A review of implementation frameworks to operationalize health technology assessment recommendations for medical technologies in the Singapore setting.

BACKGROUND: Methodologies of health technology assessment (HTA) for medical technologies are well established; yet, operational frameworks that enable appropriate uptake of HTA recommendations into routine clinical practice are lacking. This review aims to identify the key themes needed to guide the planning and implementation of HTA subsidy decisions for medical technologies such as diagnostics, medical devices, and services and to monitor their impact on a complex multipayer healthcare system like Singapore. METHODS: A literature search of implementation frameworks was conducted up to 20 December 2020 and was documented in a flow diagram. A thematic analysis of the evidence base was performed using the Braun and Clark approach to identify key themes, from which an implementation framework suitable for Singapore's healthcare system could be developed. RESULTS: The searches yielded forty-four articles for review, from which twenty themes were identified. The top ten themes constituted the key themes of implementation essential for local adaptation and were categorized into five domains: implementation strategy, organizational support, stakeholder engagement, information dissemination, and implementation outcomes and evaluation. These domains provide operational guidance to methodically identify gaps to facilitate sustainable implementation of HTA-informed medical technology subsidy decisions. CONCLUSION: A robust and adaptable implementation of HTA-informed subsidy decisions is crucial to optimize its intended impact of improving patient outcomes per dollar spent. The key themes of an implementation framework should capture the important aspects of organizational feasibility to ensure successful adoption in a complex multipayer healthcare system like Singapore.

Fluorinated graphene for promoting neuro-induction of stem cells.

Surface engineering of substrates offers the possibility of controlling the physiological functions of cells at the molecular level. Fluorinated graphene promotes the differentiation of MSCs towards neuronal lineages. Cell alignment using printed polydimethylsiloxane channel arrays on fluorinated graphene further enhances the neuro-induction of MSCs even in the absence of chemical inducers.

Flow sensing of single cell by graphene transistor in a microfluidic channel.

The electronic properties of graphene are strongly influenced by electrostatic forces arising from long-range charge scatterers and by changes in the local dielectric environment. This makes graphene extremely sensitive to the surface charge density of cells interfacing with it. Here, we developed a graphene transistor array integrated with microfluidic flow cytometry for the "flow-catch-release" sensing of malaria-infected red blood cells at the single-cell level. Malaria-infected red blood cells induce highly sensitive capacitively coupled changes in the conductivity of graphene. Together with the characteristic conductance dwell times, specific microscopic information about the disease state can be obtained.

Alkylamine capped metal nanoparticle "inks" for printable SERS substrates, electronics and broadband photodetectors.

We report a facile and general method for the preparation of alkylamine capped metal (Au and Ag) nanoparticle "ink" with high solubility. Using these metal nanoparticle "inks", we have demonstrated their applications for large scale fabrication of highly efficient surface enhanced Raman scattering (SERS) substrates by a facile solution processing method. These SERS substrates can detect analytes down to a few nM. The flexible plastic SERS substrates have also been demonstrated. The annealing temperature dependent conductivity of the nanoparticle films indicated a transition temperature above which high conductivity was achieved. The transition temperature could be tailored to the plastic compatible temperatures by using proper alkylamine as the capping agent. The ultrafast electron relaxation studies of the nanoparticle films demonstrated that faster electron relaxation was observed at higher annealing temperatures due to stronger electronic coupling between the nanoparticles. The applications of these highly concentrated alkylamine capped metal nanoparticle inks for the printable electronics were demonstrated by printing the oleylamine capped gold nanoparticles ink as source and drain for the graphene field effect transistor. Furthermore, the broadband photoresponse properties of the Au and Ag nanoparticle films have been demonstrated by using visible and near-infrared lasers. These investigations demonstrate that these nanoparticle "inks" are promising for applications in printable SERS substrates, electronics, and broadband photoresponse devices.

A simple, high yield method for the synthesis of organic wires from aromatic molecules using nitric acid as the solvent.

Using concentrated nitric acid as the solvent, and water as the non-solvent, one-dimensional (1D) organic nanowires can be synthesized in a simple, one-pot process with high yield. The method has broad validity to a wide range of aromatic molecules for the synthesis of derivatized organic wires.

