Automated bioprocess feedback operation in a high throughput facility via the integration of a mobile robotic lab assistant

Biotechnological processes development is challenging due to the sheer variety of process parameters. For efficient upstream development parallel cultivation systems have proven to reduce costs and associated timelines successfully, while offering excellent process control. However, the degree of automation of such small scale systems is comparably low and necessary sample analysis requires manual steps. Although the subsequent analysis can be performed in a high-throughput manner, the integration of analytic devices remains challenging. Especially, when cultivation and analysis laboratories are spatially separated. Mobile robots offer a potential solution, but the implementation in research laboratories is not widely adopted. Our approach demonstrates the integration of a small scale cultivation system into a liquid handling station for an automated sample procedure. The samples are transferred via a mobile robotic lab assistant and subsequently analysed by a high-throughput analyzer. The process data is stored in a centralized database. The mobile robotic workflow guarantees a flexible solution for device integration and facilitates automation. Restrictions regarding spatial separation of devices are circumvented, enabling a modular platform throughout different laboratories. The presented cultivation platform is evaluated based on industrial relevant E. coli BW25113 high cell density fed-batch cultivation. Here its suitability for accelerating bioprocess development is proven. The necessary magnesium addition for reaching high cell densities in mineral salt medium is automated via a feedback operation loop. The feedback operation loop demonstrates the possibility for advanced control options. This study sets the foundation for a fully integrated facility with different cultivation scales sharing the same data infrastructure, where the mobile robotic lab assistant physically connects the devices.

Nanomaterials for IoT Sensing Platforms and Point-of-Care Applications in South Korea

Herein, state-of-the-art research advances in South Korea regarding the development of chemical sensing materials and fully integrated Internet of Things (IoT) sensing platforms were comprehensively reviewed for verifying the applicability of such sensing systems in point-of-care testing (POCT). Various organic/inorganic nanomaterials were synthesized and characterized to understand their fundamental chemical sensing mechanisms upon exposure to target analytes. Moreover, the applicability of nanomaterials integrated with IoT-based signal transducers for the real-time and on-site analysis of chemical species was verified. In this review, we focused on the development of noble nanostructures and signal transduction techniques for use in IoT sensing platforms, and based on their applications, such systems were classified into gas sensors, ion sensors, and biosensors. A future perspective for the development of chemical sensors was discussed for application to next-generation POCT systems that facilitate rapid and multiplexed screening of various analytes.

Cartesian Meshing Spherical Earth (CMSE): A Code Package to Incorporate the Spherical Earth in SPECFEM3D Cartesian Simulations

The SPECFEM3D_Cartesian code package is widely used in simulating seismic wave propagation on local and regional scales due to its computational efficiency compared with the one-chunk version of the SPECFEM3D_Globe code. In SPECFEM3D_Cartesian, the built-in meshing tool maps a spherically curved cube to a rectangular cube using the Universal Transverse Mercator projection (UTM). Meanwhile, the geodetic east, north, and up directions are assigned as the local x–y–z directions. This causes coordinate orientation issues in simulating waveform propagation in regions larger than 6° × 6° or near the Earth’s polar regions. In this study, we introduce a new code package, named Cartesian Meshing Spherical Earth (CMSE), that can accurately mesh the 3D geometry of the Earth’s surface under the Cartesian coordinate frame, while retaining the geodetic directions. To benchmark our new package, we calculate the residual amplitude of the CMSE synthetics with respect to the reference synthetics calculated by SPECFEM3D_Globe. In the regional scale simulations with an area of 1300 km × 1300 km, we find a maximum of 5% amplitude residual for the SPECFEM3D_Cartesian synthetics using the mesh generated by the CMSE, much smaller than the maximum amplitude residual of 100% for the synthetics based on its built-in meshing tool. Therefore, our new meshing tool CMSE overcomes the limitations of the internal mesher used by SPECFEM3D_Cartesian and can be used for more accurate waveform simulations in larger regions beyond one UTM zone. Furthermore, CMSE can deal with regions at the south and north poles that cannot be handled by the UTM projection. Although other external code packages can be used to mesh the curvature of the Earth, the advantage of the CMSE code is that it is open-source, easy to use, and fully integrated with SPECFEM3D_Cartesian.

Achieving Productivity and Clean Inflow from an Unconventional Reservoir in North Kuwait

