Design of Surface Modifications for Nanoscale Sensor Applications

Nanoscale biosensors provide the possibility to miniaturize optic, acoustic and electric sensors to the dimensions of biomolecules. This enables approaching single-molecule detection and new sensing modalities that probe molecular conformation. Nanoscale sensors are predominantly surface-based and label-free to exploit inherent advantages of physical phenomena allowing high sensitivity without distortive labeling. There are three main criteria to be optimized in the design of surface-based and label-free biosensors: (i) the biomolecules of interest must bind with high affinity and selectively to the sensitive area; (ii) the biomolecules must be efficiently transported from the bulk solution to the sensor; and (iii) the transducer concept must be sufficiently sensitive to detect low coverage of captured biomolecules within reasonable time scales. The majority of literature on nanoscale biosensors deals with the third criterion while implicitly assuming that solutions developed for macroscale biosensors to the first two, equally important, criteria are applicable also to nanoscale sensors. We focus on providing an introduction to and perspectives on the advanced concepts for surface functionalization of biosensors with nanosized sensor elements that have been developed over the past decades (criterion (iii)). We review in detail how patterning of molecular films designed to control interactions of biomolecules with nanoscale biosensor surfaces creates new possibilities as well as new challenges

Comprehensive characterization of molecular interactions based on nanomechanics

Molecular interaction is a key concept in our understanding of the biological mechanisms of life. Two physical properties change when one molecular partner binds to another. Firstly, the masses combine and secondly, the structure of at least one binding partner is altered, mechanically transducing the binding into subsequent biological reactions. Here we present a nanomechanical micro-array technique for bio-medical research, which not only monitors the binding of effector molecules to their target but also the subsequent effect on a biological system in vitro. This label-free and real-time method directly and simultaneously tracks mass and nanomechanical changes at the sensor interface using micro-cantilever technology. To prove the concept we measured lipid vesicle (approximately 748*10(6) Da) adsorption on the sensor interface followed by subsequent binding of the bee venom peptide melittin (2840 Da) to the vesicles. The results show the high dynamic range of the instrument and that measuring the mass and structural changes simultaneously allow a comprehensive discussion of molecular interactions

Switching Transport through Nanopores with pH-Responsive Polymer Brushes for Controlled Ion Permeability

Several nanoporous platforms were functionalized with pH-responsive poly(methacrylic acid) (PMAA) brushes using surface-initiated atom transfer radical polymerization (SI-ATRP). The growth of the PMAA brush and its pH-responsive behavior from the nanoporous platforms were confirmed by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and atomic force microscopy (AFM). The swelling behavior of the pH-responsive PMAA brushes grafted only from the nanopore walls was investigated by AFM in aqueous liquid environment with pH values of 4 and 8. AFM images displayed open nanopores at pH 4 and closed ones at pH 8, which rationalizes their use as gating platforms. Ion conductivity across the nanopores was investigated with current–voltage measurements at various pH values. Enhanced higher resistance across the nanopores was observed in a neutral polymer brush state (lower pH values) and lower resistance when the brush was charged (higher pH values). By adding a fluorescent dye in an environment of pH 4 or pH 8 at one side of the PMAA-brush functionalized nanopore array chips, diffusion across the nanopores was followed. These experiments displayed faster diffusion rates of the fluorescent molecules at pH 4 (PMAA neutral state, open pores) and slower diffusion at pH 8 (PMAA charged state, closed pores) showing the potential of this technology toward nanoscale valve applications

A multi-center study on the attitudes of Malaysian emergency health care staff towards allowing family presence during resuscitation of adult patients

BACKGROUND The practice of allowing family members to witness on-going active resuscitation has been gaining ground in many developed countries since it was first introduced in the early 1990s. In many Asian countries, the acceptability of this practice has not been well studied. AIM We conducted a multi-center questionnaire study to determine the attitudes of health care professionals in Malaysia towards family presence to witness ongoing medical procedures during resuscitation. METHODS Using a bilingual questionnaire (in Malay and English language), we asked our respondents about their attitudes towards allowing family presence (FP) as well as their actual experience of requests from families to be allowed to witness resuscitations. Multiple logistic regression was used to analyze the association between the many variables and a positive attitude towards FP. RESULTS Out of 300 health care professionals who received forms, 270 responded (a 90% response rate). Generally only 15.8% of our respondents agreed to allow relatives to witness resuscitations, although more than twice the number (38.5%) agreed that relatives do have a right to be around during resuscitation. Health care providers are significantly more likely to allow FP if the procedures are perceived as likely to be successful (e.g., intravenous cannulation and blood taking as compared to chest tube insertion). Doctors were more than twice as likely as paramedics to agree to FP (p-value = 0.002). This is probably due to the Malaysian work culture in our health care systems in which paramedics usually adopt a 'follow-the-leader' attitude in their daily practice. CONCLUSION The concept of allowing FP is not well accepted among our Malaysian health care providers

Enzymatic biosensors towards a multiplexed electronic detection system for early cancer diagnostics

Enzymatic biosensors are expected to play a key-role in bio techno logical and biochemical analysis as shown by the success of glucose sensors in diabetes treatment. The aim of this work is to develop a multiplexed electronic detection system for early cancer diagnostics. Therefore, various enzymes were adsorbed to differently modified surfaces. Electrochemical optical waveguide lightmode spectroscopy (EC-OWLS) and electrochemical quartz crystal microbalance with dissipation (EC-QCM-D) were used to measure the mass and the activity of the adsorbed enzymes. The enzymes were specifically immobilized on a protein resistant PLL-g-PEG surface in order to reduce the loss of activity due to denaturation. In addition, enzymes were also incorporated into DNA-tagged vesicles to increase the signal and therefore the sensor sensitivity. The enzymatic activity of the different systems was compared. To further increase the sensitivity, ferrocyanide was used as an electron mediator

Ultra-dense and long-lasting shells for inorganic nanoparticles are based on cyclic polymer brushes

The application of functional, inorganic nanoparticles (NPs) within physiological environments is in the first place determined by the capability of their organic shells to protect them from any unspecific physico-chemical interaction with the surrounding medium. The most common strategy to meet this prerequisite relies on the entropic and enthalpic stabilization of NPs mediated by hydrophilic and neutral end-tethered polymers forming dense \u201cbrush\u201d shells around their inorganic cores. Concentrating on the applicability of polymer stabilizers for NPs beyond chain linearity, we demonstrate that cyclic poly-2-ethyl-2-oxazoline (PEOXA) ligands, applied on superparamagnetic Fe3O4 NPs provide enhanced colloidal stability and bioinertness in physiological media. When linear PEOXA brush shells fail in providing colloidal stabilization to NPs, the cyclic ones assure long lasting dispersions. While the thermal-induced de-hydration of linear PEOXA shells cause irreversible aggregation of the NPs due to the insufficient screening of their inorganic cores, the collapse and subsequent re-hydration of similarly grafted cyclic brushes, allow the full recovery of individually dispersed NPs. Although linear PEOXA ligands are densely grafted on Fe3O4 cores, a small plasma protein like bovine serum albumin (BSA) still physisorbs within their shells. In contrast, the impenetrable entropic shield provided by cyclic brushes efficiently prevents nonspecific interaction with proteins. All the unique properties of cyclic polymer brush shells suggest the next-generation design for the development of bioimaging and drug-delivery systems based on inorganic NPs