A review of the recent achievements and future trends on 3D printed microfluidic devices for bioanalytical applications.

3D printing has revolutionized the manufacturing process of microanalytical devices by enabling the automated production of customized objects. This technology promises to become a fundamental tool, accelerating investigations in critical areas of health, food, and environmental sciences. This microfabrication technology can be easily disseminated among users to produce further and provide analytical data to an interconnected network towards the Internet of Things, as 3D printers enable automated, reproducible, low-cost, and easy fabrication of microanalytical devices in a single step. New functional materials are being investigated for one-step fabrication of highly complex 3D printed parts using photocurable resins. However, they are not yet widely used to fabricate microfluidic devices. This is likely the critical step towards easy and automated fabrication of sophisticated, complex, and functional 3D-printed microchips. Accordingly, this review covers recent advances in the development of 3D-printed microfluidic devices for point-of-care (POC) or bioanalytical applications such as nucleic acid amplification assays, immunoassays, cell and biomarker analysis and organs-on-a-chip. Finally, we discuss the future implications of this technology and highlight the challenges in researching and developing appropriate materials and manufacturing techniques to enable the production of 3D-printed microfluidic analytical devices in a single step.

Low-cost, versatile, and highly reproducible microfabrication pipeline to generate 3D-printed customised cell culture devices with complex designs.

Cell culture devices, such as microwells and microfluidic chips, are designed to increase the complexity of cell-based models while retaining control over culture conditions and have become indispensable platforms for biological systems modelling. From microtopography, microwells, plating devices, and microfluidic systems to larger constructs such as live imaging chamber slides, a wide variety of culture devices with different geometries have become indispensable in biology laboratories. However, while their application in biological projects is increasing exponentially, due to a combination of the techniques, equipment and tools required for their manufacture, and the expertise necessary, biological and biomedical labs tend more often to rely on already made devices. Indeed, commercially developed devices are available for a variety of applications but are often costly and, importantly, lack the potential for customisation by each individual lab. The last point is quite crucial, as often experiments in wet labs are adapted to whichever design is already available rather than designing and fabricating custom systems that perfectly fit the biological question. This combination of factors still restricts widespread application of microfabricated custom devices in most biological wet labs. Capitalising on recent advances in bioengineering and microfabrication aimed at solving these issues, and taking advantage of low-cost, high-resolution desktop resin 3D printers combined with PDMS soft lithography, we have developed an optimised a low-cost and highly reproducible microfabrication pipeline. This is thought specifically for biomedical and biological wet labs with not prior experience in the field, which will enable them to generate a wide variety of customisable devices for cell culture and tissue engineering in an easy, fast reproducible way for a fraction of the cost of conventional microfabrication or commercial alternatives. This protocol is designed specifically to be a resource for biological labs with limited expertise in those techniques and enables the manufacture of complex devices across the µm to cm scale. We provide a ready-to-go pipeline for the efficient treatment of resin-based 3D-printed constructs for PDMS curing, using a combination of polymerisation steps, washes, and surface treatments. Together with the extensive characterisation of the fabrication pipeline, we show the utilisation of this system to a variety of applications and use cases relevant to biological experiments, ranging from micro topographies for cell alignments to complex multipart hydrogel culturing systems. This methodology can be easily adopted by any wet lab, irrespective of prior expertise or resource availability and will enable the wide adoption of tailored microfabricated devices across many fields of biology.

Highly Localized Chemical Sampling at Subsecond Temporal Resolution Enabled with a Silicon Nanodialysis Platform at Nanoliter per Minute Flows.

