Creating Stretchable Electronics from Dual Layer Flex-PCB for Soft Robotic Cardiac Mapping Catheters.

The authors present in this study the development of a novel method for creating stretchable electronics from dual-layer flex printed circuit boards (flex-PCBs) as a platform for soft robotic sensor arrays (SRSAs) for cardiac voltage mapping applications. There is a crucial need for devices that utilize multiple sensors and provide high performance signal acquisition for cardiac mapping. Previously, our group demonstrated how single-layer flex-PCB can be postprocessed to create a stretchable electronic sensing array. In this work, a detailed fabrication process for creating a dual-layer multielectrode flex-PCB SRSA is presented, along with relevant parameters to achieve optimal postprocessing with a laser cutter. The dual-layer flex-PCB SRSA's ability to acquire electrical signals is demonstrated both in vitro as well as in vivo on a Leporine cardiac surface. These SRSAs could be extended into full-chamber cardiac mapping catheter applications. Our results show a significant contribution towards the scalable use of dual-layer flex-PCB for stretchable electronics.

Improved Functional Assessment of Ischemic Severity Using 3D Printed Models.

Objective: To develop a novel in vitro method for evaluating coronary artery ischemia using a combination of non-invasive coronary CT angiograms (CCTA) and 3D printing (FFR3D). Methods: Twenty eight patients with varying degrees of coronary artery disease who underwent non-invasive CCTA scans and invasive fractional flow reserve (FFR) of their epicardial coronary arteries were included in this study. Coronary arteries were segmented and reconstructed from CCTA scans using Mimics (Materialize). The segmented models were then 3D printed using a Carbon M1 3D printer with urethane methacrylate (UMA) family of rigid resins. Physiological coronary circulation was modeled in vitro as flow-dependent stenosis resistance in series with variable downstream resistance. A range of physiological flow rates (Q) were applied using a peristaltic steady flow pump and titrated with a flow sensor. The pressure drop (ΔP) and the pressure ratio (Pd/Pa) were assessed for patient-specific aortic pressure (Pa) and differing flow rates (Q) to evaluate FFR3D using the 3D printed model. Results: There was a good positive correlation (r = 0.87, p < 0.0001) between FFR3D and invasive FFR. Bland-Altman analysis revealed a good concordance between the FFR3D and invasive FFR values with a mean bias of 0.02 (limits of agreement: -0.14 to 0.18; p = 0.2). Conclusions: 3D printed patient-specific models can be used in a non-invasive in vitro environment to quantify coronary artery ischemia with good correlation and concordance to that of invasive FFR.

Multilayer fabrication of durable catheter-deployable soft robotic sensor arrays for efficient left atrial mapping.

Devices that perform cardiac mapping and ablation to treat atrial fibrillation provide an effective means of treatment. Current devices, however, have limitations that either require tedious point-by-point mapping of a cardiac chamber or have limited ability to conform to the complex anatomy of a patient's cardiac chamber. In this work, a detailed, scalable, and manufacturable technique is reported for fabrication of a multielectrode, soft robotic sensor array. These devices exhibit high conformability (~85 to 90%) and are equipped with an array of stretchable electronic sensors for voltage mapping. The form factor of the device is intended to match that of the entire left atrium and has a hydraulically actuated soft robotic structure whose profile facilitates deployment from a 13.5-Fr catheter. We anticipate that the methods described in this paper will serve a new generation of conformable medical devices that leverage the unique characteristics of stretchable electronics and soft robotics.

Automatic segmentation of multiple cardiovascular structures from cardiac computed tomography angiography images using deep learning.

OBJECTIVES: To develop, demonstrate and evaluate an automated deep learning method for multiple cardiovascular structure segmentation. BACKGROUND: Segmentation of cardiovascular images is resource-intensive. We design an automated deep learning method for the segmentation of multiple structures from Coronary Computed Tomography Angiography (CCTA) images. METHODS: Images from a multicenter registry of patients that underwent clinically-indicated CCTA were used. The proximal ascending and descending aorta (PAA, DA), superior and inferior vena cavae (SVC, IVC), pulmonary artery (PA), coronary sinus (CS), right ventricular wall (RVW) and left atrial wall (LAW) were annotated as ground truth. The U-net-derived deep learning model was trained, validated and tested in a 70:20:10 split. RESULTS: The dataset comprised 206 patients, with 5.130 billion pixels. Mean age was 59.9 ± 9.4 yrs., and was 42.7% female. An overall median Dice score of 0.820 (0.782, 0.843) was achieved. Median Dice scores for PAA, DA, SVC, IVC, PA, CS, RVW and LAW were 0.969 (0.979, 0.988), 0.953 (0.955, 0.983), 0.937 (0.934, 0.965), 0.903 (0.897, 0.948), 0.775 (0.724, 0.925), 0.720 (0.642, 0.809), 0.685 (0.631, 0.761) and 0.625 (0.596, 0.749) respectively. Apart from the CS, there were no significant differences in performance between sexes or age groups. CONCLUSIONS: An automated deep learning model demonstrated segmentation of multiple cardiovascular structures from CCTA images with reasonable overall accuracy when evaluated on a pixel level.

