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ETE444 :: Lecture 7

  Dr. Mashiur Rahman
ETE444-lec7-lab-on-a-chip-microfluidics.pdf
Application of Nanotechnology
• Microfluidics and their Applications
  – Lab-on-a-Chip
  – Materials for Microfluidic Devices
  – Biochemical Analysis
  – Active Microfluidic Devices
• Single electron transistors
Microfluidics and Their Applications
• Microfluidics covers the science of fluidic
  behaviors on the micro/nanoscales and the
  engineering of design, simulation, and
  fabrication of the fluidic devices for the
  transport, delivery, and handling of fluids on
  the order of microliters or smaller volumes.
  – BioMEMS (Biological or Biomedical
    Microelectromechanical Systems)
  – Lab-on-a-chip (μTAS : Micro-Total Analysis
    Systems)
Applications
•   Inkjet printing
•   Blood analysis
•   Biochemical detection
•   Chemical synthesis
•   Drug screening/delivery
•   Protein analysis
•   DNA sequencing
Inkjet printing
An inkjet printer is any printer that places
  extremely small droplets of ink onto paper to
  create an image.
• The dots are extremely small (usually between 50
  and 60 microns in diameter), so small that they
  are tinier than the diameter of a human hair (70
  microns)!
• The dots are positioned very precisely, with
  resolutions of up to 1440x720 dots per inch (dpi).
• The dots can have different colors combined
  together to create photo-quality images.
thermal bubble inkjet printer
• Used by manufacturers such as Canon
  and Hewlett Packard, this method is
  commonly referred to as bubble jet.
• In a thermal inkjet printer, tiny
  resistors create heat, and this heat
  vaporizes ink to create a bubble. As
  the bubble expands, some of the ink
  is pushed out of a nozzle onto the
  paper.
• When the bubble "pops" (collapses), a
  vacuum is created. This pulls more ink
  into the print head from the cartridge.
  A typical bubble jet print head has
  300 or 600 tiny nozzles, and all of
  them can fire a droplet
  simultaneously.                           Picture: howstuffworks.com
Piezoelectric
Patented by Epson, this
technology uses piezo crystals. A
crystal is located at the back of
the ink reservoir of each nozzle.
The crystal receives a tiny electric
charge that causes it to vibrate.
When the crystal vibrates inward,
it forces a tiny amount of ink out
of the nozzle. When it vibrates
out, it pulls some more ink into
the reservoir to replace the ink
sprayed out.                           Picture: howstuffworks.com
Blood analysis

• A blood test is a laboratory analysis
  performed on a blood sample that is
  usually extracted from a vein in the
  arm using a needle, or via fingerprick.
• Blood tests are used to determine
  physiological and biochemical states,
  such as disease, mineral content, drug
  effectiveness, and organ function.
  Although the term blood test is used,
  most routine tests (except for most
  haematology) are done on plasma or
  serum, instead of blood cells.
Biochemical detection
• The study of the chemical
  substances and vital processes
  occurring in living organisms;
  biological chemistry;
  physiological chemistry.
Chemical synthesis
• In chemistry, chemical synthesis is purposeful execution of
  chemical reactions in order to get a product, or several products.
  This happens by physical and chemical manipulations usually
  involving one or more reactions. In modern laboratory usage, this
  tends to imply that the process is reproducible, reliable, and
  established to work in multiple laboratories.
• A chemical synthesis begins by selection of compounds that are
  known as reagents or reactants. Various reaction types can be
  applied to these to synthesize the product, or an intermediate
  product. This requires mixing the compounds in a reaction vessel
  such as a chemical reactor or a simple round-bottom flask. Many
  reactions require some form of work-up procedure before the final
  product is isolated. The amount of product in a chemical synthesis
  is the reaction yield.
Drug screening/delivery
• Drug delivery is the method or process of administering a pharmaceutical
  compound to achieve a therapeutic effect in humans or animals.
• Drug delivery technologies are patent protected formulation technologies
  that modify drug release profile, absorption, distribution and elimination
  for the benefit of improving product efficacy and safety, as well as patient
  convenience and compliance.
• Most common methods of delivery include the preferred non-invasive
  peroral (through the mouth), topical (skin), transmucosal (nasal,
  buccal/sublingual, vaginal, ocular and rectal) and inhalation routes.
• Current efforts in the area of drug delivery include the development of
  targeted delivery in which the drug is only active in the target area of the
  body (for example, in cancerous tissues) and sustained release
  formulations in which the drug is released over a period of time in a
  controlled manner from a formulation. Types of sustained release
  formulations include liposomes, drug loaded biodegradable microspheres
  and drug polymer conjugates.
Protein analysis
• Proteins (also known as polypeptides) are organic
  compounds made of amino acids arranged in a linear
  chain. The amino acids in a polymer chain are joined
  together by the peptide bonds between the carboxyl
  and amino groups of adjacent amino acid residues. The
  sequence of amino acids in a protein is defined by the
  sequence of a gene, which is encoded in the genetic
  code.




