Localized Sampling Enables Monitoring of Cell State via Inline Electrospray Ionization Mass Spectrometry

Nascent advanced therapies, including regenerative medicine and cell and gene therapies, rely on the production of cells in bioreactors that are highly heterogeneous in both space and time. Unfortunately, advanced therapies have failed to reach a wide patient population due to unreliable manufacturing processes that result in batch variability and cost prohibitive production. This can be attributed largely to a void in existing process analytical technologies (PATs) capable of characterizing the secreted critical quality attribute (CQA) biomolecules that correlate with the final product quality. The Dynamic Sampling Platform (DSP) is a PAT for cell bioreactor monitoring that can be coupled to a suite of sensor techniques to provide real-time feedback on spatial and temporal CQA content in situ. In this study, DSP is coupled with electrospray ionization mass spectrometry and direct-from-culture sampling to obtain measures of CQA content in bulk media and the cell microenvironment throughout the entire cell culture process (≈3 weeks). Post hoc analysis of this real-time data reveals that sampling from the microenvironment enables cell state monitoring (e.g., confluence, differentiation). These results demonstrate that an effective PAT should incorporate both spatial and temporal resolution to serve as an effective input for feedback control in biomanufacturing.     

The influence of air-suspended particulate concentration on the incidence of suicide attempts and exacerbation of schizophrenia

The main objective of this study was to evaluate the role of the concentration of solid air-suspended particles (SSP) in the incidence of mental disorders. The study is based on 1,871 cases, registered in the Beer-Sheva Mental Health Center (BS-MHC) at Ben-Gurion University (Israel) during a 16-month period from 2001 to 2002; 1,445 persons were hospitalized due to exacerbation of schizophrenia (ICD-10: F20–F29) and 426 after committing a suicide attempt using a variety of means as coded in the ICD-10 (ICD-10: X60-X84). Pearson and Spearman test correlations were used; the statistical significance was tested at p?<?0.1. A significant correlation between variations of SSP number concentration (N _C ) during eastern desert wind during early morning hours and number of suicide attempts, N _SU , was found (ρ?>?0.3, p?<?0.05), whereas correlation between N _C and N _SU during western air streams (sea breeze) was not observed (p?>?0.2). A trend towards positive correlation (ρ?>?0.2, p?<?0.1) between the N _C and number of persons with exacerbation of schizophrenia as manifested in psychotic attack (N _PS ) in periods with dominant eastern winds (4–9 am, local time) has been observed, while in the afternoon and evening hours (1–8 pm local time) with dominant western winds, N _C and N _PS are not correlated (p?>?0.1). Obviously, concentration of SSP is not the one and only parameter of air pollution state determining meteorological–biological impact, involving incidence of mental disorders, although its role can scarcely be overstated. However, since it is one of the simplest measured parameters, it could be widely used and helpful in the daily struggle for human life comfort in semi-arid areas as well as urban and industrial surroundings, where air pollution reaches crucial values. This study may permit determination of the limits for different external factors, which do not overcome threshold values (without provoking avalanche situations), to single out the group of people at increased risk (with according degree of statistic probability), whose reactions to the weather violations can involve the outbreak of frustration points and prevent or alleviate detrimental mental effects.     

Prospects of a Computational Origin of Life Endeavor

While the last century brought an exquisite understanding of the molecular basis of life, very little is known about the detailed chemical mechanisms that afforded the emergence of life on early earth. There is a broad agreement that the problem lies in the realm of chemistry, and likely resides in the formation and mutual interactions of carbon-based molecules in aqueous medium. Yet, present-day experimental approaches can only capture the synthesis and behavior of a few molecule types at a time. On the other hand, experimental simulations of prebiotic syntheses, as well as chemical analyses of carbonaceous meteorites, suggest that the early prebiotic hydrosphere contained many thousands of different compounds. The present paper explores the idea that given the limitations of test-tube approaches with regards to such a 'random chemistry' scenario, an alternative mode of analysis should be pursued. It is argued that as computational tools for the reconstruction of molecular interactions improve rapidly, it may soon become possible to perform adequate computer-based simulations of prebiotic evolution. We thus propose to launch a computational origin of life endeavor (http://ool.weizmann.ac.il/CORE), involving computer simulations of realistic complex prebiotic chemical networks. In the present paper we provide specific examples, based on a novel algorithmic approach, which constitutes a hybrid of molecular dynamics and stochastic chemistry. As one potential solution for the immense hardware requirements dictated by this approach, we have begun to implement an idle CPU harvesting scheme, under the title ool@home.