An approach to evaluate myocardial perfusion defect assessment for projection-based DECT: A phantom study.

INTRODUCTION: Dual-energy CT (DECT) can improve the accuracy of myocardial perfusion CT with projection-based monochromatic (DECT-MCE) and quantification of myocardial iodine in material decomposition (DECT-MD) reconstructions. However, evaluation of multiple reconstructions is laborious and the optimal reconstruction to detect myocardial perfusion defects is unknown. METHODS: Left ventricular (LV) phantoms with artificial perfusion defects were scanned using DECT and single energy cardiac computed tomography angiography (SECT). Reconstructions of DECT-MCE at 40, 70, 100 and 140 keV, DECT-MD pairs of water, iodine, iron and fat, and SECT were evaluated using a 17-segment myocardial model. The diagnostic performance of each reconstruction was calculated on a per-segment basis and compared across DECT reconstructions. RESULTS: Over 34 phantoms with artificial perfusion defects were found in 64/578 (11%) of segments, the sensitivity of DECT-MCE at 40, 70, 100, and 140 keV was 100% (95% confidence interval (CI): 93-100), 100% (95% CI: 93-100), 71% (95% CI: 56-83), and 25% (95% CI: 14-40), respectively, with a significant decline between 70 keV and 100 keV (p < 0.001). The specificity of DECT-MCE was 100% at all energies (95% CI: 99-100). As a group, the DECT-MD iodine background reconstructions had significantly lower sensitivity than the remaining modes (2.1% [95% CI, 0.05-11.1], vs. 100% [95% CI, 92.6-100], p < 0.001). Specificity of all material pair modes remained 100%. CONCLUSIONS: Using LV phantom models, the approach with the best sensitivity and specificity to assess myocardial perfusion defects with DECT are reconstructions of DECT-MCE at 40 or 70 KeV and DECT-MD without iodine background.

A Catheter-Deployable Soft Robotic Inflatable Basket for Enhanced Conformability to the Left Atrium of the Heart.

This paper presents the design, fabrication, and test results for a novel basket catheter that utilizes soft robotic technology, which can conform to complex patient anatomy. Two designs of basket-shaped balloons in three sizes are fabricated based on a CO2 laser cutting method from thin (<50 µm) thermoplastic polyurethane. The balloons are deployed in four soft-material 3D printed left atria, whose geometries are based on volume rendered segmentation of cardiac computed tomography (CT) scans. The coverage and conformability to the realistic patient anatomies is tracked with the small patches of pH paper that indicate, via a color change, contact with a basic solution that lined the 3D printed atriums. The conformability of these inflatable basket catheters is demonstrated as high as (85%) for the optimized design. To visualize the balloon's performance, microCT images of balloons deployed in 3D printed models are shown. These images show the ability of the balloons to adapt to complex patient anatomy and do not exhibit any spline bunching or other deleterious mechanical behavior. This platform has the potential to be coupled with electrical sensors for simultaneous multisensor mapping of atrial fibrillation and other cardiac arrhythmias.

Rapid Manufacturing of Thin Soft Pneumatic Actuators and Robots.

This protocol describes a method for rapid manufacturing of soft pneumatic actuators and robots with an ultrathin form factor using a heat press and a laser cutter machine. The method starts with the lamination of thermoplastic polyurethane (TPU) sheets using a heat press for 10 min at the temperature of ~93 °C. Next, the parameters of the laser cutter machine are optimized to produce a rectangular balloon with maximum burst pressure. Using the optimized parameters, the soft actuators are laser cut/welded three times sequentially. Next, a dispensing needle is attached to the actuator, allowing it to be inflated. The effect of geometrical parameters on the deflection of the actuator are studied systematically by varying the channel width and length. Finally, the performance of the actuator is characterized using an optical camera and a fluid dispenser. Conventional fabrication methods of soft pneumatic actuators based on silicone molding are time consuming (several hours). They also result in strong but bulky actuators, which limits the actuator's applications. Moreover, microfabrication of thin pneumatic actuators is both time-consuming and expensive. The proposed manufacturing method in the current work resolves these issues by introducing a fast, simple, and cost-effective fabrication method of ultrathin pneumatic actuators.

