Experimental Study of Heat Transfer and Pressure Drop Over an Array of Short Micro Pin Fins

Studies on thermal enhancement for electronic chips has been gaining prominence as increased transistor density in the chips calls for larger heat dissipation. Various enhancement techniques have been proposed ever since 1981, to enhance the heat dissipation from the chip surface. Micro pin fins have been gaining recognition as a highly favorable surface enhancement due to the design versatility it provides in the form of myriad geometric shapes and fin arrangements as opposed to convention microchannels. The micro pin fins however, present a larger pressure drop over the surface as compared to other conventional methods which reduces the thermal efficiency of the chip surface. To reduce the pressure drop associated with micro pin fins, short micro pin fins were proposed. A short micro pin fin arrangement is similar to micro pin fin arrays, with one change, in that short micro pin fins have a clearance between the fins and the top of the channel. The current study focusses on heat transfer and pressure drop over short micro pin fin arrays. Experimental studies were conducted over 10 mm × 10 mm with fin heights varying from 200 to 500 µm and clearance over the fins varying from 265 to 900 µm. Distilled water was used as the cooling medium. The heat transfer coefficient and pressure drop characteristics were evaluated at varying fin heights and varying clearance of the surfaces with an aim to identify optimum fin height and clearance parameters. The heat transfer coefficient and pressure drop data obtained from experiments were also evaluated with the correlation proposed by Tullius et al. [17]. Data showed that the highest heat transfer coefficient was observed for fins with the largest fin height. When fin clearance was evaluated for its effect on heat transfer coefficient, a hint of mixing phenomenon leading to enhancement in heat transfer coefficient was observed at higher clearance values. A higher pressure drop was observed at longer fins owing to the increased friction factor at the fin walls. The highest pressure drop of over 100 kPa was observed for a chip gasket combination which consisted of the longest fins with the least amount of clearance. It was also observed that the Nusselt number and Pressure drop correlations proposed by Tullius et al was not able to accurately predict the experimental data. However, the correlation did show the same trend as the experimental data, hence, the present correlation could be modified or used as a basis for new correlations of Nusselt number and friction factor

Utilisation of dielectric spectroscopy to measure live biomass as a PAT tool for continuous manufacturing and other applications

Following FDA\u27s PAT initiative, it is imperative that critical process parameters (CPP) that significantly impact critical quality attributes (CQA\u27s) of a process need to be monitored and controlled strictly. It is also well known that viable biomass is one such CPP, which can impact CQA\u27s in a biopharmaceutical process. In addition, for reasons already established, the present drive is to move towards process intensification and continuous biomanufacturing. The need for controlling biomass at a specific high cell concentration at high viability also spells the need for a technology that allows implementation of automatic cell bleeding strategies. Dielectric spectroscopy, often referred to as capacitance measurement, has been used for monitoring biomass in bioprocesses in real time routinely over the past two decades. Based on the ability of cells to get polarised under the influence of an infinitesimal electric field, it is only sensitive to the presence of live cells. This presentation will not only cover the need and benefit of this technology as well as the detailed theory behind it, but it will also cover the various applications it has been successfully used for. Applications surrounding monitoring biomass in suspension, microcarrier and 3D tissue cultures will be presented. Controlling complex nutrient feed and cell concentration automatically based on capacitance measurement will be discussed in detail. In this section, the strategy of automatic cell bleeding in perfusion cultures will be explained in detail. Other applications involving the use of capacitance measurement for identification and optimisation of feed timing, harvest point detection, scale up success and outlier detection will be looked into. Finally the concept of frequency scanning with dielectric spectroscopy and its application and perceived benefits will be explore