 Synthesis
DNA sequencing
• The term DNA sequencing refers to methods for determining the order of
  the nucleotide bases, adenine, guanine, cytosine, and thymine, in a
  molecule of DNA. The first DNA sequences were obtained by academic
  researchers, using laborious methods based on 2-dimensional
  chromatography in the early 1970s. Following the development of dye-
  based sequencing methods with automated analysis, DNA sequencing has
  become easier and orders of magnitude faster. Knowledge of DNA
  sequences of genes and other parts of the genome of organisms has
  become indispensable for basic research studying biological processes, as
  well as in applied fields such as diagnostic or forensic research. The advent
  of DNA sequencing has significantly accelerated biological research and
  discovery. The rapid speed of sequencing attained with modern DNA
  sequencing technology has been instrumental in the sequencing of the
  human genome, in the Human Genome Project. Related projects, often by
  scientific collaboration across continents, have generated the complete
  DNA sequences of many animal, plant, and microbial genomes.


 DNA Sequence Trace
Microfluidic system
• consist of microfluidic platforms or devices for
  – Fluidic sampling
  – Control
  – Monitoring
  – Transport
  – Mixing
  – Reaction
  – Incubation
  – Analysis
Lab-on-a-chip

• Lab-on-a-chip is becoming a revolutionary tool for
  many different applications in chemical and biological
  analyses due to its fascinating advantages (fast and low
  cost) over conventional chemical or biological
  laboratories.
• Furthermore, the simplicity of lab-on-a-chip systems
  will enable self-testing capability for patients or health
  consumers overcoming space limitation.
• The idea of lab-on-a-chip is basically to reduce
  biological or chemical laboratories to a microscale
  system, hand-held size or smaller.
Advantages
• Low cost: Many reagents and chemicals used in biological and
  chemical reactions are expensive, so the prospect of using
  very small amounts (in micro- to nanoliter range) of reagents
  and chemicals for an application is very appealing.
• Requires very small amounts of reagents/chemicals:
   – enables rapid mixing and reaction: biochemical reaction is mainly
     involved in the diffusion of two chemical or biological reagents
   – microscale fluidics reduces diffusion time as it increases reaction
     probabilities
   – practical terms, reaction products can be produced in a matter of
     seconds/minutes, whereas laboratory scale can take hours, or
     even days.
• Minimize harmful by-products: since their volume is so small
Materials for Microfluidic Devices
• Silicon
• Glass
• Polymer
Silicon
• Microfluidic channels on silicon
  substrates are usually formed
  either by wet (chemical) etching
  or by dry (plasma) etching.
Glass
• Excellent optical transparency
• Ease of electro-osmotic flow (EOF).
Fabrication techniques
1. Chemical wet etching
      • hydrofluoric acid (HF)
      • buffered hydrofluoric acid
      • a mixture of hydrofluoric acid, nitric acid, and
        deionized water (HF, HNO3,H2O)
• 2. Thermal fusion bonding
Polymer
Reasons                        Materials
• Low cost                     • Polyimide
• Ease-of-fabrication
• Favorable biochemical
                               • PMMA
  reliability                  • PDMS
• Compatibility                  (Polydimethylsiloxane)
• mass production: using
                               • Polyethylene or
   – Casting
   – Hot embossing
                                 polycarbonate
   – Injection molding
• successful
  commercialization
PDMS
• (H3C)3SiO[Si(CH3)2O]nSi(CH3)3 where n is the
  number of repeating monomer [SiO(CH3)2]
  units.
polymer micro/nano fabrication techniques

• Casting
• Hot embossing
• Injection molding
Casting
Casting is a manufacturing process by which a liquid material is usually
poured into a mold, which contains a hollow cavity of the desired shape, and
then allowed to solidify. The solidified part is also known as a casting, which is
ejected or broken out of the mold to complete the process. Casting materials
are usually metals or various cold setting materials that cure after mixing two
or more components together; examples are epoxy, concrete, plaster and
clay. Casting is most often used for making complex shapes that would be
otherwise difficult or uneconomical to make by other methods.

