Sensor fusion with on-line gas emission multisensor arrays and standard process measuring devices in baker's yeast manufacturing process

The use of a multisensor array for measuring the emission from a production-scale baker's yeast manufacturing process is reported. The sensor array, containing 14 different gas-sensitive semiconductor devices and an infrared gas sensor, was used to monitor the gas emission from a yeast culture bioreactor during fed-batch operation. The signal pattern from the sensors was evaluated in relation to two key process variables, the cell mass and the ethanol concentrations. Fusion with the on-line sensor signals for reactor weight and aeration rate made it possible to estimate cell mass and ethanol concentration using computation with backpropagating artificial neural nets. Identification of process states with the same fusion of sensor signals was realized using principal component analysis. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 427-438, 1997.     

Spatial resolution in plantar pressure measurement revisited

Plantar pressures are typically measured using sensors of finite area, so the accuracy with which one can measure true maximum pressure is dependent on sensor size. Measurement accuracy has been modeled previously for one patient's metatarsals (Lord, 1997), but has not been modeled either for general subjects or for other parts of the foot. The purposes of this study were (i) to determine whether Lord's (1997) model is also valid for heel and hallux pressures, and (ii) to examine how sensor size relates to measurement accuracy in the context of four factors common to many measurement settings: pressure pulse size, foot positioning, pressure change quantification, and gross pressure redistribution. Lord's (1997) model was first generalized and was then validated using 10 healthy walking subjects, with relatively low RMSE values on the order of 20 kPa. Next, postural data were used to show that gross pressure redistributions can be accurately quantified (p<0.002), even with rather gross sensor sizes of 30 mm. Finally, numerical analyses revealed that the relation between sensor size and measurement accuracy is highly complex, with deep dependency on the measurement context. In particular, the critical sensor widths required to achieve 90% accuracy ranged from 1.7 mm to 17.4 mm amongst the presently investigated scenarios. Since measurement accuracy varies so extensively with so many factors, the current results cannot yield specific recommendations regarding spatial resolution. It is concluded simply that no particular spatial resolution can yield a constant measurement accuracy across common plantar pressure measurement tasks.     

Glucose sensor with improved haemocompatibilty

A new biocompatible copolymer has been synthesised and used in an electrochemical enzyme-based glucose sensor. The copolymer incorporates three segments including a monomer with an electrically neutral phosphorylcholine head group that is able to reject protein adsorption and two segments that increase the affinity to polyurethane substrate. Peel and solution circulation tests showed that this material has high attachment to polyurethane. With the new copolymer as the outermost layer and the polyurethane as the diffusion-limiting membrane, the sensor showed extended linearity up to 50 mM glucose and stable output in bovine serum for 70 h. During in vivo tests, the sensor exhibited a steady current signal and a rapid transient response when the glucose concentration was raised. These results imply that the haemocompatibility of the glucose sensor coated with the new copolymer has been improved, which is crucial for a sensor used for clinical real-time monitoring. The material may also be suitable for application to other implantable devices.     

On-line monitoring and control of methanol concentration in shake-flask cultures of Pichia pastoris

The methylotrophic yeast Pichia pastoris can be used to express recombinant genes at high levels under the control of the methanol-inducible alcohol oxidase 1 (AOX1) promoter. Accurate regulation of the methanol concentration in P. pastoris cultures is necessary to maintain induction, while preventing accumulation of methanol to cytotoxic levels. We developed an inexpensive methanol sensor that uses a gas-permeable silicone rubber tube immersed in the culture medium and an organic solvent vapor detector. The sensor was used to monitor methanol concentration continuously throughout a fed-batch shake-flask culture of a P. pastoris clone producing the N-lobe of human transferrin. The sensor calibration was stable for the duration of the culture and the output signal accurately reflected the methanol concentration determined off-line by HPLC. A closed-loop control system utilizing this sensor was developed and used to maintain a 0.3% (v/v) methanol concentration in the culture. Use of this system resulted in a fivefold increase in volumetric protein productivity over levels obtained using the conventional fed-batch protocol. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 56: 279-286, 1997.     

