Virginia Pensabene | Vanderbilt University (original) (raw)

Papers by Virginia Pensabene

Chemical Communications, 2010

The dispersion of multiwalled carbon nanotubes (CNTs) in an ethylene propylene rubber matrix was ... more The dispersion of multiwalled carbon nanotubes (CNTs) in an ethylene propylene rubber matrix was investigated using an internal mixer. Poly(ethylene-co-polyvinyl acetate) (EVA) statistic copolymer was used as a dispersing agent. The effects of the concentration of the dispersing agent and the matrix viscosity on the quality of the dispersion of 1 wt % of CNTs were studied by using microscopy and rheology in the melt state. It was demonstrated that the dispersion is governed principally by the viscosity of the matrix. As expected, better dispersion was observed when the matrix exhibited a lower viscosity.

In this paper a neural interface has been designed, in terms of materials, layout and surface mor... more In this paper a neural interface has been designed, in terms of materials, layout and surface morphology. A methodology for its fabrication and characterization has been provided. This methodology is based on the use of focused ion beam (FIB), atomic force microscope (AFM) and micromanipulators, respectively for nano-modification, topographical characterization and nano-dispensing of liquid biological sample. The proposed design and

The need for toxicological studies on carbon nanotubes (CNTs) has arisen from the rapidly emergin... more The need for toxicological studies on carbon nanotubes (CNTs) has arisen from the rapidly emerging applications of CNTs well beyond material science and engineering. In order to provide a method to collect data about toxicology, we characterized by Scanning Electron Microscopy (SEM), by Energy Dispersive X-ray Spectrometry (EDS) analysis and by Focused Ion Beam (FIB) microscopy different kinds of treated CNTs. The bio-interaction was investigated seeding Crandell feline kidney fibroblasts with CNT-modified medium; a dedicated sample preparation by FIB has been defined to fix cells. In the present study, the cytotoxic effects of CNTs with 91% and 97% of purity were compared and changes in the growth behaviour of cells after 3 days in culture with modified medium have been recorded, considering also the distribution of CNTs within cells. While lower purified CNTs induced a slight cytotoxic effect, homogeneously suspended CNTs with high purity were less cytotoxic, and the rate of cell growth remained constant. CNTs aggregated in bundles, showed high adhesion on cell membrane. Interestingly, CNTs bundles were observed inside cells, underneath the cell membrane, and despite of that, cells were extended, in good vitality conditions and no cell-degeneration was observed.

Biomedical Microdevices, 2010

An increasing interest in bio-hybrid systems and cell-material interactions is evident in the las... more An increasing interest in bio-hybrid systems and cell-material interactions is evident in the last years. This leads towards the development of new nano-structured devices and the assessment of their biocompatibility. In the present study, the development of free-standing single layer poly(lactic acid) (PLA) ultra-thin films is described, together with the analysis of topography and roughness properties. The biocompatibility of the PLA films has been tested in vitro, by seeding C2C12 skeletal muscle cells, and thus assessing cells shape, density and viability after 24, 48 and 72 h. The results show that free-standing flexible PLA nanofilms represent a good matrix for C2C12 cells adhesion, spreading and proliferation. Early differentiation into myotubes is also allowed. The biocompatibility of the novel ultra-thin films as substrates for cell growth promotes their application in the fields of regenerative medicine, muscle tissue engineering, drug delivery, and—in general—in the field of bio-hybrid devices.

This paper presents the evolution of diagnostic and therapeutic procedures as a process of conver... more This paper presents the evolution of diagnostic and therapeutic procedures as a process of convergence of technologies coming from different fields and involving different disciplines. In particular, it illustrates how modern surgery evolved thanks to fundamental biology knowledge; thus, with the introduction of imaging techniques intra-operatively and with the introduction of robotics, surgical procedures became much more predictable, precise and effective. Finally, the recent developments of optics (with CMOS and CCD technologies, and with the introduction of fiber optic technologies) allowed to “see” inside the human body, thus reducing the invasiveness of surgical procedures and making diagnostic procedures adequate for an effective early discovery of pathologies. Nowadays, we are assisting to a concrete merging between microrobotics technologies and bioengineering, with the potential to bring therapeutic tools where requested and when requested, with high precision and with very limited side effects. Furthermore, nanotechnology offers the possibility to fully implement this merging, thanks to the development of dedicated theranostic nanotools suitably fitting the considered convergence scenario.

