Multi-wavelength fluorescence sensing with integrated waveguides in an optofluidic chip

Femtosecond-laser-written integrated waveguides enable multi-wavelength fluorescence sensing of flowing biomolecules in an optofluidic chip. Fluorescence from differently labeled biomolecules with distinct absorption wavelengths, encoded by uniquely modulating each excitation beam, is detected by a color-blind photodetector, and the origin of each signal is unraveled by Fourier analysis

Multi-color fluorescent DNA analysis in an integrated optofluidic lab-on-a-chip

Sorting and sizing of DNA molecules within the human genome project has enabled the genetic mapping of various illnesses. By employing tiny lab-on-a-chip devices for such DNA analysis, integrated DNA sequencing and genetic diagnostics have become feasible. However, such diagnostic chips typically lack integrated sensing capability. We address this issue by combining microfluidic capillary electrophoresis with laser-induced fluorescence detection resulting in optofluidic integration towards an on-chip bio-analysis tool [1,2]. We achieve a spatial separation resolution of 12 μm, which can enable a 20-fold enhancement in electropherogram peak resolution, leading to plate numbers exceeding one million. We demonstrate a high sizing/calibration accuracy of 99% [3], and ultrasensitive fluorescence detection (limit of detection = 65 femtomolar, corresponding to merely 2-3 molecules in the excitation/detection volume) of diagnostically relevant double-stranded DNA molecules by integrated-waveguide laser excitation. Subsequently, we introduce a principle of parallel optical processing to this optofluidic lab-on-a-chip. Different sets of exclusively color-labeled DNA fragments – otherwise rendered indistinguishable by their spatio-temporal coincidence – are traced back to their origin by modulation-frequency-encoded multi-wavelength laser excitation, fluorescence detection with a color-blind photomultiplier, and Fourier-analysis decoding. As a proof of principle, fragments from independent human genomic segments, associated with genetic predispositions to breast cancer and anemia, are extracted by multiplex ligation-dependent probe amplification, and simultaneously analyzed. Such multiple yet unambiguous optical identification of biomolecules opens new horizons for “enlightened” lab-on-a-chip devices

Fluorescence monitoring of capilarry electrophoresis separation in a lab-on-a-chip with monolithically integrated waveguides

Femtosecond-laser-written optical waveguides were monolithically integrated into a commercial lab-on-a-chip to intersect a microfluidic channel. Laser excitation through these waveguides confines the excitation window to a width of 12 μm, enabling high-spatial-resolution monitoring of different fluorescent analytes, during their migration/separation in the microfluidic channel by capillary electrophoresis. Wavelength-selective monitoring of the on-chip separation of fluorescent dyes is implemented as a proof-of-principle. We envision well-controlled microfluidic plug formation, waveguide excitation, and a low limit of detection to enable monitoring of extremely small quantities with high spatial resolution

Multi-point, multi-wavelength fluorescence monitoring of DNA separation in a lab-on-a-chip with monolithically integrated femtosecond-laser-written waveguides

Electrophoretic separation of fluorescently labeled DNA molecules in on-chip microfluidic channels was monitored by integrated waveguide arrays, with simultaneous spatial and wavelength resolution. This is an important step toward point-of-care diagnostics with multiplexed DNA assays

The resource group method in severe mental illness:Study protocol for a randomized controlled trial and a qualitative multiple case study

Background The resource group method provides a structure to facilitate patients’ empowerment and recovery processes, and to systematically engage significant others in treatment and care. A patient chooses members of a resource group (RG) that will work together on fulfilling patients’ recovery plan. By adopting shared decision-making processes and stimulating collaboration of different support systems, a broad and continuous support of patients’ chosen goals and wishes is preserved and problem solving and communication skills of the RG members are addressed. Objective The objectives of this study are (1) to establish the effectiveness of the RG method in increasing empowerment in patients with severe mental illnesses (SMI) in the Netherlands; (2) to investigate the cost-effectiveness and cost utility of the RG method; and (3) to qualitatively explore its dynamics and processes. Methods/design This multisite randomized controlled trial will compare the effects of the RG-method integrated in Flexible Assertive Community Treatment (FACT) (90 patients) with those of standard FACT (90 patients). Baseline assessments and 9-month and 18-month follow-up assessments will be conducted in face-to-face home visits. The primary outcome measure, empowerment, will be assessed using the Netherlands Empowerment List (NEL). The secondary outcomes will be quality of life (MANSA); personal, community and clinical recovery (I.ROC); general, social and community functioning (WHODAS 2.0); general psychopathological signs and symptoms (BSI-18); and societal costs (TiC-P). An economic evaluation of the cost-effectiveness and cost utility of the RG method will also be conducted. A qualitative multiple case-study will be added to collect patients’, RG members’ and professionals’ perspectives by in-depth interviews, observations and focus groups. Discussion This trial will be the first to study the effects of the RG method on empowerment in patients with SMI. By combining clinical-effectiveness data with an economic evaluation and in-depth qualitative information from primary stakeholders, it will provide a detailed overview of the RG method as a mean of improving care for patients with SMI