On-line green fluorescent protein sensor with LED excitation

We present an intensity based sensor designed for on-line monitoring of green fluorescent protein, a revolutionary marker of protein expression. The device consisted of a blue light emitting diode as the excitation source. A band pass excitation filter cut off light longer than 490 nm. The light was directed into a bifurcated optical fiber bundle with the common end inserted into a stainless steel housing equipped with a quartz window. The fiber bundle and stainless steel housing are steam sterilizable. The emission radiation was collected through a long wave pass filter to reject the excitation light shorter than 505 nm and was detected by a photomultiplier tube. The signal was amplified and sent to a computer for recording time course data. The sensor was tested in an Escherichia coli fermentation of JM105 transformed with pBAD-GFP. The on-line signal was compared to off-line fluorescence spectrophotometer measurements. The on-line profile closely followed the off-line. Western blot data showed that with a time shift, the sensor was able to both continuously and quantitatively monitor expression of green fluorescent protein on-line in real time. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55:921-926, 1997.     

An automated system for biocide testing on biofilms*

The paper presents and discusses a novel on-line real-time non-destructive continuous-flow system for biocide testing on industrial biofilms. This laboratory system is capable of monitoring changes in growth, accumulation and respiratory activity of biofilms in response to biocidal treatment. The system incorporates a fouling monitor for continuous measuring of the rate of biofilm accumulation (heat transfer resistance), a sensor for monitoring of microbial activity (oxygen meter for monitoring the rate of biofilm respiratory activity), and subsystems necessary for microbial life support and control of operation parameters. Examples of system operation and testing of oxidizing and non-oxidizing biocides are presented. Received 25 May 1997/ Accepted in revised form 25 November 1997     

Molecular epidemiology of Bordetella pertussis in Taiwan, 1993-2004: suggests one possible explanation for the outbreak of pertussis in 1997

Pertussis reemerges periodically despite high pertussis vaccination coverage in many countries. We used prn and fim3 gene sequences and pulsed-field gel electrophoresis (PFGE) to analyze the molecular epidemiology of 168 clinical isolates of Bordetella pertussis during 1993-2004, and deduced possible reasons for an outbreak in 1997 in Taiwan. In Taiwan, during 1996-1997, a shift of prn1 to prn2 was reflected in a transition of PFGE group I to group IIIa; during 2000-2001, the change from fim3A to fim3B was displayed in transition of PFGE group IIIa to group IIIb. These changes were also consistent with the two peaks of pertussis incidence in 1997 and 2000. In 1997, a larger than expected increase in the incidence of pertussis occurred and isolates were characterized by complicated pulsotypes, appearance of many new profiles and an unusual presence of prn3. Based on a high resemblance of PFGE profiles and the same virulence genes, a similar shift of circulating strains was observed in European countries as well as Taiwan; thus, the high incidence of pertussis in 1997 may be due to an international expansion of B. pertussis strains from a similar source. This study provides further elucidation of the global molecular epidemiology of B. pertussis.     

Neural network mosaic model for pupillary responses to spatial stimuli

A neural network mosaic model was developed to investigate the spatial-temporal properties of the human pupillary control system. It was based on the double-layer neural network model developed by Cannon and Robinson and the pupillary dual-path model developed by Sun and Stark. The neural network portion of the model received its input from a sensor array and consisted of a retina-like two-dimensional neuronal layer. The dual-path portion of the model was composed of interconnections of the neurons that formed a mosaic of AC transient and DC sustained paths. The spatial aggregates of the AC and DC signals were input to the AC and DC summing neurons, respectively. Finally, the weighted sum of the aggregate AC and DC signals provided the output for driving the pupillary response. An important property of the model was that it could adaptively learn from training samples by adjustment of the weights. The neural network mosaic model showed excellent performance in simulating both the traditional pupillary phenomena and the new spatial stimulation findings such as responses to change in stimulus pattern and shift of light spot. Moreover, the model could also be used for the diagnosis of clinical deficits and image processing in machine vision. Received: 12 December 1997 / Accepted in revised form: 22 April 1998     

