implantable microelectronic devices -...

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© 2015 Maysam Ghovanloo 1

Maysam Ghovanloo([email protected])

Implantable Microelectronic Devices

Implantable Microelectronic Devices

ECE 8803/4803

Fall - 2015

School of Electrical and Computer EngineeringGeorgia Institute of Technology


Implantable drug delivery systems (DDS) are designed to store and deliver small, precise doses of therapeutic drugs or medicines into the blood stream or to specific tissue sites, subsequently replacing the daily injection of drugs required for pain relief and for the treatment of many conditions and diseases such as osteoporosis, heart disease, cystic fibrosis, glaucoma, age-related macular degeneration (AMD), diabetes, refractory epilepsy, and cancer.

Implanted Drug Delivery Systems

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Outline

Webb, C.E.; Chip ShotsIEEE Spectrum, Vol. 41, Issue 10, Oct 2004 Page(s):48 - 53

Implantable Drug Delivery Systems


Why Implanted Drug Delivery?• Existing ways – pills, injection, etc.

– Not fully effective– Disruptive– Painful– Side effects

• Some newer drugs/proteins– Get chewed by liver/stomach – waste!

• NEED: smarter drugs– Go only wherever they need to go– Go there on time

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Two Smart Approaches

• Implanted microchips with drug reservoirs– Active control - initiated wirelessly - MicroChips

– Passive control – no initiation, use of sensors

• Quantum Dots – Identify/kill cancer cells selectively


MicroChips Device

• 15 mm microchip

• Transistors <--> Reservoirs

• Drug reservoir capped by Ti & Pt, accessed by Au.

• Operation triggered remotely w/ wireless link

• Successful operation in humans.

• Microchip BioTech Inc.http://microchipsbiotech.com/index.php

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Current Version• Each implant contains 100's of

micro-reservoirs, small hermetically sealed compartments, each of which store up to 1 mg of drug.

• The microchip-based implant is activated by a wireless signal which triggers the micro-reservoirs to release the drug on a pre-programmed dosing schedule.

• In addition, the implant can be built with sensors that release drug in response to physiological or metabolic changes in the patient.


Clinical Trial• The microchip platform was tested in women

with osteoporosis to deliver teriparatide, a synthetic parathyroid hormone (PTH) typically administered via daily injections to increase bone mass.

• The study found that women receiving teriparitide via the microchip-based implant absorbed the same therapeutic levels of the drug as observed in women who take daily injections (e.g., bioequivalent).

• In addition, the study found that the release profile of drug delivered via the microchip was more consistent from one dose to the next, compared to doses delivered via subcutaneous injection.

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Challenges:• How long will the devices

function reliably?– Years/decades of operation

without replacement

• Fouling – body’s response to implantable device – Thick capsule isolating device

from rest of body

– Liquids that attack device

– Degree of fouling depend on: chip’s location, type of drug inside device, kinetics of drug delivery


Some approaches to challenges

• Coat implant w/ anti-inflammatory drugs

• Have many small sensors/devices on one chip, use one at a time

• Have drug “chambers” that could be refilled from outside w/ syringes

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“Closed-loop” Systems

• Purpose: take the patient out of the loop –human error

• Close the loop with sensors that monitor/regulate body automatically

• Ex: Congestive Heart Failure (CHF)– Detect increases in pericardial fluid with sensor

part of the device

– Reduce buildup by releasing diuretic from drug-delivery part of the device


Structure of qDot NanocrystalTOP: Schematic of the overall structure of a Qdot nanocrystal conjugate. The layers represent the distinct structural elements, and are drawn roughly to scale.

BOTTOM: Relative size of Qdot nanocrystals. Qdot nanocrystals are roughly protein-sized clusters of semiconductor material.

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Quantum Dot Approach• Attach cancer drugs to quantum

dots to selectively deliver it to cancer cells

• When infrared light is shine on qDot, release the drug that attack cancer cells

• Use same approach to deliver the drug even to nucleus or mitochondria

• Reduce side effects, increase drug’s efficacy


Shuming Nie’s qDots

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Challenges• Human body is thicker than mouse’s –

harder to deliver IR light to inside organs

• Toxicity of quantum dot materials - kidney damage, heart disease, hypertension, cancer, bone & joint pain– Use coatings to cover qDots

– Alternative materials

• How long qDots last in the body?

• Which organs clear them?


Drugs Delivered When and Where They are Needed

1. Why some new protein based drugs cannot be taken orally or even through injection?

2. Why implantable drug delivery systems need both drug release mechanism as well as biochemical sensors?

3. What are the major challenges in development of the implantable drug delivery systems?

4. What are some of the solutions?

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Implantable Drugs Delivery Systems

5. What are the parameters affecting fouling in implantable BioMEMS devices?

6. How can a closed loop drug delivery system be used for eliminating heart attacks?

7. How can a closed loop drug delivery system be used for congestive heart failure?

8. How quantum dots can be used for drug delivery?

9. What properties of quantum dots is attractive in drug delivery systems?

10. What are the limitations of light-activated quantum dot drug delivery mechanisms for humans?

11. What is a possible solution to resolve the toxicity of quantum dot particles?


Outline

M.L. REED and W.K. LYE, Microsystems for drug and gene delivery

Proceedings of the IEEE, Volume 92, Issue 1, Jan 2004 Page(s):56 - 75

Implantable Drug Delivery Systems

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Drug and Gene Delivery1. What are the applications of

microfabricated drug delivery probes?

2. What are the advantages of local delivery of drugs at clinically relevant concentrations?

3. What are the pros and cons of in-plane microstructures for developing microneedles?

4. What is the lateral and longitudinal dimensions of microneedles?

5. Which layer in the skin is the most appropriate for delivery of drugs? Why?

6. Could mosquito proboscis or bee stinger be a good natural model for drug delivery microneedles?

A common house mosquito proboscis tip (Culex sp.). The proboscis contains six parts: two pairs of sharp, flexible cutters (serrated "blades" and sharp tipped "knives") surrounding a pair of fine tubes - one for sucking up blood, the other for dripping a chemical into the wound that keeps the blood flowing.

Image and text copyright © Dennis Kunkel. All rights reserved.


Drug and Gene Delivery7. What are the pros and cons of out-of-plane

microstructures for developing microneedles (compared to in-plane structures)?

8. How do Si microneedles with no lumen cab be useful in drug delivery?

9. What are the pros and cons of side openings in microneedles compared to tip openings?

10. What are some of the gene transfer techniques for introduction of foreign genes in plant and animal cells?

11. How does micromechanical piercing work?

12. What are the advantages of MEA-based (micro-enhancer arrays) delivery of genes and vaccines through skin over intramuscular or intradermal injection?

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