Precompetitive consensus building to facilitate the use of digital health technologies to support Parkinson Disease drug development through regulatory science

Innovative tools are urgently needed to accelerate the evaluation and subsequent approval of novel treatments that may slow, halt, or reverse the relentless progression of Parkinson disease (PD). Therapies that intervene early in the disease continuum are a priority for the many candidates in the drug development pipeline. There is a paucity of sensitive and objective, yet clinically interpretable, measures that can capture meaningful aspects of the disease. This poses a major challenge for the development of new therapies and is compounded by the considerable heterogeneity in clinical manifestations across patients and the fluctuating nature of many signs and symptoms of PD. Digital health technologies (DHT), such as smartphone applications, wearable sensors, and digital diaries, have the potential to address many of these gaps by enabling the objective, remote, and frequent measurement of PD signs and symptoms in natural living environments. The current climate of the COVID-19 pandemic creates a heightened sense of urgency for effective implementation of such strategies. In order for these technologies to be adopted in drug development studies, a regulatory-aligned consensus on best practices in implementing appropriate technologies, including the collection, processing, and interpretation of digital sensor data, is required. A growing number of collaborative initiatives are being launched to identify effective ways to advance the use of DHT in PD clinical trials. The Critical Path for Parkinson’s Consortium of the Critical Path Institute is highlighted as a case example where stakeholders collectively engaged regulatory agencies on the effective use of DHT in PD clinical trials. Global regulatory agencies, including the US Food and Drug Administration and the European Medicines Agency, are encouraging the efficiencies of data-driven engagements through multistakeholder consortia. To this end, we review how the advancement of DHT can be most effectively achieved by aligning knowledge, expertise, and data sharing in ways that maximize efficiencies

Experimental study of heat transfer in turbulent flows over wall-mounted cubes.

Applied Science

Manufacturing and testing flexible microfluidic devices with optical and electrical detection mechanisms

Flexible microfluidic devices made of poly(dimethylsiloxane) (PDMS) were manufactured by soft lithography, and tested in detection of ionic species using optical absorption spectroscopy and electrical measurements. PDMS was chosen due to its flexibility and ease of surface modification by exposure to plasma and UV treatment, its transparency in UV-Vis regions of the light spectrum, and biocompatibility. The dual-detection mechanism allows the user more freedom in choosing the detection tool, and a functional device was successfully tested. Optical lithography was employed for manufacturing templates, which were subsequently used for imprinting liquid PDMS by thermal curing. Gold electrodes having various widths and distances among them were patterned with optical lithography on the top part which sealed the microchannels, and the devices were employed for detection of ionic species in aqueous salt solutions as well as micro-electrolysis cells. Due to the transparency of PDMS in UV-Vis the microfluidics were also used as photoreactors, and the in-situ formed charged species were monitored by applying a voltage between electrodes. Upon addition of a colorimetric pH sensor, acid was detected with absorption spectroscopy. © 2010 Copyright SPIE - The International Society for Optical Engineering

Direct Laser Write (DLW) as a versatile tool in manufacturing templates for imprint lithography on flexible substrates

A computer-controlled laser beam recorder with a wavelength of 405 nm has been employed for patterning the deposited resist with feature sizes varying from a few hundreds of nanometers to tens of micrometers. Four inch silicon templates for hot embossing source/ drain electrodes and metallic circuit for a disposable biosensor were obtained. SEM and optical microscopy reveal accurate transfer of developed photoresist structures into the underlying silicon wafer after plasma dry etching. Etch depths between 100 - 600 nm were obtained on the templates, and were further transferred into the imprinted plastic substrate and the metallic layer. © 2009 SPIE

Modeling the residual shrinkage during lithographic processing on flexible polymer substrates

The challenge of lithographic production of electronic circuitry on polymer foil is that deformations approaching the feature sizes of the circuitry can cause considerable overlay problems and thereby malfunctioning of the devices. The substrate foil is susceptible to several types of deformations. Accurate prediction of these deformations is of great importance, as it will help to improve the production process and thereby improve the quality of the electronic devices. One of the deformations is the residual shrinkage, a deformation that occurs after application of a heat step to a polymer foil. This study presents an experimental investigation of residual shrinkage combined with a modeling approach in which the temperature dependent visco-elastic material properties of the foil are used. The model enables us to more accurately predict overlay errors. ©2010 IEEE

Double-layer imprint lithography on wafers and foils from the submicrometer to the millimeter scale

In this paper, a thermal imprint technique, double-layer nanoimprint lithography (dlNIL), is introduced, allowing complete filling of features in the dimensional range of submicrometer to millimeter. The imprinting and filling quality of dlNIL was studied on Si substrates as a model system and compared to results obtained with regular NIL (NIL) and reverse NIL (rNIL). Wavy foils were imprinted with NIL, rNIL and dlNIL and the patterning results compared and discussed. With dlNIL, a new application possibility was introduced in which two different resists having, for example, a different etch resistance to a certain plasma were combined within one imprint step. dlNIL allows extension to many resist combinations for tailored nanostructure fabrication. © 2011 American Chemical Society

Polymer substrates for flexible electronics: achievements and challenges

Flexible electronics technology can potentially result in many compelling applications not satisfied by the rigid Si-based conventional electronics. Commercially available foils such as polyethylene terephthalate (PET) and polyethylene naphthalate (PEN) have emerged as the most suitable polymer materials for wide range of flexible electronics applications. Despite the enormous progress which has been recently done on the optimization of physical and mechanical properties of PET and PEN foils, their dimensional stability at the micro-scale is still an issue during patterning of wiring by means of lithography. Consequently, the measurement of in-plane micro-deformation of foil is of great importance for understanding and predicting its thermal, hydroscopic and mechanical behaviour during processing. © (2010) Trans Tech Publications

A common gate thin film transistor on poly(ethylene naphthalate) foil using step-and-flash imprint lithography

In this paper the fabrication of flexible thin film transistors (TFTs) on poly(ethylene naphthalate) foil is reported, with the source-drain layer patterned by step-and-flash imprint lithography (SFIL) as a first step towards fully UV-imprinted TFTs. The semiconductor was deposited by inkjet printing of a blend of TIPS-pentacene/polystyrene. The bottom contact, bottom gate TFTs were fabricated with the foil reversibly glued to a carrier, enhancing the dimensional stability and flatness of the foil to result in a thinner and more homogeneously distributed residual layer thickness. The obtained performance of the TFT devices, showing a mobility of μ = 0.56 cm2 V-1 s-1 with an on/off ratio of >107 and near-zero threshold voltage, was found to be in good agreement with similar, photolithographically patterned state-of-the-art devices recently reported in literature. The results presented here show the feasibility of SFIL as a roll-to-roll compatible and down scalable patterning technique on flexible PEN foil for the fabrication of bottom-gate, bottom-contact flexible high-quality TFTs