5 results on '"Roy, Arghyamalya"'
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2. Electrophoretic Delivery of Clinically Approved Anesthetic Drug for Chronic Pain Therapy
- Author
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Roy, Arghyamalya, primary, Bersellini Farinotti, Alex, additional, Arbring Sjöström, Theresia, additional, Abrahamsson, Tobias, additional, Cherian, Dennis, additional, Karaday, Michal, additional, Tybrandt, Klas, additional, Nilsson, David, additional, Berggren, Magnus, additional, Poxson, David J., additional, Svensson, Camilla I., additional, and Simon, Daniel T., additional
- Published
- 2023
- Full Text
- View/download PDF
3. Flexible Organic Electronic Ion Pump Fabricated Using Inkjet Printing and Microfabrication for Precision In Vitro Delivery of Bupivacaine
- Author
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Cherian, Dennis, primary, Roy, Arghyamalya, additional, Farinotti, Alex Bersellini, additional, Abrahamsson, Tobias, additional, Sjöström, Theresia Arbring, additional, Tybrandt, Klas, additional, Nilsson, David, additional, Berggren, Magnus, additional, Svensson, Camilla I., additional, Poxson, David J., additional, and Simon, Daniel T., additional
- Published
- 2023
- Full Text
- View/download PDF
4. Bioelectronic Devices for Targeted Drug Delivery and Monitoring of Microbial Electrogenesis
- Author
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Roy, Arghyamalya
- Subjects
Electrophoresis ,Anestesi och intensivvård ,Anesthesiology and Intensive Care ,Fumarate ,Ion Exchange Membranes (IEM) ,Bupivacaine ,Shewanella oneidensis ,Chronic Neuropathic Pain ,Organic Electronic Ion Pump (OEIP) ,Organic Electrochemical Transistor (OECT) ,Extracellular Electron Transfer (EET) ,Microfabrication ,Drug Delivery ,Inkjet Printing ,Dorsal Root Ganglia (DRG) - Abstract
Despite a range of pain therapies available in the market, 70% of patients report so-called “breakthrough pain”. Coupled with global issues like opioid crisis, there is a clear need for advanced therapies and technologies for pain management. In this thesis we aim to develop a novel pain management therapy based on precise, fluid-flow-free delivery of anesthetic drugs directly to the peripheral nervous system (PNS) using organic electronic ion pumps (OEIPs). OEIPs are devices that can transport charged drug molecules through a permselective ion exchange membrane (IEM) under an applied electric field. In this work we used primary dorsal root ganglion (DRG) neurons as an in vitro PNS model system for neuropathic pain. The IEM was made up of custom synthesized hyberbranched polyglycerols (HPGs), which enabled the delivery of large aromatic anesthetic drug such as bupivacaine for the first time in an OEIP. Bupivacaine is a common local nerve blocker which if delivered to DRGs effectively blocks their neuronal activity which in turn blocks the pain signal to travel to the central nervous system (CNS) thereby blocking the sensation of pain. Two types of OEIP devices were fabricated and characterized in this context: capillary-based OEIPs with a probe-like form factor, and inkjet-printed flexible OEIPs with a potential towards implantable form factor. The results showed that both types of OEIP devices could deliver bupivacaine locally (delivery radius ~ 75 µm) to DRG neurons at concentrations close to 40000 times lower than the bulk/bolus means. The results demonstrated that OEIPs could achieve long-lasting and reversible nerve blockage without causing tissue damage or systemic side effects. These studies lay the foundation for future demonstrations of “iontronic” PNS pain relief in living/awake animals. On the other end of the spectrum, most of today’s modern communication is based upon our understanding of how electrons move through semiconductors. This allows one to mediate the flow of electrons by designing complex integrated circuits in the form of microchips which gives rise to smart devices such as mobile phones and computers. Likewise, in many organism’s electron transfer plays a critical role in metabolic processes in eukaryotes, which includes animals all the way down to microbes. In most of these metabolic processes, the role of the final electron