Scale-up Challenges Research Articles

How Should Enterprises Quantify and Analyze (Multi-Party) APT Cyber-Risk Exposure in their Industrial IoT Network?

Industrial Internet of Things (IIoT) networks (e.g., a smart grid industrial control system) are increasingly on the rise, especially in smart cities around the globe. They contribute to meeting the day-to-day needs (e.g., power, water, manufacturing, transportation) of the civilian society, alongside making societal businesses more efficient, productive, and profitable. However, it is also well known that IoT devices often operate on poorly configured security settings. This increases the chances of occurrence of (nation-sponsored) stealthy spread-based APT malware attacks in IIoT networks that might go undetected over a considerable period of time. Such attacks usually generate a negative first-party QoS impact with financial consequences for companies owning such IIoT network infrastructures. This impact spans (i.e., aggregates) space (i.e., the entire IIoT network or a sub-network) and time (i.e., duration of business disruption), and is a measure of significant interest to managers running their businesses atop such networks. It is of little use to network resilience boosting managers if they have to wait for a cyber-attack to happen to gauge this impact. Consequently, one of the questions that intrigues us is: can managers estimate this first-party impact prior to APT cyber-attack(s) causing financial damage to companies? In this paper, we propose the first computationally efficient and quantitative network theory framework to (a) characterize this first-party impact apriori as a statistical distribution over multiple attack configurations in a family of malware-driven APT cyber-attacks specifically launched on businesses running atop IIoT networks, (b) accurately compute the statistical moments (e.g., mean) of the resulting impact distribution, and (c) tightly bound the accuracy of worst-case risk estimate of such a distribution - captured through the tail of the distribution, using the Conditional Value at Risk (CVaR) metric. In relation to (a) above, our methodology extends the seminal Factor Analysis of Information Risk (FAIR) cyber-risk quantification methodology that does not explicitly account for network interconnections among system-risk contributing variables. We validate the effectiveness of our theory using trace-driven Monte Carlo simulations based upon test-bed experiments conducted in the FIT IoT-Lab. We further illustrate quantitatively that even if spread-based APT cyber-attacks induce a statistically light-tailed first-party cyber-loss distribution on an IIoT networked enterprise in the worst case, the aggregate multi-party cyber-risk distribution incurred by the same enterprise in supply-chain ecosystems could be heavy-tailed. This will pose significant market scale-up challenges to cyber-security improving commercial cyber (re-)insurance businesses. We subsequently propose managerial action items to mitigate the first-party cyber-risk exposure emanating from any given IIoT driven enterprise.

Stem cell-based strategies and challenges for production of cultivated meat.

Cultivated meat scale-up and industrial production will require multiple stable cell lines from different species to recreate the organoleptic and nutritional properties of meat from livestock. In this Review, we explore the potential of stem cells to create the major cellular components of cultivated meat. By using developments in the fields of tissue engineering and biomedicine, we explore the advantages and disadvantages of strategies involving primary adult and pluripotent stem cells for generating cell sources that can be grown at scale. These myogenic, adipogenic or extracellular matrix-producing adult stem cells as well as embryonic or inducible pluripotent stem cells are discussed for their proliferative and differentiation capacity, necessary for cultivated meat. We examine the challenges for industrial scale-up, including differentiation and culture protocols, as well as genetic modification options for stem cell immortalization and controlled differentiation. Finally, we discuss stem cell-related safety and regulatory challenges for bringing cultivated meat to the marketplace.

Enhancing the production of recombinant adeno-associated virus in synthetic cell lines through systematic characterization.

Recombinant adeno-associated virus (rAAV) is among the most commonly used in vivo gene delivery vehicles and has seen a number of successes in clinical application. Current manufacturing processes of rAAV employ multiple plasmid transfection or rely on virus infection and face challenges in scale-up. A synthetic biology approach was taken to generate stable cell lines with integrated genetic modules, which produced rAAV upon induction albeit at a low productivity. To identify potential factors that restrained the productivity, we systematically characterized virus production kinetics through targeted quantitative proteomics and various physical assays of viral components. We demonstrated that reducing the excessive expression of gene of interest by its conditional expression greatly increased the productivity of these synthetic cell lines. Further enhancement was gained by optimizing induction profiles and alleviating proteasomal degradation of viral capsid protein by the addition of proteasome inhibitors. Altogether, these enhancements brought the productivity close to traditional multiple plasmid transfection. The rAAV produced had comparable full particle contents as those produced by conventional transient plasmid transfection. The present work exemplified the versatility of our synthetic biology-based viral vector production platform and its potential for plasmid- and virus-free rAAV manufacturing.