Microneedle Patterning of 3D Nonplanar Surfaces on Implantable Medical Devices Using Soft Lithography.

Micropatterning is often used to engineer the surface properties of objects because it allows the enhancement or modification of specific functionalities without modification of the bulk material properties. Microneedle arrays have been explored in the past for drug delivery and enhancement of tissue anchoring; however, conventional methods are primarily limited to thick, planar substrates. Here, we demonstrate a method for the fabrication of microneedle arrays on thin flexible polyurethane substrates. These thin-film microneedle arrays can be used to fabricate balloons and other inflatable objects. In addition, these thin-filmed microneedles can be transferred, using thermal forming processes, to more complex 3D objects on which it would otherwise be difficult to directly pattern microneedles. This function is especially useful for medical devices, which require effective tissue anchorage but are a challenging target for micropatterning due to their 3D nonplanar shape, large size, and the complexity of the required micropatterns. Ultrathin flexible thermoplastic polyurethane microneedle arrays were fabricated from a polydimethylsiloxane (PDMS) mold. The technique was applied onto the nonplanar surface of rapidly prototyped soft robotic implantable polyurethane devices. We found that a microneedle-patterned surface can increase the anchorage of the device to a tissue by more than twofold. In summary, our soft lithographic patterning method can rapidly and inexpensively generate thin-film microneedle surfaces that can be used to produce balloons or enhance the properties of other 3D objects and devices.

An augmented reality system for image guidance of transcatheter procedures for structural heart disease.

The primary mode of visualization during transcatheter procedures for structrural heart disease is fluoroscopy, which suffers from low contrast and lacks any depth perception, thus limiting the ability of an interventionalist to position a catheter accurately. This paper describes a new image guidance system by utilizing augmented reality to provide a 3D visual environment and quantitative feedback of the catheter's position within the heart of the patient. The real-time 3D position of the catheter is acquired via two fluoroscopic images taken at different angles, and a patient-specific 3D heart rendering is produced pre-operatively from a CT scan. The spine acts as a fiduciary land marker, allowing the position and orientation of the catheter within the heart to be fully registered. The automated registration method is based on Fourier transformation, and has a high success rate (100%), low registration error (0.42 mm), and clinically acceptable computational cost (1.22 second). The 3D renderings are displayed and updated on the augmented reality device (i.e., Microsoft HoloLens), which can provide pre-set views of various angles of the heart using voice-command. This new image-guidance system with augmented reality provides a better visualization to interventionalists and potentially assists them in understanding of complicated cases. Furthermore, this system coupled with the developed 3D printed models can serve as a training tool for the next generation of cardiac interventionalists.

Laser Cutting as a Rapid Method for Fabricating Thin Soft Pneumatic Actuators and Robots.

Pneumatically actuated soft robots address many challenges with interfacing with delicate objects, but these actuators/robots are still bulky and require many hours to fabricate, limiting their widespread use. This article reports a novel design and manufacturing method for ultrathin soft robots and actuators (∼70 µm) using a laser-cutting machine that cuts/welds sheets of thermoplastic polyurethane (TPU) from a 2D CAD drawing. Using this method, five different soft actuators (e.g., bending, rotating, contracting) are designed, fabricated, and characterized with both planar and nonplanar motions. Furthermore, we show how stacking multiple sheets of TPU enables rapid fabrication of multifunctional actuators. Finally, a portable four-arm swimming robot is designed and fabricated without any assembly steps. This rapid fabrication method enables soft robots to go from concept to operational within minutes, and creates a new subclass of soft robots suitable for applications requiring a robot to be ultrathin, lightweight, and/or fit within small volumes.

Stereolithography for Personalized Left Atrial Appendage Occluders.

Advancements in 3D additive manufacturing have spurred the development of effective patient-specific medical devices. Prior applications are limited to hard materials, however, with few implementations of soft devices that better match the properties of natural tissue. This paper introduces a rapid, low cost, and scalable process for fabricating soft, personalized medical implants via stereolithography of elastomeric polyurethane resin. The effectiveness of this approach is demonstrated by designing and manufacturing patient-specific endocardial implants. These devices occlude the left atrial appendage, a complex structure within the heart prone to blood clot formation in patients with atrial fibrillation. Existing occluders permit residual blood flow and can damage neighboring tissues. Here, the robust mechanical properties of the hollow, printed geometries are characterized and stable device anchoring through in vitro benchtop testing is confirmed. The soft, patient-specific devices outperform non-patient-specific devices in embolism and occlusion experiments, as well as in computational fluid dynamics simulations.

