| 1. |
- Elmlund, Louise, 1981-, et al.
(author)
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A Phage Display Screening Derived Peptide with Affinity for the Adeninyl Moiety
- 2014
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In: Biosensors. - : MDPI. - 2079-6374. ; 4:2, s. 137-149
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Journal article (peer-reviewed)abstract
- Phage display screening of a surface-immobilized adenine derivative led to the identification of a heptameric peptide with selectivity for adenine as demonstrated through quartz crystal microbalance (QCM) studies. The peptide demonstrated a concentration dependent affinity for an adeninyl moiety decorated surface (KD of 968 ± 53.3 μM), which highlights the power of piezoelectric sensing in the study of weak interactions.
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| 2. |
- Elmlund, Louise, et al.
(author)
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Biotin selective polymer nano-films
- 2014
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In: Journal of Nanobiotechnology. - : Springer Science and Business Media LLC. - 1477-3155. ; 12
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Journal article (peer-reviewed)abstract
- Background: The interaction between biotin and avidin is utilized in a wide range of assay and diagnostic systems. A robust material capable of binding biotin should offer scope in the development of reusable assay materials and biosensor recognition elements. Results: Biotin-selective thin (3-5 nm) films have been fabricated on hexadecanethiol self assembled monolayer (SAM) coated Au/quartz resonators. The films were prepared based upon a molecular imprinting strategy where N, N'-methylenebisacrylamide and 2-acrylamido-2-methylpropanesulfonic acid were copolymerized and grafted to the SAM-coated surface in the presence of biotin methyl ester using photoinitiation with physisorbed benzophenone. The biotinyl moiety selectivity of the resonators efficiently differentiated biotinylated peptidic or carbohydrate structures from their native counterparts. Conclusions: Molecularly imprinted ultra thin films can be used for the selective recognition of biotinylated structures in a quartz crystal microbalance sensing platform. These films are stable for periods of at least a month. This strategy should prove of interest for use in other sensing and assay systems.
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| 3. |
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| 4. |
- Elmlund, Louise
(author)
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QCM-based sensing using biological and biomimetic interfaces
- 2014
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Doctoral thesis (other academic/artistic)abstract
- The objective of this thesis was to explore novel approaches for studying molecular recognition at biological and biomimetic surfaces using the quartz crystal microbalance (QCM) biosensor technique. The first two papers focused on the synthesis and study of biotin selective polymer films prepared using the molecularly imprinted polymer (MIP) technique. Control over polymer structure is of importance for sensor reproducibility and sensitivity, and was addressed in Paper I where a simple strategy for fabricating uniform thin biotin imprinted polymer films was employed. In Paper II the binding of biotin moieties to thin (3-5 nm) biomimetic polymer films was examined and consequences for sensor performance discussed. The potential for using QCM as a tool for assessing the binding of small peptides derived from phage display screening was presented Paper III. Here, screening of a phage peptide library against immobilized adenine resulted in candidate peptides that were studied using this technique. In Paper IV a whole cell-based biosensor was developed for studying interactions with cell membrane-incorporated targets. Epithelial cancer cells, SKOV3, were attached to QCM sensor chips and the binding of the monoclonal antibody HerceptinTM was studied. This approach demonstrates the potential of using QCM to study binding to membrane-incorporated targets, an alternative to assays based upon immobilized receptor structures lacking their natural context.
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| 5. |
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| 6. |
- Elmlund, Louise, 1981-, et al.
(author)
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Study of the Interaction of Trastuzumab and SKOV3 Epithelial Cancer Cells Using a Quartz Crystal Microbalance Sensor
- 2015
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In: Sensors. - : MDPI. - 1424-8220. ; 15:3, s. 5884-5894
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Journal article (peer-reviewed)abstract
- Analytical methods founded upon whole cell-based assays are of importance in early stage drug development and in fundamental studies of biomolecular recognition. Here we have studied the binding of the monoclonal antibody trastuzumab to human epidermal growth factor receptor 2 (HER2) on human ovary adenocarcinoma epithelial cancer cells (SKOV3) using quartz crystal microbalance (QCM) technology. An optimized procedure for immobilizing the cells on the chip surface was established with respect to fixation procedure and seeding density. Trastuzumab binding to the cell decorated sensor surface was studied, revealing a mean dissociation constant, K-D, value of 7 +/- 1 nM (standard error of the mean). This study provides a new perspective on the affinity of the antibody-receptor complex presented a more natural context compared to purified receptors. These results demonstrate the potential for using whole cell-based QCM assay in drug development, the screening of HER2 selective antibody-based drug candidates, and for the study of biomolecular recognition. This real time, label free approach for studying interactions with target receptors present in their natural environment afforded sensitive and detailed kinetic information about the binding of the analyte to the target.
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| 7. |
- Fu, Ying, 1964-, et al.
(author)
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Intrinsic blinking characteristics of single colloidal CdSe-CdS/ZnS core-multishell quantum dots
- 2019
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In: Physical Review B. - : AMER PHYSICAL SOC. - 2469-9950 .- 2469-9969. ; 99:3
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Journal article (peer-reviewed)abstract
- Fluorescence blinking of single colloidal semiconductor quantum dots (QDs) has been extensively studied, and several sophisticated models have been proposed. In this work, we derive Heisenberg equations of motion to carefully study principal transition processes, i.e., photoexcitation, energy relaxation, impact ionization and Auger recombination, radiative and nonradiative recombinations, and tunneling between core states and surface states, of the electron-hole pair in single CdSe-CdS/ZnS core-multishell QDs and show that the on-state probability density distribution of the QD fluorescence obeys the random telegraph signal theory because of the random radiative recombination of the photoexcited electron-hole pair in the QD core, while the off-state probability density distribution obeys the inverse power law distribution due to the series of random walks of the photoexcited electron in the two-dimensional surface-state network after the electron tunnels from the QD core to the QD surface. These two different blinking characteristics of the single QD are resolved experimentally by properly adjusting the optical excitation power and the bin time.
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| 8. |
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| 9. |
- Jones, Robert P., et al.
(author)
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Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
- 2019
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In: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048
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Journal article (peer-reviewed)abstract
- Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
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| 10. |
- Karlsson, Mikael, et al.
(author)
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Chemical Sensors Generated on Wafer-Scale Epitaxial Graphene for Application to Front-Line Drug Detection
- 2019
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In: Sensors. - : MDPI. - 1424-8220. ; 19:10
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Journal article (peer-reviewed)abstract
- Generation of large areas of graphene possessing high quality and uniformity will be a critical factor if graphene-based devices/sensors are to be commercialized. In this work, epitaxial graphene on a 2" SiC wafer was used to fabricate sensors for the detection of illicit drugs (amphetamine or cocaine). The main target application is on-site forensic detection where there is a high demand for reliable and cost-efficient tools. The sensors were designed and processed with specially configured metal electrodes on the graphene surface by utilizing a series of anchors where the metal contacts are directly connected on the SiC substrate. This has been shown to improve adhesion of the electrodes and decrease the contact resistance. A microfluidic system was constructed to pump solutions over the defined graphene surface that could then act as a sensor area and react with the target drugs. Several prototypic systems were tested where non-covalent interactions were used to localize the sensing components (antibodies) within the measurement cell. The serendipitous discovery of a wavelength-dependent photoactivity for amphetamine and a range of its chemical analogs, however, limited the general application of these prototypic systems. The experimental results reveal that the drug molecules interact with the graphene in a molecule dependent manner based upon a balance of -stacking interaction of the phenyl ring with graphene (p-doping) and the donation of the amine nitrogens lone pair electrons into the *-system of graphene (n-doping).
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