Organic semiconductor laser biosensor : design and performance discussion

Organic distributed feedback lasers can detect nanoscale materials and are therefore an attractive sens- ing platform for biological and medical applications. In this paper, we present a model for optimizing such laser sensors and discuss the advantages of using an organic semiconductor as the laser material in comparison to dyes in a matrix. The structure of the sensor and its operation principle are described. Bulk and surface sensing exper- imental data using oligofluorene truxene macromolecules and a conjugated polymer for the gain region is shown to correspond to modeled values and is used to assess the biosensing attributes of the sensor. A comparison between organic semiconductor and dye-doped laser sensitivity is made and analyzed theoretically. Finally, experimental and theoretical specific biosensing data is provided and methods for improving sensitivity are discussed

Micro-LED waveguide for fluorescence applications

A micro-LED-coupled multimode slab waveguide is reported for fluorescence sensing. The device consists of a 1-dimensional micro-LED array coupled to a sub-mm polymeric slab for evanescent excitation of fluorescent analytes present on the surface. Proof-principle detection of semiconductor nanocrystals down to 0.2 pM/cm2 is demonstrated

Oligofluorene truxene laser sensor : towards bacteria growth detection

Work toward the utilisation of an organic laser as a bacterial growth detector is presented here. The sensor used is an optically excited 2nd order DFB (distributed feedback laser) made of oligofluorene truxene. In the drive towards a practical bacterial growth detector, temperature stability and the optimum growth conditions of bacteria are challenges to be overcome. The resultant DFB laser exhibits a sensitivity of 9 nm/RIU

A wearable phototherapy device utilizing micro-LEDs

A conformable device for wearable phototherapy applications is presented. The device consists of a 1 mm thick elastomeric membrane edge-lit by specially fabricated micro-sized LEDs. Nanoparticle based scattering films are utilized to extract light and a uniform emission of 15 μW/cm2 is reported over an area of 2 cm2

An oligofluorene truxene based distributed feedback laser for biosensing applications

The first example of an all-organic oligofluorene truxene based distributed feedback laser for the detection of a specific protein–small molecule interaction is reported. The protein avidin was detected down to View the MathML source1μgmL−1 using our biotin-labelled biosensor platform. This interaction was both selective and reversible when biotin was replaced with desthiobiotin. Avidin detection was not perturbed by Bovine Serum Albumin up to View the MathML source50,000μgmL−1. Our biosensor offers a new detection platform that is both highly sensitive, modular and potentially re-usable

MicroLED biosensor with colloidal quantum dots and smartphone detection

A fluorescence sensor with the capability for spatially multiplexed measurements utilizing smartphone detection is presented. Bioconjugated quantum dots are used as the fluorescent tag and are excited using a blue emitting microLED (µLED). The 1-dimensional GaN µLED array is butt-coupled to one edge of the glass slide to take advantage of total internal reflection fluorescence (TIRF) principles. The bioassays on the top surface of the glass waveguide are excited and the resultant fluorescence is detected with the smartphone. The red, green, and blue channels of the digital image are utilized to spectrally separate the excitation light from the fluorescence for analysis. Using a biotin-functionalized glass slide as proof of principle, we have shown that streptavidin conjugated quantum dots can be detected down to a concentration of 8 nM

β-Amyloid 1-42 Oligomers Impair Function of Human Embryonic Stem Cell-Derived Forebrain Cholinergic Neurons