Patient-specific design of a soft occluder for the left atrial appendage.

3D printing has been used to create a wide variety of anatomical models and tools for procedural planning and training. Yet, the printing of permanent, soft endocardial implants remains challenging because of the need for haemocompatibility and durability of the printed materials. Here, we describe an approach for the rapid prototyping of patient-specific cardiovascular occluders via 3D printing and static moulding of inflatable silicone/polyurethane balloons derived from volume-rendered computed tomography scans. We demonstrate the use of the approach, which provides custom-made implants made of high-quality, durable and haemocompatible elastomeric materials, in the fabrication of devices for occlusion of the left atrial appendage-a structure known to be highly variable in geometry and the primary source of stroke for patients with atrial fibrillation. We describe the design workflow, fabrication and deployment of patient-specific left atrial appendage occluders and, as a proof-of-concept, show their efficacy using 3D-printed anatomical models, in vitro flow loops and an in vivo large animal model.

Current progress in 3D printing for cardiovascular tissue engineering.

3D printing is a technology that allows the fabrication of structures with arbitrary geometries and heterogeneous material properties. The application of this technology to biological structures that match the complexity of native tissue is of great interest to researchers. This mini-review highlights the current progress of 3D printing for fabricating artificial tissues of the cardiovascular system, specifically the myocardium, heart valves, and coronary arteries. In addition, how 3D printed sensors and actuators can play a role in tissue engineering is discussed. To date, all the work with building 3D cardiac tissues have been proof-of-principle demonstrations, and in most cases, yielded products less effective than other traditional tissue engineering strategies. However, this technology is in its infancy and therefore there is much promise that through collaboration between biologists, engineers and material scientists, 3D bioprinting can make a significant impact on the field of cardiovascular tissue engineering.

Laser-induced nanoscale thermocapillary flow for purification of aligned arrays of single-walled carbon nanotubes.

Although aligned arrays of single-walled carbon nanotubes (SWNTs) have outstanding potential for use in broad classes of advanced semiconductor devices, the relatively large population of metallic SWNTs (m-SWNTs) that results from conventional growth techniques leads to significantly degraded performance. Recently reported methods based on thermocapillary effects that enable removal of m-SWNTs from such arrays offer exceptional levels of efficiency, but the procedures are cumbersome and require multiple processing steps. Here we present a simple, robust alternative that yields pristine arrays of purely semiconducting SWNTs (s-SWNTs) by use of irradiation with an infrared laser. Selective absorption by m-SWNTs coated with a thin organic film initiates nanoscale thermocapillary flows that lead to exposure only of the m-SWNTs. Reactive ion etching eliminates the m-SWNTs without damaging the s-SWNTs; removal of the film completes the purification. Systematic experimental studies and computational modeling of the thermal physics illuminates the essential aspects of this process. Demonstrations include use of arrays of s-SWNTs formed in this manner as semiconducting channel materials in statistically relevant numbers of transistors to achieve both high mobilities (>900 cm2 V(-1) s(-1)) and switching ratios (>10(4)). Statistical analysis indicates that the arrays contain at least 99.8% s-SWNTs and likely significantly higher.

Microwave purification of large-area horizontally aligned arrays of single-walled carbon nanotubes.

Recent progress in the field of single-walled carbon nanotubes (SWNTs) significantly enhances the potential for practical use of this remarkable class of material in advanced electronic and sensor devices. One of the most daunting challenges is in creating large-area, perfectly aligned arrays of purely semiconducting SWNTs (s-SWNTs). Here we introduce a simple, scalable, large-area scheme that achieves this goal through microwave irradiation of aligned SWNTs grown on quartz substrates. Microstrip dipole antennas of low work-function metals concentrate the microwaves and selectively couple them into only the metallic SWNTs (m-SWNTs). The result allows for complete removal of all m-SWNTs, as revealed through systematic experimental and computational studies of the process. As one demonstration of the effectiveness, implementing this method on large arrays consisting of ~20,000 SWNTs completely removes all of the m-SWNTs (~7,000) to yield a purity of s-SWNTs that corresponds, quantitatively, to at least to 99.9925% and likely significantly higher.

Using nanoscale thermocapillary flows to create arrays of purely semiconducting single-walled carbon nanotubes.

