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Lab-on-a-Chip Dopamine Detection
G.S.VIRDI
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“Microfluidic Nanoparticle-Based Lab-on-a-Chip Technology: Design, Fabrication, and Biomedical Applications”
This lecture, presented by Dr. G. S. Virdi, Ex-Chief Scientist at CSIR–CEERI Pilani, provides an in-depth exploration of Microfluidic and Nanoparticle-Based Lab-on-a-Chip (LOC) technology, an innovation capable of transforming a full laboratory into a compact microscale device. With over 40 years of experience in R&D, teaching, and microelectronic device fabrication, Dr. Virdi explains how LOC systems integrate microfluidics, nano-sensors, electronics, and biochemistry on a single chip. The lecture covers the principles of microfluidics, chip materials, fabrication processes (deposition, etching, bonding), and integration of electronic circuitry. Emphasis is placed on the role of nanotechnology, including the use of nanoparticles and nanosensors to detect extremely small chemical quantities. A key highlight of the lecture is the nanoparticle-based Lab-on-a-Chip tested for dopamine detection, an important neurocompound. The device demonstrates the ability to analyze chemicals in micro/nano-liter volumes, reducing reagent cost, improving sensitivity, and enabling rapid diagnostics. Real-world applications discussed include: Drug delivery systems (insulin, chemotherapy) Point-of-care diagnostics HIV and cancer detection DNA analysis Plant biology studies High-throughput chemical analysis This lecture is highly beneficial for engineering and science students, researchers in microelectronics, nanotechnology, biosensors, biomedical engineering, and anyone pursuing work in lab-on-chip systems, microfluidics, and nano-enabled diagnostics
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“Microfluidic Nanoparticle-Based Lab-on-a-Chip Technology: Design, Fabrication, and Biomedical Applications”
- 1. Dr.G.S.Virdi Ex-.Chief Scientist CSIR-Central ElectronicsEngineering Research Institute Pilani—33303 1,India 1 Microfluidics Nano Particle Based Lab-on-a-Chip
- 2. 2 • Introduction Whatis LOC Chip materials & fabrication technology Electronic circuitry on lab-on-chips Role of Nanotechnology Advantages Disadvantages Application Conclusion Contents Dr.G.S.VIRDI
- 3. MICROFLUIDUICS :NANO PARTICLEBASED LAB - ON-A-CHIP 3 G.S.VIRDI There'splenty of room at the bottom Rechard Feynnman Dec.26,1959
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- 5. • Lab-on-a-chip refersto technologies which allow operations which normally require a laboratory synthesis and analysis of chemicals on a very miniaturized scale, within a portable or handheld device. • A typical lab-on-chip device contains micro channels, which allow liquid samples to flow inside the chip, but also integrates measuring, sensing and actuating components. 3 Introduction
- 6. • A lab-on-a-chip(LOC) is a device that integrates one or several laboratory functions on a single chip of only millimeters to a few square centimeters in size. • Lab-on-chip technology focuses on the development of hybrid devices, which integrate fluidic and electronic components onto the same chip. • Basically lab-on-chip integrate nonmaterial, micro fluidics, nanosensors, micro electrics, biochemistry, fluidic and electronic components onto the same chip. 4 Dr.G.S.VIRDI What is LOC
- 7. Dr.G.S.VIRDI 7 •lab-on-chip devices arehybrids that combine glass, silicon and various polymers like acrylic, polyester, polycarbonate, resists, thermoplastics or molds like the polydimethylsiloxane (PDMS). • Silicon, glass or polymers are suitable for making the microfluidic components of the chips; metals like gold, platinum or titanium are used for the conductive parts; silicon dioxide, silicon nitride and titanium nitride are for insulation and passivation. Chip Materials & Fabrication Technology
- 8. 8 G.S.VIRDI Microfluidics • Microfluidics refersto the behavior and control of liquidsconstrained to volumes near the μL range. • Behaviour of liquids inthe micro domain differs greatly from macroscopic fluids. • Surface tension. • Laminar flow. • Fast thermal relaxation. • Diffusion.