Microdialysis (MD) is a versatile and powerful technique for chemical profiling of biological tissues and is widely used for quantification of neurotransmitters, neuropeptides, metabolites, biomarkers, and drugs in the central nervous system as well as in dermatology, ophthalmology, and pain research. However, MD performance is severely limited by fundamental tradeoffs between chemical sensitivity, spatial resolution, and temporal response. Here, by using wafer-scale silicon microfabrication, we develop and demonstrate a nanodialysis (ND) sampling probe that enables highly localized chemical sampling with 100 µm spatial resolution and subsecond temporal resolution at high recovery rates. These performance metrics, which are 100-1000× superior to existing MD approaches, are enabled by a 100× reduction of the microfluidic channel cross-section, a corresponding drastic 100× reduction of flow rates to exceedingly slow few nL/min flows, and integration of a nanometer-thin nanoporous membrane with high transport flux into the probe sampling area. Miniaturized ND probes may allow for the minimally invasive and highly localized sampling and chemical profiling in live biological tissues with high spatiotemporal resolution for clinical, biomedical, and pharmaceutical applications.

Microfabrication of engineered Lactococcus lactis biocarriers with genetically programmed immunorecognition probes for sensitive lateral flow immunoassay of antibiotic in milk and lake water.

Micro/nanomaterials display considerable potential for increasing the sensitivity of lateral flow immunoassay (LFIA) by acting as 3D carriers for both antibodies and signals. The key to achieving high detection sensitivity depends on the probe's orientation on the material surface and its multivalent biomolecular interactions with targets. Here, we engineer Lactococcus lactis as the bacterial microcarrier (BMC) for a multivalent immunorecognition probe that was genetically programmed to display multifunctional components including a phage-screened single-chain variable fragment (scFv), an enhanced green fluorescent protein (eGFP), and a C-terminal peptidoglycan-binding domain (AcmA) anchored on BMC through the cell wall peptidoglycan. The innovative design of this biocarrier system, which incorporates a lab-on-a-chip microfluidic device, allows for the rapid and non-destructive self-assembly of the multivalent scFv-eGFP-AcmA@BMC probe, in which the 3D structure of BMC with a large peptidoglycan surface area facilitates the precisely orientated attachment and immobilization of scFv-eGFP-AcmA. This leads to a remarkable fluorescence aggregation amplification effect in LFIA, outperforming a monovalent 2D scFv-eGFP-AcmA probe for florfenicol detection. By designing a portable sensing device, we achieved an exceptionally low detection limit of 0.28 pg/mL and 0.21 pg/mL for florfenicol in lake water and milk sample, respectively. The successful microfabrication of this biocarrier holds potential to inspire innovative biohybrid designs for environment and food safety biosensing applications.

Microfabrication-based engineering of biomimetic dentin-like constructs to simulate dental aging.

Human dentin is a highly organized dental tissue displaying a complex microarchitecture consisting of micrometer-sized tubules encased in a mineralized type-I collagen matrix. As such, it serves as an important substrate for the adhesion of microbial colonizers and oral biofilm formation in the context of dental caries disease, including root caries in the elderly. Despite this issue, there remains a current lack of effective biomimetic in vitro dentin models that facilitate the study of oral microbial adhesion by considering the surface architecture at the micro- and nanoscales. Therefore, the aim of this study was to develop a novel in vitro microfabricated biomimetic dentin surface that simulates the complex surface microarchitecture of exposed dentin. For this, a combination of soft lithography microfabrication and biomaterial science approaches were employed to construct a micropitted PDMS substrate functionalized with mineralized type-I collagen. These dentin analogs were subsequently glycated with methylglyoxal (MGO) to simulate dentin matrix aging in vitro and analyzed utilizing an interdisciplinary array of techniques including atomic force microscopy (AFM), elemental analysis, and electron microscopy. AFM force-mapping demonstrated that the nanomechanical properties of the biomimetic constructs were within the expected biological parameters, and that mineralization was mostly predominated by hydroxyapatite deposition. Finally, dual-species biofilms of Streptococcus mutans and Candida albicans were grown and characterized on the biofunctionalized PDMS microchips, demonstrating biofilm-specific morphologic characteristics and confirming the suitability of this model for the study of early biofilm formation under controlled conditions. Overall, we expect that this novel biomimetic dentin model could serve as an in vitro platform to study oral biofilm formation or dentin-biomaterial bonding in the laboratory without the need for animal or human tooth samples in the future.

