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Metabolic and Clinical Biosensors

Metabolic and Clinical Biosensors. Various Metabolic and Clinical Biosensors. Various Biosensors:. Example: Protein sensor. pH sensor Glucose sensor Lactate sensor Urine sensor Blood flow and pressure sensor DNA sensor Protein sensor Bacteria sensor Others. Glucose Sensors.

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Metabolic and Clinical Biosensors

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  1. Metabolic and Clinical Biosensors

  2. Various Metabolic and Clinical Biosensors Various Biosensors: Example: Protein sensor • pH sensor • Glucose sensor • Lactate sensor • Urine sensor • Blood flow and pressure sensor • DNA sensor • Protein sensor • Bacteria sensor • Others

  3. Glucose Sensors

  4. What is Diabetes? • A condition where the body is unable to regulate the amount of glucose in the blood due to lack of insulin or the body’s inability to produce insulin. • A condition where there is too much glucose in the blood. • In the US, about 10% of the total population has diabetes. – A very serious health issue….

  5. Types 1 Diabetes • Also known as “juvenile diabetes” or “insulin-dependent diabetes” • Usually develops in children or young adults • An autoimmune disease where the immune system is destroying the cells of the pancreas • The body does not produce enough insulin to control the amount of glucose in the blood. • People with type 1 diabetes must take insulin daily

  6. Type 2 Diabetes • Also known as “adult-onset diabetes” or “non-insulin dependent diabetes” • Usually an disease of adults however is becoming more common in obese children • A disorder where there is high blood glucose due to insulin resistance or deficiency • The body is not producing enough insulin to control the glucose in the blood • Based on diet, exercise and medicine, type 2 diabetics may not need to take insulin daily

  7. What is glucose? Glucose: • A simple sugar that serves as the chief source of energy for the body.

  8. Hypoglycemia vs. Hyperglycemia • Hypoglycemia: • Low blood sugar • 60mg/dL or less • Occurs mostly in Type 1 diabetes or in elderly • Hyperglycemia: • High blood sugar • 240mg/dL or higher • Can cause damage to eyes, kidneys, heart and nerves

  9. Blood Glucose Monitoring What is it? • Blood Glucose Monitoring is a way of checking the concentration of glucose in the blood using a glucometer. What is the purpose? • Provides quick response to tell if the sugar is high or low indicating a change in diet, exercise or insulin.

  10. Why monitor blood glucose? • Reduces risk of developing complications with diabetes. • Allows diabetics to see if the insulin and other medications they are taking are working. • Gives diabetics an idea as to how exercise and food affect their blood sugar. • May prevent hypoglycemia or hyperglycemia

  11. Commercial Glucose Sensors • Biggest biosensor success story! • First made by Medisense (early 1990s), now 5 or more commercial test systems • Rapid analysis from single drop of blood (5~10% error and take 5 seconds to 1 minute) • Enzyme-electrochemical device on a slide

  12. Patient Diabetes Management • Insulin secretion by pancreas regulated by blood glucose, 4.4 to 6.6 mM normal • In diabetes, regulation breaks down • Wide swings of glucose levels • Glucose tests tell patient how much insulin to administer; or what other action to take

  13. Glucose Biosensor 1 Enzyme O2 O2 + + 2e- Glucose Glucose + 2H+ Gluconolactone + H2O2 H2O2 Electrolyte Oxygen permeable membrane Glucose permeable membrane Working electrode Oxygen-electrode based sensor for glucose • Oxygen has to exist in electrolyte (sensor performance is affected by environment) • High electrode potential (700 mV vs Ag/AgCl) – high noise

  14. Glucose Biosensor 2 The Second Generation Glucose Sensor • Replace O2 with a mediator (synthetic e- acceptor to shuttle e- from the flavin redox center of the enzyme to the electrode) • Measurements become insensitive to O2 fluctuations, and can be carried out at lower potentials (0~200 mV vs Ag/AgCl) – low noise • Enzyme mediators – dimethyl ferrocene, medolablue

  15. • Most sensors use enzyme called glucose oxidase (GO) • Most sensors are constructed on electrodes, and use a mediator to carry electrons from enzyme to GO Fc = mediator, ferrocene, an iron complex These reactions occur in the sensor: Fc Fc+ + e- (measured) GOR + 2 Fc + --> GOox + 2 Fc GOox + glucose --> GOR + gluconolactone Reach and Wilson, Anal. Chem. 64, 381A (1992) G. Ramsay, Commercial Biosensors, J. Wiley, 1998.

