), the cap is opened, transitioning the tube to an opened state. Subsequent pipetting actions are followed by pressing the closing button (blue button) to seal the cap, reverting the system to the standby state for microtube retrieval. This sequence represents the standard operation.\u003c/p\u003e\n\u003cp\u003e(2) Procedure B is initiated after opening the cap via Procedure A. Pressing the opening button again maintains the open cap state without transitioning to closure, effectively entering standby mode. This procedure is optimal for removing the microtube while keeping the cap open.\u003c/p\u003e\n\u003cp\u003e(3) Procedure C caters to situations where a microtube with an open cap is set in the standby state. Pressing the closing button seals the cap, returning the system to standby, allowing for the microtube\u0026rsquo;s removal. This procedure is dedicated to executing cap closure operations exclusively.\u003c/p\u003e\n\u003cp\u003eRegarding the described state transition, should you inadvertently activate an unintended operation, you can rectify this by subsequently pressing the appropriate button for your desired action, based on the current state of the system. This allows you to ultimately execute the intended operation. If it becomes necessary to halt the operation immediately, you can employ the stop button (red button) for this purpose. However, be advised that using the stop button will necessitate a system restart.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 5 State transition and operation procedure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis conceptual and basic design framework enables the realization of a manually operated microtube automatic capper/decapper system that meets the specified requirements and conditions.\u003c/p\u003e"},{"header":"Results and discussion","content":"\u003cp\u003eThis segment will detail the prototyping of a microtube capper derived from the aforementioned design, alongside evaluations of mechanical functionality and usability, ensuring compliance with the specified requirements and conditions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrototype model\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 6\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003epresents a prototype of the proposed manually operated microtube automatic capper/decapper system, conforming to the mechanical design outlined earlier. The front panel hosts the mini box PC switch, with the power supply connector and switch positioned at the rear. The stopper for a 2 mL microtube is placed on the back side. The prototype\u0026rsquo;s total weight is approximately 1,330 g, underscoring its compact and lightweight nature for facile transportation within a biological safety cabinet. It facilitates direct visual inspection of the microtube\u0026rsquo;s interior, whether the cap is open or closed. The exposed metal parts are primarily constructed from anodized aluminum alloy or stainless steel, and the covers are 3D-printed parts (printed by Stratasys F170, 333-60300 ABS-M30 (Ivory)). Particular damage was not observed after wiping and spraying with disinfectant alcohol.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 6 Overview of a prototype of the proposed manually operated microtube automatic capper/decapper system\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEvaluation of opening and closing cap function\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe function of the opening and closing cap of the microtube was evaluated. The microtubes used this time were Thermo Fisher #3448 (1.5 ml) and Greiner 623201 (2 ml). We verified that when the microtube capper/decapper was powered by a 15 to 24 V DC supply, connected through an AC\u0026ndash;DC converter from a 100 V AC source, and linked to a mini box PC, the device\u0026rsquo;s operating program for manual capping and decapping automatically initiated. It executed a return-to-origin operation and then entered a standby state. It took about 30 s from powering on the mini box PC to the standby state. Furthermore, we confirmed that a series of operations, such as Procedures A\u0026ndash;C, can be performed by pressing the open and close buttons as appropriate after setting the microtube in the standby state. \u003cstrong\u003eFigure 7\u003c/strong\u003e shows a series of opening and closing operations using the manual microtube capper (Procedure A). We also confirmed smooth opening and closing operations. The time from pressing the button to completing the opening and closing operations were 5.4 and 4.9 s each. The operation could be stopped immediately by pressing the stop button. Furthermore, it was driven in the same way by a mobile battery designed for notebook PCs (SANWA SUPPLY INC., 700-BTL033BK, DC12 V, 16 V, 19 V (3.6A) 17400mAh, 62.64Wh, and 700-BTL049 DC12 V (3.6A) 17400mAh, 62.64Wh).