Iron Flow Battery with Slurry Electrode for Large Scale Energy Storage: Scale-Up, Intellectual Property, and Commercialization Challenges

For large-scale energy storage, flow batteries present many advantages. These benefits include, but are not limited to, decoupling power rating from energy capacity and projected lower cost energy storage and long cycle life. Several reviews and a comprehensive handbook have come available recently describing the various flow battery chemistries and the details of cell and stack construction. However, none of the chemistries proposed are perfect and the commercialization path to widespread adoption remains challenging. For the purposes of this article, we will take a closer look at the concept and development of an all-iron slurry flow battery and the intellectual property (IP) protection and commercialization process that occurred within an academic environment.

Sodium Metal Hybrid Redox Flow Batteries Containing Sulfide and Thiophosphate Catholytes

Energy storage systems which meet the requirement for long-duration energy storage (LDES) are critical to enable widespread adoption of intermittent renewables (e.g., solar and wind) on the electric grid. DOE’s Long Duration Storage Shot has set an ambitious goal of reducing energy storage costs ≥90% by 2030. To address this challenge, the proposed work is aimed at developing low-cost, high-energy redox flow batteries (RFBs) based on earth-abundant active materials. Prior work on room temperature Na2Sx catholytes demonstrated outstanding reversibility and cycling stability in batch and flow cell configurations (e.g., reversible capacities ~200 mAh/gS with negligible fade over 250 cycles and several months of continuous testing). While precipitation of low-order polysulfides (x≤4) during discharge doesn’t negatively impact the performance of lab-scale prototypes, these ionically/electronically insulating species will present major challenges for system scaleup (e.g., inhibited charge transfer due to current collector passivation). As such, the practical cycling window of Na2Sx is restricted to soluble species (5≤x≤8) with a sulfur utilization of 125 mAh/gS. To improve the viability of room temperature Na/Na2Sx RFBs, our team recently discovered that the addition of P2S5 greatly increases the solubility of low-order sodium polysulfides through formation of previously unknown Na-P-S solvated complexes. This general class of sodium thiophosphates has tremendous, untapped potential for next-generation nonaqueous catholytes and can potentially enable reversible Na capacities exceeding 1,000 mAh/g. This presentation will describe ongoing efforts aimed at: (i) assessing key properties (electrochemical reversibility, solubility, chemical stability) of sodium thiophosphates in nonaqueous electrolytes, (ii) benchmarking the performance of lab-scale RFB prototypes containing Na-P-S catholytes and ceramic membranes, and (iii) quantifying voltage losses on electrodes polarized far from equilibrium using 3 electrode AC impedance measurements. Acknowledgements This research was conducted at Oak Ridge National Laboratory, managed by UT Battelle, LLC, for the U.S. Department of Energy (DOE) and is sponsored by the U.S. Department of Energy through the Energy Storage Program in the Office of Electricity.

(Invited) Iron Flow Battery with Slurry Electrode for Large Scale Energy Storage: Scale-up, Commercialization, and IP Challenges in an Academic Environment

Large-scale energy storage is required to meet a multitude of current energy challenges. These challenges include modernizing the grid, incorporating intermittent renewable energy sources (so as to dispatch continuous electrical energy), improving the efficiency of electricity transmission and distribution, and providing flexibility of storage independent of geographical and geological location.Through efforts supported by ARPA-E and the Department of Energy Office of Electricity, one technology we are developing utilizes an approach based on sustainable, low cost iron electrolytes in an iron flow battery (IFB). Advantages of the IFB include abundant, non-toxic, and non-corrosive materials that are used to provide an energy storage solution that has inherently safe operation and is environmentally friendly. In our approach to the all iron RFB, we introduced a flowing carbon slurry as the negative electrode as a substrate for plating iron during charging allowing storage of the plated iron in a tank external to the stack. This configuration decouples energy and power capacities. The work supported by DOE allowed us to address challenges encountered in scaling up from small laboratory cells to a large commercial size slurry IFB single cell. 1 In this presentation, we will address some of the challenges we encountered for demonstrating the technology within an academic environment in order to position it for commercial development. Even with funding to overcome the valley-of-death and technology-to-market assistance given by ARPA-E, we faced many challenges including hiring expertise to address scale-up, design and testing. We will discuss challenges faced with identifying partners and licensees for moving discovery to product. Also, we will describe the many types of interactions we had with the university Technology Transfer Office including patent disclosure, IP protection, and negotiating licenses. Acknowledgements: This research was supported by ARPA-E contract DE-AR0000352. Partial support also was received from the DOE Office of Electricity Award #1111358,0 under Dr. Imre Gyuk. 1N.S. Sinclair, R.F. Savinell and J.S. Wainright, MRS Energy & Sustainability, 2022; doi: 10.1557/s43581-022-00046-8

