Pressure-Regulated Ventilator Splitting for Disaster Relief: Design, Testing, and Clinical Experience.

The coronavirus disease 2019 (COVID-19) pandemic has revealed that even the best-resourced hospitals may lack sufficient ventilators to support patients under surge conditions. During a pandemic or mass trauma, an affordable, low-maintenance, off-the-shelf device that would allow health care teams to rapidly expand their ventilator capacity could prove lifesaving, but only if it can be safely integrated into a complex and rapidly changing clinical environment. Here, we define an approach to safe ventilator sharing that prioritizes predictable and independent care of patients sharing a ventilator. Subsequently, we detail the design and testing of a ventilator-splitting circuit that follows this approach and describe our clinical experience with this circuit during the COVID-19 pandemic. This circuit was able to provide individualized and titratable ventilatory support with individualized positive end-expiratory pressure (PEEP) to 2 critically ill patients at the same time, while insulating each patient from changes in the other's condition. We share insights from our experience using this technology in the intensive care unit and outline recommendations for future clinical applications.

Optimal directional volatile transport in retronasal olfaction.

The ability of humans to distinguish the delicate differences in food flavors depends mostly on retronasal smell, in which food volatiles entrained into the airway at the back of the oral cavity are transported by exhaled air through the nasal cavity to stimulate the olfactory receptor neurons. Little is known whether food volatiles are preferentially carried by retronasal flow toward the nasal cavity rather than by orthonasal flow into the lung. To study the differences between retronasal and orthonasal flow, we obtained computed tomography (CT) images of the orthonasal airway from a healthy human subject, printed an experimental model using a 3D printer, and analyzed the flow field inside the airway. The results show that, during inhalation, the anatomical structure of the oropharynx creates an air curtain outside a virtual cavity connecting the oropharynx and the back of the mouth, which prevents food volatiles from being transported into the main stream toward the lung. In contrast, during exhalation, the flow preferentially sweeps through this virtual cavity and effectively enhances the entrainment of food volatiles into the main retronasal flow. This asymmetrical transport efficiency is also found to have a nonmonotonic Reynolds number dependence: The asymmetry peaks at a range of an intermediate Reynolds number close to 800, because the air curtain effect during inhalation becomes strongest in this range. This study provides the first experimental evidence, to our knowledge, for adaptations of the geometry of the human oropharynx for efficient transport of food volatiles toward the olfactory receptors in the nasal cavity.

Maximizing fluorescence collection efficiency in multiphoton microscopy.

Understanding fluorescence propagation through a multiphoton microscope is of critical importance in designing high performance systems capable of deep tissue imaging. Optical models of a scattering tissue sample and the Olympus 20X 0.95NA microscope objective were used to simulate fluorescence propagation as a function of imaging depth for physiologically relevant scattering parameters. The spatio-angular distribution of fluorescence at the objective back aperture derived from these simulations was used to design a simple, maximally efficient post-objective fluorescence collection system. Monte Carlo simulations corroborated by data from experimental tissue phantoms demonstrate collection efficiency improvements of 50% - 90% over conventional, non-optimized fluorescence collection geometries at large imaging depths. Imaging performance was verified by imaging layer V neurons in mouse cortex to a depth of 850 µm.

Control of Hydroid Colony Form by Surface Heterogeneity.

The colonial hydroid Podocoryna carnea grows adherent to surfaces progressing along them by a motile stolon tip. We here ask whether the stolon tip grows preferentially within grooves etched in silicon wafers. In a series of pilot experiments, we varied the dimensions of grooves and found that stolons did not utilize grooves with a width:depth of 5:5 µm or 10:10 µm, occasionally followed grooves 25:25 µm in size, and preferentially grew within grooves of a width:depth of 50:50 µm and 100:50 µm. We then grew colonies in grids, with fixed 50:50 µm width:depth channels intersecting at 90° every 950, 700, 450, or 150 µm. We find that stolons grew within grooves early in colony ontogeny, but remained restricted to them only in the grid pattern with channel intersections every 150 µm. Finally, we created a grid in the shape of the Yale Y logo, with channels of 50:50 µm width:depth and intersections every 100 µm. The resulting colonies conformed to that of the logo. Our findings demonstrate that stolons respond to surface heterogeneity and that surface etching can be used to fabricate microfluidic circuits comprised of hydroid perisarc.

Extracorporeal Hypothermic Perfusion Device for Intestinal Graft Preservation to Decrease Ischemic Injury During Transportation.

INTRODUCTION: The small intestine is one of the most ischemia-sensitive organs used in transplantation. To better preserve the intestinal graft viability and decrease ischemia-reperfusion injury, a device for extracorporeal perfusion was developed. We present the results for the first series of perfused human intestine with an intestinal perfusion unit (IPU). METHODS: Five human intestines were procured for the protocol. (1) An experimental segment was perfused by the IPU delivering cold preservation solution to the vascular and luminal side continually at 4 ºC for 8 h. (2) Control (jejunum and ileum) segments were preserved in static cold preservation. Tissue samples were obtained for histopathologic grading according to the Park/Chiu scoring system (0 = normal, 8 = transmural infarction). RESULTS: Jejunal experimental segments scored 2.2 with the Park/Chiu system compared to the control segments, which averaged 3.2. Overall scoring for ileum experimental and control segments was equal with 1.6. CONCLUSION: This data presents proof of concept that extracorporeal intestinal perfusion is feasible. The evidence shows that the IPU can preserve the viability of human intestine, and histopathologic evaluation of perfused intestine is favorable. Our early results can eventually lead to expanding the possibilities of intestinal preservation.

A novel device to preserve intestinal tissue ex-vivo by cold peristaltic perfusion.

In the past two decades, much advancement has been made in the area of organ procurement and preservation for the transplant of kidneys, livers, and lungs. However, small intestine preservation remains unchanged. We propose a new preservation system for intestinal grafts that has the potential to increase the viability of the organ during transport. When experimented with porcine intestine, our device resulted in superior tissue quality than tissue in standard of care.

Multiphoton microscopy of cleared mouse organs.

Typical imaging depths with multiphoton microscopy (MPM) are limited to less than 300 mum in many tissues due to light scattering. Optical clearing significantly reduces light scattering by replacing water in the organ tissue with a fluid having a similar index of refraction to that of proteins. We demonstrate MPM of intact, fixed, cleared mouse organs with penetration depths and fields of view in excess of 2 mm. MPM enables the creation of large 3-D data sets with flexibility in pixel format and ready access to intrinsic fluorescence and second-harmonic generation. We present high-resolution images and 3-D image stacks of the brain, small intestine, large intestine, kidney, lung, and testicle with image sizes as large as 4,096 x 4,096 pixels.