3D-printing technology applied to the development of bio-inspired functional acoustic systems

Examples of bio-inspired technology can be found almost everywhere in society: robots with specific capabilities, materials with unique physical and chemical properties, aerodynamic systems, and architectonic structures are a few examples of taking profit of evolution-driven processes to solve common engineering problems. One field of research taking advantage of bio-inspiration is that of acoustical engineering, aiming to find solutions to problems arising from the miniaturisation of microphones and loudspeakers. Studying the auditory organs of insects to seek inspiration for new design structures is one of the best ways to solve such an important problem. Another discipline of science that has experienced a research boom is that of materials science, as development of new materials has attracted the attention of researchers. In addition, three-dimensional (3D) printers have contributed to further development in materials science making the production process more efficient. The aim of this research is to bring these fields of science together to develop novel bioinspired, polymer-based sensors presenting functional specific acoustic properties after 3D-printing. While the study of complex biological hearing systems provides inspiration to develop sensors featuring specific properties, the use of polymer-based materials allows the customization of the manufacturing process, as the produced parts adapt to the desired needs. In this thesis one such insect auditory system that has been thoroughly studied is that of the desert locust Schistocerca gregaria as it presents a simple structure that allows for acoustic frequency selectivity and displays nonlinear acoustic phenomena. Prior to the development of a bio-inspired system, a mathematical description of the mechanical response of such a structure is presented. Furthermore, the physical behaviours measured on the locust tympanal membrane have been studied using finite element analysis. The 3D-printed functional sensors have been used to determine the degree of accuracy between experimental and theoretical results.Examples of bio-inspired technology can be found almost everywhere in society: robots with specific capabilities, materials with unique physical and chemical properties, aerodynamic systems, and architectonic structures are a few examples of taking profit of evolution-driven processes to solve common engineering problems. One field of research taking advantage of bio-inspiration is that of acoustical engineering, aiming to find solutions to problems arising from the miniaturisation of microphones and loudspeakers. Studying the auditory organs of insects to seek inspiration for new design structures is one of the best ways to solve such an important problem. Another discipline of science that has experienced a research boom is that of materials science, as development of new materials has attracted the attention of researchers. In addition, three-dimensional (3D) printers have contributed to further development in materials science making the production process more efficient. The aim of this research is to bring these fields of science together to develop novel bioinspired, polymer-based sensors presenting functional specific acoustic properties after 3D-printing. While the study of complex biological hearing systems provides inspiration to develop sensors featuring specific properties, the use of polymer-based materials allows the customization of the manufacturing process, as the produced parts adapt to the desired needs. In this thesis one such insect auditory system that has been thoroughly studied is that of the desert locust Schistocerca gregaria as it presents a simple structure that allows for acoustic frequency selectivity and displays nonlinear acoustic phenomena. Prior to the development of a bio-inspired system, a mathematical description of the mechanical response of such a structure is presented. Furthermore, the physical behaviours measured on the locust tympanal membrane have been studied using finite element analysis. The 3D-printed functional sensors have been used to determine the degree of accuracy between experimental and theoretical results

Rapid prototyped microvessel flow phantom for controlled investigation of ultrasound-mediated targeted drug delivery

The ability to undertake controlled and accurate investigation of the complex features that determine microvasculature-fluid systems is essential in our progress towards successful clinical exploitation of ultrasound mediated targeted drug delivery (UmTDD). We present an engineered platform to enable accurate understanding of the microvascular flow characteristics capable of influencing UmTDD. We develop novel 3D-printed flow phantoms, accurately replicating real microvascular structures, and a new approach to investigating UmTDD phenomena that places microbubble-microvessel interactions at the heart of the problem. Our aim is to establish a robust, lab-based platform for controlled and systematic investigation of microvessel architectures as key determinants in UmTDD efficiency

Microbubble – Microvessel Interactions and their Influence on UmTDD: Simulation Study

No abstract available

Acoustic band gaps in polyatomic chains of 3D-printed resonators

Acoustic bandgaps are ranges of frequencies in a medium at which sound cannot propagate. The classical model often used in solid-state physics is that of a 1D chain of masses and springs, the analysis of which can predict the speed of sound in a material, its dispersive nature, and any forbidden sound frequencies. We use a lumped parameter model for the acoustic inertance and compliance of pipes and cavities to create 1D monatomic, diatomic, and triatomic chains that demonstrate these acoustic bandgaps experimentally. The ease of 3D-printing these devices means that this method can be used to explore bandgap engineering in acoustic systems for low-frequency applications and used as a simple platform for creating acoustic analogs of the solid-state physical problem. Furthermore, it allows us to explore novel polyatomic behavior (e.g., tetratomic and pentatomic) and could ultimately find use as filters for experiments requiring miniaturized acoustic isolation