Biomedical Materials, 2011

Polyelectrolyte layer-by-layer (LbL) nanofilms are interesting polymeric structures, built by alt... more Polyelectrolyte layer-by-layer (LbL) nanofilms are interesting polymeric structures, built by alternating adsorption of positively and negatively charged polyelectrolytes. They consist of multilayer sheets with nanometric overall thickness, and they can be used as supports and surface coatings for in vitro and in vivo cell and tissue growth and regeneration. The present study focuses on nanofilms based on alternated layers of poly(sodium-4-sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) fabricated using spin-assisted LbL assembly (SA-LbL). The fabrication process used to assemble polyelectrolyte nanofilms made of up to 60 bilayers is described, and the influence of different surface charges (i.e. changing the terminal layer) and of different film composition (e.g. varying PSS molecular weight) on cell behaviour is investigated. In particular, C2C12 skeletal muscle cells' viability, proliferation and differentiation on six different typologies of polyelectrolyte nanofilms are evaluated and quantified, giving a reference for skeletal muscle regeneration capabilities on such kind of structures.

In this work, the design and development of an integrated platform for the steering of swimming m... more In this work, the design and development of an integrated platform for the steering of swimming microrobot is reported. The system consists of: a near-spherical soft and buoyant magnetic microrobot (with a diameter of about 500 μm) conceived for operation in liquid; a wireless magnetic steering system, including a compact magnetic field generator based on two pairs of Helmholtz and Maxwell coils; an electronic system for their driving; a control software; a joypad physical user interface; and, the micro-arena as working environment. The platform design fulfills the requirements for the “Mobility Task” of the 2011 NIST Mobile Microrobotics Challenge. The results obtained from preliminary validation experiments confirm that the microrobots can move in a fully controlled way, successfully accomplishing an intricate eight-shape path, as required, in the water filled micro-arena. In particular we achieved a maximum average speed of 0.71 mm/s and an exceptionally smooth motion.

In this paper we present a method to make cells magnetotactic by using carbon nanotubes (CNTs). T... more In this paper we present a method to make cells magnetotactic by using carbon nanotubes (CNTs). The key of the method consists of a highly biocompatible dispersion of CNTs. These CNTs, once added to culture medium of neuroblastoma cells, strongly interact with the cell membrane. CNTs-conjugated cells appear to be sensitive to applied magnetic field gradient and move towards the

Measurement Science & Technology, 2010

Capsule endoscopy is an emerging field in medical technology. Despite very promising innovations,... more Capsule endoscopy is an emerging field in medical technology. Despite very promising innovations, some critical issues are yet to be addressed, such as the management and possible exploitation of the friction in the gastrointestinal environment in order to control capsule locomotion more actively. This paper presents the fabrication and testing of bio-inspired polymeric micro-patterns, which are arrays of cylindrical pillars fabricated via soft lithography. The aim of the work is to develop structures that enhance the grip between an artificial device and the intestinal tissue, without injuring the mucosa. In fact, the patterns are intended to be mounted on microfabricated legs of a capsule robot that is able to move actively in the gastrointestinal tract, thus improving the robot's traction ability. The effect of micro-patterned surfaces on the leg-slipping behaviour on colon walls was investigated by considering both different pillar dimensions and the influence of tissue morphology. Several in vitro tests on biological samples demonstrated that micro-patterns of pillars made from a soft polymer with an aspect ratio close to 1 enhanced friction by 41.7% with regard to flat surfaces. This work presents preliminary modelling of the friction and adhesion forces in the gastrointestinal environment and some design guidelines for endoscopic devices.

IEEE Transactions on Nanobioscience, 2008

A better understanding of the interactions between biological entities and nanostructures is of c... more A better understanding of the interactions between biological entities and nanostructures is of central importance for developing functionalized materials and systems such as active surfaces with adapted biocompatibility. There is clear evidence in literature that cells and proteins generally interact with nanoscale-featured surfaces. Despite this quantity of information, little is known about the functional relationship between surface properties (i.e., roughness and nanostructuration) and biomolecules interaction. The main obstacle in the achievement of this goal is a technological one. Precise and straightforward control on surface modification at the nanometer level is required for understanding how nanostructuration influences interactions at bio/nonbio interface. In this paper, the authors describe the advantages of the focused ion beam (FIB) for surface nanostructuration of any material. The use of light transmitting substrates (especially glass) is often useful when studying the influence of surface morphology-in terms of shape and feature size-on bio/nonbio interactions by using traditional methods of biology and biotechnology. A simple methodology enabling a very efficient patterning of glass surfaces is thus described and validated: the enhancement of proteins interaction on FIB-nanostructured glass surfaces is demonstrated via fluorescence assays and a relationship between the adsorbed protein concentration and the density of surface patterning is derived.