Cognitive impairment in Alzheimer's disease (AD) patients is associated with a decline in the levels of growth factors, impairment of axonal transport and marked degeneration of basal forebrain cholinergic neurons (BFCNs). Neurogenesis persists in the adult human brain, and the stimulation of regenerative processes in the CNS is an attractive prospect for neuroreplacement therapy in neurodegenerative diseases such as AD. Currently, it is still not clear how the pathophysiological environment in the AD brain affects stem cell biology. Previous studies investigating the effects of the β-amyloid (Aβ) peptide on neurogenesis have been inconclusive, since both neurogenic and neurotoxic effects on progenitor cell populations have been reported. In this study, we treated pluripotent human embryonic stem (hES) cells with nerve growth factor (NGF) as well as with fibrillar and oligomeric Aβ1-40 and Aβ1-42 (nM-µM concentrations) and thereafter studied the differentiation in vitro during 28-35 days. The process applied real time quantitative PCR, immunocytochemistry as well as functional studies of intracellular calcium signaling. Treatment with NGF promoted the differentiation into functionally mature BFCNs. In comparison to untreated cells, oligomeric Aβ1–40 increased the number of functional neurons, whereas oligomeric Aβ1–42 suppressed the number of functional neurons. Interestingly, oligomeric Aβ exposure did not influence the number of hES cell-derived neurons compared with untreated cells, while in contrast fibrillar Aβ1–40 and Aβ1–42 induced gliogenesis. These findings indicate that Aβ1–42 oligomers may impair the function of stem cell-derived neurons. We propose that it may be possible for future AD therapies to promote the maturation of functional stem cell-derived neurons by altering the brain microenvironment with trophic support and by targeting different aggregation forms of Aβ

A distributed feedback for organic semiconductor laser platform for assessing the risk of cardiovascular disease

Organic distributed feedback (DFB) lasers are a class of evanescent wave technology that can be used to measure changes in refractive index at the laser surface. These sensors are highly attractive for biosensing applications as they provide a sensitive platform for the label-free detection of a range of analytes, possibly in real-time, and they can be multiplexed for the detection of a suite of different analytes from a single test sample. The simple implementation of DFB lasers for sensing also means that they can be packaged into a compact sensing platform; this is especially true of DFB lasers incorporating an organic semiconductor as the gain layer where optical pumping may be performed with a compact source, such as a laser diode. In addition, organic semiconductor based DFB lasers have the potential for improved sensitivity relative to other organic DFB lasers (such as dye-doped) as the refractive index of organic semiconductors is generally higher, which leads to an increase in the interaction of the laser mode with the analyte binding region at the laser surface. In this thesis, the rst demonstration of an organic semiconductor (oligofluorene truxene (T3)) DFB laser for biosensing applications is described. Sensor development is focused on the ultimate aim of incorporating a T3 DFB laser into a compact and portable highthroughput sensing platform for the detection of cardiac biomarkers, Apolipoprotein B100, C-reactive protein and B-type natriuretic peptide in particular. Detection of these biomarkers is to be achieved via functionalisation of the T3 surface with oligonucleotide based probes. The structure of the T3 DFB laser is optimised experimentally and theoretically by tuning the gain layer thickness to maximise sensitivity to changes in refractive index at the laser surface, such as the binding of an analyte. The optimised laser sensor has a laser threshold of 30 µJ.cm⁻²/6 kW.cm⁻² (5 ns pulse duration) which makes optical pumping with a laser diode a possibility. The sensing potential of the DFB laser is shown via the detection of bulk solution refractive index changes and the addition of biomolecules to the laser surface, where a bulk sensitivity of 22 nm per refractive index unit is observed. The specific biosensing potential of the laser is highlighted through the functionalisation of the laser surface with biotin molecules and the subsequent detection of the complementary protein, avidin. The lowest limit of avidin detection achieved is 1µg.mL⁻¹; at this level of sensitivity, the current T3 laser is expected to be able to detect the larger and more abundant of two of the three cardiac biomarker targets, ApoB and CRP. The effects of structural changes to device sensitivity are modelled theoretically and demonstrate that detection of BNP may be achieved through the addition of a high-index cladding layer, a technique currently used for dye-doped DFB lasers. The first demonstration of a DFB laser used for reversible sensing is also presented in this thesis. Through the use of desthiobiotin, a biotin analogue, reversible avidin detection is performed. A reversible biosensor may be of particular interest for applications where a large number of repeated measurements are required, and may be prohibitive to the use of single-use, disposable sensors. Finally, functionalisation of the DFB laser with oligonucleotide