Long-term Normothermic Machine Preservation of Partial Livers: First Experience With 21 Human Hemi-livers.

OBJECTIVE: The aim of this study was to maintain long-term full function and viability of partial livers perfused ex situ for sufficient duration to enable ex situ treatment, repair, and regeneration. BACKGROUND: Organ shortage remains the single most important factor limiting the success of transplantation. Autotransplantation in patients with nonresectable liver tumors is rarely feasible due to insufficient tumor-free remnant tissue. This limitation could be solved by the availability of long-term preservation of partial livers that enables functional regeneration and subsequent transplantation. METHODS: Partial swine livers were perfused with autologous blood after being procured from healthy pigs following 70% in-vivo resection, leaving only the right lateral lobe. Partial human livers were recovered from patients undergoing anatomic right or left hepatectomies and perfused with a blood based perfusate together with various medical additives. Assessment of physiologic function during perfusion was based on markers of hepatocyte, cholangiocyte, vascular and immune compartments, as well as histology. RESULTS: Following the development phase with partial swine livers, 21 partial human livers (14 right and 7 left hemi-livers) were perfused, eventually reaching the targeted perfusion duration of 1 week with the final protocol. These partial livers disclosed a stable perfusion with normal hepatic function including bile production (5-10 mL/h), lactate clearance, and maintenance of energy exhibited by normal of adenosine triphosphate (ATP) and glycogen levels, and preserved liver architecture for up to 1 week. CONCLUSION: This pioneering research presents the inaugural evidence for long-term machine perfusion of partial livers and provides a pathway for innovative and relevant clinical applications to increase the availability of organs and provide novel approaches in hepatic oncology.

In-vitro Assessments of Clot Elicitation by Thrombogenic Fibers vs. Embolization Coils.

Late and persistent type II endoleaks (EL2) following Endovascular Aneurysm Repair (EVAR) have been recognized as an independent and significant risk factor for aneurysm sac growth and secondary procedures. Solutions are available for treatment, with varying success rates; preventive perioperative sac embolization with coils appears safe and effective. The objective of this study is to compare whole blood coagulation elicited by a textile stent-graft equipped with thrombogenic, patented "Kardiozis" fibers (PKF) to that elicited by embolization coils in an in vitro study. The approach is to establish an equivalence between PKF and coils in a static model, then to compare clot elicitation by both materials in a perfused model aneurysm chamber subjected to EL2. The weight of clot elicited during exposure to blood was the primary measurement. In the static model, PKF and coils were soaked in blood for up to 90 minutes (N = 30) and elicited similar clotting. In the dynamic model, stent-grafts equipped with PKF or coils were exposed to blood flow inside an aneurysm model for up to 3h (N = 5), with generally higher clot weights for stent-grafts with PKF (non-significant). Complete thrombosis of the aneurysm model was observed in one experimental series (positive control and stent-graft with PKF). A stent-graft with PKF elicits at least as much clot as embolization coils dispersed in an aneurysm model chamber under continuous blood flow. PKF positioned on the outer wall of stent-grafts could have a similar action as coiling of the aneurysm sac during the index EVAR.

Transplantation of a human liver following 3 days of ex situ normothermic preservation.

Current organ preservation methods provide a narrow window (usually <12 hours) to assess, transport and implant donor grafts for human transplantation. Here we report the transplantation of a human liver discarded by all centers, which could be preserved for several days using ex situ normothermic machine perfusion. The transplanted liver exhibited normal function, with minimal reperfusion injury and the need for only a minimal immunosuppressive regimen. The patient rapidly recovered a normal quality of life without any signs of liver damage, such as rejection or injury to the bile ducts, according to a 1-year follow up. This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure.

Selective parallel integration of individual metallic single-walled carbon nanotubes from heterogeneous solutions.

