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- Orban, Jenny, et al.
(författare)
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Surface nanoengineered contact lens as a wearable point-of-care diagnostics platform
- 2014
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Ingår i: 24<sup>th </sup>Anniversary World Congress on Biosensors – Biosensors 2014. - : Elsevier.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Detection of biomarkers is essential for disease prevention, diagnosis, and prognosis of early stage treatment. Ocular fluid is an extracellular fluid excreted from the tear gland. Several important markers from ocular fluid have been identified having significant clinical diagnostic value for various diseases. The contact lens is disposable, relatively cheap and serves as a platform to obtain direct intimate contact with ocular fluid and is therefore an attractive and a promising platform for point-of-care diagnostic tests. Here, we present an innovative concept of a wearable contact lens biosensor with nanoengineered biorecognition architecture based on a Layer-by-Layer (LbL) technique on the contact lens surface. This technique enables us to deposit multiple layers of biomolecules to create biorecognition layer under a mild aqueous physiological temperature and pH conditions. The fabrication of the biorecognition layer is simply through physical adsorption and has no restrictions with respect to the substrate size and topology (i.e. contact lens). The thickness of the resulting biorecognition layer is only hundreds of nanometers, and hence has minimal influence on the overall thickness of the contact lens, thus preserving the optical properties of the contact lens for vision correction. We have demonstrated that eye inflammation biomarkers such as interleukin (IL) can be captured in vitro with the contact lens, thus facilitating colorimetric affinity bioassays to measure the amount of interleukin. An in vitro ocular model composed of hydrogel-based artificial cornea and microfluidics was developed to study the performance of the contact lens biosensing platform. The contact platform was able to detect IL-1α down to the physiological concentration, which is in the range of pg mL-1. There is a recent trend away from handheld devices towards wearable systems, illustrated by popular technology such as “Google glasses” and the “i-Watch”. We believe that the concept of wearable diagnostics holds significant promise as the next generation point-of-care diagnostic platform and that this contact lens-based approach is a convenient platform for a number of important applications.
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- Wilhelm, MT, et al.
(författare)
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Isoform-specific p73 knockout mice reveal a novel role for delta Np73 in the DNA damage response pathway
- 2010
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Ingår i: Genes & development. - : Cold Spring Harbor Laboratory. - 1549-5477 .- 0890-9369. ; 24:6, s. 549-560
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Tidskriftsartikel (refereegranskat)abstract
- Mice with a complete deficiency of p73 have severe neurological and immunological defects due to the absence of all TAp73 and ΔNp73 isoforms. As part of our ongoing program to distinguish the biological functions of these isoforms, we generated mice that are selectively deficient for the ΔNp73 isoform. Mice lacking ΔNp73 (ΔNp73−/− mice) are viable and fertile but display signs of neurodegeneration. Cells from ΔNp73−/− mice are sensitized to DNA-damaging agents and show an increase in p53-dependent apoptosis. When analyzing the DNA damage response (DDR) in ΔNp73−/− cells, we discovered a completely new role for ΔNp73 in inhibiting the molecular signal emanating from a DNA break to the DDR pathway. We found that ΔNp73 localizes directly to the site of DNA damage, can interact with the DNA damage sensor protein 53BP1, and inhibits ATM activation and subsequent p53 phosphorylation. This novel finding may explain why human tumors with high levels of ΔNp73 expression show enhanced resistance to chemotherapy.
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