高灵敏度湿度传感器在植物水分生理测定中的应用

本研究评估了新型湿度传感器在植物生理生态学研究中的适用性,对传感器的性能参数、配套设备、标定和使用方法进行了分析,并以野外自然生长的植物--托里阿魏(Ferula krylovii)为例,给出了实际应用的解决方案。实验表明,新型湿度传感器具有灵敏度高,反应速度快、线性关系好、长时间的高稳定性、温度依赖性低、费用低、可连续记录等优点,能够为科研人员和不易接触到昂贵的光合仪的学生从事实验或研究探索提供光合仪以外的另一种测定湿度和蒸腾速率的选择。     

中国胯舟蛾属分类研究 （鳞翅目：舟蛾科）

系统整理了中国胯舟蛾属（Syntypistis Turner）的全部种类共20种,包括1新种黑胯舟蛾Syntypistis melana Wu et Fang,sp. Nov. 和2中国新记录种：篱胯舟蛾 Syntypistis hercules (Schintlmeister) comb. Nov.与防胯舟蛾 Syntypistis defector (Schintlmeister) comb. Nov.,后2种均为新组合。文中提供了分种检索表,新种形态描述和外生殖器特征图。模式标本保存在中国科学院动物研究所动物标本馆。     

Fluorescence protection assay: a novel homogeneous assay platform toward development of aptamer sensors for protein detection

Development of novel aptamer sensor strategies for rapid and selective assays of protein biomarkers plays crucial roles in proteomics and clinical diagnostics. Herein, we have developed a novel aptamer sensor strategy for homogeneous detection of protein targets based on fluorescence protection assay. This strategy is based on our reasoning that interaction of aptamer with its protein target may dramatically increase steric hindrance, which protects the fluorophore, fluorescein isothiocyannate (FITC), labeled at the binding pocket from accessing and quenching by the FITC antibody. The aptamer sensor strategy is demonstrated using a model protein target of immunoglobulin E (IgE), a known biomarker associated with atopic allergic diseases. The results reveal that the aptamer sensor shows substantial (>6-fold) fluorescence enhancement in response to the protein target, thereby verifying the mechanism of fluorescence protection. Moreover, the aptamer sensor displays improved specificity to other co-existing proteins and a desirable dynamic range within the IgE concentration from 0.1 to 50 nM with a readily achieved detection limit of 0.1 nM. Because of great robustness, easy operation and scalability for parallel assays, the developed homogeneous fluorescence protection assay strategy might create a new methodology for developing aptamer sensors in sensitive, selective detection of proteins.     

The commercialisation of sensor technology in clinical chemistry: an outline of the potential difficulties

Despite the numerous examples in the research literature of the potential application of biosensors in clinical chemistry, very few have reached commercialisation. Many pitfalls await the potential manufacturer of bioprobes in clinical chemistry and key areas which require substantial development are: 1. reproducibility of sensor manufacture; 2. interaction of the sensor with appropriate hardware; 3. evaluation and customer perception. This paper discusses and illustrates these problems with examples taken from the recent introduction of ion-selective electrode analysers in regular clinical use. Many similar problems are envisaged for the commercialisation of biosensors and extensive collaboration is essential between researchers, manufacturers and users to overcome the difficulties.     

Combination of fluorescence microscopy and nanomotion detection to characterize bacteria

Antibiotic‐resistant pathogens are a major health concern in everyday clinical practice. Because their detection by conventional microbial techniques requires minimally 24 h, some of us have recently introduced a nanomechanical sensor, which can reveal motion at the nanoscale. By monitoring the fluctuations of the sensor, this technique can evidence the presence of bacteria and their susceptibility to antibiotics in less than 1 h. Their amplitude correlates to the metabolism of the bacteria and is a powerful tool to characterize these microorganisms at low densities. This technique is new and calls for an effort to optimize its protocol and determine its limits. Indeed, many questions remain unanswered, such as the detection limits or the correlation between the bacterial distribution on the sensor and the detection's output. In this work, we couple fluorescence microscopy to the nanomotion investigation to determine the optimal experimental protocols and to highlight the effect of the different bacterial distributions on the sensor. Copyright © 2013 John Wiley & Sons, Ltd.     