Confirmatory factor analysis and differential relationships of the two subdomains of negative symptoms in chronically ill psychotic patients

Research suggests a two factor structure for negative symptoms in patients with psychotic disorders: social amotivation (SA) and expressive deficits (ED). Applying this two-factor structure in clinical settings may provide valuable information with regard to outcomes and to target treatments. We aimed to investigate 1) whether the factor structure is also supported in chronically ill patients with a psychotic disorder and 2) what the relationship is between these factors and functioning (overall functioning and living situation), depressive symptoms and quality of life. 1157 Patients with a psychotic disorder and a duration of illness of 5 years or more were included in the analysis (data selected from the Pharmacotherapy Monitoring Outcome Survey; PHAMOUS). A confirmatory factor analysis was performed using items of the Positive and Negative Syndrome Scale that were previously identified to reflect negative symptoms (N1-4, N6, G5, G7, G13, G16). Subsequently, regression analysis was performed on outcomes. The results confirmed the distinction between SA (N2, N4, G16) and ED (N1, N3, N6, G5, G7, G13) in chronically ill patients. Both factors were related to worse overall functioning as measured with the Health of the Nation Outcome Scales, ED was uniquely associated with residential living status. Higher scores for SA were associated with more depressive symptoms and worse quality of life. Thus, SA is most strongly related to level of social-emotional functioning, while ED are more related to living situation and thereby are indicative of level of everyday functioning. This subdivision may be useful for research purposes and be a valuable additional tool in clinical practice and treatment development

Who benefits from individual placement and support?:A meta-analysis

Aims Individual placement and support (IPS) is an evidence-based service model to support people with mental disorders in obtaining and sustaining competitive employment. IPS is increasingly offered to a broad variety of service users. In this meta-analysis we analysed the relative effectiveness of IPS for different subgroups of service users both based on the diagnosis and defined by a range of clinical, functional and personal characteristics. Methods We included randomised controlled trials that evaluated IPS for service users diagnosed with any mental disorder. We examined effect sizes for the between-group differences at follow-up for three outcome measures (employment rate, job duration and wages), controlling for methodological confounders (type of control group, follow-up duration and geographic region). Using sensitivity analyses of subgroup differences, we analysed moderating effects of the following diagnostic, clinical, functional and personal characteristics: severe mental illness (SMI), common mental disorders (CMD), schizophrenia spectrum disorders, mood disorders, duration of illness, the severity of symptoms, level of functioning, age, comorbid alcohol and substance use, education level and employment history. Results IPS is effective in improving employment outcomes compared to the control group in all subgroups, regardless of any methodological confounder. However, IPS was relatively more effective for service users with SMIs, schizophrenia spectrum disorders and a low symptom severity. Although IPS was still effective for people with CMD and with major depressive disorder, it was relatively less effective for these subgroups. IPS was equally effective after both a short and a long follow-up period. However, we found small, but clinically not meaningful, differences in effectiveness of IPS between active and passive control groups. Finally, IPS was relatively less effective in European studies compared to non-European studies, which could be explained by a potential benefits trap in high welfare countries. Conclusions IPS is effective for all different subgroups, regardless of diagnostic, clinical, functional and personal characteristics. However, there might be a risk of false-positive subgroup outcomes and results should be handled with caution. Future research should focus on whether, and if so, how the IPS model should be adapted to better meet the vocational needs of people with CMD and higher symptom severity

Fluorescence monitoring of capillary electrophoresis separation of biomolecules with monolithically integrated optical waveguides

Monolithic integration of optical waveguides in a commercial lab-on-a-chip by femtosecond-laser material processing enables arbitrary 3D geometries of optical sensing structures in combination with fluidic microchannels. Integrated fluorescence monitoring of molecular separation, as applicable in point-of-care diagnostic bioassays is demonstrated

Monitoring of DNA molecules in a lab on a chip with femtosecond laser written waveguides

Using femtosecond laser writing, optical waveguides were monolithically integrated into a commercial microfluidic lab-on-a-chip device, with the waveguides intersecting a microfluidic channel. Continuous-wave laser excitation through these optical waveguides confines the excitation window to a width of 12 um, enabling high-resolution monitoring of the passage of different types of fluorescent analytes, when migrating and being separated in the microfluidic channel by microchip capillary electrophoresis. We demonstrate on-chip-integrated waveguide excitation and detection of a biologically relevant species, fluorescently labeled Deoxyribonucleic acid (DNA) molecules, as well as separation of different dyes, Rhodamine-6G and Rhodamine-B during microchip capillary electrophoresis. Well-controlled plug formation as required for on-chip integrated capillary electrophoresis separation of DNA molecules, and the combination of waveguide excitation and a low detection limit will enable monitoring of extremely small quantities with high spatial resolution