Casting is a 6000 year old process.[2] The oldest surviving casting is a copper
frog from 3200 BC.
Hot embossing
Hot embossing is essentially the stamping of a pattern into a polymer softened
by raising the temperature of the polymer just above its glass transition
temperature. The stamp used to define the pattern in the polymer may be made
in a variety of ways including micromachining from silicon, LIGA, and machining
using a CNC tool (for making large features). A wide variety of polymers have
been successfully hot embossed with micron-scale (and below) size features,
including polycarbonate and PMMA. This technique is used primarily for defining
micro-channels and wells for fluidic devices. The benefits of this approach are
the ability to take advantage of the wide range of properties of polymers, as well
as the potential to economically mass produce parts with micron-scale features.
Injection molding
Injection molding (British English: moulding) is a manufacturing process for
producing parts from both thermoplastic and thermosetting plastic materials.
Material is fed into a heated barrel, mixed, and forced into a mold cavity where
it cools and hardens to the configuration of the mold cavity.
After a product is designed, usually by an industrial designer or an engineer,
molds are made by a moldmaker (or toolmaker) from metal, usually either
steel or aluminium, and precision-machined to form the features of the desired
part. Injection molding is widely used for manufacturing a variety of parts, from
the smallest component to entire body panels of cars.
ETE444-lec7-lab-on-a-chip-microfluidics.pdf
Disposable Smart Lab-on-a-Chip for Blood Analysis
                             The disposable lab-on-a-chip
                             cartridge has been fabricated
                             using plastic micro-injection
                             molding and plastic-to-plastic
                             direct bonding techniques.
                             The biochip cartridge consists
                             of a fixed volume
                             microdispenser based on the
                             sPROMs (structurally
                             programmable microfluidic
                             system) technique, an air-
                             bursting, on-chip pressure
                             source, and electrochemical
                             biosensors.
ETE444-lec7-lab-on-a-chip-microfluidics.pdf
ETE444-lec7-lab-on-a-chip-microfluidics.pdf
Microchip PCR
• The PCR reaction is a thermal cycling procedure for amplifying a nucleic acid
  target. PCR is used to amplify DNA targets and a reverse transcriptase-PCR
  (RT-PCR) is used for RNA targets.
• PCR is a three step process in which each step is performed at a different
  temperature.
   – 1. In the first step, double-stranded DNA is denatured at a temperature
      of approximately 95 °C.
   – 2. Next, each of the two single strands of DNA are hybridized (annealed)
      to pairs of oligonucleotide primers at approximately 55 °C.
   – 3. In the final step, a thermostable magnesium ion-dependent
      polymerase derived from Thermophilus aquaticus (Taq polymerase)
      synthesizes complementary DNA in the region flanked by the primers
      using added deoxynucleotide triphosphates (dNTP) at approximately 72
      °C (extension).
Microchip PCR




Schematic of a flow-through-type of PCR microchip. The serpentine reaction microchannel
crosses each of three zones (T1, T2, T3) each of which is set at a different temperature
ETE444-lec7-lab-on-a-chip-microfluidics.pdf
Microchip PCR Products
• However, despite strong indications that the development
  of microchip-based PCR analyzers are nearing completion,
  few have been commercialized. One example of a PCR
  microchip-based device is the miniature analytical thermal
  cycling instrument (MATCHI) system (Smart Cycler see
  www.cepheid.com). This is a battery-powered portable,
  real-time, integrated analytical system based on PCR
  performed in an array of silicon microchambers [52, 59,
  61]. The entire system fits inside a briefcase for ease of
  transport. Applications identified for this nucleic acid
  analysis device include forensic, environmental and
  agricultural analyses and detecting biowarfare agents [62,
  63, 64].
Commercial products
Lab-on-a-chip :: Diseases & Devices
Optical detection of proteins