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 7 Opening and closing cap motion (Procedure A)\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEvaluation of the operation time of pipetting tasks\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe working times were compared between the full manual operation and the manual operation using the microtube capper/decapper. The comparison tasks were determined with reference to the procedures performed in the sample pretreatment process of the PCR-based diagnosis. \u003cstrong\u003eFigure 8\u003c/strong\u003e shows the pipetting task sequences of full manual operation and manual operation using the microtube capper/decapper. The evaluation pipetting task involves dispensing 150 \u0026mu;L from a cryopreservation tube (SARSTEDT 72. 694. 100. 02) containing 1,000 \u0026mu;L of tap water to a microtube: Thermo Fisher #3448 (1.5 ml) containing 600 \u0026mu;L of tap water. One lot is 12 pieces. \u003cstrong\u003eFigure 9\u003c/strong\u003e shows the arrangement of cryopreservation tubes and microtubes and opening/closing cap and aspiration/dispensing position. The tubes before aspiration/dispensing are arranged on the right side, and the tubes after aspiration/dispensing are arranged on the left side.\u003c/p\u003e\n\u003cp\u003eThe experimental setup is shown in \u003cstrong\u003eFigure 10\u003c/strong\u003e. Before starting the experiment, a subject (right-handed, nonprofessional), one of the authors, was required to familiarize himself with the pipetting task. The subject ran four trials (12 pieces \u0026times; 4 lots) for each condition, each of which was video-recorded. Each operation time shown in Fig. 8 (handling and opening cap time, pipetting time and closing cap and the handling time) was retrieved based on the video. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 8 Pipetting task sequences of full manual operation and manual operation using the microtube capper/decapper\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 9 Arrangement of cryopreservation tubes and microtubes and opening/closing cap and aspiration/dispensing position\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 10 Experimental setup for evaluation of operating time of pipetting tasks\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 11\u003c/strong\u003e shows the experimental results of handling and opening cap time, pipetting time and closing cap and handling time by box plots, and the average operation time of one piece by bar graph. Due to some operational sequence errors in the first trial, the box plot data excluded the operation times affected by these errors. However, it was included in the average working time per piece. The first trial had a large variation, but the second to fourth trials had a smaller variation by learning curve. The time required to open and close the cap, including tube handling, was approximately 1\u0026ndash;2 s longer when using the microtube capper/decapper relative to the full manual operation. No significant difference existed in dispensing time. The time taken to open and close the cap using the microtube capper was about 5 s each, but if parallel operations are possible during the opening and closing operations, the impact on the overall operation time is small, so the opening and closing time of the cap using the microtube capper is acceptable. Furthermore, the capper can markedly reduce the burden on the operator when opening and closing the microtube cap. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 11 Experimental results of h\u003c/strong\u003e\u003cstrong\u003eandling and opening cap time, p\u003c/strong\u003e\u003cstrong\u003eipetting time, closing cap and handling time and average operation time of one piece.