Breaking Barriers: Exploring Neurotransmitters through In Vivo vs. In Vitro Rivalry.

Neurotransmitter analysis plays a pivotal role in diagnosing and managing neurodegenerative diseases, often characterized by disturbances in neurotransmitter systems. However, prevailing methods for quantifying neurotransmitters involve invasive procedures or require bulky imaging equipment, therefore restricting accessibility and posing potential risks to patients. The innovation of compact, in vivo instruments for neurotransmission analysis holds the potential to reshape disease management. This innovation can facilitate non-invasive and uninterrupted monitoring of neurotransmitter levels and their activity. Recent strides in microfabrication have led to the emergence of diminutive instruments that also find applicability in in vitro investigations. By harnessing the synergistic potential of microfluidics, micro-optics, and microelectronics, this nascent realm of research holds substantial promise. This review offers an overarching view of the current neurotransmitter sensing techniques, the advances towards in vitro microsensors tailored for monitoring neurotransmission, and the state-of-the-art fabrication techniques that can be used to fabricate those microsensors.

Microfabrication of Gelatin Methacrylate/Hydroxyapatite Composites by Utilizing Alternate Soaking Process.

To construct a complex three-dimensional (3D) structure mimicking bone microstructure, hydrogel models of polymerized gelatin methacrylate (pGelMA) were fabricated by using stereolithography and modified with hydroxyapatite (HAp) via an alternate soaking process (ASP) using a solution of calcium and phosphate ions. Fabricated pGelMA line models whose widths were designed as 100, 300, and 600 µm were modified with HAp by ASP by changing the immersion time and number of cycles. After ASP, all of the line models with widths of 100, 300, and 600 µm were successfully modified with HAp, and large amounts of HAp were covered with the fabricated models by increasing both the immersion time and the number of cycles in ASP. HAp was observed near the surface of the line model with a width of 600 µm after ASP at an immersion time of 10 s, while the entire model was modified with HAp using ASPs for longer immersion times. The adhesion and spread of mesenchymal stem cells (MSCs) on the pGelMA-HAp discs depended on the ASP conditions. Moreover, the HAp modification of 3D pyramid models without alteration of the microstructure was also conducted. This two-step fabrication method of first fabricating frameworks of hydrogel models by stereolithography and subsequently modifying the fabricated models with HAp will lead to the development of 3D cell culture systems to support bone grafts or to create biological niches, such as artificial bone marrow.

Recent advancements in Mg-based micromotors for biomedical and environmental applications.

Synthetic micro/nanomotors have attracted considerable attention due to their promising potential in the field of biomedicine. Despite their great potential, major micromotors require chemical fuels or complex devices to generate external physical fields for propulsion. Therefore, for future practical medical and environmental applications, Mg-based micromotors that exhibit water-powered movement and thus eliminate the need for toxic fuels, and that display optimal biocompatibility and biodegradability, are attracting attention. In this review, we summarized the recent microarchitectural design of Mg-based micromotors for biomedical applications. We also highlight the mechanism for realizing their water-powered motility. Furthermore, recent biomedical and environmental applications of Mg-based micromotors are introduced. We envision that advanced Mg-based micromotors will have a profound impact in biomedicine.

Transforming medical device biofilm control with surface treatment using microfabrication techniques.

