Performance of label-free optical biosensors: What is figure of merit (not) telling us?

Here we study the analytical performance of label-free optical biosensors with respect to analyte-induced refractive index changes that can be measured by a biosensor (refractive index resolution). We present an analytical model that interrelates the refractive index resolution and the parameters of the optical platform of a biosensor. We demonstrate that the figure of merit (FOM), which has been widely used to design optical platforms of label-free optical biosensors, is not an appropriate metric to guide the design or predict the performance of label-free optical biosensors. Therefore, we propose an extended definition of FOM that addresses its limitations. We confirm the validity of the proposed approach by both numerical simulations and experiments. Finally, we show that the analytical model of the refractive index resolution not only makes it possible to predict the performance of a biosensor but also provides strategies for achieving optimal performance.

Actuated plasmonic nanohole arrays for sensing and optical spectroscopy applications.

Herein, we report a new approach to rapidly actuate the plasmonic characteristics of thin gold films perforated with nanohole arrays that are coupled with arrays of gold nanoparticles. The near-field interaction between the localized and propagating surface plasmon modes supported by the structure was actively modulated by changing the distance between the nanoholes and nanoparticles and varying the refractive index symmetry of the structure. This approach was applied by using a thin responsive hydrogel cushion, which swelled and collapsed by a temperature stimulus. The detailed experimental study of the changes and interplay of localized and propagating surface plasmons was complemented by numerical simulations. We demonstrate that the interrogation and excitation of the optical resonance to these modes allow the label-free SPR observation of the binding of biomolecules, and is applicable for in situ SERS studies of low molecular weight molecules attached in the gap between the nanoholes and nanoparticles.

Analyte transport to micro- and nano-plasmonic structures.

The study of optical affinity biosensors based on plasmonic nanostructures has received significant attention in recent years. The sensing surfaces of these biosensors have complex architectures, often composed of localized regions of high sensitivity (electromagnetic hot spots) dispersed along a dielectric substrate having little to no sensitivity. Under conditions such that the sensitive regions are selectively functionalized and the remaining regions passivated, the rate of analyte capture (and thus the sensing performance) will have a strong dependence on the nanoplasmonic architecture. Outside of a few recent studies, there has been little discussion on how changes to a nanoplasmonic architecture will affect the rate of analyte transport. We recently proposed an analytical model to predict transport to such complex architectures; however, those results were based on numerical simulation and to date, have only been partially verified. In this study we measure the characteristics of analyte transport across a wide range of plasmonic structures, varying both in the composition of their base plasmonic element (microwires, nanodisks, and nanorods) and the packing density of such elements. We functionalized each structure with nucleic acid-based bioreceptors, where for each structure we used analyte/receptor sequences as to maintain a Damköhler number close to unity. This method allows to extract both kinetic (in the form of association and dissociation constants) and analyte transport parameters (in the form of a mass transfer coefficient) from sensorgrams taken from each substrate. We show that, despite having large differences in optical characteristics, measured rates of analyte transport for all plasmonic structures match very well to predictions using our previously proposed model. These results highlight that, along with optical characteristics, analyte transport plays a large role in the overall sensing performance of a nanoplasmonic biosensor.

Advances in Surface Plasmon Resonance Imaging and Microscopy and Their Biological Applications.

Surface plasmon resonance microscopy and imaging are optical methods that enable observation and quantification of interactions of nano- and microscale objects near a metal surface in a temporally and spatially resolved manner. This review describes the principles of surface plasmon resonance microscopy and imaging and discusses recent advances in these methods, in particular, in optical platforms and functional coatings. In addition, the biological applications of these methods are reviewed. These include the detection of a broad variety of analytes (nucleic acids, proteins, bacteria), the investigation of biological systems (bacteria and cells), and biomolecular interactions (drug-receptor, protein-protein, protein-DNA, protein-cell).

Human parainfluenza virus infection after hematopoietic stem cell transplantation: risk factors, management, mortality, and changes over time.

Human parainfluenza viruses (HPIVs) are uncommon, yet high-risk pathogens after hematopoietic stem cell transplant (HCT). We evaluated 5178 pediatric and adult patients undergoing HCT between 1974 and 2010 to determine the incidence, risk factors, response to treatment, and outcome of HPIV infection as well as any change in frequency or character of HPIV infection over time. HPIV was identified in 173 patients (3.3%); type 3 was most common (66%). HPIV involved upper respiratory tract infection (URTI; 57%), lower respiratory tract infection (LRTI; 9%), and both areas of the respiratory tract (34%), at a median of 62 days after transplantation. In more recent years, HPIV has occurred later after HCT, whereas the proportion with nosocomial infection and mortality decreased. Over the last decade, HPIV was more common in older patients and in those receiving reduced intensity conditioning (RIC). RIC was a significant risk factor for later (beyond day +30). HPIV infections, and this association was strongest in patients with URTI. HCT using a matched unrelated donor (MURD), mismatched related donor (MMRD), age 10 to 19 years, and graft-versus-host disease (GVHD) were all risk factors for HPIV infections. LRTI, early (<30 days), age 10 to 19 years, MMRD, steroid use, and coinfection with other pathogens were risk factors for mortality. The survival of patients with LRTI, especially very early infections, was poor regardless of ribavirin treatment. HPIV incidence remains low, but may have delayed onset associated with RIC regimens and improving survival. Effective prophylaxis and treatment for HPIV are needed.