Containment sensors for the determination of L-lactate and glucose

This paper reports some new results on enzyme based silicon containment sensors. For the first time an L-lactate sensor in containment technology is presented. Through optimization of the buffer system the stability of the lactate sensor was enhanced and the linear response of over 10 mM was achieved. The glucose sensor has also been optimized for a large linear measurement range exceeding 30 mM. A two-enzyme chip with glucose and lactate sensor elements which were integrated on one silicon chip is presented. The response behaviour of the two-enzyme chip was very similar to the single chip behaviour. No cross-talking effects could be observed. A fabrication process for mass-production is described.     

SLE – Hematopoietic stem cell transplantation for systemic lupus erythematosus

Hematopoietic stem cell transplantation was first reported for patients with systemic lupus erythematosus in 1997. The procedure has since been performed worldwide including in Europe, in Brazil, and in China. A National Institutes of Health-funded phase III clinical trial of hematopoietic stem cell transplantation for refractory systemic lupus erythematosus is anticipated to begin in 2003. Encouraging responses are raising new hope about the role of adult hematopoietic stem cells in systemic lupus erythematosus.     

Chemoselective biosensors

New opportunities for biosensors are now appearing in clinical and genetic diagnostics, genomics, environmental protection, food processing and safety, drug discovery and bioprocess monitoring. Concerns about the cost, stability and selectivity of previous sensor technologies are being addressed by developing new recognition systems and their integration into transducers, micro- and nanofabricated devices, array technologies and novel magnetic, acoustic and optical transduction systems.     

Correlation between genetic and cytogenetic maps of the rat

To correlate rat genetic linkage maps with cytogenetic maps, we localized 25 new cosmid-derived simple sequence length polymorphism (SSLP) markers and 14 existing genetic markers on cytogenetic bands of chromosomes, using fluorescence in situ hybridization (FISH). Next, a total of 58 anchor loci, consisting of the 39 new and 19 previously reported ones, were integrated into the genetic linkage maps. Since most of the new anchor loci were developed to be localized near the terminals of the genetic or cytogenetic maps for each chromosome, the orientation and coverage of the whole genetic linkage maps were determined or confirmed with respect to the cytogenetic maps. Thus, we provide here a new base for rat genetic maps. Received: 9 September 1997 / Accepted: 11 November 1997     

SLE - hematopoietic stem cell transplantation for systemic lupus erythematosus

Hematopoietic stem cell transplantation was first reported for patients with systemic lupus erythematosus in 1997. The procedure has since been performed worldwide including in Europe, in Brazil, and in China. A National Institutes of Health-funded phase III clinical trial of hematopoietic stem cell transplantation for refractory systemic lupus erythematosus is anticipated to begin in 2003. Encouraging responses are raising new hope about the role of adult hematopoietic stem cells in systemic lupus erythematosus.     

Novel micromachined silicon sensor for continuous glucose monitoring

The construction and the application properties of a micro-machined silicon sensor for continuous glucose monitoring are presented. The sensor uses the conventional enzymatic conversion of glucose with amperometric detection of H(2)O(2). The innovation is the precise diffusion control of the analyte through a porous silicon membrane into a silicon etched cavity containing the immobilised enzyme. A variation of the number and size of the membrane pores allows to adjust the linear range of the sensor to the respective requirement. The sensor was tested in vitro as well as in clinical studies, being supplied with interstitial fluid. The cavity sensor was designed for a linear range between 0.5 and 20 mM. A signal response time of below 30 s and a signal stability exceeding 1 week is shown. By using a double cavity sensor falsification of the glucose signal by interfering substances can be compensated. In clinical trials the sensor measured continuously in interstitial fluid for up to 18 h without any signal drift and with good correlation to blood glucose reference values.     

Estimation of the Transition/Transversion Ratio

A simple method for estimating the transition/transversion ratio was developed. This method can be applied to not only two sequences but also more than two sequences. The statistical properties of the method and some other methods were examined by numerical computation and computer simulation. The results obtained showed that, in terms of bias and variance, the new method gives a better estimate of the transition/transversion ratio than do the other examined methods. The new method was applied to human and chimpanzee mitochondrial control region sequences. Received: 22 September 1997 / Accepted: 1 November 1997