Radiation therapy frequently involves highly customized and complex treatments, employing sophisticated equipment, that require extensive patient-specific validation to verify the accuracy of the treatment plan as part of the clinical quality assurance (QA) process. This paper introduces a novel, reconfigurable QA phantom developed for the spatial validation of radiosurgery treatments of multiple brain metastases (MBM). This phantom works in conjunction with existing Electronic Portal Imaging Detector (EPID) technology to rapidly verify MBM treatment plans with sub-millimeter accuracy. The device provides a 12 x 12 x 12 cm3 active volume and multiple, independently configurable markers, in the form of 3 mm diameter radiopaque spheres, which serve as surrogates for brain lesions. The device is lightweight, portable, can be set up by a single operator, and is adaptable for use with external beam radiotherapy (EBRT) techniques and stereotactic linear accelerators (LINACs). This paper presents the device design and fabrication, along with initial testing and validation results both in the laboratory, using a coordinate measuring machine (CMM) and under simulated clinical conditions, using a radiosurgery treatment plan with 15 lesions. The device has been shown to place markers in space with a 0.45 mm root-mean-square (RMS) error which is satisfactory for initial clinical use. The device is undergoing further testing under simulated clinical conditions and improvements to reduce marker positional error.

This paper presents the design, fabrication, and experimental validation of a novel low-cost implantable pump for the treatment of refractory ascites (RA) based on local magnetic actuation (LMA). A reciprocating positive displacement pump displaces liquid unidirectionally through magnetic coupling with a magnetic controller placed on the outside of the patient's body. The proposed solution is intuitive to use given an alignment algorithm that exploits externally placed magnetic field sensors (MFS). The implantable device has a catheter-like shape, is electronic free (no on-board battery), has low fabrication cost (<8 USD), and is able to generate a flow-rate of 3.65 L/h while effectively pumping fluids with various viscosity (1–5.5 cP). RA is commonly treated via costly paracentesis or invasive surgical placement of a transjugular portosystemic shunt (TIPS). The proposed solution can be implanted with minimally invasive techniques and can be used on a daily basis to drain a set amount of liquid, without requiring recurrent hospital visits.

While three-dimensional (3D) printing of biological matter is of increasing interest, current linear 3D printing processes lack the efficiency at scale required to mass manufacture products made of biological matter. This paper introduces a device for a newly developed parallel additive manufacturing technology for production of 3D objects, which addresses the need for faster, industrial scale additive manufacturing methods. The technology uses multilayer cryolithography (MLCL) to make biological products faster and in larger quantities by simultaneously printing two-dimensional (2D) layers in parallel and assembling the layers into a 3D structure at an assembly site, instead of sequentially and linearly assembling a 3D object from individual elements as in conventional 3D printing. The technique uses freezing to bind the 2D layers together into a 3D object. This paper describes the basic principles of MLCL and demonstrates the technology with a new device used to manufacture a very simple product that could be used for tissue engineering, as an example. An evaluation of the interlayer bonding shows that a continuous and coherent structure can be made from the assembly of distinct layers using MLCL.

Lumbar fusion surgery has grown in popularity as a solution to lower back pain. Surgical site infection (SSI) is a serious complication of spinal surgery, affecting as high as 8.5% of the patient population. If the SSI cannot be eradicated with intravenous antibiotics, the next step is second surgery, which increases the cost imposed on the patient and extends recovery time. An implantable ultrasound-triggered polyether ether ketone device for the dispersal of antibiotics has been developed as a potential solution. In this study, the device was constructed of bioabsorbable medical grade polymer, enabling gradual degradation, and manufactured via fused filament fabrication (FFF). A novel bioabsorbable filament was manufactured and validated with gel permeation chromatography (GPC) and differential scanning calorimetry (DSC). The filament was consistent in molecular weight and thermal properties (p = 0.348 and p = 0.487, respectively). The filament was utilized for FFF of the device. Dimensional accuracy of the device was assessed with μCT analysis. Dimensional differences between the printed device and intended design were minimal. Degradation of raw material, filament, and the device was performed in accordance to ASTM F1635-16 for a month to determine how melting the material impacted the degradation properties. The degradation rate was found to be similar among the samples weeks one through three however, the raw material degraded at a slower rate by the final week (p = 0.039). This study demonstrated the feasibility of utilizing medical grade bioabsorbable polymers in FFF.