acceptor is played by oxygen (aerobic respiration). However, there are few families of bacterial cells that we know today have evolved in special ways allowing them to respire or “breathe” through metals/metal oxides when exposed to anaerobic conditions. In electromicrobiology, this is termed as extracellular electron transfer (EET), wherein the microbes shuttle electrons from inside of their cells to the outside, in presence of favorable extracellular electron acceptors. The EET process has thus been exploited in various microbial electrochemical systems (MESs) such as microbial fuel cells (MFCs), biosensors, and bio-photovoltaic cells to name a few. In this thesis, we have carried out a detailed study examining the EET process in MESs and ways to amplify such signals in broadly two major approaches: Bioelectrochemical and device optimization. Under bioelectrochemical means, we have shown that we can amplify EET signal of exoelectrogens such as Shewanella oneidensis MR-1 in a standard microbial bioreactor set up containing fumarate (a common carbon food source) by up to 50x times without the excess cell growth in the reactor. This study helped to unravel few unknown mysteries of the EET and bust few of its well-studied myths in the process. However, to record EET, traditionally one still requires large area/volume of electrodes with sufficiently high concentration of bacteria to remain well above the threshold signal-to-noise ratio. So under device optimization route, we combined S.oneidensis with an electrochemical transistor termed as Organic Microbial Electrochemical Transistor (OMECT). With OMECT we successfully monitored and amplified EET events from small number of microbial cells on a microscale area (500 µm x 500 µm) in real time without the need big/bulky/expensive signal amplifying instruments. Interestingly, the OMECT platform also revealed an order of magnitude faster EET response of S. oneidensis MR-1 to lactate compared to studies using classical electrochemical approaches thus underlying one of the major advantages of the miniaturized bioelectronic device. Trots att det finns många sätt att behandla smärta hos patienter uppger 70 procent att de drabbas av smärta som kommer tillbaka efter att de tagit medicinen. Många smärtmediciner är opioider och beroendeframkallande. Därför finns ett starkt behov att utveckla en ny avancerad lösning på smärtproblemen. Vår lösning är att tillföra anestesimedel i exakt mängd och fri från vätskeflöde direkt till det yttre nervsystemet genom organiska elektroniska jonpumpar (OEIP). Dessa jonpumpar kan transportera laddade läkemedelsmolekyler genom ett permselektivt jonbytarmembran när elektriska fält används. Vi använde primära dorsalrotganglion (DRG) neuroner som ett in vitro PNS-modellsystem för neuropatisk smärta. För första gången kan vi tillföra stora aromatiska anestesimedelsmolekyler som bupivacaine genom att använda OEIP. Bupivacaine är en vanlig lokal nervblockerare som effektivt blockerar neuronal aktivitet från DRG. Därför når inte smärtsignalerna fram till centrala nervsystemet (CNS). Detta blev möjligt genom specialtillverkade hyperbranched polyglyceroler (HPG). Vi tillverkade och testade två typer av OEIP- enheter: kapillärbaserade och sondliknande samt bläckstråletryckta och flexibla OEIP-er som kan implanteras. Båda typerna kan överföra bupivacaine till DRG neuroner lokalt (leverensradie ~75 µm) och i mycket låg koncentration (40 000 gånger lägre än bulk/ bolus). Resultaten visade att OEIP åstadkom en effektiv och reversibel blockering av nerverna. Nerverna blockerades utan att vävnaden tog skada och utan systematiska biverkningar. Dessa studier är grundläggande för framtida försök att lindra PNS-smärta hos levande/vakna djur genom iontronik. I många organismer spelar överföringen av elektroner en betydelsefull roll för metaboliska processer. Syre är den slutliga elektronacceptatorn i många av desa processer (aerob andning). Emellertid finns det få bakterier som kan "andas" genom metaller eller metalloxider när de utsätts för anaeroba förhållanden. Detta kallas extracellulär elektronöverföring (EET) i elektromikrobiologi. I EET skjuter mikroberna elektroner från insidan av sina celler till utsidan om där