Min-Chieh Chuang

Nanotheranostics--a review of recent publications.

Theranostics is referred to as a treatment strategy that combines therapeutics with diagnostics, aiming to monitor the response to treatment and increase drug efficacy and safety, which would be a key part of personalized medicine and require considerable advances in predictive medicine. Theranostics associates with both a diagnosis that tests patients for possible reactions to taking new medication and targeted drug delivery based on the test results. Emerging nanotechnology provides a great deal of opportunity to design and develop such combination agents, permitting the delivery of therapeutics and concurrently allowing the detection modality to be used not only before or after but also throughout the entire treatment regimen. The introduction of nanotheranostics into routine health care has still a long way to go, since evaluations on cytotoxicity, genotoxicity, and immunotoxicity of prospective nanotheranostics, demonstration of cost-effectiveness, and availability of appropriate accessible testing systems are still required. An extensive review, from a chemistry point of view, of the recent development of nanotheranostics and its in vitro and in vivo applications are herein presented.

Enzyme logic gates for the digital analysis of physiological level upon injury.

A biocomputing system composed of a combination of AND/IDENTITY logic gates based on the concerted operation of three enzymes: lactate oxidase, horseradish peroxidase and glucose dehydrogenase was designed to process biochemical information related to pathophysiological conditions originating from various injuries. Three biochemical markers: lactate, norepinephrine and glucose were applied as input signals to activate the enzyme logic system. Physiologically normal concentrations of the markers were selected as logic 0 values of the input signals, while their abnormally increased concentrations, indicative of various injury conditions were defined as logic 1 input. Biochemical processing of different patterns of the biomarkers resulted in the formation of norepiquinone and NADH defined as the output signals. Optical and electrochemical means were used to follow the formation of the output signals for eight different combinations of three input signals. The enzymatically processed biochemical information presented in the form of a logic truth table allowed distinguishing the difference between normal physiological conditions, pathophysiological conditions corresponding to traumatic brain injury and hemorrhagic shock, and abnormal situations (not corresponding to injury). The developed system represents a biocomputing logic system applied for the analysis of biomedical conditions related to various injuries. We anticipate that such biochemical logic gates will facilitate decision-making in connection to an integrated therapeutic feedback-loop system and hence will revolutionize the monitoring and treatment of injured civilians and soldiers.

Microneedle array-based carbon paste amperometric sensors and biosensors

The design and characterization of a microneedle array-based carbon paste electrode towards minimally invasive electrochemical sensing are described. Arrays consisting of 3 × 3 pyramidal microneedle structures, each with an opening of 425 µm, were loaded with a metallized carbon paste transducer. The renewable nature of carbon paste electrodes enables the convenient packing of hollow non-planar microneedles with pastes that contain assorted catalysts and biocatalysts. Smoothing the surface results in good microelectrode-to-microelectrode uniformity. Optical and scanning electron micrographs shed useful insights into the surface morphology at the microneedle apertures. The attractive performance of the novel microneedle electrode arrays is illustrated in vitro for the low-potential detection of hydrogen peroxide at rhodium-dispersed carbon paste microneedles and for lactate biosensing by the inclusion of lactate oxidase in the metallized carbon paste matrix. Highly repeatable sensing is observed following consecutive cycles of packing/unpacking the carbon paste. The operational stability of the array is demonstrated as well as the interference-free detection of lactate in the presence of physiologically relevant levels of ascorbic acid, uric acid, and acetaminophen. Upon addressing the biofouling effects associated with on-body sensing, the microneedle carbon paste platform would be attractive for the subcutaneous electrochemical monitoring of a number of physiologically relevant analytes.

Enzymatic AND Logic Gates Operated Under Conditions Characteristic of Biomedical Applications

Experimental and theoretical analyses of the lactate dehydrogenase and glutathione reductase based enzymatic AND logic gates in which the enzymes and their substrates serve as logic inputs are performed. These two systems are examples of the novel, previously unexplored class of biochemical logic gates that illustrate potential biomedical applications of biochemical logic. They are characterized by input concentrations at logic 0 and 1 states corresponding to normal and pathophysiological conditions. Our analysis shows that the logic gates under investigation have similar noise characteristics. Both significantly amplify random noise present in inputs; however, we establish that for realistic widths of the input noise distributions, it is still possible to differentiate between the logic 0 and 1 states of the output. This indicates that reliable detection of pathophysiological conditions is indeed possible with such enzyme logic systems.

Flexible thick-film glucose biosensor: Influence of mechanical bending on the performance

The influence of the bending-induced mechanical stress of flexible Nafion/GOx/carbon screen-printed electrodes (SPEs) upon the performance of such glucose biosensors has been examined. Surprisingly, such flexible enzyme/polymer-SPEs operate well following a severe bending-induced mechanical stress (including a 180 degrees pinch), and actually display a substantial sensitivity enhancement following their mechanical bending. The bending-induced sensitivity enhancement is observed only for the amperometric detection of the glucose substrate but not for measurements of hydrogen peroxide, catechol or ferrocyanide at coated or bare SPEs. These (and additional) data indicate that the bending effect is associated primarily with changes in the biocatalytic activity. Such sensitivity enhancement is more pronounced at elevated glucose levels, reflecting the bending-induced changes in the biocatalytic reaction. Factors affecting the bending-induced changes in the performance are examined. While our data clearly indicate that flexible enzyme/polymer-SPEs can tolerate a severe mechanical stress and hold promise as wearable glucose biosensors, delivering the sample to the active sensor surface remains the major challenge for such continuous health monitoring.