We present novel medical devices for safe surgical puncturing, in particular a cannula for the treatment of retinal vein occlusion (RVO). This passive mechanical device has an adjustable stroke and exerts a puncturing force independent of operator applied displacement. The innovative feature of this tool is that puncturing stroke is decoupled from operator input thereby minimizing the possibility of overpuncturing. This is achieved using our concept of stability programming, where the user modifies the mechanism strain energy as opposed to imposing direct displacement which is the case for standard bistable mechanisms. Ultra-fast laser three-dimensional (3D) printing is used to manufacture the needle in glass. A microfluidic channel is integrated into the needle tip for drug injection. Numerical simulations and experimental measurements validate the mechanical stability behavior of the puncture mechanism and characterize its puncturing stroke and force.

Detection and capture of circulating tumor cells (CTCs) with microfluidic chips hold significance in cancer prognosis, diagnosis, and anti-cancer treatment. The counting of CTCs provides potential tools to evaluate cancer stages as well as treatment progress. However, facing the challenge of rareness in blood, the precise enumeration of CTCs is challenging. In the present research, we designed an inertial-deformability hybrid microfluidic chip using a long spiral channel with trapezoid-circular pillars and a capture zone. To clinically validate the device, the microfluidic chip has been tested for the whole blood and lysed blood with a small number of CTCs (colorectal and nonsmall-cell lung cancer) spiked in. The capture efficiency reaches over 90% for three types of cancer cell lines at the flow rate of 1.5 mL/h. Following numerical modeling was conducted to explain the working principle and working condition (Reynolds number below 10 and Dean number around 1). This design extended the effective capture length, improved the capture efficiency, and made the CTC enumeration much easier. We believe that this hybrid chip is promising clinically in the CTCs enumeration, evaluation of cancer therapy, and pharmacological responses.

As a necessary pathway to man-made organs, organ-on-chips (OOC), which simulate the activities, mechanics, and physiological responses of real organs, have attracted plenty of attention over the past decade. As the maturity of three-dimensional (3D) cell-culture models and microfluidics advances, the study of OOCs has made significant progress. This review article provides a comprehensive overview and classification of OOC microfluidics. Specifically, the review focuses on OOC systems capable of being used in preclinical drug screening and development. Additionally, the review highlights the strengths and weaknesses of each OOC system toward the goal of improved drug development and screening. The various OOC systems investigated throughout the review include, blood vessel, lung, liver, and tumor systems and the potential benefits, which each provides to the growing challenge of high-throughput drug screening. Published OOC systems have been reviewed over the past decade (2007–2018) with focus given mainly to more recent advances and improvements within each organ system. Each OOC system has been reviewed on how closely and realistically it is able to mimic its physiological counterpart, the degree of information provided by the system toward the ultimate goal of drug development and screening, how easily each system would be able to transition to large scale high-throughput drug screening, and what further improvements to each system would help to improve the functionality, realistic nature of the platform, and throughput capacity. Finally, a summary is provided of where the broad field of OOCs appears to be headed in the near future along with suggestions on where future efforts should be focused for optimized performance of OOC systems in general.

