client: mike sabo - pulse therapeutics,...
TRANSCRIPT
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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