Biofilm deposition on indwelling medical devices and implanted biomaterials is frequently attributed to the prevalence of resistant infections in humans. Further, the nature of persistent infections is widely believed to have a biofilm etiology. In this study, the wettability of commercially available indwelling medical devices was explored for the first time, and its effect on the formation of biofilm was determined in vitro. Surprisingly, all tested indwelling devices were found to be hydrophilic, with surface water contact angles ranging from 60° to 75°. First, we established a thriving Candida albicans biofilm growth at 24 hours. in YEPD at 30°C and 37°C plus serum in vitro at Cyclic olefin copolymer (COC) modified surface, which was subsequently confirmed via scanning electron microscopy, while their cellular metabolic function was assessed using the XTT cell viability assay. Surfaces with patterned wettability show that a contact angle of 110° (hydrophobic) inhibits C. albicans planktonic and biofilm formation completely compared to robust growth at a contact angle of 40° (hydrophilic). This finding may provide a novel antimicrobial strategy to prevent biofilm growth and antimicrobial resistance on indwelling devices and prosthetic implants. Overall, this study provides valuable insights into the surface characteristics of medical devices and their potential impact on biofilm formation, leading to the development of improved approaches to control and prevent microbial biofilms and re-infections.

The speed and acceleration of the ball carrier and tackler into contact during front-on tackles in rugby league.

The aim was to use a combination of video analysis and microtechnology (10 Hz global positioning system [GPS]) to quantify and compare the speed and acceleration of ball-carriers and tacklers during the pre-contact phase (contact - 0.5s) of the tackle event during rugby league match-play. Data were collected from 44 professional male rugby league players from two Super League clubs across two competitive matches. Tackle events were coded and subject to three stages of inclusion criteria to identify front-on tackles. 10 Hz GPS data was synchronised with video to extract the speed and acceleration of the ball-carrier and tackler into each front-on tackle (n = 214). Linear mixed effects models (effect size [ES], confidence intervals, p-values) compared differences. Overall, ball-carriers (4.73 ± 1.12 m∙s-1) had greater speed into front-on tackles than tacklers (2.82 ± 1.07 m∙s-1; ES = 1.69). Ball-carriers accelerated (0.67 ± 1.01 m∙s-2) into contact whilst tacklers decelerated (-1.26 ± 1.36 m∙s-2; ES = 1.74). Positional comparisons showed speed was greater during back vs. back (ES = 0.66) and back vs. forward (ES = 0.40) than forward vs. forward tackle events. Findings can be used to inform strategies to improve performance and player welfare.

Using Microtechnology and the Fourier Transform for the Analysis of Effective Activity Time in Professional Soccer.

ABSTRACT: Oliva-Lozano, JM, Chmura, P, Granero-Gil, P, and Muyor, JM. Using microtechnology and the Fourier Transform for the analysis of effective activity time in professional soccer. J Strength Cond Res 37(12): 2491-2495, 2023-This study aimed to investigate the use of the fast Fourier transform (FFT) for the analysis of effective activity time in professional soccer by (a) exploring the relationship between this variable and standard external load parameters and (b) analyzing the effective activity time during official professional soccer matches. Twenty-six male players participated in the study. Each player was categorized as midfielder, central defender, full-back, wide-midfielder, or forward. Tracking systems based on inertial sensors (4 3D accelerometers, 3 3D gyroscopes, and 1 magnetometer), and global positioning systems technology were used to collect external load measures for 35 matches. Each match was analyzed considering 15-minute periods to explore the evolution of effective activity time during the matches. The extra time from each match was also included. Fast Fourier transform duration may be a representative variable of effective activity time, given the strong positive correlation with the external load variables ( p < 0.001). The linear regression analysis showed that the variables that significantly contributed to the model ( R2 = 0.97) were the total of steps and the distance covered. The mean effective activity time in soccer match play was ∼48.69 minutes. This time significantly changed depending on factors such as the period of the match ( F = 239.05; p < 0.001; ηp 2 = 0.60) or playing position ( F = 16.99; p < 0.001; ηp 2 = 0.06). The greatest effective activity time was observed for all playing positions in the 0'-15' period. However, the 60'-75' period showed the lowest effective activity times compared with the rest of the 15-minute periods for all positions except for forwards (75'-90'). From a practical standpoint, sports performance practitioners may consider these results to improve the individualization of training and match demands. Also, a more accurate indicator of exercise intensity may be obtained (e.g., multiplying the rating of perceived exertion by the effective activity time).