Multifunctional microelectrode array (mMEA) chip for neural-electrical and neural-chemical interfaces: Characterization of comb interdigitated electrode towards dopamine detection

Microelectrode array platforms have attracted considerable interest owing to their ability to facilitate interactive communications between investigators and neuronal network. We herein present an integrated multifunctional microelectrode array (mMEA) chip harnessed with multiple measurement modalities of both neural-electrical and neural-chemical recordings to enable simultaneous monitoring of action potential and the level of the specific neurotransmitter. A dopamine sensor modality fabricated in interdigitated electrodes (IDE) fashion was realized and characterized, subsequently applied to trace dopamine exocytosis in PC12 cells cultured on such mMEA chip. Facile fabrication process leveraging electroplating technique to implement the regulation of gap width was investigated and resulted in preferred IDE configuration. Collection efficiency and amplification effect were systematically evaluated. The as-fabricated sensing device exhibited a favorable diffusion-determining behavior reflected by the steady state current output, and in virtue of this feature, to detect dopamine in connection with limit of detection at 0.62 μM. The current signal was observed linear against the level of dopamine over the investigated concentration range with a resulting sensitivity of 0.096 nA μM(-1).

Electrochemical sensor for multiplex screening of genetically modified DNA: Identification of biotech crops by logic-based biomolecular analysis

Genetically modified (GM) technique, one of the modern biomolecular engineering technologies, has been deemed as profitable strategy to fight against global starvation. Yet rapid and reliable analytical method is deficient to evaluate the quality and potential risk of such resulting GM products. We herein present a biomolecular analytical system constructed with distinct biochemical activities to expedite the computational detection of genetically modified organisms (GMOs). The computational mechanism provides an alternative to the complex procedures commonly involved in the screening of GMOs. Given that the bioanalytical system is capable of processing promoter, coding and species genes, affirmative interpretations succeed to identify specified GM event in terms of both electrochemical and optical fashions. The biomolecular computational assay exhibits detection capability of genetically modified DNA below sub-nanomolar level and is found interference-free by abundant coexistence of non-GM DNA. This bioanalytical system, furthermore, sophisticates in array fashion operating multiplex screening against variable GM events. Such a biomolecular computational assay and biosensor holds great promise for rapid, cost-effective, and high-fidelity screening of GMO.

Implantable Graphene-based Neural Electrode Interfaces for Electrophysiology and Neurochemistry in In Vivo Hyperacute Stroke Model

Implantable microelectrode arrays have attracted considerable interest due to their high temporal and spatial resolution recording of neuronal activity in tissues. We herein presented an implantable multichannel neural probe with multiple real-time monitoring of neural-chemical and neural-electrical signals by a nonenzymatic neural-chemical interface, which was designed by creating the newly developed reduced graphene oxide-gold oxide (rGO/Au2O3) nanocomposite electrode. The modified electrode on the neural probe was prepared by a facile one-step cyclic voltammetry (CV) electrochemical method with simultaneous occurrence of gold oxidation and GOs reduction to induce the intimate attachment by electrostatic interaction using chloride ions (Cl(-)). The rGO/Au2O3-modified electrode at a low deposition scan rate of 10 mVs(-1) displayed significantly improved electrocatalytic activity due to large active areas and well-dispersive attached rGO sheets. The in vitro amperometric response to H2O2 demonstrated a fast response of less than 5 s and a very low detection limit of 0.63 μM. In in vivo hyperacute stroke model, the concentration of H2O2 was measured as 100.48 ± 4.52 μM for rGO/Au2O3 electrode within 1 h photothrombotic stroke, which was much higher than that (71.92 μM ± 2.52 μM) for noncoated electrode via in vitro calibration. Simultaneously, the somatosensory-evoked potentials (SSEPs) test provided reliable and precise validation for detecting functional changes of neuronal activities. This newly developed implantable probe with localized rGO/Au2O3 nanocomposite electrode can serve as a rapid and reliable sensing platform for practical H2O2 detection in the brain or for other neural-chemical molecules in vivo.

Biosensors with Built-In Biomolecular Logic Gates for Practical Applications

Molecular logic gates, designs constructed with biological and chemical molecules, have emerged as an alternative computing approach to silicon-based logic operations. These molecular computers are capable of receiving and integrating multiple stimuli of biochemical significance to generate a definitive output, opening a new research avenue to advanced diagnostics and therapeutics which demand handling of complex factors and precise control. In molecularly gated devices, Boolean logic computations can be activated by specific inputs and accurately processed via bio-recognition, bio-catalysis, and selective chemical reactions. In this review, we survey recent advances of the molecular logic approaches to practical applications of biosensors, including designs constructed with proteins, enzymes, nucleic acids, nanomaterials, and organic compounds, as well as the research avenues for future development of digitally operating “sense and act” schemes that logically process biochemical signals through networked circuits to implement intelligent control systems.

Efficient electrocatalytic oxidation of water: minimization of catalyst loading by an electrostatic assembly of hydrous iridium oxide colloids

Exploiting an effective catalyst has been an essential and significant task in the development of electrochemical water oxidation. A highly electrocatalytic iridium oxide colloidal electrode, prepared by the electrostatic assembly fashion, is reported herein. Poly(allylamine hydrochloride) (PAH) was utilized to facilitate the formation of stable PAH/iridium oxide colloid clusters, resulting in a high catalytic utility (turnover efficiency of 6.36 ± 0.25 s−1 at low overpotential, η = 0.28 V) towards the oxygen evolution reaction (OER), with the smallest Ir loading (Γcov = 2.3 × 10−9 mol cm−2) of any yet reported. A variety of examinations and approaches were conducted to gain better understanding of such electrostatically assembled architecture and to identify hexahydroxyiridate(IV), [Ir(OH)6]2−, as the key active catalytic species.