\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEvaluation of the cooling function\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe cooling function using the cooling boxes was evaluated. The cooling box was prototyped by a 3D printer (printed by Formlabs Form 3, Resin Rigid 4000 V1). The capacities of the small and large cooling boxes were 32.3 mL and 55.5 mL, respectively. \u003cstrong\u003eFigure 12\u003c/strong\u003e shows the experimental conditions for the cooling function. The experiments were conducted under four conditions: (1) No-cooling box sample, (2) Small cooling box sample (Tap water ice), (3) Small cooling box sample (frozen gel), and (4) Large cooling box sample (Tap water ice). Furthermore, under all experimental conditions, room temperature and left indoor samples were simultaneously measured. The temperature was measured by K-Thermocouple (HIOKI 9810) in the microtube bottom and middle position and recorded by a data logger (HIOKI LR8431). An hour of data was acquired. Tap water ice or frozen gel was used as the cooling material. After putting tap water or gel (Contents of Snow Pack R-20 by MIE Chemical Industry) in the cooling box and cooling it in a freezer (\u0026minus;17℃) to freeze, experiments of the cooling functions were conducted. A 1,000 \u0026mu;L of tap water in the microtube: Thermo Fisher #3448 (1.5 ml) was cooled to approximately 0\u0026deg;C\u0026ndash;4\u0026deg;C with crushed ice. \u003cstrong\u003eFigure 13\u003c/strong\u003e shows the experimental setup for the cooling functions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 14\u003c/strong\u003e shows the experimental results of the cooling functions as the average value of time series data acquired three times under the same conditions. The room temperatures were 22\u0026deg;C \u0026minus;23\u0026deg;C in all cases, and the experiments were conducted in almost the same temperature environment. In the case of the no-cooling function, the temperature rises after the measurement starts, rising to about 35℃ in 20\u0026ndash;30 min, and then remaining almost constant. The heat sources are thought to be the mini box PC and motor position control system (Maxon EPOS2 24/2). In contrast, using the cooling box caused the temperature of the tap water in the microtube to be maintained at about 5℃ or less for about 20\u0026ndash;40 min. Although no noticeable difference was observed between the tap water ice and the frozen gel, the cooling function was maintained for a long time, depending on the difference in capacity between large and small boxes. While precise temperature control over long periods proved challenging with a cooling box\u0026ndash;based cooling function, it effectively sustained the coolness of the microtube contents for short durations. The cooling performance is expected to improve through methods such as inserting a heat-insulating material between heat sources (the mini box PC and the Maxon EPOS2 24/2) and placing cooling material under the microtube. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 12 Experimental conditions for cooling function\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 13 Experimental setup for cooling function\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 14 Experimental results of the cooling functions.\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion on required specifications and preconditions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe considerations for the abovementioned requirement specifications and preconditions are summarized below.\u003c/p\u003e\n\u003cp\u003e(1) Operators can manually insert and remove microtubes from the capper/decapper.\u003c/p\u003e\n\u003cp\u003e(2) The device accommodates the opening and closing of caps on both 1.5 mL and 2 mL microtubes.\u003c/p\u003e\n\u003cp\u003e(3) Using procedures A, B, and C, microtubes can be inserted and removed with their caps in both the open and closed states.\u003c/p\u003e\n\u003cp\u003e(4) The size, weight, and power source of the device are compatible for use within a biological safety cabinet, and the device is easy to carry (easy to put in and take out of the cabinet)\u003c/p\u003e\n\u003cp\u003e(5) The operating procedures are straightforward and simple, with only pushing buttons.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(6) This device allows visual observation of the microtube\u0026rsquo;s interior when the cap is in open and closed positions.\u003c/p\u003e\n\u003cp\u003e(7) The device is operable with a mobile battery.\u003c/p\u003e\n\u003cp\u003e(8) It is cleanable with alcohol or similar disinfectants.