Investigating the Use of a Liquid Immunogenic Fiducial Eluter Biomaterial in Cervical Cancer Treatment.

Globally, cervical cancer is the fourth leading cancer among women and is dominant in resource-poor settings in its occurrence and mortality. This study focuses on developing liquid immunogenic fiducial eluter (LIFE) Biomaterial with components that include biodegradable polymers, nanoparticles, and an immunoadjuvant. LIFE Biomaterial is designed to provide image guidance during radiotherapy similar to clinically used liquid fiducials while enhancing therapeutic efficacy for advanced cervical cancer. C57BL6 mice were used to grow subcutaneous tumors on bilateral flanks. The tumor on one flank was then treated using LIFE Biomaterial prepared with the immunoadjuvant anti-CD40, with/without radiotherapy at 6 Gy. Computed tomography (CT) and magnetic resonance (MR) imaging visibility were also evaluated in human cadavers. A pharmacodynamics study was also conducted to assess the safety of LIFE Biomaterial in healthy C57BL6 female mice. Results showed that LIFE Biomaterial could provide both CT and MR imaging contrast over time. Inhibition in tumor growth and prolonged significant survival (* p < 0.05) were consistently observed for groups treated with the combination of radiotherapy and LIFE Biomaterial, highlighting the potential for this strategy. Minimal toxicity was observed for healthy mice treated with LIFE Biomaterial with/without anti-CD40 in comparison to non-treated cohorts. The results demonstrate promise for the further development and clinical translation of this approach to enhance the survival and quality of life of patients with advanced cervical cancer.

Pre-Clinical Investigations of the Pharmacodynamics of Immunogenic Smart Radiotherapy Biomaterials (iSRB).

The use of an immunogenic smart radiotherapy biomaterial (iSRB) for the delivery of anti-CD40 is effective in treating different cancers in animal models. This study further characterizes the use of iSRBs to evaluate any associated toxicity in healthy C57BL6 mice. iSRBs were fabricated using a poly-lactic-co-glycolic-acid (PLGA) polymer mixed with titanium dioxide (TiO2) nanoparticles incorporated into its matrix. Animal studies included investigations of freely injected anti-CD40, anti-CD40-loaded iSRBs, unloaded iSRBs and control (healthy) animal cohorts. Mice were euthanized at pre-determined time points post-treatment to evaluate the serum chemistry pertaining to kidney and liver toxicity and cell blood count parameters, as well as pathology reports on organs of interest. Results showed comparable liver and kidney function in all cohorts. The results indicate that using iSRBs with or without anti-CD40 does not result in any significant toxicity compared to healthy untreated animals. The findings provide a useful reference for further studies aimed at optimizing the therapeutic efficacy and safety of iSRBs and further clinical translation work.

Functionalization of pristine graphene for the synthesis of covalent graphene-polyaniline nanocomposite.

Polyaniline (PANI) is one of the most studied conducting polymers owing to its high electrical conductivity, straightforward synthesis and stability. Graphene-supported PANI nanocomposite materials combine the superior physical properties of graphene, synergistically enhancing the performance of PANI as well as giving rise to new properties. Covalent nanocomposites have shown to give higher stability and better performance than their non-covalent counterparts, however, the covalent graphene-PANI nanocomposite are primarily prepared from graphene oxide. We report a new method to synthesize covalent graphene-PANI nanocomposites from pristine graphene. Using few-layer graphene (FLG) flakes as the model system, we first conjugated aniline to FLG via a perfluorophenyl azide (PFPA)-mediated coupling chemistry. A subsequent in situ polymerization of aniline gave polyaniline covalently grafted on the FLG surface. Characterization by FTIR, TEM, SEM, XPS, XRD and electrochemistry confirmed the successful conjugation of PANI to FLG. The grafting density of PANI was estimated by thermal analysis to be ∼26%. As the PFPA-mediated coupling chemistry is applicable to other carbon materials including carbon nanotubes and fullerene, the method developed in this work can be readily adapted to grow PANI on these materials.

Demonstration of biofilm removal from type 304 stainless steel using pulsed-waveform electropolishing.