The distal head of the natural orifice transluminal endoscopic surgery (NOTES) platform commonly uses the structure of a snake bone, which cannot rotate, and the manufacturing is often time-consuming. A novel rotatable, one-element snake bone for NOTES is proposed. This paper first describes the movement mechanism and actuation. The new structure, which is composed of hinge pairs for bending and track-sled rings for rotation, was designed to reach a 90 deg bending angle and 62 deg rotational angle. The workspace of the snake bone was derived using screw theory and was simulated on matlab . The relationship between the angle and wire displacement was analyzed in detail. The new snake bone system bent and rotated by manipulating control wires that were actuated by DC motors, and its angular movements were measured by motion sensors with an angle error within ±2.6 deg. The snake bone was mounted on a flexible tube, inserted into a colonoscopy model, and navigated by motor actuation to eventually reach the cecum. The experimental results demonstrate the new snake bone's ability to travel through a natural orifice by rotating and bending, which satisfies the mobility requirement for NOTES.

The shelf life of point-of-care and rapid diagnostic tests (POC-RDTs) is commonly compromised by abrupt temperature changes during storage, transportation, and use. This situation is especially relevant in tropical regions and resource-constrained settings where cold chain may be unreliable. Here, we report the use of novel and low-cost passive thermal shield (TS) made from laminated phase change material (PCM) to reduce thermal overload in POC-RDTs. Validation of the proposed design was done through numerical simulation and testing of an octadecane shield prototype in contact with a lateral flow immunoassay. The use of our TS design provided 30–45 min delay in thermal equilibration under constant and oscillating heat load challenges resembling those of field use. The addition of a thin PCM protection layer to POC-RDTs can be a cost-effective, scalable, and reliable solution to provide additional thermal stability to these devices.

This paper presents the design of a mechanically driven artificial speech device to be used by laryngectomees as an affordable alternative to an electrolarynx (EL). Design objectives were based on feedback from potential end users. The device implements a mainspring powered gear train that drives a striker. The striker impacts a suspended drum-like head, producing sound. When pressed against the neck, the head transmits sound into the oral cavity, allowing the user to produce intelligible speech. The dynamics of the vibrating head and sound pressure levels (SPLs) produced at the mouth were measured to compare performance between the device and a common, commercially available EL. The results showed comparable performance and sound output.

Intensity modulated radiation therapy (IMRT) is performed on a regular basis in the clinic to create complex radiation fields to treat cancer, but it has not been implemented in microradiotherapy (mRT) for preclinical systems. A multileaf collimator (MLC) is an integral part of a radiotherapy system that allows IMRT application. Presented here is the development of a key component of an open source mRT system for preclinical research. We have designed and fabricated a binary micro multileaf collimator (bmMLC) for mRT that can provide 1 mm or better resolution at isocenter and attenuate over 98% of a 250 kVp X-ray beam. This is the smallest collimator system designed for RT systems, with 20 brass leaves, each 0.5 mm thick, creating a physical field opening of 1 cm × 1 cm. The mode of actuation for the leaves was rotational, rather than linear, which is typical in larger clinical RT systems. The design presented here met the identified design requirements and represents a rigorous design process, during which several less successful designs were investigated and eventually discarded. After the fabrication of the design, dosimetric characteristics were tested and requirements were met. The final bmMLC designs and technical documents are made available as open-source.

An adjustable-length intramedullary (IM) nail may reduce both complications secondary to fracture fixation and manufacturing costs. We hypothesized that our novel nail would have suitable mechanical performance. To test this hypothesis, we manufactured three prototypes and evaluated them in quasi-static axial compression and torsion and quasi-static four-point bending. Prototypes were dynamically evaluated in both cyclic axial loading and four-point bending and torsion-to-failure. The prototypes exceeded expectations; they were comparable in both quasi-static axial stiffness (1.41 ± 0.37 N/m in cervine tibiae and 2.30 ± 0.63 in cadaver tibiae) and torsional stiffness (1.05 ± 0.26 N·m/deg in cervine tibiae) to currently used nails. The quasi-static four-point bending stiffness was 80.11 ± 09.360, greater than reported for currently used nails. A length-variance analysis indicates that moderate changes in length do not unacceptably alter bone-implant axial stiffness. After 103,000 cycles of axial loading, the prototype failed at the locking screws, comparable to locking screw failures seen clinically. The prototypes survived 1,000,000 cycles of four-point bend cyclic loading, as indicated by a consistent phase angle throughout cyclic loading. The torsion-to-failure test suggests that the prototype has adequate resistance to applied torques that might occur during the healing process. Together, these results suggest that our novel IM nail performs sufficiently well to merit further development. If brought to market, this adjustable-length IM nail could reduce both patient complications and healthcare costs.

