Printing MEMS: Application of Inkjet Techniques to the Manufacturing of Inertial Accelerometers.

In the last few years, the manufacturing of microelectromechanical systems (MEMS) by means of innovative tridimensional and bidimensional printing technologies has significantly catalyzed the attention of researchers. Inkjet material deposition, in particular, can become a key enabling technology for the production of polymer-based inertial sensors characterized by low cost, high manufacturing scalability and superior sensitivity. In this paper, a fully inkjet-printed polymeric accelerometer is proposed, and its manufacturing steps are described. The manufacturing challenges connected with the inkjet deposition of SU-8 as a structural material are identified and addressed, resulting in the production of a functional spring-mass sensor. A step-crosslinking process allows optimization of the final shape of the device and limits defects typical of inkjet printing. The resulting device is characterized from a morphological point of view, and its functionality is assessed in performing optical readout. The acceleration range of the optimized device is 0-0.7 g, its resolution is 2 × 10-3 g and its sensitivity is 6745 nm/g. In general, the work demonstrates the feasibility of polymeric accelerometer production via inkjet printing, and these characteristic parameters demonstrate their potential applicability in a broad range of uses requiring highly accurate acceleration measurements over small displacements.

Inkjet-Assisted Electroformation of Magnetically Guidable Water Striders for Interfacial Microfluidic Manipulation.

Gerridae, colloquially called water striders, are a peculiar class of insects characterized by the extraordinary ability to walk on the surface of water bodies. Owing to this capacity, they constitute an ideal source of inspiration for designing untethered microdevices capable of navigating the interface between two fluids. Such steerable micrometric objects can be of great interest for various applications, ranging from the handling of floating objects to the remote control of microreactions and the manipulation of self-assembled monolayers. This paper describes the realization of artificial water striders via an inkjet-assisted electroforming approach. Inkjet deposition patterns the negative mask, which is subsequently filled with different layers of metals through electroforming. One of such layers is the magnetic alloy NiFe, which allows wireless propulsion of the striders by means of externally applied magnetic fields. The magnetic actuation tests prove good maneuverability at the water-air and silicone oil-air interfaces, with superior control over the speed and position of the devices. The surface of the devices is modified to tune its superficial energy in order to maximize buoyancy on these different combinations of fluids. A magnetic field-controlled strider manipulates a droplet and demonstrates collecting oil microdroplets and synthesizing platinum nanoparticles by chemical microreactions. Finally, the remotely operated microrobot could be employed in laboratories as a real avatar of chemists.

Layer-by-Layer Fabrication of Hydrogel Microsystems for Controlled Drug Delivery From Untethered Microrobots.

Targeted drug delivery from untethered microrobots is a topic of major interest in current biomedical research. The possibility to load smart materials able to administer active principles on remotely in vivo guidable microdevices constitutes one of the most attractive opportunities to overcome the drawbacks of classical untargeted delivery methodologies. Hydrogels, in particular, are ideal candidates as drug-carrying materials due to their biocompatibility, low cost, and ease of manufacturing. On the other hand, these polymers suffer from poor control over release rate and overall released amount. Starting from these premises, the present article demonstrates the possibility to tune the release of hydrogels applied on magnetically steerable microrobots by fabricating microsystems via layer-by-layer self-assembly. By doing this, the diffusion of chemicals from the hydrogel layers to the external environment can be optimized and the phenomenon of burst release can be strongly limited. The microrobotic platforms employed to transport the hydrogel active material are fabricated by employing 3D printing in combination with wet metallization and present a gold layer on their surface to enhance biocompatibility. The maneuverability of microdevices coated with both thin and thick multilayers is investigated, individuating optimized parameters for efficient actuation.

Albumin Oxidation Status in Sepsis Patients Treated With Albumin or Crystalloids.

