Artificial Neurons on Flexible Substrates: A Fully Printed Approach for Neuromorphic Sensing.

Printed electronic devices have demonstrated their applicability in complex electronic circuits. There is recent progress in the realization of neuromorphic computing systems (NCSs) to implement basic synaptic functions using solution-processed materials. However, a fully printed neuron is yet to be realised. We demonstrate a fully printed artificial neuromorphic circuit on flexible polyimide (PI) substrate. Characteristic features of individual components of the printed system were guided by the software training of the NCS. The printing process employs graphene ink for passive structures and In2O3 as active material to print a two-input artificial neuron on PI. To ensure a small area footprint, the thickness of graphene film is tuned to target a resistance and to obtain conductors or resistors. The sheet resistance of the graphene film annealed at 300 °C can be adjusted between 200 Ω and 500 kΩ depending on the number of printed layers. The fully printed devices withstand a minimum of 2% tensile strain for at least 200 cycles of applied stress without any crack formation. The area usage of the printed two-input neuron is 16.25 mm2, with a power consumption of 37.7 mW, a propagation delay of 1 s, and a voltage supply of 2 V, which renders the device a promising candidate for future applications in smart wearable sensors.

Realization and training of an inverter-based printed neuromorphic computing system.

Emerging applications in soft robotics, wearables, smart consumer products or IoT-devices benefit from soft materials, flexible substrates in conjunction with electronic functionality. Due to high production costs and conformity restrictions, rigid silicon technologies do not meet application requirements in these new domains. However, whenever signal processing becomes too comprehensive, silicon technology must be used for the high-performance computing unit. At the same time, designing everything in flexible or printed electronics using conventional digital logic is not feasible yet due to the limitations of printed technologies in terms of performance, power and integration density. We propose to rather use the strengths of neuromorphic computing architectures consisting in their homogeneous topologies, few building blocks and analog signal processing to be mapped to an inkjet-printed hardware architecture. It has remained a challenge to demonstrate non-linear elements besides weighted aggregation. We demonstrate in this work printed hardware building blocks such as inverter-based comprehensive weight representation and resistive crossbars as well as printed transistor-based activation functions. In addition, we present a learning algorithm developed to train the proposed printed NCS architecture based on specific requirements and constraints of the technology.

Simultaneous determination of acyclovir, ganciclovir, and (R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine in human plasma using high-performance liquid chromatography.

Acyclovir, ganciclovir and (R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine are active in vitro against the Epstein-Barr virus (EBV) but their in vivo anti-EBV activity is not well understood. We developed a novel, sensitive high-performance liquid chromatography assay with ultraviolet detection for measuring acyclovir, ganciclovir and (R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine in human plasma to identify quantitative relationships between in vitro anti-EBV activity and therapeutic response. Characteristics of the assay include a low plasma volume (200 microL), perchloric acid protein precipitation, use of penciclovir as the internal standard, run times less than 8 min and a 50 ng/mL lower limit of quantification. The within- and between-assay variability is 0.7-4.8 and 1.0-7.9%, respectively. Accuracy for all three drugs ranges from 89.5 to 106.4% for four quality controls (50, 100, 1000 and 10,000 ng/mL). This assay supports pharmacokinetic and pharmacodynamic studies of candidate anti-EBV drugs in children and adults with EBV infections.

Progress Report on "From Printed Electrolyte-Gated Metal-Oxide Devices to Circuits".

Printed electrolyte-gated oxide electronics is an emerging electronic technology in the low voltage regime (≤1 V). Whereas in the past mainly dielectrics have been used for gating the transistors, many recent approaches employ the advantages of solution processable, solid polymer electrolytes, or ion gels that provide high gate capacitances produced by a Helmholtz double layer, allowing for low-voltage operation. Herein, with special focus on work performed at KIT recent advances in building electronic circuits based on indium oxide, n-type electrolyte-gated field-effect transistors (EGFETs) are reviewed. When integrated into ring oscillator circuits a digital performance ranging from 250 Hz at 1 V up to 1 kHz is achieved. Sequential circuits such as memory cells are also demonstrated. More complex circuits are feasible but remain challenging also because of the high variability of the printed devices. However, the device inherent variability can be even exploited in security circuits such as physically unclonable functions (PUFs), which output a reliable and unique, device specific, digital response signal. As an overall advantage of the technology all the presented circuits can operate at very low supply voltages (0.6 V), which is crucial for low-power printed electronics applications.

An isocratic liquid chromatography method for determining HIV non-nucleoside reverse transcriptase inhibitor and protease inhibitor concentrations in human plasma.