Cardiovascular disease (CVD), as the most prevalent human disease, incorporates a broad spectrum of cardiovascular system malfunctions/disorders. While cardiac transplantation is widely acknowledged as the optional treatment for patients suffering from end-stage heart failure (HF), due to its related drawbacks, such as the unavailability of heart donors, alternative treatments, i.e., implanting a ventricular assist device (VAD), it has been extensively utilized in recent years to recover heart function. However, this solution is thought problematic as it fails to satisfactorily provide lifelong support for patients at the end-stage of HF, nor does is solve the problem of their extensive postsurgery complications. In recent years, the huge technological advancements have enabled the manufacturing of a wide variety of reliable VAD devices, which provides a promising avenue for utilizing VAD implantation as the destination therapy (DT) in the future. Along with typical VAD systems, other innovative mechanical devices for cardiac support, as well as cell therapy and bioartificial cardiac tissue, have resulted in researchers proposing a new HF therapy. This paper aims to concisely review the current state of VAD technology, summarize recent advancements, discuss related complications, and argue for the development of the envisioned alternatives of HF therapy.

Three-dimensional (3D) bioprinting offers innovative research vectors for tissue engineering. However, commercially available bioprinting platforms can be cost prohibitive to small research facilities, especially in an academic setting. The goal is to design and fabricate a low-cost printing platform able to deliver cell-laden fluids with spatial accuracy along the X, Y, and Z axes of 0.1 mm. The bioprinter consists of three subassemblies: a base unit, a gantry, and a shuttle component. The platform utilizes four stepper motors to position along three axes and a fifth stepper motor actuating a pump. The shuttle and gantry are each driven along their respective horizontal axes via separate single stepper motor, while two coupled stepper motors are used to control location along the vertical axis. The current shuttle configuration allows for a 5 mL syringe to be extruded within a work envelope of 180 mm × 160 mm × 120 mm (X, Y, Z). The shuttle can easily be reconfigured to accommodate larger volume syringes. An attachment for a laser pen is located such that printing material may be light-activated pre-extrusion. Positional fidelity was established with calipers possessing a resolution to the nearest hundredth millimeter. The motors associated with the X and Y axes were calibrated to approximately 0.02 mm per motor impulse. The Z axis has a theoretical step distance of ∼51 nm, generating 0.04% error over a 10 mm travel distance. The A axis, or pump motor, has an impulse distance of 0.001 mm. The volume extruded by a single impulse is dictated by the diameter of the syringe used. With a 5 mL syringe possessing an inner diameter of 12.35 mm, the pump pushes as little as 0.119 μ L. While the Z axis is tuned to the highest resolution settings for the motor driver, the X, Y, and A axes can obtain higher or lower resolution via physical switches on the motor drivers.

Interventional catheter ablation treatment is a noninvasive approach for normalizing heart rhythm in patients with arrhythmia. Catheter ablation can be assisted with magnetic resonance imaging (MRI) to provide high-contrast images of the heart vasculature for diagnostic and intraprocedural purposes. Typical MRI images are captured using surface imaging coils that are external to the tissue being imaged. The image quality and the scanning time required for producing an image are directly correlated to the distance between the tissue being imaged and the imaging coil. The objective of this work is to minimize the spatial distance between the target tissue and the imaging coil by placing the imaging coil directly inside the heart using an expandable origami catheter structure. In this study, geometrical analysis is utilized to optimize the size and shape of the origami structure and MRI scans are taken to confirm the MRI compatibility of the structure. The origami expandable mechanism could also be applied to other medical device designs that require expandable structures.