Microfabrication and lab-on-a-chip devices promotein vitromodeling of neural interfaces for neuroscience researches and preclinical applications.

Neural tissues react to injuries through the orchestration of cellular reprogramming, generating specialized cells and activating gene expression that helps with tissue remodeling and homeostasis. Simplified biomimetic models are encouraged to amplify the physiological and morphological changes during neural regeneration at cellular and molecular levels. Recent years have witnessed growing interest in lab-on-a-chip technologies for the fabrication of neural interfaces. Neural system-on-a-chip devices are promisingin vitromicrophysiological platforms that replicate the key structural and functional characteristics of neural tissues. Microfluidics and microelectrode arrays are two fundamental techniques that are leveraged to address the need for microfabricated neural devices. In this review, we explore the innovative fabrication, mechano-physiological parameters, spatiotemporal control of neural cell cultures and chip-based neurogenesis. Although the high variability in different constructs, and the restriction in experimental and analytical access limit the real-life applications of microphysiological models, neural system-on-a-chip devices have gained considerable translatability for modeling neuropathies, drug screening and personalized therapy.

High-aspect-ratio three-dimensional polymer and metallic microstructure microfabrication using two-photon polymerization.

Creating micrometer-resolution high-aspect-ratio three-dimensional (3D) structures remain very challenging despite significant microfabrication methods developed for microelectromechanical systems (MEMS). This is especially the case when such structures are desired to be metallic to support electronic applications. Here, we present a microfabrication process that combines two-photon-polymerization (2PP) printing to create a polymeric high-aspect-ratio three-dimensional structure and electroless metal plating that selectively electroplates only the polymeric structure to create high-aspect-ratio 3D metallic structures having micrometer-resolution. To enable this, the effect of various 2PP processing parameters on SU-8 photoresist microstructures were first systematically studied. These parameters include laser power, slicing/hatching distances, and pre-/post-baking temperature. This optimization resulted in a maximum aspect ratio (height to width) of ~ 12. Following this polymeric structure printing, electroless plating using Tollens' Reagent were utilized to selectively coat silver particles only on the polymeric structure, but not on the silicon substrate. The final 3D metallic structures were evaluated in terms of their resistivity, reproducibly showing resistivity of ~ 10-6 [Ω·m]. The developed 3D metallic structure microfabrication process can be further integrated with conventional 2D lithography to achieve even more complex structures. The developed method overcomes the limitations of current MEMS fabrication processes, allowing a variety of previously impossible metallic microstructures to be created.

Vat photopolymerization 3D printed microfluidic devices for organ-on-a-chip applications.

Organs-on-a-chip, or OoCs, are microfluidic tissue culture devices with micro-scaled architectures that repeatedly achieve biomimicry of biological phenomena. They are well positioned to become the primary pre-clinical testing modality as they possess high translational value. Current methods of fabrication have facilitated the development of many custom OoCs that have generated promising results. However, the reliance on microfabrication and soft lithographic fabrication techniques has limited their prototyping turnover rate and scalability. Additive manufacturing, known commonly as 3D printing, shows promise to expedite this prototyping process, while also making fabrication easier and more reproducible. We briefly introduce common 3D printing modalities before identifying two sub-types of vat photopolymerization - stereolithography (SLA) and digital light processing (DLP) - as the most advantageous fabrication methods for the future of OoC development. We then outline the motivations for shifting to 3D printing, the requirements for 3D printed OoCs to be competitive with the current state of the art, and several considerations for achieving successful 3D printed OoC devices touching on design and fabrication techniques, including a survey of commercial and custom 3D printers and resins. In all, we aim to form a guide for the end-user to facilitate the in-house generation of 3D printed OoCs, along with the future translation of these important devices.

Silicon microfabrication technologies for biology integrated advance devices and interfaces.