finns gynnsamma extracellulära elektronacceptorer. EET-processen har utnyttjats i olika mikrobiella elektrokemiska system ( MES) som mikrobiella bränsleceller (MFC), biosensorer och bio-fotovoltaiska celler. I denna avhandling har vi detaljstuderat EET-processen och studerat två sätt att tillämpa sådana signaler: bioelektrokemisk och enhetsoptimering. Vi kan förstärka EET-signaler från exoelektrogener, som Shewanella oneidensin MR-1, upp till 50 gånger i en standard mikrobiell bioreaktor som innehåller fumarat (en vanlig kolmatkälla) utan överskott av celltillväxt i reaktor. Denna studie hjälpte oss att lösa flera mysterier och avliva några myter kring EET-processen. För att registrera EET med tillräckligt signal-brusförhållande behöver vi elektroder med stor area/volym och hög koncentration av bakterier. Under enhetsomprimeringen kombinerade vi S.oneidensis med en elektrokemisk transistor för att skapa Organic Microbial Electrochemical Transistor (OMECT). Vi använde denna OMECT för att framgångsrikt övervaka och förstärka EET-signaler från ett litet antal mikrobiella celler och på en mikroskala (500 µm x 500 µm) i realtid. Det fanns inget behov av stora, bulkiga och dyra instrument för att förstärka signalerna. Intressant nog fann vi att signalerna från S.oenidensis MR-1 på laktat, som sänds av OMECT-plattformen, var snabbare jämfört med klassiska elektrokemiska metoder. Detta är den stora fördelen med miniatyriserade bioelektroniska enheter.
- Published
- 2023
5. Single-walled Carbon Nanotubes Wrapped with Charged Polysaccharides Enhance Extracellular Electron Transfer.
- Author
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Shiraki T, Niidome Y, Roy A, Berggren M, Simon DT, Stavrinidou E, and Méhes G
- Subjects
- Electron Transport, Materials Testing, Particle Size, Biocompatible Materials chemistry, Biocompatible Materials pharmacology, Electrodes, Nanotubes, Carbon chemistry, Shewanella metabolism, Polysaccharides chemistry, Polysaccharides pharmacology
- Abstract
Microbial electrochemical systems (MESs) rely on the microbes' ability to transfer charges from their anaerobic respiratory processes to electrodes through extracellular electron transfer (EET). To increase the generally low output signal in devices, advanced bioelectrical interfaces tend to augment this problem by attaching conducting nanoparticles, such as positively charged multiwalled carbon nanotubes (CNTs), to the base carbon electrode to electrostatically attract the negatively charged bacterial cell membrane. On the other hand, some reports point to the importance of the magnitude of the surface charge of functionalized single-walled CNTs (SWCNTs) as well as the size of functional groups for interaction with the cell membrane, rather than their polarity. To shed light on these phenomena, in this study, we prepared and characterized well-solubilized aqueous dispersions of SWCNTs functionalized by either positively or negatively charged cellulose-derivative polymers, as well as with positively charged or neutral small molecular surfactants, and tested the electrochemical performance of Shewanella oneidensis MR-1 in MESs in the presence of these functionalized SWCNTs. By simple injection into the MESs, the positively charged polymeric SWCNTs attached to the base carbon felt (CF) electrode, and as fluorescence microscopy revealed, allowed bacteria to attach to these structures. As a result, EET currents continuously increased over several days of monitoring, without bacterial growth in the electrolyte. Negatively charged polymeric SWCNTs also resulted in continuously increasing EET currents and a large number of bacteria on CF, although SWCNTs did not attach to CF. In contrast, SWCNTs functionalized by small-sized surfactants led to a decrease in both currents and the amount of bacteria in the solution, presumably due to the detachment of surfactants from SWCNTs and their detrimental interaction with cells. We expect our results will help researchers in designing materials for smart bioelectrical interfaces for low-scale microbial energy harvesting, sensing, and energy conversion applications.
- Published
- 2024
- Full Text
- View/download PDF
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