Pneumatic delivery of untethered microgrippers for minimally invasive biopsy.

The surgical biopsy is one of the most widely utilized medical procedures for diagnosis of a number of diseases. In order to enable less invasive biopsies, we have previously developed and applied residual stress and physiologically activated sub-millimeter sized untethered grippers. Here, we report a controlled, pneumatic system and methodology for pressurized delivery of untethered microgrippers (µ-grippers) to improve the efficacy of tissue excision. The approach is compatible with current minimally invasive laparoscopic and endoscopic methods. Using a model experimental system, we observed that pneumatic delivery significantly improves the efficiency of the tissue attachment-µ-grippers attach up to 30-fold better on vertically oriented tissues, and up to 3.5-fold better on horizontally oriented tissues as compared to experiments without pressurized delivery. Hence, the use of pneumatics in the delivery of untethered microdevices could significantly enhance their efficiency in minimally invasive biopsy procedures.

Biopsy using a magnetic capsule endoscope carrying, releasing, and retrieving untethered microgrippers.

This paper proposes a new wireless biopsy method where a magnetically actuated untethered soft capsule endoscope carries and releases a large number of thermo-sensitive, untethered microgrippers (µ-grippers) at a desired location inside the stomach and retrieves them after they self-fold and grab tissue samples. We describe the working principles and analytical models for the µ-gripper release and retrieval mechanisms, and evaluate the proposed biopsy method in ex vivo experiments. This hierarchical approach combining the advanced navigation skills of centimeter-scaled untethered magnetic capsule endoscopes with highly parallel, autonomous, submillimeter scale tissue sampling µ-grippers offers a multifunctional strategy for gastrointestinal capsule biopsy.

Silane surface modification for improved bioadhesion of esophageal stents.

Stent migration occurs in 10-40% of patients who undergo placement of esophageal stents, with higher migration rates seen in those treated for benign esophageal disorders. This remains a major drawback of esophageal stent therapy. In this paper, we propose a new surface modification method to increase the adhesion between self-expandable metallic stents (SEMS) and tissue while preserving their removability. Taking advantage of the well-known affinity between epoxide and amine terminated silane coupling agents with amine and carboxyl groups that are abundant in proteins and related molecules in the human body; we modified the surfaces of silicone coated esophageal SEMS with these adhesive self-assembled monolayers (SAMs). We utilized vapor phase silanization to modify the surfaces of different substrates including PDMS strips and SEMS, and measured the force required to slide these substrates on a tissue piece. Our results suggest that surface modification of esophageal SEMS via covalent attachment of protein-binding coupling agents improves adhesion to tissue and could offer a solution to reduce SEMS migration while preserving their removability.

Origami inspired self-assembly of patterned and reconfigurable particles.

There are numerous techniques such as photolithography, electron-beam lithography and soft-lithography that can be used to precisely pattern two dimensional (2D) structures. These technologies are mature, offer high precision and many of them can be implemented in a high-throughput manner. We leverage the advantages of planar lithography and combine them with self-folding methods(1-20) wherein physical forces derived from surface tension or residual stress, are used to curve or fold planar structures into three dimensional (3D) structures. In doing so, we make it possible to mass produce precisely patterned static and reconfigurable particles that are challenging to synthesize. In this paper, we detail visualized experimental protocols to create patterned particles, notably, (a) permanently bonded, hollow, polyhedra that self-assemble and self-seal due to the minimization of surface energy of liquefied hinges(21-23) and (b) grippers that self-fold due to residual stress powered hinges(24,25). The specific protocol described can be used to create particles with overall sizes ranging from the micrometer to the centimeter length scales. Further, arbitrary patterns can be defined on the surfaces of the particles of importance in colloidal science, electronics, optics and medicine. More generally, the concept of self-assembling mechanically rigid particles with self-sealing hinges is applicable, with some process modifications, to the creation of particles at even smaller, 100 nm length scales(22, 26) and with a range of materials including metals(21), semiconductors(9) and polymers(27). With respect to residual stress powered actuation of reconfigurable grasping devices, our specific protocol utilizes chromium hinges of relevance to devices with sizes ranging from 100 µm to 2.5 mm. However, more generally, the concept of such tether-free residual stress powered actuation can be used with alternate high-stress materials such as heteroepitaxially deposited semiconductor films(5,7) to possibly create even smaller nanoscale grasping devices.

Biopsy with thermally-responsive untethered microtools.

Thermally activated, untethered microgrippers can reach narrow conduits in the body and be used to excise tissue for diagnostic analyses. As depicted in the figure, the feasibility of an in vivo biopsy of the porcine bile duct using untethered microgrippers is demonstrated.

Self-folding devices and materials for biomedical applications.

