Biosensors_Lecture10

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    Responsive Drug DeliverySystems

    Lecture 10

    Traditional Drug Dosing

    Medicine or injections

    Each person responds uniquely Noticeable symptoms are not sufficient to support

    timely and accurate dosing

    Examples- diabetes, cardiovascular disease, acute

    pain

    Controlled release frequent exposure, side effects,

    tolerance

    02:22 Biosensors 2

    Responsive Drug Delivery System

    Applying micromachining, biosensors, telemetry, and

    other techniques at the interface of analytical

    chemistry and bioengineering to revolutionize drug

    delivery

    Responsive drug delivery:

    SensingDelivery

    Micro-fabrication

    Telemetry

    02:22 Biosensors 3

    Responsive Drug Delivery Systems:

    Combination of Biosensors & controlled release

    system

    Revolutionized medicine by enabling individualized

    therapy

    Sense continuously to manage unpredictable

    condition Immediate respond with appropriate

    countermeasure

    Give the patients more flexibility and less disruption

    of the daily life

    02:22 Biosensors 4

    ICD (implantable cardio defibrillator)

    Located inside patients body-

    sense-deliver drug

    Monitors heart beat

    Sensing:

    highly sensitive, selective

    and robust sensors-monitor

    small volumes of body fluids

    Protein engineering, molecular

    biology-bioreagents-biosensors

    Human physiology, physiological

    fluids- affect biosensors

    02:22 Biosensors 5

    Insulin Pumps

    An insulin reservoir (like a

    regular syringe)

    A small battery operated pump

    A computer chip for control

    Infusion set- a thin plastic tube

    to deliver insulin to the body

    Pump therapy

    A basal rate & bolus insulin

    Combination with Glucosesensors

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    Glucowatch

    Reverse iontophoresis (a.k.a.

    Electromotive Drug Administration

    (EMDA))- interstitial fluid.

    Biographer: non-invasive, watch-like

    device that measures glucose

    AutoSensor: a plastic part that

    snaps into the Biographer and sticks

    to the skin.

    Noninvasive & automatic reading

    every 10 mins up to 13h

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    How does Glucowatch work?

    Based on reverse

    iontophoresis

    A low electric current pulls

    glucose through the skin.

    Glucose is accumulated in

    two gel collection discs in

    the AutoSensor.

    Another electrode in the

    AutoSensor measures the

    glucose.

    02:22 Biosensors 8

    Enzymatic pathway

    Glucose oxidase

    catalyze oxidization of

    glucose in hydrogel

    Hydrogen peroxide

    reacts on the platinum

    electrode, providing

    electrons

    Current is proportional

    to glucose

    02:22 Biosensors 9

    Comparison of Glucose Readings

    02:22 Biosensors 10

    Advantage of closed loop drug delivery:

    life sustaining benefit for cardiac

    serve as alarm angina, stroke, cancer, etc

    Alpha Dx, the OPTI critical care analyser, the senDX

    100, I-Stat point of care blood analysis

    Medtronic MiniMed sensor, MiniMeds 2007

    implantable insulin pump- 72 hrs

    02:22 Biosensors 11

    The Importance of Control

    Programmed release controlled by microchips

    More flexibility & less pain

    Reduced the risk of side effects

    More than 200,000 people in the US wear insulin

    pumps

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    Limitations: Biocompatability and foreign body

    responseSolutions: use of biomimetic surfaces,

    polyethylene oxide coatings,NO releasing material

    Delivery: 2 types of commercial delivery system

    1. implantable infusion pump2. noninvasive reverse iontophoretic

    devices Piezo actuated silicon micropump using

    MEMS size 16X12X1.86mm, flow rate 100 l/h.

    02:22 Biosensors 13

    Types of responsive drug delivery systems

    02:22 Biosensors 14

    Commercially available

    Implantable fusion pumps

    Noninvasive reverse ion-tophoresis devices

    Controlled release

    Duros implant technology

    Responsive

    Closed loop

    Responsive polymers

    Micro and miniature

    systems

    Microfabricated sacrificial

    valves

    Artificial muscle

    miniature valves

    Preprogrammed to deliver at any release rate through a catheter to a

    specific body location

    Electric current applied across skin to extract analyte from within/beneaththe skin

    Continuous release for pain medication, individually tailored using an

    osmotic gradient

    Delivers as a function of sensor signal;includes sensing and release systems

    Release from a smart polymer i n response to a stimulus

    Contains nano- to low-microliter volumes of therapeutic agents in

    individually sealed reservoirs; drug is released by electrochemically

    removing each microvials lid

    Based on a soft hydrogel and polymer blend

    that mimics natural muscle functions

    Duros controlled release device

    Pain medication

    4mm diameter, 44mm

    length holds 150L drug

    and deliver at rate

    0.4L/day.

    Responsive delivery

    release physiologicalsignal

    Smart polymers deliver

    drug biological stimulus

    Antigen-antibody

    interaction

    02:22 Biosensors 15

    Controlled-release device

    Affecting factors:

    Compositions of osmotic agent

    Thickness of semipermeable membrane

    Surface area

    Antigen-antibody interaction smart polymers

    A semi-interpenetrating

    polyacrylamide (PAAm)

    hydrogel

    Antigenrabbit

    immunoglobulin G

    (rabbit IgG)

    Antibodygoat anti-

    rabbit IgG (GAR IgG)

    02:22 Biosensors 17

    Antigen-antibody interaction smart polymers

    02:22 Biosensors 18

    Effect of free antigen concentration on the

    hydrogen swelling rationAntigen recognition by antigen-antibody

    semi-IPN hydrogel

    Takashi Miyata et al., Nature, vol 399 ,766

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    Antigen-antibody interaction smart polymers

    Reversible swelling

    changes

    Antigen-responsive

    permeation

    (a model protein

    drug haemoglobin

    through a membrane

    fabricated from

    hydrogel )

    02:22 Biosensors 19

    Schematic of a Self Regulating

    Responsive Therapeutic System

    Microfabrication:

    Nonconventional MEMS polymeric materials

    control surface properties

    Microreservoirs store sensing reagents/active drug

    solid or liquid form

    Eg. Microchip based device mechanism -

    elecrochemical dissolution of metal cover film Soft hydrogel and polymer valves

    -mimic natural muscle

    02:22 Biosensors 21

    Telemetry

    Wireless transmission of data

    Integrated with defibrillators, pumps or retinalprosthetics

    Monitor intrauterine pressure changes, bodytemperature and heart rate of a fetus

    Pill sized wireless cameras and image sensorsendoscopic capsules

    02:22 Biosensors 22

    Future perspectives and challenges

    Combination of sensing and delivery

    Small and easy to implant and remove, patient

    compliance

    Long-lived, biocompatible and inexpensive

    Inert, mechanically strong, comfortable for patient

    Safe from accidental release, easy to fabricate and

    sterilize and allow high drug loading

    Continuous monitoring, telemetric data transfer and

    allow physician intervention if needed

    02:22 Biosensors 23

    Control- circadian rhythm

    Norplant - Subcutaneous

    implantation contraceptive

    device

    Incorporating telemetry

    access sensor and delivery at

    all times.

    02:22 Biosensors 24