Optical detection of proteins and reagent storage and delivery. (i) Schematic representation
of the POCKET immunoassay powered by a 9 V battery. (ii) Actual device. (iii) Apparent silver
absorbance values of anti-HIV-1 antibodies from HIV-positive patients and control patients.
(iv) Schematic representation of reagent-loaded cartridges. (v) Overlay of fluorescence and
brightfield images of the immunoreaction area, with fluorescent signal corresponding to
presence of labeled detection antibodies on antigen stripes. The concentrations indicated
above the picture refer to the concentration of sample tested in each microchannel.
Optical detection of proteins




Immunomagnetic separation and detection of proteins with CMOS Hall sensors. (i)
Schematic representation with inset showing actual chip. (ii) Comparison of the
outputs of CMOS chip and ELISA
detecting nucleic acids




Integrated nanolitre DNA analysis device. (i) Schematic
representation with two liquid samples and electrophoresis gel
present. (ii) Optical micrograph of device.

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ETE444-lec7-lab-on-a-chip-microfluidics.pdf

  • 1. ETE444 :: Lecture 7 Dr. Mashiur Rahman
  • 3. Application of Nanotechnology • Microfluidics and their Applications – Lab-on-a-Chip – Materials for Microfluidic Devices – Biochemical Analysis – Active Microfluidic Devices • Single electron transistors
  • 4. Microfluidics and Their Applications • Microfluidics covers the science of fluidic behaviors on the micro/nanoscales and the engineering of design, simulation, and fabrication of the fluidic devices for the transport, delivery, and handling of fluids on the order of microliters or smaller volumes. – BioMEMS (Biological or Biomedical Microelectromechanical Systems) – Lab-on-a-chip (μTAS : Micro-Total Analysis Systems)
  • 5. Applications • Inkjet printing • Blood analysis • Biochemical detection • Chemical synthesis • Drug screening/delivery • Protein analysis • DNA sequencing
  • 6. Inkjet printing An inkjet printer is any printer that places extremely small droplets of ink onto paper to create an image. • The dots are extremely small (usually between 50 and 60 microns in diameter), so small that they are tinier than the diameter of a human hair (70 microns)! • The dots are positioned very precisely, with resolutions of up to 1440x720 dots per inch (dpi). • The dots can have different colors combined together to create photo-quality images.
  • 7. thermal bubble inkjet printer • Used by manufacturers such as Canon and Hewlett Packard, this method is commonly referred to as bubble jet. • In a thermal inkjet printer, tiny resistors create heat, and this heat vaporizes ink to create a bubble. As the bubble expands, some of the ink is pushed out of a nozzle onto the paper. • When the bubble "pops" (collapses), a vacuum is created. This pulls more ink into the print head from the cartridge. A typical bubble jet print head has 300 or 600 tiny nozzles, and all of them can fire a droplet simultaneously. Picture: howstuffworks.com
  • 8. Piezoelectric Patented by Epson, this technology uses piezo crystals. A crystal is located at the back of the ink reservoir of each nozzle. The crystal receives a tiny electric charge that causes it to vibrate. When the crystal vibrates inward, it forces a tiny amount of ink out of the nozzle. When it vibrates out, it pulls some more ink into the reservoir to replace the ink sprayed out. Picture: howstuffworks.com
  • 9. Blood analysis • A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick. • Blood tests are used to determine physiological and biochemical states, such as disease, mineral content, drug effectiveness, and organ function. Although the term blood test is used, most routine tests (except for most haematology) are done on plasma or serum, instead of blood cells.
  • 10. Biochemical detection • The study of the chemical substances and vital processes occurring in living organisms; biological chemistry; physiological chemistry.
  • 11. Chemical synthesis • In chemistry, chemical synthesis is purposeful execution of chemical reactions in order to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions. In modern laboratory usage, this tends to imply that the process is reproducible, reliable, and established to work in multiple laboratories. • A chemical synthesis begins by selection of compounds that are known as reagents or reactants. Various reaction types can be applied to these to synthesize the product, or an intermediate product. This requires mixing the compounds in a reaction vessel such as a chemical reactor or a simple round-bottom flask. Many reactions require some form of work-up procedure before the final product is isolated. The amount of product in a chemical synthesis is the reaction yield.