\u003c/p\u003e\n\u003cp\u003e(9) The device has a cooling function for specimens and reagents within the microtube.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(10) Quantitative evaluations of the risk of contamination from specimen scattering, virus exposure, and aerosol generation during cap manipulation are currently being conducted and will be reported separately.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eManual handling of microtube caps poses a contamination and infection risk, compromising both diagnosis/experiment accuracy and worker safety. However, a device for manually opening and closing microtube caps without direct contact is absent. Therefore, leveraging the technology of our initially developed versatile microtube capper/decapper system for laboratory automation, we have developed a manually operated microtube equipped with an automatic capper/decapper system for clinical and biological laboratory personnel. The suit to the required specifications and preconditions and the usefulness of the proposed manual microtube capper/decapper were validated through various experiments and demonstrations.\u003c/p\u003e\n\u003cp\u003eIn the future, we plan to perform quantitative evaluations of contamination risk using the proposed microtube capper/decapper system. Furthermore, we plan to proceed with the social implementation of the proposed system. Given the extensive use of microtubes in diverse clinical and biological experiments, we believe that the proposed system can markedly reduce the workload of personnel across numerous clinical and biological laboratories.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePCR\u0026nbsp; \u0026nbsp;\u0026nbsp;Polymerase chain reaction\u003c/p\u003e\n\u003cp\u003eLED \u0026nbsp; \u0026nbsp;Light-Emitting Diode\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eM.J. spearheaded the conceptual planning and design, the mechanical design, and the verification experiments for evaluations, in addition to drafting the initial manuscript. R.N. was instrumental in developing the control system, along with the design and implementation of the control software. Y.S., R.Y., T.K., and J.Y. were pivotal in defining the specifications and prerequisites for the conceptual design and carried out usability evaluations of the prototype for the proposed manually operated microtube automatic capper/decapper system. All authors have reviewed and endorsed the final manuscript.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank Kawasaki City Institute for Public Health, Yamaguchi Prefectural Institute of Public Health and Environment, Hirakata City Public Health Center, National Mie Hospital, H.U. Group Research Institute G.K., and Laboratory Automation Supplier\u0026apos;s Association for their comments and suggestions with required specifications and usability of the manually operated microtube automatic capper/decapper system.\u003c/p\u003e\n\u003cp\u003eThe authors wish to express their gratitude to the CREST, Japan Science and Technology Agency, for their support.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by JST, CREST Grant Number JPMJCR20H5, Japan.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWorld Health Organization (WHO), Diagnostic testing for SARS-CoV-2, https://www.who.int/publications/i/item/diagnostic-testing-for-sars-cov-2, accessed 21 Apr. 2024.\u003c/li\u003e\n\u003cli\u003eTruong V, Viken K, Geng Z, Barkan S, Johnson B, Ebeling MC, Montezuma SR, Ferrington DA, Dutton JR (2021) Automating Human Induced Pluripotent Stem Cell Culture and Differentiation of iPSC-Derived Retinal Pigment Epithelium for Personalized Drug Testing SLAS Technology 2021, Vol. 26(3): 287\u0026ndash;299, doi.org/10.1177/2472630320972110\u003c/li\u003e\n\u003cli\u003eThomas RJ, Hope AD, Hourd P, Baradez M, Miljan EA, Sinden JD, Williams DJ (2009) Automated, serum-free production of CTX0E03: a therapeutic clinical grade human neural stem cell line. Biotechnology Letters, Vol.31, Issue.8:1167\u0026ndash;1172, 2009. dio 10.1007/s10529-009-9989-1\u003c/li\u003e\n\u003cli\u003eBernard CJ, Connors D, Barber L, Jayachandra S, Bullen A, Cacace A (2004) Adjunct Automation to the Cellmate\u0026trade; Cell Culture Robot. JALA, Vol.9, Issue.4 209\u0026ndash;217.