(John B. Goodenough Award of The Electrochemical Society) Oxide Revolution in Energy Storage

Lithium-ion batteries have become an integral part of our daily life. The triumph of lithium-ion batteries is due to their much higher energy density compared to the other rechargeable battery systems. The high energy density along with superior cycling stability became possible because of the use of oxide cathodes in lithium-ion cells. There are only three families of cathodes for practical lithium-ion cells, and all the three of them are oxides: layered, spinel, and polyanion oxide cathodes.As we move forward with vehicle electrification and renewable energy storage, multiple parameters, such as cost, energy density, power density, cycle life, safety, and environmental impact, need to be balanced. Among them, cost along with sustainability and supply chain issues is at the forefront. Cathode is the most expensive component in the cell. The oxide cathodes will still dominate the field, but with fierce efforts to reduce or eliminate less abundant and expensive metals in the cathode. This presentation will focus on eliminating the most expensive cobalt from layered oxide cathodes, then reducing the next expensive nickel in oxide cathodes, and finally replacing/eliminating lithium with sodium in oxide cathodes.Reducing or eliminating cobalt in layered oxide cathodes by increasing the nickel content helps to increase the energy density and reduce the cost, but cathodes with high nickel contents are plagued with cycle, thermal, and air instabilities along with severe scale-up challenges. This presentation will focus on overcoming these challenges with controlled compositional and synthesis designs along with a profound understanding of the intricacies involved with the aid of advanced characterization methodologies. Particularly, issues, such as what different dopants really do, which dopant does what, and which is critical between surface reactivity and crack, in stabilizing high-nickel cathodes will be discussed. The dependence of surface reorganization/degradation pathways on electrolytes and the importance of electrolyte composition and high-voltage stability in stabilizing the cathode-electrolyte interphase will be presented with both graphite and lithium-metal anodes.Finally, elimination of both cobalt and lithium while reducing the nickel content much further down will be described with sodium batteries based on layered oxide cathodes. Tailored electrolyte designs that provide long-life sodium cells with suppressed dendrites and enhanced safety will be presented.

Low Temperature Epitaxial LiMn2O4 Cathodes Enabled by NiCo2O4 Current Collector for High-Performance Microbatteries.

Epitaxial cathodes in lithium-ion microbatteries are ideal model systems to understand mass and charge transfer across interfaces, plus interphase degradation processes during cycling. Importantly, if grown at <450 °C, they also offer potential for complementary metal-oxide-semiconductor (CMOS) compatible microbatteries for the Internet of Things, flexible electronics, and MedTech devices. Currently, prominent epitaxial cathodes are grown at high temperatures (>600 °C), which imposes both manufacturing and scale-up challenges. Herein, we report structural and electrochemical studies of epitaxial LiMn2O4 (LMO) thin films grown on a new current collector material, NiCo2O4 (NCO). We achieve this at the low temperature of 360 °C, ∼200 °C lower than existing current collectors SrRuO3 and LaNiO3. Our films achieve a discharge capacity of >100 mAh g-1 for ∼6000 cycles with distinct LMO redox signatures, demonstrating long-term electrochemical stability of our NCO current collector. Hence, we show a route toward high-performance microbatteries for a range of miniaturized electronic devices.

Bioengineered Enzymes and Precision Fermentation in the Food Industry.