  • 12. Drug screening/delivery • Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. • Drug delivery technologies are patent protected formulation technologies that modify drug release profile, absorption, distribution and elimination for the benefit of improving product efficacy and safety, as well as patient convenience and compliance. • Most common methods of delivery include the preferred non-invasive peroral (through the mouth), topical (skin), transmucosal (nasal, buccal/sublingual, vaginal, ocular and rectal) and inhalation routes. • Current efforts in the area of drug delivery include the development of targeted delivery in which the drug is only active in the target area of the body (for example, in cancerous tissues) and sustained release formulations in which the drug is released over a period of time in a controlled manner from a formulation. Types of sustained release formulations include liposomes, drug loaded biodegradable microspheres and drug polymer conjugates.
  • 13. Protein analysis • Proteins (also known as polypeptides) are organic compounds made of amino acids arranged in a linear chain. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues. The sequence of amino acids in a protein is defined by the sequence of a gene, which is encoded in the genetic code. Synthesis
  • 14. DNA sequencing • The term DNA sequencing refers to methods for determining the order of the nucleotide bases, adenine, guanine, cytosine, and thymine, in a molecule of DNA. The first DNA sequences were obtained by academic researchers, using laborious methods based on 2-dimensional chromatography in the early 1970s. Following the development of dye- based sequencing methods with automated analysis, DNA sequencing has become easier and orders of magnitude faster. Knowledge of DNA sequences of genes and other parts of the genome of organisms has become indispensable for basic research studying biological processes, as well as in applied fields such as diagnostic or forensic research. The advent of DNA sequencing has significantly accelerated biological research and discovery. The rapid speed of sequencing attained with modern DNA sequencing technology has been instrumental in the sequencing of the human genome, in the Human Genome Project. Related projects, often by scientific collaboration across continents, have generated the complete DNA sequences of many animal, plant, and microbial genomes. DNA Sequence Trace
  • 15. Microfluidic system • consist of microfluidic platforms or devices for – Fluidic sampling – Control – Monitoring – Transport – Mixing – Reaction – Incubation – Analysis
  • 16. Lab-on-a-chip • Lab-on-a-chip is becoming a revolutionary tool for many different applications in chemical and biological analyses due to its fascinating advantages (fast and low cost) over conventional chemical or biological laboratories. • Furthermore, the simplicity of lab-on-a-chip systems will enable self-testing capability for patients or health consumers overcoming space limitation. • The idea of lab-on-a-chip is basically to reduce biological or chemical laboratories to a microscale system, hand-held size or smaller.
  • 17. Advantages • Low cost: Many reagents and chemicals used in biological and chemical reactions are expensive, so the prospect of using very small amounts (in micro- to nanoliter range) of reagents and chemicals for an application is very appealing. • Requires very small amounts of reagents/chemicals: – enables rapid mixing and reaction: biochemical reaction is mainly involved in the diffusion of two chemical or biological reagents – microscale fluidics reduces diffusion time as it increases reaction probabilities – practical terms, reaction products can be produced in a matter of seconds/minutes, whereas laboratory scale can take hours, or even days. • Minimize harmful by-products: since their volume is so small
  • 18. Materials for Microfluidic Devices • Silicon • Glass • Polymer
  • 19. Silicon • Microfluidic channels on silicon substrates are usually formed either by wet (chemical) etching or by dry (plasma) etching.
  • 20. Glass • Excellent optical transparency • Ease of electro-osmotic flow (EOF).
  • 21. Fabrication techniques 1. Chemical wet etching • hydrofluoric acid (HF) • buffered hydrofluoric acid • a mixture of hydrofluoric acid, nitric acid, and deionized water (HF, HNO3,H2O) • 2. Thermal fusion bonding
  • 22. Polymer Reasons Materials • Low cost • Polyimide • Ease-of-fabrication • Favorable biochemical • PMMA reliability • PDMS • Compatibility (Polydimethylsiloxane) • mass production: using • Polyethylene or – Casting – Hot embossing polycarbonate – Injection molding • successful commercialization
  • 23. PDMS • (H3C)3SiO[Si(CH3)2O]nSi(CH3)3 where n is the number of repeating monomer [SiO(CH3)2] units.
  • 24. polymer micro/nano fabrication techniques • Casting • Hot embossing • Injection molding
  • 25. Casting Casting is a manufacturing process by which a liquid material is usually poured into a mold, which contains a hollow cavity of the desired shape, and then allowed to solidify. The solidified part is also known as a casting, which is ejected or broken out of the mold to complete the process. Casting materials are usually metals or various cold setting materials that cure after mixing two or more components together; examples are epoxy, concrete, plaster and clay. Casting is most often used for making complex shapes that would be otherwise difficult or uneconomical to make by other methods. Casting is a 6000 year old process.[2] The oldest surviving casting is a copper frog from 3200 BC.