Polymeric ultra-thin films, also called nanosheets, show peculiar properties in terms of thicknes... more Polymeric ultra-thin films, also called nanosheets, show peculiar properties in terms of thickness, flexibility and chemical structure. For these reasons, they were proposed as nanoplasters for localized drug release or as a new solution for closing endoluminal surgical wounds. This paper presents the fabrication and characterization of free-standing nanosheets loaded with iron oxide nanoparticles, which can be manipulated in liquid environment by means of magnetic fields. A theoretical model of magnetic manipulation of the nanosheet is proposed and validated by dragging the film with a permanent magnet mounted on an industrial robotic arm. Controlling the magnetic sheet in liquid environment represents a first step towards the application of these nanostructures as free-standing carriers to be released and magnetically controlled in endoluminal surgery or as plasters with nanometric thickness to be delivered in situ on surgical incisions. Furthermore, these magnetic nanofilms can be adapted and used as micro and nanocomponents for the design of a novel generation of magnetic actuated polymeric microrobots.

Minimally Invasive Therapy & Allied Technologies, 2010

In order to minimize the invasiveness of laparoscopic surgery, different techniques are emerging ... more In order to minimize the invasiveness of laparoscopic surgery, different techniques are emerging from research to clinical practice. Whether the incision is performed on the outsideas in Single Port Laparoscopy (SPL)or on the insideas in Natural Orifice Transluminal Endoscopic Surgery (NOTES)of the patient's body, inserting and operating all the instruments from a single access site seems to be the next challenge in surgery. Magnetic guidance has been recently proposed for controlling surgical tools deployed from a single access. However, the exponential drop of magnetic field with distance makes this solution suitable only for the upper side of the abdominal cavity in nonobese patients. In the present paper we introduce a polymeric anchoring mechanism to lock surgical assistive tools inside the gastric cavity, based on the use of mucoadhesive films. Mucoadhesive properties of four formulations, with different chemical components and concentration, are evaluated by using both in vitro and ex vivo test benches on porcine stomach samples. Hydration of mucoadhesive films by contact with the aqueous mucous layer is analyzed by means of in vitro swelling tests, whereas optimal preloading conditions and adhesion performances, in terms of detachment force, supported weight and size are investigated ex vivo. Mucoadhesion is observed with all the four formulations. For a contact area of 113 mm 2 , the maximum normal and shear detachment forces withstood by the adhesive film are 2,6 N and 1 N respectively. These values grow up to 12,14 N and 4,5 N when the contact area increases to 706 mm 2 . Lifetime of the bonding on the inner side of the stomach wall was around two hours. Mucoadhesive anchoring represents a fully biocompatible and safe approach to deploy multiple assistive surgical tools on mucosal tissues by minimizing the number of access ports. This technique has been quantitatively assessed ex vivo for anchoring on the inner wall of the gastric cavity or in gastroscopic surgery. By properly varying the chemical formulation, this approach can be extended to other cavities of the human body.

A novel approach for the design of magnetically-propelled microrobots is proposed as an effective... more A novel approach for the design of magnetically-propelled microrobots is proposed as an effective solution for swimming in a liquid medium. While intrinsic neutral buoyancy of a microrobot per se simplifies propulsion in the liquid environments, softness makes it compliant with delicate environments, such as the human body, thus guaranteeing a safe interaction with soft structures. With this aim, two groups of soft microrobots with paramagnetic and ferromagnetic behaviors were designed, fabricated and their features were experimentally analyzed. In agreement with the theoretical predictions, in the performed trials the ferromagnetic microrobots showed orientation capabilities in response to the magnetic field that could not be achieved by the paramagnetic one. Moreover, it was observed that the ferromagnetic microrobot could reach higher speed values (maximum value of 0.73 body length/s) than the paramagnetic prototype.

Journal of Nanotechnology in Engineering and Medicine, 2010

Polymeric ultrathin films, also called nanofilms or nanosheets, show peculiar properties making t... more Polymeric ultrathin films, also called nanofilms or nanosheets, show peculiar properties making them potentially useful for several applications in biomedicine, eg, as nanoplasters for localized drug release or as a new solution for closing endoluminal surgical wounds. In this sense, ...

Procedia Chemistry, 2009

This paper describes the fabrication and initial characterization of an ultra-thin silicon PIN de... more This paper describes the fabrication and initial characterization of an ultra-thin silicon PIN detector using a new technique in silicon nanotechnology. In collaboration with the Nuclear Physics Division and the Lund Nano Lab at Lund University, we have developed and manufactured ultra thin -detectors for spectroscopic applications. The fabrication process has been carried out using a double-polished silicon substrate n-type wafer and locally thinning by means of a 10:1 solution of 25% tetramethyl ammonium hydroxide (TMAH) with Isopropyl alcohol. More than 100 detectors of different thicknesses, down to 5 with active areas ranging from 0.71 to 0.172 , have been fabricated. The main design considerations of our thin detectors were a very low leakage current below 12 nA and a low full depletion voltage at a reverse bias less than 1.5 V. Finally, most of our thin detectors offer an energy resolution (FWHM) as low as 31 keV for 5.487 MeV alpha particles from a source.