Enzymes have been used in the food processing industry for many years. However, the use of native enzymes is not conducive to high activity, efficiency, range of substrates, and adaptability to harsh food processing conditions. The advent of enzyme engineering approaches such as rational design, directed evolution, and semi-rational design provided much-needed impetus for tailor-made enzymes with improved or novel catalytic properties. Production of designer enzymes became further refined with the emergence of synthetic biology and gene editing techniques and a plethora of other tools such as artificial intelligence, and computational and bioinformatics analyses which have paved the way for what is referred to as precision fermentation for the production of these designer enzymes more efficiently. With all the technologies available, the bottleneck is now in the scale-up production of these enzymes. There is generally a lack of accessibility thereof of large-scale capabilities and know-how. This review is aimed at highlighting these various enzyme-engineering strategies and the associated scale-up challenges, including safety concerns surrounding genetically modified microorganisms and the use of cell-free systems to circumvent this issue. The use of solid-state fermentation (SSF) is also addressed as a potentially low-cost production system, amenable to customization and employing inexpensive feedstocks as substrate.

Integrated continuous melt granulation-based powder-to-tablet line: Process investigation and scale-up on the same equipment

In the last decades, continuous manufacturing (CM) has become a research priority in the pharmaceutical industry. However, significantly fewer scientific researches address the investigation of integrated, continuous systems, a field that needs further exploration to facilitate the implementation of CM lines. This research outlines the development and optimization of an integrated, polyethylene glycol aided melt granulation-based powder-to-tablet line that operates fully continuously. The flowability and tabletability of a caffeine-containing powder mixture were improved through twin-screw melt granulation resulting in the production of tablets with improved breaking force (from 15 N to over 80 N), excellent friability, and immediate release dissolution. The system was also conveniently scaleable: the production speed could be increased from 0.5 kg/h to 8 kg/h with only minimal changes in the process parameters and using the same equipment. Thereby the frequent challenges of scale-up can be avoided, such as the need for new equipment and separate optimization.

Abstract 79: The Impact of COVID-19 on HPV Immunization Programs in Countries With High Cervical Cancer Burdens: Global and National Perspectives

Abstract Purpose: The COVID-19 pandemic has had a considerable impact on HPV immunization efforts within low-and-middle-income countries (LMICs). This is a cause for concern as LMICs account for the global burden of deaths attributable to cervical cancer; yet the direct and indirect impacts of COVID-19 on HPV immunization programs have not been well described in the literature. Our study explored COVID-19 specific challenges in HPV vaccine introduction and scale-up in LMICs through interviewing stakeholders with context specific knowledge in cervical cancer prevention efforts within LMICs. Methods: This qualitative study involved a stakeholder analysis coupled with semi-structured in-depth interviews with n=31 global stakeholders (i.e. academic institutions, global immunization partners) and national stakeholders (i.e. ministry of health officials, non-governmental organizations). Purposive sampling was used to select participants with content knowledge and experience in HPV vaccine programming. Data was analyzed using qualitative content analysis. Inductive codes were categorized into broader themes describing challenges HPV vaccination programs faced during the COVID-19 pandemic. Results: Five broad themes emerged from the analysis: HPV vaccine prioritization, funding considerations, supply chain challenges, HPV vaccine delivery platforms and catch-up dosing, and vaccine hesitancy. The amplified focus of COVID-19 vaccines resulted in decreased prioritization and funding towards HPV vaccination efforts. In certain settings, HPV vaccines were found to be the least prioritized antigen. Decreased demand, coupled with global supply chain shortages due to COVID-19, resulted in sizeable challenges for HPV vaccine introduction and scale-up. Nearly all stakeholders described how anti-COVID-19 vaccine sentiments magnified hesitancy towards HPV vaccines. Particularly revealing, were delivery challenges as a consequence of school closures. This resulted in stakeholders’ acknowledgment of the need to establish alternative delivery platforms and strategies for catch-up dosing. Conclusion: Understanding how emerging infectious disease outbreaks impact HPV vaccination efforts in countries with high cervical cancer burdens is critical. Increasing HPV vaccine prioritization within countries, developing strategies to overcome existing shortfalls, along with addressing vaccine hesitancy will be key in generating momentum towards HPV immunization programs. Citation Format: Dominique Guillaume, Due-e-Nayab Waheed, Mieke Schlieff1, Kirthini Muralidharan, Alex Vorsters, Rupali Limaye. The Impact of COVID-19 on HPV Immunization Programs in Countries With High Cervical Cancer Burdens: Global and National Perspectives [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 79.