The dielectrophoretic separation of individual metallic single-walled carbon nanotubes (SWNTs) from heterogeneous solutions and their simultaneous deposition between electrodes is achieved and confirmed by direct electric transport measurements. Out-of-solution guided parallel assembly of individual SWNTs was investigated for electric field frequencies between 1 and 200 MHz. At 200 MHz, 19 of the 22 deposited SWNTs (86%) displayed metallic behavior, whereas at lower frequencies the expected random growth distribution of 1/3 metallic SWNTs prevailed. A threshold separation frequency of 188 MHz is extracted from a surface-conductivity model, and a conductivity weighting factor is introduced to elucidate the separation frequency dependence. Low-frequency experiments and numerical simulations show that long-range nanotube transport is governed by hydrodynamic effects whereas local trapping is dominated by dielectrophoretic forces. The electrokinetic framework of dielectrophoresis in low-concentration solutions is thus provided and allows a deeper understanding of the underlying mechanisms in dielectrophoretic deposition processes for long and large-diameter SWNT-based low-resistance device integration.

An electrical method for the measurement of the thermal and electrical conductivity of reduced graphene oxide nanostructures.

This paper introduces an electrical four-point measurement method enabling thermal and electrical conductivity measurements of nanoscale materials. The method was applied to determine the thermal and electrical conductivity of reduced graphene oxide flakes. The dielectrophoretically deposited samples exhibited thermal conductivities in the range of 0.14-2.87 W m(-1) K(-1) and electrical conductivities in the range of 6.2 x 10(2)-6.2 x 10(3) Omega(-1) m(-1). The measured properties of each flake were found to be dependent on the duration of the thermal reduction and are in this sense controllable.

Steady-state low thermal resistance characterization apparatus: The bulk thermal tester.

The reliability of microelectronic devices is largely dependent on electronic packaging, which includes heat removal. The appropriate packaging design therefore necessitates precise knowledge of the relevant material properties, including thermal resistance and thermal conductivity. Thin materials and high conductivity layers make their thermal characterization challenging. A steady state measurement technique is presented and evaluated with the purpose to characterize samples with a thermal resistance below 100 mm(2) K/W. It is based on the heat flow meter bar approach made up by two copper blocks and relies exclusively on temperature measurements from thermocouples. The importance of thermocouple calibration is emphasized in order to obtain accurate temperature readings. An in depth error analysis, based on Gaussian error propagation, is carried out. An error sensitivity analysis highlights the importance of the precise knowledge of the thermal interface materials required for the measurements. Reference measurements on Mo samples reveal a measurement uncertainty in the range of 5% and most accurate measurements are obtained at high heat fluxes. Measurement techniques for homogeneous bulk samples, layered materials, and protruding cavity samples are discussed. Ultimately, a comprehensive overview of a steady state thermal characterization technique is provided, evaluating the accuracy of sample measurements with thermal resistances well below state of the art setups. Accurate characterization of materials used in heat removal applications, such as electronic packaging, will enable more efficient designs and ultimately contribute to energy savings.

In situ assembly in confined spaces of coated particle scaffolds as thermal underfills with extraordinary thermal conductivity.

In situ assembly of high thermal conductivity materials in severely confined spaces is an important problem bringing with it scientific challenges but also significant application relevance. Here we present a simple, affordable, and reproducible methodology for synthesizing such materials, composed of hierarchical diamond micro/nanoparticle scaffolds and an ethylenediamine coating. An important feature of the assembly process is the utilization of ethylenediamine as an immobilizing agent to secure the integrity of the microparticle scaffolds during and after each processing step. After other liquid components employed in the scaffolds assembly dry out, the immobilization agent solidifies forming a stable coated particle scaffold structure. Nanoparticles tend to concentrate in the shell and neck regions between adjacent microparticles. The interface between core and shell, along with the concentrated neck regions of nanoparticles, significantly enhance the thermal conductivity, making such materials an excellent candidate as thermal underfills in the electronics industry, where efficient heat removal is a major stumbling block toward increasing packing density. We show that the presented structures exhibit nearly 1 order of magnitude improvement in thermal conductivity, enhanced temperature uniformity, and reduced processing time compared to commercially available products for electronics cooling, which underpins their potential utility.

Decoupled cantilever arms for highly versatile and sensitive temperature and heat flux measurements.