Miniaturization is the trend to manufacture ever smaller devices and this process requires knowledge, experience, understanding of materials, manufacturing techniques and scaling laws. The fabrication techniques used in semiconductor industry deliver an exceptionally high yield of devices and provide a well-established platform. Today, these miniaturized devices are manufactured with high reproducibility, design flexibility, scalability and multiplexed features to be used in several applications including micro-, nano-fluidics, implantable chips, diagnostics/biosensors and neural probes. We here provide a review on the microfabricated devices used for biology driven science. We will describe the ubiquity of the use of micro-nanofabrication techniques in biology and biotechnology through the fabrication of high-aspect-ratio devices for cell sensing applications, intracellular devices, probes developed for neuroscience-neurotechnology and biosensing of the certain biomarkers. Recently, the research on micro and nanodevices for biology has been progressing rapidly. While the understanding of the unknown biological fields -such as human brain- has been requiring more research with advanced materials and devices, the development protocols of desired devices has been advancing in parallel, which finally meets with some of the requirements of biological sciences. This is a very exciting field and we aim to highlight the impact of micro-nanotechnologies that can shed light on complex biological questions and needs.

Influence of game period and game action in the physical requirements of basketball referees / Influencia del periodo y acción de juego en las exigencias físicas de árbitros de baloncesto

This study aimed to identify internal and external workload demands in professional referees, and to analyse the influence of the situational variables Game Period and Game Action. Three professional referees of the highest category were monitored during a national elite game. WIMU PRO™ inertial devices were used for workload monitoring via microtechnology, ultra-wide band and heart rate (HR) telemetry. The referees worked at around 82%HRMAX and spent 75% of the time at walking-jogging speed (0-12km/h). Game Action influenced the external workload (total distance and per intensities, impacts, player load, maximum and mean speed) while Game Period influenced the internal load (HRMEAN, HRMAX, %HRMAX and per intensities). Workload quantification in competition and the evaluation of the effect of situational variables are essential for setting up performance profiles and designing individual programmes that improve the training of basketball referees. (AU)

Construction of intelligent moving micro/nanomotors and their applications in biosensing and disease treatment.

Micro/nanomotors are containers that pass through liquid media and carry cargo. Because they are tiny, micro/nanomotors exhibit excellent potential for biosensing and disease treatment applications. However, their size also makes overcoming random Brownian forces very challenging for micro/nanomotors moving on targets. Additionally, to achieve desired practical applications, the expensive materials, short lifetimes, poor biocompatibility, complex preparation methods, and side effects of micro/nanomotors must be addressed, and potential adverse effects must be evaluated both in vivo and in practical applications. This has led to the continuous development of key materials for driving micro/nanomotors. In this work, we review the working principles of micro/nanomotors. Metallic and nonmetallic nanocomplexes, enzymes, and living cells are explored as key materials for driving micro/nanomotors. We also consider the effects of exogenous stimulations and endogenous substance conditions on micro/nanomotor motions. The discussion focuses on micro/nanomotor applications in biosensing, treating cancer and gynecological diseases, and assisted fertilization. By addressing micro/nanomotor shortcomings, we propose directions for further developing and applying micro/nanomotors.

Multicellular dynamics on structured surfaces: Stress concentration is a key to controlling complex microtissue morphology on engineered scaffolds.

