RESEARCH POSTER PRESENTATION DESIGN © 2012

www.PosterPresentations.com

Currently, the process of drug delivery for cancer patients in

chemotherapy is very inefficient, and there is minimal control over the

drugs once they enter the patient’s bloodstream. Chemotherapeutic drugs

are often dispersed throughout the bloodstream rather than targeting

tumorous locations exclusively. In addition, highly concentrated drugs can

be helpful, but would impose serious damage if not properly controlled.

Pulse Therapeutics has developed an innovative technology for drug

delivery in stroke patients using drug-conjugated magnetic nanoparticles

(NPs). Due to the size of the particles and the strength of the applied

magnetic field, this technology is limited to areas of the human body with

low fluid flow, such as the brain ventricles.

The market needs a more effective chemotherapeutic drug delivery

system that can target specific locations of interest within a patient’s body.

With this new system, doctors should be allowed to increase effective

dosage during the treatment process. A high concentration of

chemotherapeutic drugs will allow for a shorter treatment time thus

increasing the effectiveness of the process without causing severe

repercussions or side-effects.

Background & Need

Design Overview

The device contains these following main components: the support

frame with frame base (light green and dark blue), the rotation assembly

(light blue), the tilting assembly (yellow), the main motor (red) and motor

housing (purple), the magnet (green), and the movement motors (orange).

Magnetic Device DesignOverview

In order to determine the appropriate ultrasound and transducer

specifications, it is imperative to understand how Doppler ultrasound

utilizes the unique properties of the superparamagnetic NPs to track its

movement. Recent studies have shown that Doppler ultrasound imaging

can be used to detect the movement of iron oxide NPs if magneto-motive

ultrasound imaging is used. In magneto-motive ultrasound imaging,

magnetic NPs are ‘subjected to modulating magnetic fields and these

modulations are detected as frequency shifts in Doppler ultrasound

measurements’ [1]. This technique works best when the NPs exhibit

superparamagnetic properties and is made up of iron oxide particles; this is

due to the idea that iron oxide NPs have a strong magnetic susceptibility

relative to the magnetic susceptibility of tissue, making it a good contrast

agent for ultrasound imaging [2].

Since the nanoparticles provided by Pulse Therapeutics, Inc. is

(Fe3O4), a superparamagnetic iron oxide NP derivative, and since dynamic

magnetic field is required for movement control of NPs, the magneto-

motive ultrasound imaging technique applied on Doppler ultrasound

proves to be an effective method for NP tracking for this design project.

Because the NPs will travel in the cerebrospinal fluid, a low flow velocity

system, and since the rotating magnet will move the NPs at a considerably

faster speed than the speed of the cerebrospinal fluid as tested in vitro,

there will be a noticeable color contrast in Doppler image.

Imaging Modality

Future Directions

Further improvements can be applied to the magnetic device design.

The need for a precise control method for control of NP movement in 3D

range of motion was not completely solved in this project. Such a control

method would be essential for use of this device during a clinical

procedure. Currently, the magnetic device design is suitable for a proof of

concept through an in vitro procedure, but for a clinical trial more

extensive modifications must be applied.

The next step would be to create a precise control mechanism which

can be implemented into the magnetic device design. This would be done

through a programmed control algorithm which would be able to move the

magnet with respect to the position of the particles during treatment by

precisely controlling each motor’s power output. The algorithm would

require more extensive analysis of the particle motion, such as location and

velocity with respect to time. To achieve this, further analysis of the

magnetic device properties must be performed. Eventually, the goal of a

programmed control algorithm is to replace manual control of the device.

Conclusions

By combining each part of this design project, including the magnetic

device design, incorporation of imaging technology, and the phantom

design, the primary goals for the project have been attained. In summary,

this project proposes a way to provide a proof of concept through an in

vitro procedure with the rotating magnetic device, in which a phantom

replicates NP behavior in brain ventricles and an imaging technology is

used to show the ability to track these NPs. Therefore, with further

developments, the project has considerable potential in regards to clinical

setting applications, and producing a novel and efficient drug delivery

system for brain tumors.