A bioelectronic platform using a graphene-lipid bilayer interface.

The electronic properties of graphene can be modulated by charged lipid bilayer adsorbing on the surface. Biorecognition events which lead to changes in membrane integrity can be monitored electrically using an electrolyte-gated biomimetic membrane-graphene transistor. Here, we demonstrate that the bactericidal activity of antimicrobial peptides can be sensed electrically by graphene based on a complex interplay of biomolecular doping and ionic screening effect.

Direct voltammetric detection of DNA and pH sensing on epitaxial graphene: an insight into the role of oxygenated defects.

In this paper, we carried out detailed electrochemical studies of epitaxial graphene (EG) using inner-sphere and outer-sphere redox mediators. The EG sample was anodized systematically to investigate the effect of edge plane defects on the heterogeneous charge transfer kinetics and capacitive noise. We found that anodized EG, consisting of oxygen-related defects, is a superior biosensing platform for the detection of nucleic acids, uric acids (UA), dopamine (DA), and ascorbic acids (AA). Mixtures of nucleic acids (A, T, C, G) or biomolecules (AA, UA, DA) can be resolved as individual peaks using differential pulse voltammetry. In fact, an anodized EG voltammetric sensor can realize the simultaneous detection of all four DNA bases in double stranded DNA (dsDNA) without a prehydrolysis step, and it can also differentiate single stranded DNA from dsDNA. Our results show that graphene with high edge plane defects, as opposed to pristine graphene, is the choice platform in high resolution electrochemical sensing.

High mobility, printable, and solution-processed graphene electronics.

The ability to print graphene sheets onto large scale, flexible substrates holds promise for large scale, transparent electronics on flexible substrates. Solution processable graphene sheets derived from graphite can form stable dispersions in solutions and are amenable to bulk scale processing and ink jet printing. However, the electrical conductivity and carrier mobilities of this material are usually reported to be orders of magnitude poorer than that of the mechanically cleaved counterpart due to its higher density of defects, which restricts its use in electronics. Here, we show that by optimizing several key factors in processing, we are able to fabricate high mobility graphene films derived from large sized graphene oxide sheets, which paves the way for all-carbon post-CMOS electronics. All-carbon source-drain channel electronics fabricated from such films exhibit significantly improved transport characteristics, with carrier mobilities of 365 cm(2)/(V.s) for hole and 281 cm(2)/(V.s) for electron, measured in air at room temperature. In particular, intrinsic mobility as high as 5000 cm(2)/(V.s) can be obtained from such solution-processed graphene films when ionic screening is applied to nullify the Coulombic scattering by charged impurities.

High-throughput synthesis of graphene by intercalation-exfoliation of graphite oxide and study of ionic screening in graphene transistor.

We report a high-throughput method of generating graphene monolayer (>90% yield) from weakly oxidized, poorly dispersed graphite oxide (GO) aggregates. These large-sized GO aggregates consist of multilayer graphite flakes which are oxidized on the outer layers, while the inner layers consist of pristine or mildly oxidized graphene sheets. Intercalation-exfoliation of these GO aggregates by tetrabutylammonium cations yields large-sized conductive graphene sheets (mean sheet area of 330 +/- 10 microm(2)) with high monolayer yield. Thin-film field-effect transistors made from these graphene sheets exhibit high mobility upon nullifying Coulomb scattering by ionic screening. Ionic screening versus chemical doping effects of different ions such as chloride and fluoride on these graphene films were investigated with a combination of in situ Raman spectroscopy and transport measurement.

Solution-gated epitaxial graphene as pH sensor.

A solution-gate field effect transistor (SGFET) has been fabricated on few-layer graphene (FLG). The ideally polarizable graphene/aqueous electrolyte interface allows the capacitive charging of the surface by hydroxyl (OH-) and hydroxonium ions (H3O+). The conductivity versus gate potential curve exhibits "V" shaped ambipolar transfer characteristics of graphene, with hole and electron mobilities of 3600 cm2/Vs and 2100 cm2/Vs, respectively. The shift of the negative gate potential with pH shows a supra-Nernstian response of 99 meV/pH. Our work points to the potential application of graphene in ultrafast and ultralow noise chemical or biological sensors.