  • 26. Hot embossing Hot embossing is essentially the stamping of a pattern into a polymer softened by raising the temperature of the polymer just above its glass transition temperature. The stamp used to define the pattern in the polymer may be made in a variety of ways including micromachining from silicon, LIGA, and machining using a CNC tool (for making large features). A wide variety of polymers have been successfully hot embossed with micron-scale (and below) size features, including polycarbonate and PMMA. This technique is used primarily for defining micro-channels and wells for fluidic devices. The benefits of this approach are the ability to take advantage of the wide range of properties of polymers, as well as the potential to economically mass produce parts with micron-scale features.
  • 27. Injection molding Injection molding (British English: moulding) is a manufacturing process for producing parts from both thermoplastic and thermosetting plastic materials. Material is fed into a heated barrel, mixed, and forced into a mold cavity where it cools and hardens to the configuration of the mold cavity. After a product is designed, usually by an industrial designer or an engineer, molds are made by a moldmaker (or toolmaker) from metal, usually either steel or aluminium, and precision-machined to form the features of the desired part. Injection molding is widely used for manufacturing a variety of parts, from the smallest component to entire body panels of cars.
  • 29. Disposable Smart Lab-on-a-Chip for Blood Analysis The disposable lab-on-a-chip cartridge has been fabricated using plastic micro-injection molding and plastic-to-plastic direct bonding techniques. The biochip cartridge consists of a fixed volume microdispenser based on the sPROMs (structurally programmable microfluidic system) technique, an air- bursting, on-chip pressure source, and electrochemical biosensors.
  • 32. Microchip PCR • The PCR reaction is a thermal cycling procedure for amplifying a nucleic acid target. PCR is used to amplify DNA targets and a reverse transcriptase-PCR (RT-PCR) is used for RNA targets. • PCR is a three step process in which each step is performed at a different temperature. – 1. In the first step, double-stranded DNA is denatured at a temperature of approximately 95 °C. – 2. Next, each of the two single strands of DNA are hybridized (annealed) to pairs of oligonucleotide primers at approximately 55 °C. – 3. In the final step, a thermostable magnesium ion-dependent polymerase derived from Thermophilus aquaticus (Taq polymerase) synthesizes complementary DNA in the region flanked by the primers using added deoxynucleotide triphosphates (dNTP) at approximately 72 °C (extension).
  • 33. Microchip PCR Schematic of a flow-through-type of PCR microchip. The serpentine reaction microchannel crosses each of three zones (T1, T2, T3) each of which is set at a different temperature
  • 35. Microchip PCR Products • However, despite strong indications that the development of microchip-based PCR analyzers are nearing completion, few have been commercialized. One example of a PCR microchip-based device is the miniature analytical thermal cycling instrument (MATCHI) system (Smart Cycler see www.cepheid.com). This is a battery-powered portable, real-time, integrated analytical system based on PCR performed in an array of silicon microchambers [52, 59, 61]. The entire system fits inside a briefcase for ease of transport. Applications identified for this nucleic acid analysis device include forensic, environmental and agricultural analyses and detecting biowarfare agents [62, 63, 64].
  • 38. Optical detection of proteins Optical detection of proteins and reagent storage and delivery. (i) Schematic representation of the POCKET immunoassay powered by a 9 V battery. (ii) Actual device. (iii) Apparent silver absorbance values of anti-HIV-1 antibodies from HIV-positive patients and control patients. (iv) Schematic representation of reagent-loaded cartridges. (v) Overlay of fluorescence and brightfield images of the immunoreaction area, with fluorescent signal corresponding to presence of labeled detection antibodies on antigen stripes. The concentrations indicated above the picture refer to the concentration of sample tested in each microchannel.
  • 39. Optical detection of proteins Immunomagnetic separation and detection of proteins with CMOS Hall sensors. (i) Schematic representation with inset showing actual chip. (ii) Comparison of the outputs of CMOS chip and ELISA
  • 40. detecting nucleic acids Integrated nanolitre DNA analysis device. (i) Schematic representation with two liquid samples and electrophoresis gel present. (ii) Optical micrograph of device.