Inflammation and oxidative stress characterize sepsis and determine its severity. In this study, we investigated the relationship between albumin oxidation and sepsis severity in a selected cohort of patients from the Albumin Italian Outcome Study (ALBIOS). A retrospective analysis was conducted on the oxidation forms of human albumin [human mercapto-albumin (HMA), human non-mercapto-albumin form 1 (HNA1) and human non-mercapto-albumin form 2 (HNA2)] in 60 patients with severe sepsis or septic shock and 21 healthy controls. The sepsis patients were randomized (1:1) to treatment with 20% albumin and crystalloid solution or crystalloid solution alone. The albumin oxidation forms were measured at day 1 and day 7. To assess the albumin oxidation forms as a function of oxidative stress, the 60 sepsis patients, regardless of the treatment, were grouped based on baseline sequential organ failure assessment (SOFA) score as surrogate marker of oxidative stress. At day 1, septic patients had significantly lower levels of HMA and higher levels of HNA1 and HNA2 than healthy controls. HMA and HNA1 concentrations were similar in patients treated with albumin or crystalloids at day 1, while HNA2 concentration was significantly greater in albumin-treated patients (p < 0.001). On day 7, HMA was significantly higher in albumin-treated patients, while HNA2 significantly increased only in the crystalloids-treated group, reaching values comparable with the albumin group. When pooling the septic patients regardless of treatment, albumin oxidation was similar across all SOFA groups at day 1, but at day 7 HMA was lower at higher SOFA scores. Mortality rate was independently associated with albumin oxidation levels measured at day 7 (HMA log-rank = 0.027 and HNA2 log-rank = 0.002), irrespective of treatment group. In adjusted regression analyses for 90-day mortality, this effect remained significant for HMA and HNA2. Our data suggest that the oxidation status of albumin is modified according to the time of exposure to oxidative stress (differences between day 1 and day 7). After 7 days of treatment, lower SOFA scores correlate with higher albumin antioxidant capacity. The trend toward a positive effect of albumin treatment, while not statistically significant, warrants further investigation.

Red phosphorus decorated electrospun carbon anodes for high efficiency lithium ion batteries.

Electrospinning is a powerful and versatile technique to produce efficient, specifically tailored and high-added value anodes for lithium ion batteries. Indeed, electrospun carbon nanofibers (CNFs) provide faster intercalation kinetics, shorter diffusion paths for ions/electrons transport and a larger number of lithium insertion sites with respect to commonly employed powder materials. With a view to further enhance battery performances, red phosphorous (RP) is considered one of the most promising materials that can be used in association with CNFs. RP/CNFs smart combinations can be exploited to overcome RP low conductivity and large volume expansion during cycling. In this context, we suggest a simple and cost effective double-step procedure to obtain high-capacity CNFs anodes and to enhance their electrochemical performances with the insertion of red phosphorous in the matrix. We propose a simple dropcasting method to confine micro- and nanosized RP particles within electrospun CNFs, thus obtaining a highly efficient, self-standing, binder-free anode. Phosphorous decorated carbon mats are characterized morphologically and tested in lithium ion batteries. Results obtained demonstrate that the reversible specific capacity and the rate capability of the obtained composite anodes is significantly improved with respect to the electrospun carbon mat alone.

3D Printing of Cantilever-Type Microstructures by Stereolithography of Ferromagnetic Photopolymers.

In the present work, prototypes of polymeric cantilever-based magnetic microstructures were fabricated by means of stereolithography (SL). To this end, a UV-curable system suitable for high-resolution SL-processing was formulated by blending a bifunctional acrylic monomer with photoinitiator and visible dye whose content was tuned to tailor resin SL sensitivity. Subsequently, to confer ferromagnetic properties to the photopolymer, two different strategies were implemented. A two-step approach involved selective deposition of a metal layer on photopolymer SL-cured surfaces through an electroless plating process. On the other hand, SL-processable ferromagnetically responsive nanocomposites (FRCs) were obtained by directly loading magnetite nanoparticles within the photopolymer matrix. In order to achieve high-printing resolution, resin SL sensitivities were studied as a function of the various additives contents. Photocalorimetric analyses were also performed to investigate the photopolymer conversion efficiency upon light exposure. High-performing formulations were characterized by reduced penetration depth (<50 µm) and small critical energies thus enabling for fast printing of micrometric structures. Finally, the self-standing characteristics of the resin combined with the layered-fashion deposition typical of the 3D printing technologies were exploited for the fabrication of cantilever (CL)-based beams presented as possible magnetic sensors. As a demonstration of the feasibility of the two approaches, the magnetic beams were successfully actuated and their sensing performances in terms of static deflection vs applied magnetic field applied were qualitatively studied. Being not restricted to CL-based geometries, the combination of SL-printing with the formulation of novel smart photopolymers open the way toward the fabrication of high-customized complex 3D models integrating functional microstructures.

Elevated plasma heparin-binding protein is associated with early death after resuscitation from cardiac arrest.