This article describes an electrochemical method to remove bacterial biofilm from a stainless steel (SS) surface using a potential pulse/reverse pulse technique. This technique employs a periodic waveform that consists of anodic and cathodic pulses. The pulses can effectively strip a thin layer of metal off the SS surface, along with the adherent biofilm, in a saline solution. Not only can the pulses effectively remove biofilm from the SS surface, but they also regenerate the original mirror-like shiny surface. The importance of this electrochemical biofilm removal method is its wide applicability for any types of biofilms. That is, instead of directly removing the biofilm, it removes a very thin layer of the metal under the biofilm. Thus, the removal process is independent to the nature of the biofilms. Furthermore, this electrochemical biofilm removal method is rapid (less than 30 s of potential pulse time) and does not require hazardous chemicals.

Priming the Abscopal Effect Using Multifunctional Smart Radiotherapy Biomaterials Loaded with Immunoadjuvants.

In this study, we investigate the use of multifunctional smart radiotherapy biomaterials (SRBs) loaded with immunoadjuvants for boosting the abscopal effect of local radiotherapy (RT). SRBs were designed similar to currently used inert RT biomaterials, incorporating a biodegradable polymer with reservoir for loading payloads of the immunoadjuvant anti-CD40 monoclonal antibody. Lung (LLC1) tumors were generated both on the right and left flank of each mouse, with the left tumor representing metastasis. The mice were randomized and divided into eight cohorts with four cohorts receiving image-guided RT (IGRT) at 5 Gy and another similar four cohorts at 0 Gy. IGRT and Computed Tomography (CT) imaging were performed using a small animal radiation research platform (SARRP). Tumor volume measurements for both flank tumors and animal survival was assessed over 25 weeks. Tumor volume measurements showed significantly enhanced inhibition in growth for the right flank tumors of mice in the cohort treated with SRBs loaded with CD40 mAbs and IGRT. Results also suggest that the use of polymeric SRBs with CD40 mAbs without RT could generate an immune response, consistent with previous studies showing such response when using anti-CD40. Overall, 60% of mice treated with SRBs showed complete tumor regression during the observation period, compared to 10% for cohorts administered with anti-CD40 mAbs, but no SRB. Complete tumor regression was not observed in any other cohorts. The findings justify more studies varying RT doses and quantifying the immune-cell populations involved when using SRBs. Such SRBs could be developed to replace currently used RT biomaterials, allowing not only for geometric accuracy during RT, but also for extending RT to the treatment of metastatic lesions.

Naked-Eye Coulometric Sensor Using a Longitudinally Oriented Ag Band Electrode in a Microfluidic Channel.

In this Article, we report a coulometric sensing platform that is capable of sensing analytes on a working electrode and providing a visual readout of the analyte concentration on a silver (Ag) band counter electrode in a microchannel. The display mechanism relies on the electro-oxidation of metallic Ag as a complementary reaction to the sensing reduction reaction. The Ag band counter electrode is arranged longitudinally in a microchannel while the frontal tip of the band electrode directly faces a gold (Au) working electrode, which lies across the microchannel. The Ag oxidation always occurs at the band electrode's tip region that faces the working electrode due to the Ohmic potential drop across the solution in the microchannel. The decrement of the Ag electrode, which is clearly measurable with the naked eye, correlates linearly with an analyte concentration (e.g., 0.1-2.5 mM p-benzoquinone) and with an analyte feeding rate (i.e., a sample solution flow rate of 1.0-75.0 µL min(-1)). The platform design is also effective for a model analyte of horseradish peroxidase (HRP)-avidin in the dynamic range of 0.1-3.0 µg mL(-1).

Electronic conductivity of films of electroflocculated 2 nm iridium oxide nanoparticles.

The electronic conductivity of films of iridium oxide (IrO(x)) composed of ca. 2 nm nanoparticles (NPs) is strongly dependent on the film oxidation state. The Ir(IV)O(x) NPs can be electrochemically converted to several oxidation states, ranging from Ir(III) to Ir(V) oxides. The NP films exhibit a very high apparent conductivity, e.g., 10(-2) S cm(-1), when the NPs are in the oxidized +4/+5 state. When the film is fully reduced to its Ir(III) state, the apparent conductivity falls to 10(-6) S cm(-1).

Two-channel microelectrochemical bipolar electrode sensor array.