Locomotion Trajectory Generation For Legged Robots

This thesis addresses the problem of generating smooth and efficiently executable locomotion trajectories for legged robots under contact constraints. In addition, we want the trajectories to have the property that small changes in the foot position generate small changes in the joint target path. The first part of this thesis explores methods to select poses for a legged robot that maximises the workspace reachability while maintaining stability and contact constraints. It also explores methods to select configurations based on a reduced-dimensional search of the configuration space. The second part analyses time scaling strategy which tries to minimize the execution time while obeying the velocity and acceleration constraints. These two parts effectively result in smooth feasible trajectories for legged robots. Experiments on the RoboSimian robot demonstrate the effectiveness and scalability of the strategies described for walking and climbing on a rock climbing wall

Bacterial production of poly-γ-glutamic acid and evaluation of its effect on the viability of probiotic microorganisms

A thesis submitted for the degree of Doctor of Philosophy By Aditya Bhat, MScPoly-γ-glutamic acid (γ-PGA) is a naturally occurring biopolymer made up of repeating units of glutamic acid and can be potentially used for multiple applications. This study compared the production of γ-PGA by eight bacteria (B. subtilis 23856, B. subtilis 23857, B. subtilis 23858 B. subtilis 23859, B. subtilis natto, B. licheniformis 1525, B. licheniformis 6816 and B. licheniformis 9945a) in GS and E media. B. subtilis natto and B. licheniformis 9945a have been investigated extensively for γ-PGA production, however, the remaining six have not previously been used. Using the eight bacteria, yields of up to 22.3 g/l were achieved in shake flasks. On characterization, it was observed that γ-PGA with different properties (crystallinity, acid/salt form and molecular weights ranging from 3,000 Da to 871,000 Da) was produced. Production of γ-PGA by B. subtilis natto in GS medium was scaled up using a fermenter and was tested for novel probiotic applications. The survival of probiotics during freeze drying, storage and ingestion was improved by combining them with a γ-PGA matrix. For L. paracasei, 10% γ-PGA protected the cells significantly better (P 0.05) to 10% sucrose. This study also demonstrated the potential use of a non-dairy foodstuff (orange juice) for delivery of probiotics. Two Bifidobacteria strains protected with γ-PGA survived significantly better (P < 0.05) in orange juice for 39 days, with a log reduction in viability of less than 2.99 CFU/ml, when compared to unprotected cells, which showed complete loss in viability by day 20. In addition, γ-PGA protection improved survival of Bifidobacteria in a solution mimicking the environment of the stomach. γ-PGA-protected Bifidobacteria showed little (< 0.47 log CFU/ml) or no loss in viability when stored in simulated gastric juice (pH 2.0) for four hours, whereas unprotected cells died within two hours

Controlling continuous high cell density perfusion culture with the Alternating Tangential Flow system in real time using radio-frequency impendance

Many cGMP cell culture processes are now based on a continuous high cell density perfusion bioreactor system. Control of the feed or addition rates to maintain pseudo-steady-state conditions in these bioreactors can be especially challenging due to high and fluctuating cell concentrations that can rapidly change environmental conditions. With infrequent manual daily sampling based on offline cell counting, the control system can have too little information on which to base an appropriate decision to manipulate the process. Tight control of the perfusion or concentrate addition rate allows the bioreactor to be operated under the optimum conditions for maximum recombinant protein production. The perfusion is typically started on day 2-3 after inoculation when the cells are still in an exponential batch growth phase and before nutrient limitation occurs. A robust automatic perfusion rate control system based on the Alternating Tangential Flow or ATF system (Repligen,USA)) combined with an on-line live biomass monitor probe using Radio Frequency Impedance ( Aber Instruments, UK) is now being used in cell culture manufacturing processes. The system operates in a completely closed loop i.e. no samples need to be taken to obtain process information. In the control algorithm, a cell specific perfusion rate (CSPR) is specified and the signal from the biomass probe is converted into a perfusion flow rate through calculation and implementation with a variable speed controlled pump. For a continuous increase in perfusion, a live biomass probe is interfaced with the harvest pump, such that the perfusion rate is increased as a linear function of the cell density determined by the biomass probe, based on a desired CSPR. In this poster we show three examples of combining the ATF and live biomass probes. In the first example the bioreactor perfusion was controlled at a constant CSPR by the biomass probe to automatically increase the feed rate as cell density increased. The probe accurately estimated the viable cell density throughout the run with cell densities up to 110 million viable cells /mL. In the second example the probe was shown to immediately spot a sudden increase in live cell density caused by too much media being pumped out in error. For the final study, the capacitance was scanned within a wide range of frequency values (100–19,490 kHz). For the measured spectroscopic data, partial least squares regression (PLS), Cole–Cole, and linear modeling were applied and compared in order to predict VCD. The Cole–Cole model and the PLS model provided reliable prediction over the entire cultivation