BACKGROUND: An intense systemic inflammatory response is observed following reperfusion after cardiac arrest. Heparin-binding protein (HBP) is a granule protein released by neutrophils that intervenes in endothelial permeability regulation. In the present study, we investigated plasma levels of HBP in a large population of patients resuscitated from out-of-hospital cardiac arrest. We hypothesized that high circulating levels of HBP are associated with severity of post-cardiac arrest syndrome and poor outcome. METHODS: Plasma was obtained from 278 patients enrolled in a prospective multicenter observational study in 21 intensive care units (ICU) in Finland. HBP was assayed at ICU admission and 48 h later. Multiple organ dysfunction syndrome (MODS) was defined as the 24 h Sequential Organ Failure Assessment (SOFA) score ≥ 12. ICU death and 12-month Cerebral Performance Category (CPC) were evaluated. Multiple linear and logistic regression tests and receiver operating characteristic curves with area under the curve (AUC) were performed. RESULTS: Eighty-two percent of patients (229 of 278) survived to ICU discharge and 48 % (133 of 276) to 1 year with a favorable neurological outcome (CPC 1 or 2). At ICU admission, median plasma levels of HBP were markedly elevated, 15.4 [9.6-31.3] ng/mL, and persisted high 48 h later, 14.8 [9.8-31.1] ng/mL. Admission levels of HBP were higher in patients who had higher 24 h SOFA and cardiovascular SOFA score (p < 0.0001) and in those who developed MODS compared to those who did not (29.3 [13.7-60.1] ng/mL vs. 13.6 [9.1-26.2] ng/mL, p < 0.0001; AUC = 0.70 ± 0.04, p = 0.0001). Admission levels of HBP were also higher in patients who died in ICU (31.0 [17.7-78.2] ng/mL) compared to those who survived (13.5 [9.1-25.5] ng/mL, p < 0.0001) and in those with an unfavorable 12-month neurological outcome compared to those with a favorable one (18.9 [11.3-44.3] ng/mL vs. 12.8 [8.6-30.4] ng/mL, p < 0.0001). Admission levels of HBP predicted early ICU death with an AUC of 0.74 ± 0.04 (p < 0.0001) and were independently associated with ICU death (OR [95 %CI] 1.607 [1.076-2.399], p = 0.020), but not with unfavorable 12-month neurological outcome (OR [95 %CI] 1.154 [0.834-1.596], p = 0.387). CONCLUSIONS: Elevated plasma levels of HBP at ICU admission were independently associated with early death in ICU.

Circulating presepsin (soluble CD14 subtype) as a marker of host response in patients with severe sepsis or septic shock: data from the multicenter, randomized ALBIOS trial.

PURPOSE: Presepsin is a soluble fragment of the cluster-of-differentiation marker protein 14 (CD14) involved in pathogen recognition by innate immunity. We evaluated the relation between its circulating concentration, host response, appropriateness of antibiotic therapy, and mortality in patients with severe sepsis. METHODS: Plasma presepsin was measured 1, 2, and 7 days after enrollment of 997 patients with severe sepsis or septic shock in the multicenter Albumin Italian Outcome Sepsis (ALBIOS) trial. They were randomized to albumin or crystalloids. We tested with univariate and adjusted models the association of single measurements of presepsin or changes over time with clinical events, organ dysfunctions, appropriateness of antibiotic therapy, and ICU or 90-day mortality. RESULTS: Presepsin concentration at baseline (946 [492-1,887] ng/L) increased with the SOFA score, the number of prevalent organ dysfunctions or failures, and the incidence of new failures of the respiratory, coagulation, liver, and kidney systems. The concentration decreased in ICU over 7 days in patients with negative blood cultures, and in those with positive blood cultures and appropriate antibiotic therapy; it increased with inappropriate antibiotic therapy (p = 0.0009). Baseline presepsin was independently associated with, and correctly reclassified, the risk of ICU and 90-day mortality. Increasing concentrations of presepsin from day 1 to day 2 predicted higher ICU and 90-day mortality (adjusted p < 0.0001 and 0.01, respectively). Albumin had no effect on presepsin concentration. CONCLUSIONS: Presepsin is an early predictor of host response and mortality in septic patients. Changes in concentrations over time seem to reflect the appropriateness of antibiotic therapy.

Plasma n-3 polyunsaturated fatty acids in chronic heart failure in the GISSI-Heart Failure Trial: relation with fish intake, circulating biomarkers, and mortality.

UNLABELLED: Treatment with long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) can improve clinical outcomes in patients with heart failure (HF). Circulating levels of n-3 PUFA, an objective estimation of exposure, have never been measured in a large cohort of patients with HF. METHODS: We measured n-3 PUFA in plasma phospholipids at baseline and after 3 months in 1,203 patients with chronic HF enrolled in the GISSI-Heart Failure trial and randomized to n-3 PUFA 1 g/daily or placebo. N-3 PUFA levels were related to clinical characteristics, pharmacologic treatments, dietary habits, circulating biomarkers, and mortality. RESULTS: Baseline n-3 PUFA (5.1 ± 1.8 mol%) was associated with dietary fish intake, with an average difference of 43% between patients with the lowest and highest consumptions (P < .0001). Baseline eicosapentaenoic acid (EPA) but not docosahexaenoic acid (DHA) was inversely related to C-reactive protein, pentraxin-3, adiponectin, natriuretic peptide, and troponin levels. Three-month treatment with n-3 PUFA raised their levels by 43%, independently of dietary fish consumption; increases in EPA levels were associated with decreased pentraxin-3. Low baseline levels of EPA but not DHA were no longer related to higher mortality after the addition of circulating biomarkers to multivariable models. CONCLUSION: Before supplementation, circulating n-3 PUFA levels in patients with chronic HF mainly depend on dietary fish consumption and are inversely related to inflammatory markers and disease severity. Three-month treatment with n-3 PUFA markedly enriched circulating EPA and DHA, independently of fish intake, and lowered pentraxin-3. Low EPA levels are inversely related to total mortality in patients with chronic HF.

