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7/31/2019 Biosensors_Lecture10
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11.05.2012
1
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
02:22 Biosensors 6
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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
02:22 Biosensors 7
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
02:22 Biosensors 12
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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