Scale-up challenges in the production of nanomedicines from lab to industry

Scale-up challenges in the production of nanomedicines from lab to industry

Mass Transport of Diazomethane across Teflon AF2400 Membrane for Scale-Up Development

Diazomethane is an attractive C1 building block in organic chemistry, but its hazardous nature presents scale-up challenges to this date. The use of a Teflon AF2400 membrane, most commonly in a tube-in-tube reactor setup, is the current state-of-the-art methodology for inherently safer laboratory-scale generation, separation, and consumption of anhydrous diazomethane. For the successful scale-up of this membrane process, the key mass transfer coefficient of the AF2400 membrane, its permeability for diazomethane, was investigated. We report in this contribution a novel methodology to determine diazomethane permeability for the rational scale-up of membrane processes for the safe handling of diazomethane. Missing physical properties of diazomethane were established, and the full mass balance of in situ-generated diazomethane within the tube-in-tube reactor was experimentally validated. A numerical model of the membrane reactor system in combination with experimental data yielded a permeability value of 414 barrer. This result enables scale-up development of the laboratory membrane reactor toward production-scale systems.

Empty and Full AAV Capsid Charge and Hydrophobicity Differences Measured with Single-Particle AFM.

Adeno-associated virus (AAV) is showing promise as a therapy for diseases that contain a single-gene deletion or mutation. One major scale-up challenge is the removal of empty or non-gene of interest containing AAV capsids. Analytically, the empty capsids can be separated from full capsids using anion exchange chromatography. However, when scaled up to manufacturing, the minute changes in conductivity are difficult to consistently obtain. To better understand the differences in the empty and full AAV capsids, we have developed a single-particle atomic force microscopy (AFM) method to measure the differences in the charge and hydrophobicity of AAV capsids at the single-particle level. The atomic force microscope tip was functionalized with either a charged or a hydrophobic molecule, and the adhesion force between the functionalized atomic force microscope tip and the virus was measured. We measured a change in the charge and hydrophobicity between empty and full AAV2 and AAV8 capsids. The charge and hydrophobicity differences between AAV2 and AAV8 are related to the distribution of charge on the surface and not the total charge. We propose that the presence of nucleic acids inside the capsid causes minor but measurable changes in the capsid structure that lead to measurable surface changes in charge and hydrophobicity.

Best Practices and Guidelines (2022) for Scale-up and Technology Transfer in Freeze Drying Based on Case Studies. Part 2: Past Practices, Current Best Practices, and Recommendations

Scale-up and transfer of lyophilization processes remain very challenging tasks considering the technical challenges and the high cost of the process itself. The challenges in scale-up and transfer were discussed in the first part of this paper and include vial breakage during freezing at commercial scale, cake resistance differences between scales, impact of differences in refrigeration capacities, and geometry on the performance of dryers. The second part of this work discusses successful and unsuccessful practices in scale-up and transfer based on the experience of the authors. Regulatory aspects of scale-up and transfer of lyophilization processes were also outlined including a topic on the equivalency of dryers. Based on an analysis of challenges and a summary of best practices, recommendations on scale-up and transfer of lyophilization processes are given including projections on future directions in this area of the freeze drying field. Recommendations on the choice of residual vacuum in the vials were also provided for a wide range of vial capacities.Graphical

Exploring the Power of Thermosonication: A Comprehensive Review of Its Applications and Impact in the Food Industry

Thermosonication (TS) has been identified as a smart remedy for the shortcomings of heat treatment, which typically requires prolonged exposure to high temperatures. This technique combines moderate heat treatment with acoustic energy to eliminate harmful microorganisms and enzymes in food products. Unlike conventional heat treatment, thermosonication utilizes short holding times, allowing for the preservation of food products' phytochemical compounds and sensory characteristics. The benefits and challenges of this emerging technology, such as equipment cost, limited availability of data, inconsistent results, high energy consumption, and scale-up challenges, have been assessed, and the design process for using ultrasound in combination with mild thermal treatment has been discussed. TS has proven to be a promising technique for eliminating microorganisms and enzymes without compromising the nutritional or sensory quality of food products. Utilizing natural antimicrobial agents such as ascorbic acid, Nisin, and ε-polylysine (ε-PL) in combination with thermosonication is a promising approach to enhancing the safety and shelf life of food products. Further research is required to enhance the utilization of natural antimicrobial agents and to acquire a more comprehensive comprehension of their impact on the safety and quality of food products.