Utilisation of capacitance measurement (dielectric spectroscopy) to monitor, control and improve viral vector and virus-based vaccine production

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Monitoring live stem cells in suspension and attached to carriers in conventional and single use bioreactors

Embryonic stem cells are promising cell sources for regenerative medicine and organ replacement after disease or injury. Traditional single use bioreactors such as the Sartorius Biostat Rocking Motion bag are being used for growing up these cells at the larger scale and a number of companies are developing fully automated, closed bioreactor systems specifically for growth of stem cells for clinical applications eg Xpand (Holland), Pall(USA). The stem cells in the bioreactors need to be monitored and controlled for both product quality and to satisfyGMPrequirements and one of the most important parameters is the concentration of live cells. On-line monitoring of the live cell concentration can be used to monitor process irregularities, define when suffcient cells are available for the patient or it might be the trigger point for providing additonal feed to the bioreactor. It can also save costs as the information can be used to abort the cell culture or optimize the process. Sampling for cell concentrations should be avoided to eliminate the risk of contamination. Moreover, with stem cell cultures once embroid bodies form it is both difficult to take a representative sample and to get a true cell count using a trypsin pre-treatment. The same problems occur if the cells are grown on micro-carriers. Ideally the cell concentration should be measured in real time using a non-invasive sensor and Radio Frequency Impedance (RFI) spectroscopy is a very promising tool for this application. RFI is already widely used in large scaleGMPsuspension and micro-carrier cell culture and single use probes have been developed by Aber Instruments (Aberystwyth, UK). In this poster, we provide a number of examples of how RFI has been used to monitor and control stem cell cultures in bioreactors up to 1L in volume. The performance of a disposable biomass probe to measure mesenchymal stem cells grown on micro-carriers in a rocking motion bag will also be presented

Live biomass sensors and their integration and application in single use technology

The detection of biomass is one of the most requested parameters in industrial cell cultivation. The knowledge of the biomass progress during a fermentation process gives deeper process knowledge and control and helps to define harvest or infection points. Offline methods like visual cell counting or semi-automated systems still dominate the biomass detection in industrial cell cultivation. But these offline methods based on taking a representative sample cannot monitor the process continuously. The radio frequency impedance (RFI) method for online in-situ detection of viable biomass has already become well established in biopharmaceutical applications using traditional reusable fermenter equipment. On the other hand, industrial cell cultivation tends more and more to single use (SU) fermentation equipment. This paper shows comprehensive results of a standardized online biomass measurement solution for SU fermenter systems which is fully integrated into the standard fermenter control system and tailored to the SU fermentation bags Sartorius BioPAT®ViaMass biomass sensors, integrated in a range of single use rocking motion (RM) and stirred tank reactors (STR) from 20L up 2000L were used for the experiments. These systems use RF impedance based method (Aber Instruments Ltd) to determine the biomass in the single use bioreactors. The capacitance signals of the BioPAT® ViaMass sensors were compared with the viable cell density of the offline Cedex HiRes measurement as a reference. Data will also be presented from a new rocking motion bag (Xapand, Holland) for growing up stem cells. The performance of a disposable biomass probe to measure mesenchymal stem cells grown on microcarriers will also be presented