probes is described. Several different techniques are explored for immobilisation of oligonucleotide probes on the T3 surface, with click chemistry and sulfhydryl linkage chemistries showing the most promise.Organic distributed feedback (DFB) lasers are a class of evanescent wave technology that can be used to measure changes in refractive index at the laser surface. These sensors are highly attractive for biosensing applications as they provide a sensitive platform for the label-free detection of a range of analytes, possibly in real-time, and they can be multiplexed for the detection of a suite of different analytes from a single test sample. The simple implementation of DFB lasers for sensing also means that they can be packaged into a compact sensing platform; this is especially true of DFB lasers incorporating an organic semiconductor as the gain layer where optical pumping may be performed with a compact source, such as a laser diode. In addition, organic semiconductor based DFB lasers have the potential for improved sensitivity relative to other organic DFB lasers (such as dye-doped) as the refractive index of organic semiconductors is generally higher, which leads to an increase in the interaction of the laser mode with the analyte binding region at the laser surface. In this thesis, the rst demonstration of an organic semiconductor (oligofluorene truxene (T3)) DFB laser for biosensing applications is described. Sensor development is focused on the ultimate aim of incorporating a T3 DFB laser into a compact and portable highthroughput sensing platform for the detection of cardiac biomarkers, Apolipoprotein B100, C-reactive protein and B-type natriuretic peptide in particular. Detection of these biomarkers is to be achieved via functionalisation of the T3 surface with oligonucleotide based probes. The structure of the T3 DFB laser is optimised experimentally and theoretically by tuning the gain layer thickness to maximise sensitivity to changes in refractive index at the laser surface, such as the binding of an analyte. The optimised laser sensor has a laser threshold of 30 µJ.cm⁻²/6 kW.cm⁻² (5 ns pulse duration) which makes optical pumping with a laser diode a possibility. The sensing potential of the DFB laser is shown via the detection of bulk solution refractive index changes and the addition of biomolecules to the laser surface, where a bulk sensitivity of 22 nm per refractive index unit is observed. The specific biosensing potential of the laser is highlighted through the functionalisation of the laser surface with biotin molecules and the subsequent detection of the complementary protein, avidin. The lowest limit of avidin detection achieved is 1µg.mL⁻¹; at this level of sensitivity, the current T3 laser is expected to be able to detect the larger and more abundant of two of the three cardiac biomarker targets, ApoB and CRP. The effects of structural changes to device sensitivity are modelled theoretically and demonstrate that detection of BNP may be achieved through the addition of a high-index cladding layer, a technique currently used for dye-doped DFB lasers. The first demonstration of a DFB laser used for reversible sensing is also presented in this thesis. Through the use of desthiobiotin, a biotin analogue, reversible avidin detection is performed. A reversible biosensor may be of particular interest for applications where a large number of repeated measurements are required, and may be prohibitive to the use of single-use, disposable sensors. Finally, functionalisation of the DFB laser with oligonucleotide probes is described. Several different techniques are explored for immobilisation of oligonucleotide probes on the T3 surface, with click chemistry and sulfhydryl linkage chemistries showing the most promise

Initial investigations of a novel bioluminescence method for imaging dental demineralization

Abstract Objectives In this in vitro study, a bioluminescent marker was investigated for its potential to illuminate the assessment of dental caries and dental erosion, which are significant clinical and public health problems, through its binding of those ions, notably Ca2+, known to be released during the process of demineralization. Materials and Methods The light output from the selected bioluminescent marker was investigated in several experiments, including: (a)contact with a range of Ca2+ ion concentrations; (b) treatment of extracted teeth with solutions of differing pH, followed by application of the bioluminescence marker to assess Ca2+ ion release; and (c) application of the marker to freshly extracted teeth with natural and artificially created caries lesions on occlusal and smooth surfaces to image the Ca2+ ion distribution. Results The results of: experiment (a) showed that the light output from the marker increases with increasing Ca2+ concentration and of experiment (b) showed increases in light being observed as increasingly acidic solutions were applied. The results of experiment (c) showed the bioluminescence images of the extracted teeth produced “demineralization maps” of the imaged surfaces. Conclusions These results demonstrate the ability of a novel bioluminescence technology to image Ca2+ ions on tooth enamel surfaces which has potential in dental caries and dental erosion applications and provides the scientific basis for the ongoing development of that novel technology