Li-S batteries, what's next?

Lithium-sulfur (Li-S) batteries have undergone a dramatic transition in the last two decades. Research has evolved from tackling more fundamental challenges associated with the chemistry of sulfur, such as the polysulfide shuttle effect and the low conductivity of sulfur, via cathode engineering to solving the technical challenges associated with making practical high-energy batteries, such as lowering the electrolyte amount and stabilizing the Li-metal anode. This level of technology readiness has even encouraged several companies to seriously consider the Li-S technology viable for commercialization. With the view that both academia and industry are closer to the pursuit of developing practical Li-S cells for consumer use, we highlight in this commentary some avenues for solving both the remaining technical challenges as well as scale-up and manufacturing challenges.

Influence of surface chemistry and channel shapes on the lithium-ion separation in metal-organic-framework-nanochannel membranes

Metal-organic-framework-based channel (MOFC) membranes have great potential in ion separation due to their high flexibility than polycrystalline MOF membranes. Although a few single-MOFC membranes with high ion selectivity and permeability have been reported, the scale-up of MOFC membranes from single-channel membranes to multichannel membranes remains a challenge as defects with the system are escalated, limiting their practical application. Minimizing defects in multichannel MOFC membranes is the key to solving this scale-up challenge. Herein, the surface chemistry of polyethylene terephthalate (PET) nanochannel substrate was firstly tuned by a chemical modification to enhance the binding between the PET nanochannel walls and UiO-66-(COOH)2 MOF crystals. Further investigation of the influences of PET nanochannels' size, shape, and channel density on the selectivity revealed that the cylindrical and ethylenediamine (EDA)-functionalized single PET-UiO-66-(COOH)2 MOFC membrane exhibited an ultrahigh Li+/Mg2+ selectivity of 3077-fold over those of previous single-MOFC works. Furthermore, cylindrical, EDA-functionalized, multichannel UiO-66-(COOH)2 MOFC membranes with a channel density of 106/cm2 have been fabricated to achieve 50-fold Li+/Mg2+ selectivity and a vast enhancement of Li + conductance for 6 orders of magnitude. As the first example of scaling up the MOFC membrane, this work provides a fundamental basis and experimental techniques for MOF membrane synthesis and lithium-ion extractions.

A Mini-Review on Syngas Fermentation to Bio-Alcohols: Current Status and Challenges

Biomass gasification produces syngas, mainly comprised of CO and H2 along with H2S, CO2, N2, and tar compounds. Inorganic carbon present in syngas as CO and CO2 can be utilized for the production of several value-added chemicals including ethanol, higher alcohols, fuels, and hydrogen. However, chemical sequestration operates at a high temperature of 300–500 °C and pressure of 3–5 MPa in the presence of heavy metal catalysts. Catalyst regeneration and the maintenance of high temperature and pressure increased the cost of operation. Microorganisms like algae and bacteria including Acetobacterium and Clostridium also have the potential to sequester carbon from the gas phase. Research has emphasized the production of microbial metabolites with a high market value from syngas. However, scale-up and commercialization of technology have some obstacles like inefficient mass transfer, microbial contamination, inconsistency in syngas composition, and requirement for a clean-up process. The current review summarizes the recent advances in syngas production and utilization with special consideration of alcohol and energy-related products along with challenges for scale-up.

Smart urban traffic zones – demonstration of three smart zones in Sweden based on geofencing and sensor data

Starting September 2020 and ending September 2022, the project “Smart Urban Traffic Zones” has demonstrated three different set-ups of smart urban traffic zones in the Cities of Stockholm and Gothenburg, Sweden. These zones are based on geofencing technology, smart sensors and V2X communication. The pilots have mainly been aimed at improving road safety for vulnerable road users, increasing transport efficiency in the urban environment, and creating a more flexible use of public space in the city. The results show that it is possible to set-up smart zones with this purpose and that the main challenges for scale-up are related to legal requirements, processes for data sharing and information management.