An efficient, isocratic high performance liquid chromatography (HPLC) method for determining human immunodeficiency virus (HIV) non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in plasma is advantageous for laboratories participating in clinical trials and therapeutic drug monitoring (TDM) programs, or conducting small animal research. The combination of isocratic reversed phase chromatography using an S-3, 3.0 mm x 150 mm column along with low plasma volume (200 microl), rapid liquid-liquid extraction, and detection at a single wavelength (212 nm) over a short run time makes this method valuable. Within and between assay variability ranges from 0.8 to 3.5% and 1.2-6.2%, respectively. Accuracy ranges from 91.0 to 112.8% for four quality controls (50, 100, 1000, and 10,000 ng/ml) for all drugs measured (efavirenz, nevirapine, amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir).

High-performance liquid chromatographic method for the determination of gemcitabine and 2',2'-difluorodeoxyuridine in plasma and tissue culture media.

Gemcitabine, a pyrimidine antimetabolite undergoes metabolism by plasma and liver cytidine deaminase to form the inactive compound, 2',2'-difluorodeoxyuridine (dFdU). The parent molecule is activated by intracellular phosphorylation. To evaluate the population pharmacokinetics in patients receiving gemcitabine, and to test the relation between gemcitabine infusion rate and antitumor activity in an in vitro bioreactor cell culture system, we developed and validated a sensitive and specific HPLC-UV method for gemcitabine and dFdU. Deproteinized plasma is vortexed, centrifuged, and 25 microL of the acidified extract sample is injected onto a Waters Spherisorb 4.6 mm x 250 mm, 5 microm C18 column at 40 degrees C. The mobile phase (flow rate, 1.0 mL/min) consists of 10:90 (v/v) acetonitrile-aqueous buffer (50 mM sodium phosphate and 3.0 mM octyl sulfonic acid, pH 2.9). Gemcitabine, dFdU, and the internal standard, 2'-deoxycytidine (2'dC) were detected with UV wavelength set at 267 nm. The standard curves for gemcitabine in both matrices ranged from 2 to 200 microM, and for dFdU in plasma, from 2 to 100 microM. Within-run and between-run component precision (CV%) was

Valacyclovir pharmacokinetics and exploratory pharmacodynamics in young adults with Epstein-Barr virus infectious mononucleosis.

Primary Epstein-Barr virus (EBV) infection often results in infectious mononucleosis and is associated with serious sequelae. No treatment is approved for EBV infection, and an antiviral intervention would be significant. The objectives of this study are to characterize the pharmacokinetics and explore the pharmacodynamics of acyclovir in plasma and oral washings of 8 subjects receiving 7 days of valacyclovir 1500 mg twice daily for EBV infectious mononucleosis. Virologic and clinical responses are assessed over 12 days. Acyclovir is measured by liquid chromatography/ultraviolet detection. EBV DNA is quantitated by TaqMan polymerase chain reaction. NONMEM VI and linear regression are used for data analysis. Acyclovir profiles in plasma and oral washings are consistent with a 1-compartment model. Final model estimates of clearance, volume of distribution, and fraction of acyclovir in oral wash supernatant are 49.9 L/h, 74.1 L, and 1.14%, respectively. The quantity of EBV DNA in oral washings and blood, and the severity of illness, measured by a graded scale, decrease during treatment. After treatment, viral rebound occurs in oral washings but not in blood, and the severity of illness continues to decline. Acyclovir pharmacokinetic parameters do not correlate with response metrics. These results support further studies of valacyclovir for EBV infectious mononucleosis.

A randomized crossover study to determine bioequivalence of generic and brand name nevirapine, zidovudine, and lamivudine in HIV-negative women in India.

Low-cost generic antiretroviral drugs are available in resource-limited settings for treatment of HIV infections. However, few bioequivalence data in specific populations in which these generics are likely to be used are available. We conducted a randomized crossover bioequivalence study of generic and brand name formulations of nevirapine, zidovudine, and lamivudine in HIV-negative Indian women using US Food and Drug Administration (FDA) criteria. Subjects took single doses of all formulations separated by a 14-day washout period. Plasma concentrations were measured over 96 hours during each study period. Average bioequivalence was determined using natural log-transformed maximum concentration (C(max)) and area-under-the-concentration-time curve (AUC) mean ratio data. Fifteen Indian women were enrolled. The 90% confidence intervals for nevirapine (14 subjects) and lamivudine (15 subjects) C(max), AUC from 0 to the last measurable time point (AUC(0-t)), and AUC from 0 to infinity (AUC(0-infinity)) mean ratios and zidovudine (15 subjects) AUC(0-t) and AUC(0-infinity) mean ratios were all within 0.80 to 1.25. However, the 90% confidence interval for zidovudine C(max) mean ratio was 0.70 to 1.46. Generic and brand name nevirapine and lamivudine met FDA average bioequivalence criteria. Lack of average bioequivalence for zidovudine was found for C(max) but is not expected to be clinically significant, because the total AUC values were similar between formulations.