- 9. Why use Nanofluidics • Sample savings - nL of enzyme, not juL • Faster analyses - can heat, cool small volumes quickly • Integration - combine lots of steps onto a single device • Novel physics - diffusion, surface tension, and surface effects dominate This can actually lead to faster reactions! G.S.VIRDI 7 9
- 10. Microfluidics Components • Nanofluid pumps- for moving fluid - • Nano fluid channels and chambers for transporting and storing fluid G.S.VIRDI • Nano fluid valves- for isolation of fluid • Nano electrode - to provide potential or current , or to detect signals • Mixers- structures to prompt mixing at the micro scale • Nano Sensors - flow parameter sensors and chemicalparamete Ir sensors 1 01 0
- 11. G.S.VIRDI 1 1 Nano fluidics-Considering volumes ■ The volume of a spherical droplet of water , 50pm in diameter (D), given by, 4n/3 (D/2) 3=(n /6) D 3 = n /6 ( 5.10E- 5 ) 3 » (6.5 10) E-15 ■ As 1m 3 = 1000 litres, Volume of the droplet = (6.5 10) E-12 litre ( 65 pl). Micro fluidic volumes are often in the border of nl. 1 1
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- 16. LAB -ON-A-CHIP /Mixer/Reactor Connecting Reagent Sample Injector SampleInlet Carrier & Reagent Inlet Waste Out let < = > Micro Flow Cell with Microsensors Microchannels > Includes sample preparation > Separation and detection system on a small single chip. G.S.VIRDI 1 6
- 17. Capillary 2 Lab-on-a-Chip forChemical Analysis Valve1 Reservoir Reagent Valve2 G1 G3 PCR Channels G4 2 Sample +ve G5 Pump Vent G6 G7 +ve Capillary1 Out -ve -Ve 2 4 2 5 CEERI PILANI, I3 N 3 DIA G.S.VIRDI 1 7
- 18. Design of Lab-On-a-Chipfor Chemical Analysis 18 G.S.VIRDI
- 19. Lab-on-chip fabrication techniquesare analogous to those of microelectronics, since closely related micro fabrication and integration methodologies are shared by both. There are 3 way of fabrication process:- Deposition method Etching process Bonding Dr.G.S.VIRDI 1 9 Fabrication Process
- 20. Deposition method •Here wecan use any vapour deposition process that produces thin metal, ceramic, or compound films, through thermal oxidation in a gas chamber at an elevated temperature. (a) Metallization of the substrate by sputtering a metal film of Au, Pt, or ITO. (b) Spin coating of photosensitive resist film onto the metal film. 7 Dr.G.S.VIRDI
- 21. In lab-on-chip fabricationtechnology, patterning is the transfer of outlines of features (which define micro channels, microelectrodes, or other components) on the top of a substrate by means of ultraviolet illumination via a photo mask. (c)exposure of the photosensitive film via a photo mask that results in the transfer of the desired electrode patterns onto the photosensitive film. (d)after photo-development, chemical etching removes the bare metalized areas, which results in the formation of the electrodes. Etching Process Dr.G.S.VIRDI
- 22. After patterning allfeatures on substrates (micro channels, elements, inlets, etc), the base plate and the cover plate must be bonded in order to seal the chip. It is possible to bond silicon, glass, or rigid polymer plates, by bonding Bond the PDMS channel to a glass substrate 9 Dr.G.S.VIRDI Bonding
- 23. 2 3 • The sensoris followed by an analogue front-end, which conditions the measuring signal, analogue-to digital converters (ADC), and a digital signal processor that analyses the signal. Electronic circuitry on lab-on- chips Dr.G.S.VIRDI
- 24. 2 4 • The signalscan be electrical, optical, etc. The analyzed data further sent via a bus to external computer for post-processing, or even visualized on integrated displays or external screen Dr.G.S.VIRDI
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- 27. Nano ParticleBased Lab-on-a-Chip Role of Nanotechnology • Nanosensorsare also a key element of many lab- on-a- chip systems.Sensors havebeen developed using Nano materialslikecarbonnano tubes,Au capable of detecting very low concentrations, down to singlemolecules. These are extremelyusefulin allowinga high degree of analytical flexibilityin a lab-on-a-chip system without increasing the overallsize of the device. G.S.VIRDI 3 92 7
- 28. Nano ParticleBased Lab-on-a-Chip G.S.VIRDI PHOTOGRAPHOF FABRICATED LAB ON A CHIP 4^ Separation of Ascorbic acid and Dopamine 4 22 8
- 29. Curren t / mA 29 G.S.VIRD I Potential/ V vs.SCE :Nano particle based Lab on a Chip Separation of Ascorbic Acid and Dopamine
- 30. Nano Particle BasedLab-On-a-Chip 30 G.S.VIRDI Drug Delivery System Drug delivery Diabetes • IV fluids Chemotherapy Pain killers Estimated number of diabetes patients U.S ^Europe eWorld WHO DATA
- 31. Insulin drug deliverysystem G.S.VIRDI CEERI PILANI 4 53 1
- 32. Point of careDiagnoses 4 6 G.S.VIRD I 3 2
- 33. 33 G.S.VIRDI Use of LOCIn HIV detection 40 million people are infected with HIV.. 1.3 million of these people receive anti-retroviral treatment. Around 90% of people with HIV have never been tested for the disease. Measuring the number of CD4+ T lymphocytes in a person’s blood is an accurate way to determine if a person has HIV. At the moment, flow cytometry is the gold standard for obtaining CD4 counts Recently such a cytometer was developed for just $5. In such devices it is possible to quickly diagnose and potentially treat diseases.