Tissue engineers have utilised a variety of three-dimensional (3D) scaffolds for controlling multicellular dynamics and the resulting tissue microstructures. In particular, cutting-edge microfabrication technologies, such as 3D bioprinting, provide increasingly complex structures. However, unpredictable microtissue detachment from scaffolds, which ruins desired tissue structures, is becoming an evident problem. To overcome this issue, we elucidated the mechanism underlying collective cellular detachment by combining a new computational simulation method with quantitative tissue-culture experiments. We first quantified the stochastic processes of cellular detachment shown by vascular smooth muscle cells on model curved scaffolds and found that microtissue morphologies vary drastically depending on cell contractility, substrate curvature, and cell-substrate adhesion strength. To explore this mechanism, we developed a new particle-based model that explicitly describes stochastic processes of multicellular dynamics, such as adhesion, rupture, and large deformation of microtissues on structured surfaces. Computational simulations using the developed model successfully reproduced characteristic detachment processes observed in experiments. Crucially, simulations revealed that cellular contractility-induced stress is locally concentrated at the cell-substrate interface, subsequently inducing a catastrophic process of collective cellular detachment, which can be suppressed by modulating cell contractility, substrate curvature, and cell-substrate adhesion. These results show that the developed computational method is useful for predicting engineered tissue dynamics as a platform for prediction-guided scaffold design. STATEMENT OF SIGNIFICANCE: Microfabrication technologies aiming to control multicellular dynamics by engineering 3D scaffolds are attracting increasing attention for modelling in cell biology and regenerative medicine. However, obtaining microtissues with the desired 3D structures is made considerably more difficult by microtissue detachments from scaffolds. This study reveals a key mechanism behind this detachment by developing a novel computational method for simulating multicellular dynamics on designed scaffolds. This method enabled us to predict microtissue dynamics on structured surfaces, based on cell mechanics, substrate geometry, and cell-substrate interaction. This study provides a platform for the physics-based design of micro-engineered scaffolds and thus contributes to prediction-guided biomaterials design in the future.

Rapid prototyping of microfluidic chips enabling controlled biotechnology applications in microspace.

Rapid prototyping of microfluidic chips is a key enabler for controlled biotechnology applications in microspaces, as it allows for the efficient design and production of microfluidic systems. With rapid prototyping, researchers and engineers can quickly create and test new microfluidic chip designs, which can then be optimized for specific applications in biotechnology. One of the key advantages of microfluidic chips for biotechnology is the ability to manipulate and control biological samples in a microspace, which enables precise and controlled experiments under well-defined conditions. This is particularly useful for applications such as cell culture, drug discovery, and diagnostic assays, where precise control over the biological environment is crucial for obtaining accurate results. Established methods, for example, soft lithography, 3D printing, injection molding, as well as other recently highlighted innovative approaches, will be compared and challenges as well as limitations will be discussed. It will be shown that rapid prototyping of microfluidic chips enables the use of advanced materials and technologies, such as smart materials and digital sensors, which can further enhance the capabilities of microfluidic systems for biotechnology applications. Overall, rapid prototyping of microfluidic chips is an important enabling technology for controlled biotechnology applications in microspaces, as well as for upscaling it into macroscopic bioreactors, and its continued development and improvement will play a critical role in advancing the field. The review will highlight recent trends in terms of materials and competing approaches and shed light on current challenges on the way toward integrated microtechnologies. Also, the possibility to easy and direct implementation of novel functions (membranes, functionalization of interfaces, etc.) is discussed.

Flexible Organic Electronic Ion Pump Fabricated Using Inkjet Printing and Microfabrication for Precision In Vitro Delivery of Bupivacaine.

The organic electronic ion pump (OEIP) is an on-demand electrophoretic drug delivery device, that via electronic to ionic signal conversion enables drug delivery without additional pressure or volume changes. The fundamental component of OEIPs is their polyelectrolyte membranes which are shaped into ionic channels that conduct and deliver ionic drugs, with high spatiotemporal resolution. The patterning of these membranes is essential in OEIP devices and is typically achieved using laborious microprocessing techniques. Here, the development of an inkjet printable formulation of polyelectrolyte is reported, based on a custom anionically functionalized hyperbranched polyglycerol (i-AHPG). This polyelectrolyte ink greatly simplifies the fabrication process and is used in the production of free-standing OEIPs on flexible polyimide (PI) substrates. Both i-AHPG and the OEIP devices are characterized, exhibiting favorable iontronic characteristics of charge selectivity and the ability to transport aromatic compounds. Further, the applicability of these technologies is demonstrated by the transport and delivery of the pharmaceutical compound bupivacaine to dorsal root ganglion cells with high spatial precision and effective nerve blocking, highlighting the applicability of these technologies for biomedical scenarios.