With Lab-on-Chip devices being a fast growing industry due to the rising prevalence of chronic diseases and the increasing demand for point-of-care testing, further facilitated by the advent of the global pandemic, there is a constant need to improve the devices by integrating different functionalities into the Lab-on-Chip cartridge, like flow metering, that compliment the device performance. In this thesis, I have presented my work on the design, implementation and characterization of a thermal flow meter based on calorimetric principle, for microfluidic applications, carried out at the Bio lab of STMicroelectronics. The idea was to come up with a generic, adaptable model of a functional liquid flow meter cartridge, which could later be modified and incorporated into the disposable Lab-on-Chip cartridges of the Point-of-Care diagnostic devices under development at STMicroelectronics. As the first step, I developed a flow meter cartridge model to be used as a prototype to carry out the study. With the working of the flow meter based on the principle of heat transfer, a flow meter cartridge with PT100 Resistance Temperature Detectors placed across the microfluidic channel, functioning as the heat sensing elements, was implemented to understand the effect of the transferred heat on the Sensing Resistors by measuring their resistances in a 4-wire configuration, when periodic current pulses were passed through a central heating element with just air in the channel. I observed peaks in both the Sensing Resistances corresponding to the current pulses, which demonstrated how a heat transfer across the channel reflected in the Sensing Resistors. I then fabricated a functional cartridge prototype with thin gold strips across the channel forming stable Sensing and Heating elements. This was achieved by gold coating using a sputtering machine followed by laser engraving to cut out the resistances in the desired form and position. The experiments conducted on this cartridge demonstrated how the flow rate of water pumped through the channel were reflected in the amplitudes of the resistance peaks of the Sensing Resistor in the path of the flow, which gave information on both the magnitude and direction of the water flow. The read-out mechanism was also modified at each stage to achieve improvement in performance. During the last part of my work, in order to translate the information obtained from the Sensing Resistances mathematically to estimate the actual flow rate, employing a Sensirion liquid flow meter as the gold standard, I worked on two different algorithms. One was based on the computation of the difference between the variances of the two Sensing Resistances and the subsequent comparison of the inverse of the values thus obtained, scaled by a correction factor, with the measured flow rate. This method was found to provide reasonable estimates of the flow rate in the range of 200 to 2000 microlitre/min. The second method was based on the calculation of the difference between the two Sensing Resistances and using a scaled version of its inverse to estimate the flow rate. This computation allowed an estimation of low flow rates in the range of about 100 microlitre/min. Having been able to develop a functional prototype of the flow meter cartridge, its incorporation into a real Lab-on-Chip device, like the STMicroelectronics CRISPR-Cas cartridge, and the further improvements based on the understanding of its dynamic range, sensitivity and accuracy would form the basis for future study. As a preliminary step, I was able to successfully incorporate and test the flow meter design (although with a single Sensing Resistor) into the channel of the CRISPR-Cas cartridge, with the Sensing Resistor peaks showing change in behaviour when water was pumped through the channel. This however needs to be subject to further study for design improvements and performance analysis.
I dispositivi Lab-on-Chip rappresentano un'industria in forte crescita a causa dell'aumento della prevalenza delle malattie croniche e della crescente domanda di test diagnostici Point-of-Care, ulteriormente facilitata dall'avvento della pandemia. Per questo motivo, c'è un costante bisogno di migliorare i dispositivi integrando diverse funzionalità nella cartuccia Lab-on-Chip, come ad esempio la misurazione del flusso, che completano le prestazioni del dispositivo. In questa tesi, ho presentato il mio lavoro sul design, l'implementazione e la caratterizzazione di un sensore di flusso termico basato sul principio della calorimetria, per applicazioni microfluidiche, svolto presso il Bio lab di STMicroelectronics. L'idea era quella di creare un modello generico e adattabile di una cartuccia funzionale di misurazione del flusso di liquido, che potesse poi essere modificato e incorporato nelle cartucce Lab-on-Chip usa e getta dei dispositivi diagnostici Point-of-Care in fase di sviluppo presso STMicroelectronics. Come primo passo, ho sviluppato un modello di cartuccia di flussimetro da usare come prototipo per condurre lo studio. Ho implementato una cartuccia di flussimetro con sensori di temperatura PT100 posizionati sul canale microfluidico, che funzionano come elementi di rilevamento del calore. È stata implementata per comprendere l'effetto del trasferimento di calore sui resistori di sensing misurando le loro resistenze in una configurazione a 4 fili, con impulsi di corrente periodici che passavano attraverso un elemento di riscaldamento centrale con solo aria nel canale. Ho osservato picchi in entrambe le resistenze di sensing corrispondenti agli impulsi di corrente, dimostrando come il trasferimento di calore attraverso il canale si rifletta sulle resistenze di sensing. In seguito, ho realizzato un prototipo di cartuccia funzionale con sottili strisce d'oro lungo il canale che formavano elementi di misura e riscaldamento stabili. Ciò è stato ottenuto utilizzando un dispositivo per lo sputtering dell'oro seguito da engraving laser per ottenere le resistenze nella forma e nella posizione desiderate. Gli esperimenti condotti su questa cartuccia hanno dimostrato come il flusso di acqua pompato attraverso il canale si riflettesse nell'ampiezza dei picchi di resistenza del sensore di rilevamento