As the connection at the proximal tip plays an important role for sensing guidewires, we compared various sensing guidewires with regard to their proximal connectors. The strengths and weaknesses of each are discussed and recommendations for future development are provided. A literature search limited to the English language for the time period from the 1960s to the 2010s has been performed on the USPTO database, Espacenet, and Web of Science. The results have been categorized on the basis of the connector design. A comprehensive overview and classification of proximal connectors for sensing guidewires used for cardiovascular interventions is presented. The classification is based on both the type of connector (fixed or removable) and the type of connection (physical, wireless, or a combination). Considering the complexity of the currently prototyped and tested connectors, future connector development will necessitate an easy and cost-effective manufacturing process that can ensure safe and robust connections.

Recent advances in medical robotics have initiated a transition from rigid serial manipulators to flexible or continuum robots capable of navigating to confined anatomy within the body. A desire for further procedure minimization is a key accelerator for the development of these flexible systems where the end goal is to provide access to the previously inaccessible anatomical workspaces and enable new minimally invasive surgical (MIS) procedures. While sophisticated navigation and control capabilities have been demonstrated for such systems, existing manufacturing approaches have limited the capabilities of millimeter-scale end-effectors for these flexible systems to date and, to achieve next generation highly functional end-effectors for surgical robots, advanced manufacturing approaches are required. We address this challenge by utilizing a disruptive 2D layer-by-layer precision fabrication process (inspired by printed circuit board manufacturing) that can create functional 3D mechanisms by folding 2D layers of materials which may be structural, flexible, adhesive, or conductive. Such an approach enables actuation, sensing, and circuitry to be directly integrated with the articulating features by selecting the appropriate materials during the layer-by-layer manufacturing process. To demonstrate the efficacy of this technology, we use it to fabricate three modular robotic components at the millimeter-scale: (1) sensors, (2) mechanisms, and (3) actuators. These modules could potentially be implemented into transendoscopic systems, enabling bilateral grasping, retraction and cutting, and could potentially mitigate challenging MIS interventions performed via endoscopy or flexible means. This research lays the ground work for new mechanism, sensor and actuation technologies that can be readily integrated via new millimeter-scale layer-by-layer manufacturing approaches.

This paper presents a miniature wrist that can be integrated into needle-sized surgical instruments. The wrist consists of a nitinol tube with asymmetric cutouts that is actuated by a single tendon to provide high distal curvature. We derive and experimentally validate kinematic and static models for the wrist and describe several prototype wrists, illustrating the straightforward fabrication and scalability of the design. We experimentally investigate fatigue life, the concept of tip-first bending, and practical use of the wrist with a concentric tube robot in an endonasal surgical scenario.

This paper reports recent results from an ongoing effort to develop an implantable accelerometer-based heart-monitoring device for ischemia monitoring. The latest device prototype utilizes a new and more compact accelerometer (1.2 × 1.5 × 0.8 mm 3 ), a prototype device from Bosch SensorTec, Reutlingen, Germany. This paper presents the fabrication and testing of the device, including an explorative study of the effect of the capsule shape on the stability of the implanted device in the heart tissue. The stability study indicated sufficient stability of the device and a higher resistance to retraction for one of the capsule designs. The device was able to carry out acceleration monitoring and it meets the leakage current requirements of the IEC60601 standard.

Point-of-care diagnostic devices, micrototal analysis ( μ TAS) systems, lab-on-a-chip development, and biomedical research rely heavily upon microfluidic management and innovative micropump design. Here, we describe the design and prototype deployment of a magnetic shape memory (MSM) micropump capable of submicroliter per minute flow rates. The pump contains no valves or moving parts in the fluid channel and is capable of bidirectional fluid transport. This pump was employed as the mechanism to deliver small intracranial dosages of ketamine and tetrodotoxin (TTX) at 0.33 μ l/min during in vivo electrophysiological recordings in anesthetized rats, performing to required specifications.