  16. Glucose biosensor test strips (~$0.50-1.00 ea.) Dry coating of GO + Fc e’s Meter Read glucose electrodes Patient adds drop of blood, then inserts slide into meter Patient reads glucose level on meter Output: Amperometry Constant E I t

  17. Research on glucose sensors • Non-invasive biosensors - skin, saliva, tear • Implantable glucose sensors to accompany artificial pancreas - feedback control of insulin supply • Typical use 3-4 weeks for implantable sensor in humans • Failure involved fouling and inflammation Google smart contact lens

  18. Continuous Glucose Monitoring

  19. What is Continuous Glucose Monitoring (CGM)? • Continuous Glucose Monitoring systems use a tiny sensor inserted under the skin to check glucose levels in tissue fluid. • The sensor stays in place for several days to a week and then must be replaced. • A transmitter sends information about glucose levels via radio waves from the sensor to a wireless device.

  20. How It Works A: Insulin Pump that is set up to receive radio transmissions, from label D, and controls the administration of insulin. B: Insulin Transfusion Set that is attached to the body and remains in use for up to three days before requiring replacement. C: A tiny glucose sensor that is inserted into subcutaneous tissue, also requires replacement after three days of use. D: Small light weight device attached to the glucose sensor and is used to transmit the collected data to a digital read out, in this case the insulin pump.

  21. Advantages of Continuous Glucose Monitoring • Frequency of testing = more data to work with • Viewing of trends allowing easier predictions and fine tuning of treatment. • Less frequent need for finger sticks • Less likelihood of complications because of uncontrolled diabetes.

  22. Disadvantages of Continuous Glucose Monitoring • Safety- The implanted sensor is designed to be used, currently, for a short period of time. • Efficiency and Accuracy- Current day sensors do not always work properly for the first few hours after insertion because the bodies immune system tries to fight against the foreign object causing blood sugar reading to not be as accurate as desired. • Cost- Although more effective in predicting future levels of glucose, the out of pocket expense can be significantly higher because some insurance companies view this currently as experimental treatment.

  23. Futuristic Approach

  24. Cell transplantation device motivation Semipermeable membrane Hormone deficiency diseases Nutrient Cell • Diabetes • Parkinson’s disease • Parathyroid disease Antibody Oxygen Therapeutic factor Antibody • Hormone injection • Organ transplantation • Cell transplantation

  25. Previous approaches Alginate-based containers Self-assembled containers Encapsulated the pancreatic islet Johns Hopkins, Gracias lab Issues Issues • Non-uniform porosity • Low mechanical / chemical stability • Not biocompatible (Ni, Cr, Cu) • No cell encapsulation

  26. Nanoporous microcontainer J. Kwon, K. Trivedi, JB Lee, et al., JVST B, 2010 B. Gimi, J. Kwon, JB Lee, et al., Biomedical Microdevices, 2010 B. Gimi, J. Kwon, JB Lee, et al., J. Diabetes Sci. Tech., 2010 K. Nemani, JB Lee, et al., Journal of Microencapsulation, 2011 • The cell loaded base and the lid bonded in bio-friendly aqueous environments • Medical grade photocuredadhesive and modified SU-8 bonding successful β-cell encapsulation Hollow cuboid base Male structure Nanoporous lid

  27. Why microneedles? • Skin • Stratum corneum: 10~15 m (dead cell), Epidermis: 50~100 m, Dermis: > 500 m (nerves and blood vessels) • Microneedle array • Patch-type painless drug delivery and body fluid sampling

  28. Microneedle-based glucose sensor Y. Yoon, JB Lee, et al., Transducers, 2011 • Microneedle-based glucose sensor • ~85% of bio sensor in the market is glucose sensor • Sharp Si microneedle (painless blood sampling) • Multi-walled carbon nanotube growth + Platinum nanoparticle deposition (increase surface area for improved sensitivity) 380 μm After wet etch (sharp Si microneedle) After DRIE After Pt NP deposition After MWCNT deposition

  29. Microneedle-based painless diabetes test strip • Microneedle-based diabetes test strip • Ag/AgCl reference electrode (RE) integrated • Sensitivity 17.73 ± 3 μA/mM-cm2 • Selectivity tested with ascorbic acid and 0.1 mM acetaminophen • Mobile health care • Use a smartphone as a glucose meter • SD-like adapter board and app Sensor + microneedle Dedicated glucose meter Micro-SD-like adapter board

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