Jurassic Kerogen shale/carbonate reservoir in North Kuwait provides the same challenges as North American shales in addition to ones not yet comparable to any other analogue reservoir globally. It is the Kerogen's resource density; however, that makes this play so attractive. Like ‘conventional’ unconventional in the US and Canada this kerogen is believed to be a source rock and is on the order of micro-to nano-Darcy permeability. As such, industry learnings show that likely long horizontal laterals with multiple hydraulic fractures will be necessary to make commercial wells. Following this premise, the immediate objective is to establish clean inflow into wellbore as the previous attempts to appraise failed due to "creep" of particulate material and formation flowing into the wellbore. Achieving this milestone will confirm that this formation is capable of solids free inflow and will open a new era in unconventional in Kuwait. Planning for success, the secondary objective is to then upscale to full field development. The main uncertainties lie in both producibility and ‘frac-ability’, and certainly, these challenges are not trivial. A fully integrated testing program was applied to both better understand the rock mechanical properties and to land on an effective frac design. Scratch, unconfined stress, proppant embedment and fluid compatibility tests were conducted on full core samples for geo-mechanics to prepare a suite of strength measurements ahead of frac design and to custom-design the fracture treatment and "controlled" flowback programs to establish inflow from Kerogen without "creep". Unlike developed shale reservoirs, the Jurassic Kerogen tends to become unconsolidated when treated. The pre-frac geomechanics tests will be outlined in this paper with the primary objective of finding the most competent reservoir unit to select the limited perforation interval to frac through so that formation competency can be maintained. Previous attempts failed to maintain a competent rock matrix even only after pumping data-fracs. Acidizing treatments also turn the treated rock volume into sludgy material with no in-situ stability nor ability to deliver "clean inflow". A propped fracturing treatment with resin-coated bauxite was successfully placed in December 2019 in a vertical appraisal well perforated over 6 ft at 12 spf shot density. "Controlled" flowback carried out in January 2020 achieved the strategically critical "clean inflow" with reservoir fluids established to surface. Special proppant technologies provided by an industry leading manufacturer overcame the embedment effects and to control solids flowback. A properly designed choke schedule to balance unloading with a delicate enough drawdown to avoid formation failure was executed. Local oilfields relied on the vast reserves and produced easily from carbonate reservoirs that required only perforating or acid squeezes to easily meet or exceed high production expectations. This unconventional undertaking in Kuwait presents a real challenge as it is a complete departure from the ways of working yet it points towards a very high upside potential should the appraisal campaign can be completed effectively.

Challenges and Strategies in Developing an Enzymatic Wearable Sweat Glucose Biosensor as a Practical Point-Of-Care Monitoring Tool for Type II Diabetes

Recently, several studies have been conducted on wearable biosensors. Despite being skin-adhesive and mountable diagnostic devices, flexible biosensor patches cannot truly be considered wearable biosensors if they need to be connected to external instruments/processors to provide meaningful data/readings. A realistic and usable wearable biosensor should be self-contained, with a fully integrated device framework carefully designed and configured to provide reliable and intelligent diagnostics. There are several major challenges to achieving continuous sweat monitoring in real time for the systematic and effective management of type II diabetes (e.g., prevention, screening, monitoring, and treatment) through wearable sweat glucose biosensors. Consequently, further in-depth research regarding the exact interrelationship between active or passive sweat glucose and blood glucose is required to assess the applicability of wearable glucose biosensors in functional health monitoring. This review provides some useful insights that can enable effective critical studies of these unresolved issues. In this review, we first classify wearable glucose biosensors based on their signal transduction, their respective challenges, and the advanced strategies required to overcome them. Subsequently, the challenges and limitations of enzymatic and non-enzymatic wearable glucose biosensors are discussed and compared. Ten basic criteria to be considered and fulfilled in the development of a suitable, workable, and wearable sweat-based glucose biosensor are listed, based on scientific reports from the last five years. We conclude with our outlook for the controllable, well-defined, and non-invasive monitoring of epidermal glucose for maximum diagnostic potential in the effective management of type II diabetes.

The post COVID-19 healthcare landscape and the use of long-acting injectable antipsychotics for individuals with schizophrenia and bipolar I disorder: the importance of an integrated collaborative-care approach

Background Long-acting injectable antipsychotics (LAIs) are an essential maintenance treatment option for individuals with schizophrenia or bipolar I disorder (BP-I). This report summarizes a roundtable discussion on the impact of COVID-19 on the mental healthcare landscape and use of LAIs for individuals with schizophrenia or BP-I. Methods Ten experts and stakeholders from diverse fields of healthcare participated in a roundtable discussion on the impact of the COVID-19 pandemic, treatment challenges, and gaps in healthcare for individuals with schizophrenia or BP-I, informed by a literature search. Results Individuals with schizophrenia or BP-I are at increased risk of COVID-19 infection and increased risk of mortality after COVID-19 diagnosis. LAI prescriptions decreased early on in the pandemic, driven by a decrease in face-to-face consultations. Mental healthcare services are adapting with increased use of telehealth and home-based treatment. Clinical workflows to provide consistent, in-person LAI services include screening for COVID-19 exposure and infection, minimizing contact, and ensuring mask-wearing by individuals and staff. The importance of continued in-person visits for LAIs needs to be discussed so that staff can share that information with patients, their caregivers, and families. A fully integrated, collaborative-care model is the most important aspect of care for individuals with schizophrenia or BP-I during and after the COVID-19 pandemic. Conclusions The COVID-19 pandemic has highlighted the importance of a fully integrated collaborative-care model to ensure regular, routine healthcare contact and access to prescribed treatments and services for individuals with schizophrenia and BP-I.