Additive manufacturing of an insect bio-inspired hair acoustic sensor

Nature surrounds us with many bizarre and inspirational mechanisms. Insects are miniature organisms that can have exceptionally efficient and functional sensory receptors. Acoustic and air flow mechanoreceptors, commonly called trichoid sensilla or trichobothria, are used in different shapes and sizes by several insect species. The goal of this work is to develop hair-like sensor structures inspired by the Barathra brassicae caterpillar and adult Buthus occitanus scorpion. An early version of the sensor has been developed and realised using additive manufacturing. Mechanical analysis shows that the sensor design can be altered to move at different frequencies by changing its structure. Early development to convert mechanical displacement into an electric signal has begun and an electric response is recorded, albeit signal conditioning is required to be usable

Integrated multi-material portable 3D-printed platform for electrochemical detection of dopamine and glucose

3D-printing has become a fundamental part of research in many areas of investigation since it provides rapid and personalized production of parts that meet very specific user needs. Biosensing is not an exception, and production of electrochemical sensors that can detect a variety of redox mediators and biologically relevant molecules has been widely reported. However, most 3D-printed electrochemical sensors detailed in the literature rely on big, individual, single-material electrodes that require large sample volumes to perform effectively. Our work exploits multi-material fused filament fabrication 3D-printing to produce a compact electrochemical sensor able to operate with only 100 μL of sample. We report cyclic voltammetry, differential pulse voltammetry, and chronoamperometry results to assess sensor performance and sensitivity. We investigated the influence of layer print orientation and layer thickness on the electrochemical performance of the sensor, and used the optimal parameters to produce the final device. The integrated 3D-printed platform successfully detects electrochemical activity for hexaammineruthenium(III) chloride and potassium ferricyanide (0.1 mM to 2 mM in 100 mM KCl), dopamine (50 μM to 1 mM in 1×PBS), and glucose via mediated amperometric glucose oxidase enzyme-based sensing (1 mM to 12 mM in 1×PBS), indicating good acceptance of biological modification. These results reveal the exciting potential of multi-material 3D-printing and how it can be used for the rapid development of efficient, small, integrated, personalized electrochemical biosensors

Additive manufacture of small-scale metamaterial structures for acoustic and ultrasonic applications

Acoustic metamaterials are large-scale materials with small-scale structures. These structures allow for unusual interaction with propagating sound and endow the large-scale material with exceptional acoustic properties not found in normal materials. However, their multi-scale nature means that the manufacture of these materials is not trivial, often requiring micron-scale resolution over centimetre length scales. In this review, we bring together a variety of acoustic-metamaterial designs and separately discuss ways to create them using the latest trends in additive manufacturing. We highlight the advantages and disadvantages of different techniques that act as barriers towards the development of realisable acoustic metamaterials for practical audio and ultrasonic applications, and speculate on potential future developments

3D-printed high-resolution microchannels for contrast enhanced ultrasound research

Systemically circulating microbubbles are used as contrast agents to aid both drug targeting and delivery using ultrasound. Exploiting their acoustic behaviour in small diameter vessels is critical for both applications, but the highly controlled experiments required to support this are not possible in vivo and challenging in vitro. Experimental platforms with small diameter channels (below 200 microns) are not readily available nor able to represent vascular geometries, leaving the existence and extent of microbubble-microvessel interactions incompletely defined. In this work we present a 3D-printed microchannel platform using tissue-mimicking hydrogels featuring radii down to 75 microns. We demonstrate application to study microbubble behaviour via acoustic backscatter under controlled environments in physiologically-relevant conditions

Investigating multi-material hydrogel three-dimensional printing for in vitro representation of the neo-vasculature of solid tumours : a comprehensive mechanical analysis and assessment of nitric oxide release from human umbilical vein endothelial cells

Many solid tumours (e.g. sarcoma, carcinoma and lymphoma) form a disorganized neo-vasculature that initiates uncontrolled vessel formation to support tumour growth. The complexity of these environments poses a significant challenge for tumour medicine research. While animal models are commonly used to address some of these challenges, they are time-consuming and raise ethical concerns. In vitro microphysiological systems have been explored as an alternative, but their production typically requires multi-step lithographic processes that limit their production. In this work, a novel approach to rapidly develop multi-material tissue-mimicking, cell-compatible platforms able to represent the complexity of a solid tumour's neo-vasculature is investigated via stereolithography three-dimensional printing. To do so, a series of acrylate resins that yield covalently photo-cross-linked hydrogels with healthy and diseased mechano-acoustic tissue-mimicking properties are designed and characterized. The potential viability of these materials to displace animal testing in preclinical research is assessed by studying the morphology, actin expression, focal adhesions and nitric oxide release of human umbilical vein endothelial cells. These materials are exploited to produce a simplified multi-material three-dimensional printed model of the neo-vasculature of a solid tumour, demonstrating the potential of our approach to replicate the complexity of solid tumours in vitro without the need for animal testing

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe