Barriers and facilitators to the implementation of osteoarthritis management programmes in primary or community care settings: a systematic review and qualitative framework synthesis protocol.

Despite consistent international guidelines for osteoarthritis (OA) management, evidence-based treatments are underutilised. OA management programmes (OAMPs) are being implemented internationally to address this evidence-practice gap. An OAMP is defined as a 'model of evidence-based, non-surgical OA care that has been implemented in a real-world setting'. Our objective is to identify, synthesise and appraise qualitative research identifying anticipated or experienced micro (individual/behavioural), meso (organisational) or macro (context/system) level barriers or facilitators to the implementation of primary or community care-based OAMPs. Five electronic databases will be searched for papers published between 2010 and 2021. Qualitative or mixed-methods studies that include qualitative data on the anticipated or experienced barriers or facilitators to the implementation of primary or community care-based OAMPs, from the perspective of service users or service providers, will be included. The review will be reported using the PRISMA and ENTREQ guidelines. A data extraction form will be used to provide details of the included studies. Data will be analysed and identified barriers and facilitators will be mapped onto an appropriate implementation framework, such as the Theoretical Domains Framework. The appropriate JBI critical appraisal tools will be used to assess methodological quality, while the GRADE-CERQual approach will be used to assess confidence in the findings. Translation of evidence-based guidelines into practice is challenging and reliant on the quality of implementation. By comparing and contrasting anticipated and experienced barriers, this review will determine the extent of congruence between the two, and provide valuable insights into the views and experiences of key stakeholders involved in the implementation of OAMPs. The mapping of identified barriers and facilitators to behaviour change theory will enhance the applicability and construct validity of our findings and will offer significant utility for future development and implementation of OAMPs. Registration: This protocol was registered with PROSPERO (CRD42021255698) on 15/07/21.

Single-molecule detection of deoxyribonucleoside triphosphates in microdroplets.

A new approach to single-molecule DNA sequencing in which dNTPs, released by pyrophosphorolysis from the strand to be sequenced, are captured in microdroplets and read directly could have substantial advantages over current sequence-by-synthesis methods; however, there is no existing method sensitive enough to detect a single nucleotide in a microdroplet. We have developed a method for dNTP detection based on an enzymatic two-stage reaction which produces a robust fluorescent signal that is easy to detect and process. By taking advantage of the inherent specificity of DNA polymerases and ligases, coupled with volume restriction in microdroplets, this method allows us to simultaneously detect the presence of and distinguish between, the four natural dNTPs at the single-molecule level, with negligible cross-talk.

High bandwidth on-chip capacitive tuning of microtoroid resonators.

We report on the design, fabrication and characterization of silica microtoroid based cavity opto-electromechanical systems (COEMS). Electrodes patterned onto the microtoroid resonators allow for rapid capacitive tuning of the optical whispering gallery mode resonances while maintaining their ultrahigh quality factor, enabling applications such as efficient radio to optical frequency conversion, optical routing and switching applications.

Ultrasensitive optomechanical magnetometry.

A cavity optomechanical magneto-meter operating in the 100 pT range is reported. The device operates at earth field, achieves tens of megahertz bandwidth with 60 µm spatial resolution and microwatt optical-power requirements. These unique capabilities may have a broad range of applications including cryogen-free and microfluidic magnetic resonance imaging (MRI), and investigation of spin-physics in condensed matter systems.

Electrochemically-gated delivery of analyte bands in microfluidic devices using bipolar electrodes.

A method for controlling enrichment, separation, and delivery of analytes into different secondary microchannels using simple microfluidic architecture is described. The approach, which is based on bipolar electrochemistry, requires only easily fabricated electrodes and a low-voltage DC power supply: no pumps or valves are necessary. Upon application of a voltage between two driving electrodes, passive bipolar electrodes (BPEs) are activated that result in formation of a local electric field gradient. This gradient leads to separation and enrichment of a pair of fluorescent analytes within a primary microfluidic channel. Subsequently, other passive BPEs can be activated to deliver the enriched tracers to separate secondary microchannels. The principles and performance underpinning the method are described.

Dual-channel bipolar electrode focusing: simultaneous separation and enrichment of both anions and cations.

In this paper we show that a microelectrochemical cell comprising two parallel microchannels spanned by a single bipolar electrode can be used to simultaneously enrich and separate both anions and cations within a single microchannel. This is possible because reduction and oxidation of water at the cathodic and anodic poles of the bipolar electrode, respectively, lead to ion depletion zones. Specifically, TrisH(+) is neutralized by OH(-) at the cathodic pole, while acetate buffer is neutralized by H(+) at the anodic pole. This action creates a local electric field gradient having both positive and negative components, and hence positive and negative ions follow their respective field gradients leading to separation. In the presence of an opposing counter-flow (pressure driven flow in this case), enrichment also occurs. In addition to separation and enrichment in a single channel, it is also possible to simultaneously enrich cations in one microchannel and anions in the other. Enrichment is achieved by controlling experimental parameters, including the type of buffer and the direction and magnitude of the opposing counter-flow.

Enrichment of cations via bipolar electrode focusing.

We have previously demonstrated up to 5 × 10(5)-fold enrichment of anionic analytes in a microchannel using a technique called bipolar electrode focusing (BEF). Here, we demonstrate that BEF can also be used to enrich a cationic fluorescent tracer. The important point is that chemical modification of the microchannel walls enables reversal of the electroosmotic flow (EOF), enabling cations, instead of anions, to be enriched via an electric field gradient focusing mechanism. Reversal of the EOF has significant consequences on the formation and shape of the region of the buffer solution depleted of charge carriers (depletion zone). Electric field measurements and numerical simulations are used to elucidate the factors influencing the depletion zone. This information is used to understand and control the location and shape of the depletion zone, which in turn influences the stability and concentration of the enriched band.

Bipolar electrode depletion: membraneless filtration of charged species using an electrogenerated electric field gradient.

We report a method for removing ions from aqueous solutions without the use of a membrane. The approach, which we call bipolar electrode depletion (BED), is based on the formation of an asymmetric electric field profile in a microchannel containing a bipolar electrode (BPE). The asymmetric field arises from local increases in conductivity caused by faradaic reactions at the BPE. We show how the asymmetric field can be used to deplete anions from a microchannel via a combination of electrophoresis and electroosmosis. We also apply this approach to filter an anionic species from a mixture of charged and neutral species being transported through a microchannel via electroosmosis. This technique could be utilized for desalination or filtration of any species possessing a net charge (e.g. heavy-metals, bacteria, proteins, or functionalized-nanoparticles).

Label-free electrochemical monitoring of concentration enrichment during bipolar electrode focusing.

We show that a label-free electrochemical method can be used to monitor the position of an enriched analyte band during bipolar electrode focusing in a microfluidic device. The method relies on formation of a depleted buffer cation region, which is responsible for concentration enrichment of the charged analyte. However, this depletion region also leads to an increase in the local electric field in the solution near a bipolar electrode (BPE), and this in turn results in enhanced faradaic reactions (oxidation and reduction of water) at the BPE. Therefore, it is possible to detect the presence of the concentrated analyte band by measuring the current passing through the BPE used for concentration enrichment, or the concentrated band can be detected at a secondary BPE dedicated to that purpose. Both experiments and simulations are presented that fully elucidate the underlying phenomenon responsible for these observations.

Bipolar electrode focusing: faradaic ion concentration polarization.

Bipolar electrode (BPE) focusing locally enriches charged analytes in a microchannel along an electric field gradient that opposes a counter-flow. This electric field gradient forms at the boundary of an ion depletion zone generated by the BPE. Here, we demonstrate concentration enrichment of a fluorescent tracer by up to 500,000-fold. The use of a dual-channel microfluidic configuration, composed of two microchannels electrochemically connected by a BPE, enhances the rate of enrichment (up to 71-fold/s). Faradaic reactions at the ends of the BPE generate ion depletion and enrichment zones in the two, separated channels. This type of device is equivalent to previously reported micro/nanochannel junction arrangements used for ion concentration polarization, but it is experimentally more flexible and much simpler to construct.

Bipolar electrode focusing: tuning the electric field gradient.

Bipolar electrode (BPE) focusing is a developing technique for enrichment and separation of charged analytes in a microfluidic channel. The technique employs a bipolar electrode that initiates faradaic processes that subsequently lead to formation of an ion depletion zone. The electric field gradient resulting from this depletion zone focuses ions on the basis of their individual electrophoretic mobilities. The nature of the gradient is of primary importance to the performance of the technique. Here, we report dynamic measurements of the electric field gradient showing that it is stable over time and that its axial position in the microchannel is directly correlated to the location of an enriched tracer band. The position of the gradient can be tuned with pressure-driven flow. We also show that a steeper electric field gradient decreases the breadth of the enriched tracer band and therefore enhances the enrichment process. The slope of the gradient can be tuned by altering the buffer concentration: higher concentrations result in a steeper gradient. Coating the channel with the neutral block co-polymer Pluronic also results in enhanced enrichment.

Emission enhancement within gold spherical nanocavity arrays.

Gold nanocavity arrays were prepared on fluorine-doped tin oxide on glass by electrochemical deposition of gold through monolayers of polystyrene spheres. The impact of the resulting spherical cap architecture on the photophysics of solutions and self-assembled monolayers of luminophore encapsulated within the nanocavities is reported for the first time. From conventional confocal fluorescence microscopy, the emission intensity of solutions of [Ru(bpy)(2)(Qbpy)](2+) (where bpy is 2,2'-bipyridyl and Qbpy is 2,2':4,4'':4,4''-quarterpyridyl) and fullerene (C(60)) encapsulated within the 820 nm diameter nanocavities was demonstrated to increase by approximately an order of magnitude compared with that of the associated bulk solution. Comparison was also made with the emission observed for luminophore solution encapsulated in cobalt nanocavities of comparable dimensions, where plasmonic interactions are not anticipated. Again, approximately an order of magnitude enhancement was observed for the gold arrays. Luminescence lifetime imaging revealed that the enhancement of the emission intensity of this solution within the nanocavity was accompanied by a small but significant decrease in the luminescent lifetime for [Ru(bpy)(2)(Qbpy)](2+). Enhancement was, in addition, strongly influenced by the wavelength of excitation, suggesting that plasmonics may play a role in the enhancement of the excitation process. An important observation from confocal imaging studies was that the dimensions of the luminophore emission field from solution within the cavities were significantly smaller than the dimensions of the cavity aperture and corresponded to a little more than that of the point spread function of the microscope. This indicates that its origin is significantly smaller than the wavelength of the emitted light and suggests that luminescence enhancement is highly localised. When the array was filled with a solution of [Ru(bpy)(2)(Qbpy)](2+) the emission spectrum of this complex was red shifted and broadened compared with that of the bulk solution, typical of the formation of a luminescent surface film. In addition, significant enhancement was only observed when the solution was sonicated into the array. Both these observations suggest that the emission enhancement is localised near the bottom of the cavity. Self-assembled monolayers of [Ru(bpy)(2)(Qbpy)](2+) were formed on the array and approximately 7 orders of magnitude enhancement of the Raman signal was achieved. Significantly, the emission intensity was approximately 4-fold higher for the monolayer than for a solid film under the same conditions, but surface quenching is thought to play a significant role in the observed decrease in lifetime for the monolayer of this complex on the array.