TY  - JOUR
A1  - Morgner, Frank
A1  - Stufler, Stefan
A1  - Geissler, Daniel
A1  - Medintz, Igor L.
A1  - Algar, W. Russ
A1  - Susumu, Kimihiro
A1  - Stewart, Michael H.
A1  - Blanco-Canosa, Juan B.
A1  - Dawson, Philip E.
A1  - Hildebrandt, Niko
T1  - Terbium to quantum dot FRET Bioconjugates for clinical diagnostics  influence of human plasma on optical and assembly properties
JF  - Sensors
N2  - Forster resonance energy transfer (FRET) from luminescent terbium complexes (LTC) as donors to semiconductor quantum dots (QDs) as acceptors allows extraordinary large FRET efficiencies due to the long Forster distances afforded. Moreover, time-gated detection permits an efficient suppression of autofluorescent background leading to sub-picomolar detection limits even within multiplexed detection formats. These characteristics make FRET-systems with LTC and QDs excellent candidates for clinical diagnostics. So far, such proofs of principle for highly sensitive multiplexed biosensing have only been performed under optimized buffer conditions and interactions between real-life clinical media such as human serum or plasma and LTC-QD-FRET-systems have not yet been taken into account. Here we present an extensive spectroscopic analysis of absorption, excitation and emission spectra along with the luminescence decay times of both the single components as well as the assembled FRET-systems in TRIS-buffer, TRIS-buffer with 2% bovine serum albumin, and fresh human plasma. Moreover, we evaluated homogeneous LTC-QD FRET assays in QD conjugates assembled with either the well-known, specific biotin-streptavidin biological interaction or, alternatively, the metal-affinity coordination of histidine to zinc. In the case of conjugates assembled with biotin-streptavidin no significant interference with the optical and binding properties occurs whereas the histidine-zinc system appears to be affected by human plasma.
KW  - FRET
KW  - quantum dots
KW  - terbium
KW  - luminescence lifetime
KW  - blood
KW  - plasma
KW  - clinical diagnostics
KW  - biotin
KW  - streptavidin
KW  - histidin
KW  - immunoassay
Y1  - 2011
U6  - https://doi.org/10.3390/s111009667
SN  - 1424-8220
VL  - 11
IS  - 10
SP  - 9667
EP  - 9684
PB  - MDPI
CY  - Basel
ER  - 
TY  - JOUR
A1  - Stoessel, Daniel
A1  - Schulte, Claudia
A1  - dos Santos, Marcia C. Teixeira
A1  - Scheller, Dieter
A1  - Rebollo-Mesa, Irene
A1  - Deuschle, Christian
A1  - Walther, Dirk
A1  - Schauer, Nicolas
A1  - Berg, Daniela
A1  - da Costa, Andre Nogueira
A1  - Maetzler, Walter
T1  - Promising Metabolite Profiles in the Plasma and CSF of Early Clinical
JF  - Frontiers in Aging Neuroscience
N2  - Parkinson's disease (PD) shows high heterogeneity with regard to the underlying molecular pathogenesis involving multiple pathways and mechanisms. Diagnosis is still challenging and rests entirely on clinical features. Thus, there is an urgent need for robust diagnostic biofluid markers. Untargeted metabolomics allows establishing low-molecular compound biomarkers in a wide range of complex diseases by the measurement of various molecular classes in biofluids such as blood plasma, serum, and cerebrospinal fluid (CSF). Here, we applied untargeted high-resolution mass spectrometry to determine plasma and CSF metabolite profiles. We semiquantitatively determined small-molecule levels (<= 1.5 kDa) in the plasma and CSF from early PD patients (disease duration 0-4 years; n = 80 and 40, respectively), and sex-and age-matched controls (n = 76 and 38, respectively). We performed statistical analyses utilizing partial least square and random forest analysis with a 70/30 training and testing split approach, leading to the identification of 20 promising plasma and 14 CSF metabolites. The semetabolites differentiated the test set with an AUC of 0.8 (plasma) and 0.9 (CSF). Characteristics of the metabolites indicate perturbations in the glycerophospholipid, sphingolipid, and amino acid metabolism in PD, which underscores the high power of metabolomic approaches. Further studies will enable to develop a potential metabolite-based biomarker panel specific for PD
KW  - biomarker
KW  - untargeted metabolomics
KW  - neurodegeneration
KW  - plasma
KW  - CSF
KW  - machinelearning
Y1  - 2018
U6  - https://doi.org/10.3389/fnagi.2018.00051
SN  - 1663-4365
VL  - 10
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  -