Microfabricated cantilever beams have been used in microelectromechanical systems for a variety of sensor and actuator applications. Bimorph cantilevers accurately measure temperature change and heat flux with resolutions several orders of magnitude higher than those of conventional sensors such as thermocouples, semiconductor diodes, as well as resistance and infrared thermometers. The use of traditional cantilevers, however, entails a series of important measurement limitations, because their interactions with the sample and surroundings often create parasitic deflection forces and the typical metal layer degrades the thermal sensitivity of the cantilever. The paper introduces a design to address these issues by decoupling the sample and detector section of the cantilever, along with a thermomechanical model, the fabrication, system integration, and characterization. The custom-designed bi-arm cantilever is over one order of magnitude more sensitive than current commercial cantilevers due to the significantly reduced thermal conductance of the cantilever sample arm. The rigid and immobile sample section offers measurement versatility ranging from photothermal absorption, near-field thermal radiation down to contact, conduction, and material thermal characterization measurements in nearly identical configurations.

Guided assembly of metal and hybrid conductive probes using floating potential dielectrophoresis.

We present the site-selective, parallel and reproducible formation of conductive gold and tetrathiafulvalene-gold (TTF-Au) hybrid micro- and nanowires from their respective ion salt and cation-radical solutions. While the formation of micro- and nanowires by means of dielectrophoresis with directly coupled electrodes has been thoroughly investigated in recent studies, we present here the first relevant example of metal and hybrid wire assembly obtained by floating potential dielectrophoresis. In this configuration, the assembly of micro- and nanowires is achieved by capacitively coupling a large electrode (bias electrode) to a conductive substrate (p-doped Si) separated by an insulating oxide layer. In contrast to former studies, this allows parallel production of micro- and nanowires with only one pair of electrodes connected to a sine wave generator. We further demonstrate that these structures are suitable probes for localized surface enhanced Raman spectroscopy (SERS).

Aqueous dispersion and dielectrophoretic assembly of individual surface-synthesized single-walled carbon nanotubes.

The successful dispersion and large-scale parallel assembly of individual surface-synthesized large-diameter (1-3 nm) single-walled carbon nanotubes (SWNTs), grown by chemical vapor deposition (CVD), is demonstrated. SWNTs are removed from the growth substrate by a short, low-energy ultrasonic pulse to produce ultrapure long-term stable surfactant-stabilized solutions. Subsequent dielectrophoretic deposition bridges individual, straight, and long SWNTs between two electrodes. Electrical characterization on 223 low-resistance devices (R(average) approximately 200 kOmega) evidences the high quality of the SWNT raw material, prepared solution, and contact interface. The research reported herein provides an important framework for the large-scale industrial integration of carbon nanotube-based devices, sensors, and applications.

Methane, a gas produced by enteric bacteria, slows intestinal transit and augments small intestinal contractile activity.

The presence of methane on lactulose breath test among irritable bowel syndrome (IBS) subjects is highly associated with the constipation-predominant form. Therefore, we set out to determine whether methane gas can alter small intestinal motor function. In dogs, small intestinal fistulae were created to permit measurement of intestinal transit. Using a radiolabel, we evaluated transit during infusion of room air and subsequently methane. In this model, small intestinal infusion of methane produced a slowing of transit in all dogs by an average of 59%. In a second experiment, guinea pig ileum was pinned into an organ bath for the study of contractile activity in response to brush strokes applied to the mucosa. The force of contraction was measured both orad and aborad to the stimulus. The experiment was repeated while the bath was gassed with methane. Contractile activities orad and aborad to the stimulus were significantly augmented by methane compared with room air (P < 0.05). In a third experiment, humans with IBS who had undergone a small bowel motility study were compared such that subjects who produced methane on lactulose breath test were compared with those producing hydrogen. The motility index was significantly higher in methane-producing IBS patients (1,851 +/- 861) compared with hydrogen producers (1,199 +/- 301) (P < 0.05). Therefore, methane, a gaseous by-product of intestinal bacteria, slows small intestinal transit and appears to do so by augmenting small bowel contractile activity.