\u003c/li\u003e\n\u003cli\u003eShen Y, Guo D, Long F, Mateos LA, Ding H, Xiu Z, Hellman RB, King A, Chen S, Zhang C, Tan H (2021) Robots Under COVID-19 Pandemic: A Comprehensive Survey. IEEE Access VOLUME 9, 2021 P.P.1590-1615. DOI: 10.1109/ACCESS.2020.3045792\u003c/li\u003e\n\u003cli\u003eABB Robots Accelerate COVID-19 Testing in Singapore. https://new.abb.com/news/detail/68679/abbrobots-accelerate-covid-19-testing-in-singapore, accessed 21 Apr. 2024.\u003c/li\u003e\n\u003cli\u003eVillanueva-Ca\u0026ntilde;as JL, Gonzalez-Roca E, Unanue AG, Titos E, Mart\u0026iacute;nez Yoldi MJ, Vergara G\u0026oacute;mez A, Puig Butill\u0026eacute; JA (2020) ROBOCOV: An affordable open-source robotic platform for SARS-CoV-2 testing by RT-qPCR. BioRxiv, doi.org/10.1101/2020.06.11.140285\u003c/li\u003e\n\u003cli\u003eKawasaki Heavy Industries, Kawasaki Launches Automated PCR Testing Services, https://global.kawasaki.com/en/corp/newsroom/news/detail/?f=20201022_4409, accessed 21 Apr. 2024.\u003c/li\u003e\n\u003cli\u003eKanda GN, Tsuzuki T, Terada M, Sakai N, Motozawa N, Masuda T, Nishida M, Watanabe CT, Higashi T, Horiguchi SA, Kudo T, Kamei M, Sunagawa GA, Matsukuma K, Sakurada T, Ozawa Y, Takahashi M, Takahashi K, Natsume T (2022) Robotic search for optimal cell culture in regenerative medicine. eLife 2022;11:e77007. doi.org/10.7554/eLife.77007\u003c/li\u003e\n\u003cli\u003eLiu AW, Villar-Briones A, Luscombe NM, Plessy C (2022) Automated phenol-chloroform extraction of high molecular weight genomic DNA for use in long-read single-molecule sequencing. F1000Research 2022, 11:240. doi.org/10.12688/f1000research.109251.1\u003c/li\u003e\n\u003cli\u003eFoundation for Promotion of Material Science and Technology of Japan, PCR testing of the novel coronavirus disease (COVID-19) using pretreatment automation system starting in July 2022 (in Japanese), https://www.mst.or.jp/corporate/tabid/1486/Default.aspx, accessed 21 Apr. 2024.\u003c/li\u003e\n\u003cli\u003eLare P, Calvo S, Gazeau Mi (2007) Automation for opening and closing tubes fitted with a swinging cap. US Patent Application Publication US 2007/0110624 A1 May 17 2007.\u003c/li\u003e\n\u003cli\u003eUmeno M (2016) Robot hand and robot. US Patent 94,46,525 B2 Sep 20 2016.\u003c/li\u003e\n\u003cli\u003eLee SD (2019) Tube opening and closing device and dispensing system including same. US Patent 11,572,263 B2 Feb 7 2023.\u003c/li\u003e\n\u003cli\u003eJinno M, Nonoyama R (2024) Automatic microtube capper/decapper system for clinical examinations and biological experiments. Robomech Journal (Submitted on 2024.03.18)\u003c/li\u003e\n\u003cli\u003eTOMY DIGITAL BIOLOGY CO., LTD., Multi Spin, https://www.digital-biology.co.jp/manufactured/products/centrifuges/multi-spin/, accessed 21 Apr. 2024.\u003c/li\u003e\n\u003cli\u003eNichiryo Co.,Ltd., Desktop Compact-Size General Purpose Equipment https://www.nichiryo.co.jp/en/productline/desktop.html, accessed 21 Apr. 2024.\u003c/li\u003e\n\u003cli\u003eScientific Industries, Inc., Vortex Mixers, https://www.scientificindustries.com/votrex-mixers-and-shakers/vortex-shakers.html, accessed 21 Apr. 2024.\u003c/li\u003e\n\u003cli\u003eLabnet, Vortex Mixer, https://www.labnetinternational.com/products/agitation-equipment/vortexers/vortex-mixer, accessed 21 Apr. 2024.\u003c/li\u003e\n\u003cli\u003eEppendorf SE, Manual Pipettes \u0026amp; Dispensers, https://www.eppendorf.com/us-en/eShop-Products/Liquid-Handling/Manual-Pipettes-Dispensers-c-WebPSub-H-44564, accessed 21 Apr. 2024.\u003c/li\u003e\n\u003cli\u003eThermo Fisher Scientific Inc., Finnpipette Systems, https://assets.thermofisher.com/TFS-Assets/LCD/brochures/Finnpipette-F1-and-Finnpipette-F2-brochure.pdf, accessed 21 Apr. 2024.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"robomech-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"robo","sideBox":"Learn more about [ROBOMECH Journal](http://robomechjournal.springeropen.com/)","snPcode":"40520","submissionUrl":"https://submission.nature.com/new-submission/40520/3","title":"ROBOMECH Journal","twitterHandle":"@SpringerEng","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Laboratory automation, Mechanism design, Microtube, Clinical examination, Biological experiment, Manual operation","lastPublishedDoi":"10.21203/rs.3.rs-4300601/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4300601/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Polymerase chain reaction (PCR) is an effective method for diagnosing infectious diseases and has been the primary method throughout the novel coronavirus disease (COVID-19) pandemic. PCR tests (from specimen collection to result acquisition) involve sample pretreatment, nucleic acid