We report a two-channel microelectrochemical sensor that communicates between separate sensing and reporting microchannels via one or more bipolar electrodes (BPEs). Depending on the contents of each microchannel and the voltage applied across the BPE, faradaic reactions may be activated simultaneously in both channels. As presently configured, one end of the BPE is designated as the sensing pole and the other as the reporting pole. When the sensing pole is activated by a target, electrogenerated chemiluminescence (ECL) is emitted at the reporting pole. Compared to previously reported single-channel BPE sensors, the key advantage of the multichannel architecture reported here is physical separation of the ECL reporting cocktail and the solution containing the target. This prevents chemical interference between the two channels.

Design and operation of microelectrochemical gates and integrated circuits.

Here we report a simple design philosophy, based on the principles of bipolar electrochemistry, for the operation of microelectrochemical integrated circuits. The inputs for these systems are simple voltage sources, but because they do not require much power they could be activated by chemical or biological reactions. Device output is an optical signal arising from electrogenerated chemiluminescence. Individual microelectrochemical logic gates are described first, and then multiple logic circuits are integrated into a single microfluidic channel to yield an integrated circuit that can perform parallel logic functions. AND, OR, NOR, and NAND gates are described. Eventually, systems such as those described here could provide on-chip data processing functions for lab-on-a-chip devices.

Bipolar electrodes: a useful tool for concentration, separation, and detection of analytes in microelectrochemical systems.

Over the past decade, bipolar electrochemistry has emerged from relative obscurity to provide a promising new means for integrating electrochemistry into lab-on-a-chip systems. This article describes the fundamental operating principles of bipolar electrodes, as well as several interesting applications.

A sensing platform based on electrodissolution of a Ag bipolar electrode.

Here we report a new type of sensing platform that is based on electrodissolution of a metallic bipolar electrode (BPE). When the target DNA binds to the capture probe at the cathodic pole of the BPE, it triggers the oxidation and dissolution of Ag metal present at the anodic pole. The loss of Ag is easily detectable with the naked eye or a magnifying glass and provides a permanent record of the electrochemical history of the electrode. More importantly, the decrease in the length of the BPE can be directly correlated to the number of electrons passing through the BPE and hence to the sensing reaction at the cathode.

Snapshot voltammetry using a triangular bipolar microelectrode.

In this paper, we report a new electroanalytical technique we call snapshot voltammetry. This method combines the properties of bipolar electrodes with electrogenerated chemiluminescence (ECL) to provide a means for recording optical voltammograms in a single micrograph. In essence, the information in a snapshot voltammogram is contained in the spatial domain rather than in the time domain, which is the case for conventional voltammetry. The use of a triangle-shaped bipolar electrode stabilizes the interfacial potential difference along its length. Basic electrochemical parameters extracted from snapshot voltammograms are in good agreement with those obtained by conventional voltammetry. Although not explicitly demonstrated in this paper, this method offers the possibility of using arrays of bipolar electrodes to obtain numerous snapshot voltammograms simultaneously.

A large-scale, wireless electrochemical bipolar electrode microarray.

We report a microelectrochemical array composed of 1000 individual bipolar electrodes that are controlled with just two driving electrodes and a simple power supply. The system is configured so that faradaic processes occurring at the cathode end of each electrode are correlated to light emission via electrogenerated chemiluminescence (ECL) at the anode end. This makes it possible to read out the state of each electrode simultaneously. The significant advance is that the electrode array is fabricated on a glass microscope slide and is operated in a simple electrochemical cell. This eliminates the need for microfluidic channels, provides a fabrication route to arbitrarily large electrode arrays, and will make it possible to place sensing chemistries onto each electrode using a robotic spotter.

Wireless electrochemical DNA microarray sensor.

We report an electrochemical DNA microarray sensor whose function is controlled with just two wires regardless of the number of individual sensing electrodes. The bipolar sensing electrode is modified with probe DNA, and the anode end of each electrode is configured to emit light (electrogenerated chemiluminescence) upon hybridization of cDNA labeled with electrocatalytic (oxygen reduction) Pt nanoparticles at the cathode. The important finding is that DNA can be selectively detected at an array of three electrodes. In principle, however, this advance provides a means for controlling the potential of many electrodes using just two wires and then indirectly determining the current flowing through all of them simultaneously by correlating light emission to current.