References[1] John, Renu, and Stephen A. Boppart. Current Medical Chemotherapy 14th ser. 18 (2011): 2103-114. National

Institute of Health. Web. 8 Nov. 2013.

[2] Oh, Junghwan, Marc D. Feldman, Jeehyun Kim, Chris Condit, Stanislav Emelianov, and Thomas E. Milner.

"Detection of Magnetic Nanoparticles in Tissue Using Magneto -motive Ultrasound." Nanotechnology 17 (2006):

4183-190. Pubmed. Web. 5 Nov. 2013.

[3] Cole, David, and Antonio Sassano. Ultrasound: Physics and Technology. By Vivien Gibbs. 3rd ed. Vol. 1. China:

Elsevier, 2009. 37-50. Print.

[4] Roselli, Robert J., and Kenneth R. Diller . Biotransport: Principles and Applications. 1st ed.

New York: Springer Science Business Media, 2011. p. 139. eBook.

Project Scope

The goal of the design project is to develop an improved mechanism for

transporting chemotherapeutic agents with control to tumorous areas,

which includes:

1. Designing a device with adequate size specifications that generates

an exterior magnetic field and

2. Incorporating a tracking system through imaging technologies that

allow visualization of the particles inside the patient’s body;

3. Determining correct parameters when the device is in operation to

obtain the most desirable clinical results, and

4. Outlining a control mechanism that can be used to control the

movement of the particles in delivering the drugs and recollecting the

nanoparticles after treatment.

Design Requirements

Design Process

Magnet Device Design

– Rectangular vs. Conical vs. Spherical System

Imaging Modality

– Doppler Ultrasound

Imaging Phantom

– 3D Brain Tumor Phantom

Client: Mike Sabo - Pulse Therapeutics, Inc.

Chris Peng, Blessan Sebastian, Arvin Soepriatna – Group 37

Novel Drug Delivery in Pediatric Medulloblastoma

Parameters Specifications

Imaging Phantom Size < 3x3 ft

Imaging Phantom Weight ≤ 40 lbs

Magnet Device Dimensions < 3x3 ft

Magnetic Field Strength < 1 T

Imaging Depth < 10 cm

Standard Operation Time < 4 hrs

System Power Inlet Standard 110V

Budget $15,000

Parameters Specifications

Exposure Safety High, up to 4 hours

Resolution High, up to 8 cm deep

Compatibility with Dynamic Magnetic Field

High

Imaging Approach Non-invasive

Image Acquisition Duration Real-time Imaging

Size Small enough to allow free movement of magnets around the

patient’s head

Maneuverability High

Signal to Noise Ratio (SNR) High

Chosen Transducer

In order to obtain a high resolution image with good contrast

between bone, tissue, and nanoparticle interfaces, the frequency range and

the type of array of the probe needs to be considered. A high beam steering

angle will allow for control over the angle of insonation without excessive

movement of the probe[3].

Parameters Motor for Joint A Motor for Joint B

Type of Motor Stepper Motor Stepper Motor

Torque 10 N∙m 300 N∙m

Power 5 W 100 W

Size < 15 cm in all 3 axis < 15 cm in all 3 axis

Step Angle < 2o < 5o

Weight < 10 lbs < 20 lbs

AC/DC DC DC

Cost < $500 < $500

Phantom Design

SafetyPrimary hazards categorized with HIGH risk level:

– Drawing-in nearby magnetic materials during testing.

– Rotating magnet in close proximity to user or patient.

– Machine Instability due to improper device positioning.

– Excessive force/exertion due to careless handling of magnetic

device.

Device Design Top View with Dimensions (Support Base Hidden for Clarity)

Rotation Assembly (blue) with control demonstration. Tilt Assembly (yellow) with control demonstration.

Assembly Motor Specifications

Specific Parts

Parameters Specification

Frequency Range 3-5 MHz

Type of Array Linear Phased Array

Imaging Depth 40-60 mm

Resolution 1 mm axial x 1 mm lateral

Steering Angle 60-90 degrees

Cost