Among the remarkable variety of semiconducting nanomaterials that have been discovered over the past two decades, single-walled carbon nanotubes remain uniquely well suited for applications in high-performance electronics, sensors and other technologies. The most advanced opportunities demand the ability to form perfectly aligned, horizontal arrays of purely semiconducting, chemically pristine carbon nanotubes. Here, we present strategies that offer this capability. Nanoscale thermocapillary flows in thin-film organic coatings followed by reactive ion etching serve as highly efficient means for selectively removing metallic carbon nanotubes from electronically heterogeneous aligned arrays grown on quartz substrates. The low temperatures and unusual physics associated with this process enable robust, scalable operation, with clear potential for practical use. We carry out detailed experimental and theoretical studies to reveal all of the essential attributes of the underlying thermophysical phenomena. We demonstrate use of the purified arrays in transistors that achieve mobilities exceeding 1,000 cm(2) V(-1) s(-1) and on/off switching ratios of ∼10,000 with current outputs in the milliamp range. Simple logic gates built using such devices represent the first steps toward integration into more complex circuits.

Quantitative thermal imaging of single-walled carbon nanotube devices by scanning Joule expansion microscopy.

Electrical generation of heat in single-walled carbon nanotubes (SWNTs) and subsequent thermal transport into the surroundings can critically affect the design, operation, and reliability of electronic and optoelectronic devices based on these materials. Here we investigate such heat generation and transport characteristics in perfectly aligned, horizontal arrays of SWNTs integrated into transistor structures. We present quantitative assessments of local thermometry at individual SWNTs in these arrays, evaluated using scanning Joule expansion microscopy. Measurements at different applied voltages reveal electronic behaviors, including metallic and semiconducting responses, spatial variations in diameter or chirality, and localized defect sites. Analytical models, validated by measurements performed on different device structures at various conditions, enable accurate, quantitative extraction of temperature distributions at the level of individual SWNTs. Using current equipment, the spatial resolution and temperature precision are as good as ∼100 nm and ∼0.7 K, respectively.

Epitaxial growth of three-dimensionally architectured optoelectronic devices.

Optoelectronic devices have long benefited from structuring in multiple dimensions on microscopic length scales. However, preserving crystal epitaxy, a general necessity for good optoelectronic properties, while imparting a complex three-dimensional structure remains a significant challenge. Three-dimensional (3D) photonic crystals are one class of materials where epitaxy of 3D structures would enable new functionalities. Many 3D photonic crystal devices have been proposed, including zero-threshold lasers, low-loss waveguides, high-efficiency light-emitting diodes (LEDs) and solar cells, but have generally not been realized because of material limitations. Exciting concepts in metamaterials, including negative refraction and cloaking, could be made practical using 3D structures that incorporate electrically pumped gain elements to balance the inherent optical loss of such devices. Here we demonstrate the 3D-template-directed epitaxy of group III-V materials, which enables formation of 3D structured optoelectronic devices. We illustrate the power of this technique by fabricating an electrically driven 3D photonic crystal LED.

Nanoscale, electrified liquid jets for high-resolution printing of charge.

Nearly all research in micro- and nanofabrication focuses on the formation of solid structures of materials that perform some mechanical, electrical, optical, or related function. Fabricating patterns of charges, by contrast, is a much less well explored area that is of separate and growing interesting because the associated electric fields can be exploited to control the behavior of nanoscale electronic and mechanical devices, guide the assembly of nanomaterials, or modulate the properties of biological systems. This paper describes a versatile technique that uses fine, electrified liquid jets formed by electrohydrodynamics at micro- and nanoscale nozzles to print complex patterns of both positive and negative charges, with resolution that can extend into the submicrometer and nanometer regime. The reported results establish the basic aspects of this process and demonstrate the capabilities through printed patterns with diverse geometries and charge configurations in a variety of liquid inks, including suspensions of nanoparticles and nanowires. The use of printed charge to control the properties of silicon nanomembrane transistors provides an application example.

Alignment controlled growth of single-walled carbon nanotubes on quartz substrates.

Single-walled carbon nanotubes (SWNTs) possess extraordinary electrical properties, with many possible applications in electronics. Dense, horizontally aligned arrays of linearly configured SWNTs represent perhaps the most attractive and scalable way to implement this class of nanomaterial in practical systems. Recent work shows that templated growth of tubes on certain crystalline substrates yields arrays with the necessary levels of perfection, as demonstrated by the formation of devices and full systems on quartz. This paper examines advanced implementations of this process on crystalline quartz substrates with different orientations, to yield strategies for forming diverse, but well-defined horizontal configurations of SWNTs. Combined experimental and theoretical studies indicate that angle-dependent van der Waals interactions can account for nearly all aspects of alignment on quartz with X, Y, Z, and ST cuts, as well as quartz with disordered surface layers. These findings provide important insights into methods for guided growth of SWNTs, and possibly other classes of nanomaterials, for applications in electronics, sensing, photodetection, light emission, and other areas.