Acta Biomaterialia, 2011

Ultrathin films (also called nanofilms) are two-dimensional (2-D) polymeric structures with poten... more Ultrathin films (also called nanofilms) are two-dimensional (2-D) polymeric structures with potential application in biology, biotechnology, cosmetics and tissue engineering. Since they can be handled in liquid form with micropipettes or tweezers they have been proposed as flexible systems for cell adhesion and proliferation. In particular, with the aim of designing a novel patch for bone or tendon repair and healing, in this work the biocompatibility, adhesion and proliferation activity of Saos-2, MRC-5 and human and rat mesenchymal stem cells on poly(lactic acid) nanofilms were evaluated. The nanofilms did not impair the growth and differentiation of osteoblasts and chondrocytes. Moreover, nanofilm adhesion to rabbit joints was evident under ex vivo conditions.

Fullerenes Nanotubes and Carbon Nanostructures, 2009

Advanced Robotics, 2011

Soft-bodied magnetically actuated microrobots could be developed by including controlled dispersi... more Soft-bodied magnetically actuated microrobots could be developed by including controlled dispersions of magnetic nanoparticles into polymeric micro-fabricated structures. The characterization and actuation of magnetically active soft-bodied microrobots by tailored magnetic fields is, thus, a key issue for the design, full control and further development of these mobile micro-systems. In this work, the authors demonstrate the predictable and controllable transportation of polymeric flexible nanofilms embedding super-paramagnetic nanoparticles, by developing and quantitatively validating a model of the magnetic force acting on such structures, thus paving the way towards the wireless magnetic actuation of soft-bodied microrobots. The magnetic forces generated in our experimental conditions range from about 10 –9 to 10–6 N, with typical velocities for the nanofilms ranging between about 0.1 and 2.3 mm/s. For the entire range, a good agreement between theoretical model predictions and measured data is obtained (average normalized error δ =3. 65%). The proposed approach for microrobotic development targets challenging environments, where keywords are liquid or wet micro-structured environments, like in biomedical applications.

Surgical Endoscopy and Other Interventional Techniques

Background Flexible endoscopic procedures in the gastric cavity are usually performed by operativ... more Background Flexible endoscopic procedures in the gastric cavity are usually performed by operative instruments introduced through the working channels of a gastroscope. To enable additional functions and to widen the spectrum of possible surgical procedures, assistive internal surgical instruments (AISI) may be deployed through the esophagus and fixed onto the gastric wall for the entire duration of the procedure. This paper presents a solution for deploying, positioning, and anchoring AISI inside the stomach by exploiting a chemical approach. Methods A mucoadhesive polymer was synthesized and tested inside the stomach. In vivo trials were performed on a porcine model by introducing the AISI provided with mucoadhesive by means of an overtube through the mouth. Targeted deployment was achieved by a purposely developed delivery device, passed through the operative channel of a gastroscope. The total time for deployment, positioning, and anchoring of the AISI was evaluated by testing the procedure with passive modules (10, 12, 15, 20 mm in diameter) and active devices: e.g., a miniaturized wired camera and a wireless illumination module. The time and force required for the detachment of the modules were measured. Results The whole procedure of in vivo deployment, positioning, and attachment of an AISI was performed in approximately 6 min. A preload force of 5 N for 3 min was required for anchoring the modules. The stable adhesion was maintained for a maximum of 110 min. Thanks to the positioning of the camera in the fundus, a wide view of the gastric cavity was obtained. The force required to detach the modules reached 2.8 N. Conclusions Mucoadhesive anchoring represents a completely biocompatible and safe solution for stable positioning of AISI onto mucosal tissue. This novel polymeric mechanism can be useful for designing intraluminal accessories and tools that enhance surgeons’ performances in endoluminal procedures.

Biomedical Microdevices, 2007

“Neurocompatibility” is a broad definition which comprises aspects of biocompatibility, chemical ... more “Neurocompatibility” is a broad definition which comprises aspects of biocompatibility, chemical and physical surface properties, and biostability of an artificial substrate interfaced with a neural tissue. The main issue coming from the analysis of the state of art of neuroprosthesis and neuron/electrode interfaces is the strong influence of electrode surface morphology on neurocompatibility. Enhanced functions of neurons have been observed on nano-structured materials. This paper proposes the use of focused ion beam (FIB) technology as high precision machining technique to modify the surface morphology of an interface material. By controlling the ion milling in three dimensions, the fabrication of a surface with any predefined morphology becomes possible with nanometric precision. In vitro tests on PC12 cells cultured on surfaces with different morphologies show that the surface morphology influences the cell adhesion. Experimental results suggest an enhancement of the interaction between cells and artificial surfaces at a specific scale (tens of nanometres) which is the typical scale of cellular interaction in the extra-cellular matrix (ECM) of living organisms.