The impact of peritransplant warfarin use on renal transplant outcome.

BACKGROUND: The unplanned nature of kidney transplantation necessitates that patients undergo surgery without prior cessation of warfarin. Our study analyses the impact of warfarin treatment in the peritransplant period on graft outcome and perioperative transfusion requirements. METHODS: We identified 31 patients undergoing deceased donor kidney transplantation who were concurrently receiving warfarin therapy, between 2000 and 2008. A random, sex-matched, adult, deceased donor control group of 62 patients was generated from the Irish transplant database. RESULTS: The warfarin group were older (mean 47.5 vs. 42.5 years, p=0.067) and had spent longer on dialysis prior to transplantation (mean 3.5 vs. 2.1 years, p=0.004). Graft survival in the warfarin group was not significantly different at 1-, 3- and 5-year follow-ups. There was no statistically significant difference in red blood cell transfusions between the groups (45% vs. 29%, p=0.2). Warfarin patients had a prolonged mean cold ischaemia time (22.3 vs. 18.5 hours, p=0.002). CONCLUSION: This study demonstrates excellent short- and long-term results for kidney transplantation in patients requiring warfarin at the time of transplantation.

Individually determined dosing of filgrastim after autologous peripheral stem cell transplantation in patients with malignant lymphoma--results of a prospective multicentre controlled trial.

OBJECTIVES: To explore the safety and effectiveness of the individually determined application granulocyte-colony stimulating factor (G-CSF) after autologous peripheral blood stem cell transplantation (ASCT). METHODS: The administration of G-CSF from day +5 (arm A) was compared in a randomised, controlled trial with delayed, individually determined administration (G-CSF started when WBC >or= 0.5 x 10(9)/L and ANC >or= 0.1 x 10(9)/L or at day +10; arm B), and with placebo (arm C). RESULTS: One hundred and six patients, median age 45 (range 21-64), all with malignant lymphoma treated with BEAM chemotherapy were analysed. A significant difference in the time to neutrophil engraftment and in the duration of neutropenia <0.5 x 10(9)/L and <1.0 x 10(9)/L was observed between the arms (P = 0.04-<0.0001) with a 1-d prolongation of the median durations in arm B in comparison with arm A but a 2-4-d prolongation in the placebo arm C in comparison with arm B. The median number and range of days to neutrophil engraftment >0.5 x 10(9)/L after graft re-infusion was 10 (9-14) in arm A; 11 (9-19) in arm B; and 14 (10-30) in arm C (P < 0.0001). Engraftment of platelets to >20 x 10(9)/L and >50 x 10(9)/L was significantly delayed in the arms using G-CSF in comparison with placebo (P = 0.04-0.002) without any increase in bleeding or in transfusion requirement. There was no difference in the incidence and duration of transplant-related complications and their treatment between the arms. CONCLUSIONS: Our study has confirmed the safety of individually determined administration of G-CSF. The optimal timing of G-CSF application after ASCT in patients with good-quality grafts is shortly before expected spontaneous engraftment.

The changes of serum leptin and soluble leptin receptor levels in patients undergoing mobilization of peripheral blood stem cells before autologous stem cells transplantation.

BACKGROUND AND OBJECTIVES: Leptin was demonstrated to stimulate the proliferation of hematopoietic stem cells in vitro, but there is scarce information concerning serum leptin levels in patients with hematological diseases. The aim of our study was to measure serum leptin levels in patients undergoing mobilization of peripheral blood stem cells (PBSC) before autologous stem cell transplantation (ASCT). DESIGN AND METHODS: Eighteen patients indicated for ASCT were included in the study. The blood samples were obtained before the initiation of mobilization chemotherapy, at the phase of maximal leukopenia and on the second day of stem cell harvest. Serum leptin levels, soluble leptin receptor, cortisol, insulin, tumor necrosis factor alpha (TNFalpha), and interleukin-1 receptor antagonist (IL-1ra) levels were measured in the withdrawn samples. RESULTS: The basal values of parameters measured except for higher levels of IL-1ra in mobilized group did not differ significantly from those of a control group of healthy subjects. Serum leptin levels decreased significantly at the leukopenia phase and remained suppressed in the stem cell harvest phase (means +/- standard error means (SEM): 12.2 +/- 2.4 vs. 7.7 +/- 1.5 vs. 9.3 +/- 1.9 ng mL(-1)). No significant changes were found in soluble leptin receptor, insulin, cortisol, and TNFalpha levels throughout three measurements, while IL-1ra levels increased significantly in the SC harvest phase compared to the previous two measurements. INTERPRETATION AND CONCLUSIONS: As no metabolic variations explaining suppressed leptin levels were found, this suppression could be the result either of G-CSF administration or increased leptin consumption by activated stem cells.