Effects of n-3 polyunsaturated fatty acids on malignant ventricular arrhythmias in patients with chronic heart failure and implantable cardioverter-defibrillators: A substudy of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca (GISSI-HF) trial.

BACKGROUND: The antiarrhythmic effects of n-3 polyunsaturated fatty acids (n-3PUFA) in ischemic heart disease have been demonstrated; however, studies in patients surviving malignant ventricular arrhythmias of different etiologies treated with an implantable cardioverter-defibrillator (ICD) have given conflicting results. The purpose of this study was to assess the antiarrhythmic effect of n-3PUFA versus placebo in 566 patients with heart failure enrolled in the GISSI-HF trial who received an ICD for secondary or primary prevention of ventricular fibrillation (VF) or tachycardia (VT). METHODS: Clinical data and arrhythmic event recordings extracted from the device memory were obtained. We tested the treatment effect by a multivariate Cox model adjusting for all clinical parameters associated with the primary end point defined as time to first appropriate ICD discharge for VT/VF. RESULTS: In the 566 patients with at least one recorded follow-up visit, 1363 VT and 316 VF episodes were terminated by ICD pacing or shock over a median follow-up of 928 days. The incidence of the primary end point event was 27.3% in the n-3PUFA group and 34.0% in the placebo group (adjusted hazard rate = 0.80, 95% CI 0.59-1.09, P = .152). Patients who received 1, 2 to 3, or >3 ICD discharges were 8.9%, 7.1%, and 11.1% in the n-3PUFA group, compared with slightly higher rates of 11.1%, 10.7%, and 12.1% in the placebo group (overall P = .30). Patients with the highest 3-month increase in plasma n-3PUFA had a somewhat lower incidence of arrhythmic events. CONCLUSIONS: The results of this study, though not statistically significant, support prior evidences of an antiarrhythmic effect of n-3PUFA in patients with ICD, although they leave open the issue of whether this effect leads to a survival benefit.

Incorporation and washout of n-3 polyunsaturated fatty acids after diet supplementation in clinical studies.

Current evidence suggests that at least part of the cardioprotective benefits of consumption of long-chain n-3 polyunsaturated fatty acids (PUFAs) relates to their incorporation into the phospholipids of cardiac cell membranes. Dietary supplementation with purified extracts of n-3 PUFAs derived from fish oil rapidly alters the composition of fatty acids in blood cell membranes and in other tissues. The present review summarises the time-course and dose-dependent incorporation and washout of n-3 PUFAs in the clinical setting and discusses the implications of these pharmacokinetic data in terms of biological effects.

Early modifications of fatty acid composition in plasma phospholipids, platelets and mononucleates of healthy volunteers after low doses of n-3 polyunsaturated fatty acids.

OBJECTIVES: Although previous data suggested that only doses of 4 g/day or higher of n-3 polyunsaturated fatty acids (PUFA) have had a beneficial effect in the prevention of atherosclerosis and cardiovascular diseases, the GISSI-Prevenzione Study in a 3-year trial showed that 1 g/day reduced total and cardiovascular mortality in over 11,000 post-infarction patients. The aim of this study was to investigate the time course and the extent of incorporation of n-3 fatty acids in plasma and blood cells after 1 g/day of n-3 PUFA, the dose effective in the GISSI-Prevenzione in comparison with higher doses. METHODS: Thirty-six healthy volunteers were given 1, 2 and 4 g/day of n-3 PUFA ethyl esters for 12 weeks, followed by a 4-week washout. Blood was collected at weeks 0, 1, 2, 4, 8, 12 and 16 and used for lipid profile analysis and measurement of fatty acid composition in plasma phospholipids, platelets and mononucleates. RESULTS: Total n-3 PUFA increased by 2.0-, 2.2- and 2.9-fold versus baseline after 12-week treatment with 1, 2 and 4 g respectively. A statistically significant raise of total n-3 PUFA was seen in platelets and mononucleates. Among individual n-3 PUFA, 22:5 n-3 was enriched early and dose dependently in plasma phospholipids, platelets and mononucleates; the raise of 22:6 n-3 was less marked especially in platelets and mononucleates. CONCLUSIONS: One gram per day of n-3 PUFA induces fast (within 1 week) and striking changes in blood composition of PUFA that may well explain their beneficial effects against cardiovascular diseases.