Because the native cellular environment is 3D, there is a need to extend planar, micro- and nanostructured biomedical devices to the third dimension. Self-folding methods can extend the precision of planar lithographic patterning into the third dimension and create reconfigurable structures that fold or unfold in response to specific environmental cues. Here, we review the use of hinge-based self-folding methods in the creation of functional 3D biomedical devices including precisely patterned nano- to centimeter scale polyhedral containers, scaffolds for cell culture and reconfigurable surgical tools such as grippers that respond autonomously to specific chemicals.

Monitoring of magnetic targeting to tumor vasculature through MRI and biodistribution.

AIMS: The development of noninvasive imaging techniques for the assessment of cancer treatment is rapidly becoming highly important. The aim of the present study is to show that magnetic cationic liposomes (MCLs), incorporating superparamagnetic iron oxide nanoparticles (SPIONs), are a versatile theranostic nanoplatform for enhanced drug delivery and monitoring of cancer treatment. MATERIALS & METHODS: MCLs (with incorporated high SPION cargo) were administered to a severe combined immunodeficiency mouse with metastatic (B16-F10) melanoma grown in the right flank. Pre- and post-injection magnetic resonance (MR) images were used to assess response to magnetic targeting effects. Biodistribution studies were conducted by ¹¹¹In-labeled MCLs and the amount of radioactivity recovered was used to confirm the effect of targeting for intratumoral administrations. RESULTS: We have shown that tumor signal intensities in T2-weighted MR images decreased by an average of 20 ± 5% and T2* relaxation times decreased by 14 ± 7 ms 24 h after intravenous administration of our MCL formulation. This compares to an average decrease in tumor signal intensity of 57 ± 12% and a T2* relaxation time decrease of 27 ± 8 ms after the same time period with the aid of magnetic guidance. CONCLUSION: MR and biodistribution analysis clearly show the efficacy of MCLs as MRI contrast agents, prove the use of magnetic guidance, and demonstrate the potential of MCLs as agents for imaging, guidance and therapeutic delivery.

Chitosan film containing poly(D,L-lactic-co-glycolic acid) nanoparticles: a platform for localized dual-drug release.

PURPOSE: To characterize and evaluate chitosan film containing PLGA nanoparticles (NPs) as a platform for localized dual-drug release. METHODS: Fluorescent Paclitaxel (FPTX), a hydrophobic drug, was incorporated into PLGA NPs. FPTX-loaded PLGA NPs and Carboxyfluorescein (CF), a hydrophilic model drug, were embedded into chitosan films. Release of CF and NPs from chitosan and release of FPTX from PLGA NPs were monitored by fluorescence. The stability of the platform was observed through SEM and dynamic light scattering (DLS). RESULTS: Chitosan films containing CF and FPTX-loaded PLGA NPs showed a biphasic release profile. In the first phase, 78% of CF and 34% of NPs were released within few days. In the second phase, the release was slower, showing an additional release of 22% of CF and 18% of NPs after 3 weeks. SEM images and DLS measurements showed that NP release depends on film degradation rate. FPTX-loaded PLGA NPs showed the release of 19.8% of total drug in 2 days, and no additional release was detected in the next 26 days. CONCLUSIONS: The ability of chitosan film containing PLGA NPs to coat gold surface and to incorporate and release two different drugs of different hydrophilicity make it a promising platform for localized dual-drug release.

Nanoporous inorganic membranes or coatings for sustained drug delivery in implantable devices.

The characteristics of nanoporous inorganic coatings on implants or on implantable devices are reviewed. The commonly used nanoporous materials, such as aluminum oxide (Al(2)O(3)), titanium oxide (TiO(2)) and porous silicon are highlighted with illustrative examples. The critical issues for sustained release systems are examined and the elution profiles of nanoporous coatings are discussed. The available data shows that these systems can be used effectively for sustained release applications. They satisfy the basic biocompatibility tests, meet the requirements of drug loading and sustained release profiles extending to several weeks and also are compatible with current implant technologies. Nanoporous inorganic coatings are well suited to provide improved efficacy and integration of implants in a variety of therapeutic situations.

Large scale 3D vertical assembly of single-wall carbon nanotubes at ambient temperatures.

We demonstrate three-dimensional directed assembly of single-wall carbon nanotubes (SWNT) into porous alumina nanotemplates on silicon substrates by means of electrophoresis and dielectrophoresis at ambient temperatures. Assembled SWNT provided an interconnection between the surface and base of the nanotemplate. I-V measurements clearly show that the connection between silicon and SWNT is established inside the templates. This technique is particularly useful for large scale, rapid, 3D assembly of SWNT over centimeter square areas under mild conditions for nanoscale electronics applications.