posizionato lungo il percorso del flusso, fornendo informazioni sull'ampiezza e sulla direzione del flusso d'acqua. Il meccanismo di lettura è stato anche modificato ad ogni step per ottenere un miglioramento delle prestazioni. Durante l'ultima parte del mio lavoro, al fine di tradurre matematicamente le informazioni ottenute dalle resistenze di sensing per stimare il flusso effettivo, impiegando un misuratore di flusso di liquido Sensirion come gold standard, ho lavorato su due diversi algoritmi. Uno si basava sul calcolo della differenza tra le varianze delle due resistenze di sensing e la successiva comparazione dell'inverso dei valori così ottenuti, scalata da un fattore di correzione, con il flusso misurato. Questo metodo è stato utilizzato per fornire stime ragionevoli del flusso nel range di 200-2000 microlitre/min. Il secondo metodo si basava sul calcolo della differenza tra le due resistenze di sensing e sull'utilizzo di una versione scalata del suo inverso per stimare il flusso. Questo calcolo ha permesso di stimare flussi bassi nell'intervallo di circa 100 microlitre/min. Dopo aver sviluppato un prototipo funzionale della cartuccia del flussimetro, il suo inserimento in un vero dispositivo Lab-on-Chip, come la cartuccia CRISPR-Cas della STMicroelectronics, e gli ulteriori miglioramenti basati sulla comprensione del suo range dinamico, sensibilità e accuratezza costituiranno la base per studi futuri. Sono riuscito a incorporare e testare con successo il progetto del flussometro (sebbene con un singolo resistore di sensing) nel canale della cartuccia CRISPR-Cas. I picchi del resistore di sensing hanno mostrato un cambiamento di comportamento quando l'acqua è stata pompata attraverso il canale. Tuttavia, questo aspetto deve essere ulteriormente studiato per migliorare il design e analizzare le prestazioni.
Design, Implementation and Characterization of a Thermal-Mass Flow Meter for Microfluidics
GOPINATH, ASWATHI
2022/2023
Abstract
With Lab-on-Chip devices being a fast growing industry due to the rising prevalence of chronic diseases and the increasing demand for point-of-care testing, further facilitated by the advent of the global pandemic, there is a constant need to improve the devices by integrating different functionalities into the Lab-on-Chip cartridge, like flow metering, that compliment the device performance. In this thesis, I have presented my work on the design, implementation and characterization of a thermal flow meter based on calorimetric principle, for microfluidic applications, carried out at the Bio lab of STMicroelectronics. The idea was to come up with a generic, adaptable model of a functional liquid flow meter cartridge, which could later be modified and incorporated into the disposable Lab-on-Chip cartridges of the Point-of-Care diagnostic devices under development at STMicroelectronics. As the first step, I developed a flow meter cartridge model to be used as a prototype to carry out the study. With the working of the flow meter based on the principle of heat transfer, a flow meter cartridge with PT100 Resistance Temperature Detectors placed across the microfluidic channel, functioning as the heat sensing elements, was implemented to understand the effect of the transferred heat on the Sensing Resistors by measuring their resistances in a 4-wire configuration, when periodic current pulses were passed through a central heating element with just air in the channel. I observed peaks in both the Sensing Resistances corresponding to the current pulses, which demonstrated how a heat transfer across the channel reflected in the Sensing Resistors. I then fabricated a functional cartridge prototype with thin gold strips across the channel forming stable Sensing and Heating elements. This was achieved by gold coating using a sputtering machine followed by laser engraving to cut out the resistances in the desired form and position. The experiments conducted on this cartridge demonstrated how the flow rate of water pumped through the channel were reflected in the amplitudes of the resistance peaks of the Sensing Resistor in the path of the flow, which gave information on both the magnitude and direction of the water flow. The read-out mechanism was also modified at each stage to achieve improvement in performance. During the last part of my work, in order to translate the information obtained from the Sensing Resistances mathematically to estimate the actual flow rate, employing a Sensirion liquid flow meter as the gold standard, I worked on two different algorithms. One was based on the computation of the difference between the variances of the two Sensing Resistances and the subsequent comparison of the inverse of the values thus obtained, scaled by a correction factor, with the measured flow rate. This method was found to provide reasonable estimates of the flow rate in the range of 200 to 2000 microlitre/min. The second method was based on the calculation of the difference between the two Sensing Resistances and using a scaled version of its inverse to estimate the flow rate. This computation allowed an estimation of low flow rates in the range of about 100 microlitre/min. Having been able to develop a functional prototype of the flow meter cartridge, its incorporation into a real Lab-on-Chip device, like the STMicroelectronics CRISPR-Cas cartridge, and the further improvements based on the understanding of its dynamic range, sensitivity and accuracy would form the basis for future study. As a preliminary step, I was able to successfully incorporate and test the flow meter design (although with a single Sensing Resistor) into the channel of the CRISPR-Cas cartridge, with the Sensing Resistor peaks showing change in behaviour when water was pumped through the channel. This however needs to be subject to further study for design improvements and performance analysis.| File | Dimensione | Formato | |
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Thesis_AswathiGopinath.pdf
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Descrizione: Design, Implementation and Characterization of a Thermal-Mass Flow Meter for Microfluidics
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https://hdl.handle.net/10589/210736