extraction, and PCR procedure. Automating the pretreatment process is crucial to mitigate the risk of infection for workers and to reduce the likelihood of sample contamination-triggered misdiagnosis, particularly when handling centrifuge tubes, cryopreservation tubes, and microtubes. Robotic systems have been engineered to automate cell culture and PCR-based diagnosis , predominantly designed for use with screw-capped containers. However, this leaves a notable gap in automation solutions for microtubes equipped with press-type caps. To address this gap, we developed a versatile microtube capper/decapper system. On the other hand, many tasks of manual operation using microtubes, which are routinely conducted in clinical tests and biological experiments, were performed. Despite the risks of contamination and infection derived from the manual handling of microtube caps, which can compromise diagnosis/experiment accuracy and worker safety, devices for manually opening and closing microtube caps without direct contact remain lacking. Therefore, leveraging the technology from the developed versatile microtube capper/decapper system for laboratory automation, we created a manually operated microtube equipped with an automatic capper/decapper system tailored for personnel in clinical and biological laboratories.\nIn this study, we first examined the required specifications and prerequisites for a manual microtube capper/decapper and clarified the operating methods, operating procedures, operation environment, device size, accompanying functions, etc. Based on the required specifications and preconditions, we proceeded with the mechanical and control design of the conceptual model, manufactured a prototype, and confirmed its basic functions and performance. The compliant to the required specifications and preconditions and the usefulness of the proposed manual microtube capper/decapper were validated through various experiments and demonstrations. Because microtubes are used in various clinical tests and biological experiments, we believe that the proposed system can markedly reduce the workload for personnel across numerous clinical and biological laboratories.","manuscriptTitle":"Manually operated microtube automatic capper/decapper system for clinical laboratory and biological laboratory personnel","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-25 17:35:15","doi":"10.21203/rs.3.rs-4300601/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-16T03:47:39+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-15T14:42:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-05T16:04:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"182449114129841956356877160356806836550","date":"2024-06-20T06:34:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"220038643251831320751047577535602190840","date":"2024-06-17T06:22:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"92817691605458596832807222105222104274","date":"2024-06-03T22:10:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-10T03:59:20+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-23T12:34:50+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-22T08:37:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"ROBOMECH Journal","date":"2024-04-21T11:57:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"robomech-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"robo","sideBox":"Learn more about [ROBOMECH Journal](http://robomechjournal.springeropen.com/)","snPcode":"40520","submissionUrl":"https://submission.nature.com/new-submission/40520/3","title":"ROBOMECH Journal","twitterHandle":"@SpringerEng","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7068072a-3208-4dec-b4bb-1fcacbcacd3d","owner":[],"postedDate":"April 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-09-30T16:00:43+00:00","versionOfRecord":{"articleIdentity":"rs-4300601","link":"https://doi.org/10.1186/s40648-024-00281-3","journal":{"identity":"robomech-journal","isVorOnly":false,"title":"ROBOMECH Journal"},"publishedOn":"2024-09-27 15:57:11","publishedOnDateReadable":"September 27th, 2024"},"versionCreatedAt":"2024-04-25 17:35:15","video":"","vorDoi":"10.1186/s40648-024-00281-3","vorDoiUrl":"https://doi.org/10.1186/s40648-024-00281-3","workflowStages":[]},"version":"v1","identity":"rs-4300601","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4300601","identity":"rs-4300601","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}