- 34. 34 G.S.VIRDI Use of LOCfor Plant Studies Lab-on-a-chip devices could be used to characterize pollen tube guidance. Specifically, plant on a chip is a miniaturized device in which pollen tissues and ovules could be incubated for plant sciences studies.
- 35. 35 G.S.VIRDI Use of LOCfor Plant Studies Lab-on-a-chip devices could be used to characterize pollen tube guidance. Specifically, plant on a chip is a miniaturized device in which pollen tissues and ovules could be incubated for plant sciences studies.
- 36. LOC DNA DIAGNOSTICS 36 G.S.VIRDI GEL LOADING THERMAL REACTION -Glass Silicon PC Board Wire Bonds Gins* Substrate Ti-Pt Electrodes TiO/SiO P Doping Air Lines P xylvleiie lasers 1 Oxide Silicon Substrate D R O P METER INC- SAMPLE LOADING
- 37. LOC CANCER DRUG 37 G.S.VIRDI >Asmall plastic chip developed with nanotechnology that holds the key to determining whether a patient is resistant to cancer drugs or has infections like malariaThe chip can also pinpoint infectious diseases in a herd of cattle.
- 38. • • Faster analysisandresponse times due to short diffusion distances, fast heating, high surfaceto volume ratios,small heat capacities. • Betterprocess control because of a fasterresponseof the system(e.g. thermal control for exothermicchemical reactions) • Compactness of the systems due to integrationof Microfluidics : much functionality and small volumes • Massive parallelizationdue to compactness, which allows high-throughput analysis Nano Particle Based Lab-on-a-Chip 5 4 G.S.VIRDI 3 8
- 39. • Faster analysisand response times due to short diffusion distances, fast heating, high surface to volume ratios, small heat capacities. • Better process control because of a faster response of the system (e.g. thermal control for exothermic chemical reactions) • Compactness of the systems due to integration of much functionality and small volumes • Massive parallelization due to compactness, which allows high-throughput analysis • Lower fabrication costs, allowing cost-effective disposable chips, fabricated in mass production 13 Dr.G.S.VIRDI Advantages
- 40. • Novel technologyand therefore not yet fully developed. • LOCs more complex than in conventional lab equipment. • Detection principles may not always scale down in a positive way, leading to low signal-to-noise ratios. 14 Dr.G.S.VIRDI Disadvantages
- 41. •Personalised medicine •Point-of-care diagnostics •Marinesensors •Monitor pollution •Monitor pandemics / diseases •Link to medical and patient databases •Usage as terminal testers •Military medicine 15 Dr.G.S.VIRDI Application
- 42. •Future advancements inlab-on-a-chip technology will always depend on at least two major scientific disciplines - microfluidics, and molecular biology. Nanotechnology will play a key role in tying these two fields together as the technology progresses. •Despite the hurdles always associated with commercialization of a new technology, viable examples of these devices are beginning to appear on the market. It seems that lab-on-a-chip technology will become increasingly important in the coming years, both in the medical world and in the chemical industry 16 Dr.G.S.VIRDI Conclusions
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