Proposal Outline Examples

The first of these examples provides an appropriate level of detail for a project that is

scheduled to complete the proposal in the last week of the quarter. There is some

paragraph text and some details in outline form. A few sections are still placeholders

for content that will be added later.

The second example contains quite a bit of draft text in the introduction. This text is not

necessary in the outline, but this document is the starting point for your draft proposal,

so go ahead and include as much text as you like. It is appropriate to have this much

done already if you plan to have your proposal nearly complete by week 8 or 9 of the

quarter. On the other hand, this example omits much of the outline. The remaining

sections should be included as a scaffold for the rest of the paper, as they were in the

first example.

-CMN

IMPROVED ANESTHESIA PACKAGING

Group Members: Hendrik Dorssers, Drew Matsuura, Aaron Stewart, and Ryan White

Primary Mentor: Dr. Kenneth Gow

Date: March 11th, 2016

Abstract:

Background and Significance

Statement of Problem:

● Sharp edges associated with opening ampoules/vials

● Debris that results from opening ampoules - contamination/filter needle

● Multiple people needed to open

● Possibility of getting poked or cut with glass/metal edges

Review of Current Devices

Vials

● Majority of anesthetic drugs and many other drugs are stored in vials

● Glass container with permanent rubber stopcock

● Sealed with thick aluminum foil cap as a tamper-evident seal

● Peeling off aluminum foil reveals a sharp edge that can lacerate

● Risk of needle punctures when drawing up fluid

Ampoules

● Only used for the most unstable of drug compounds; fairly rare

● Sealed glass container that are required to broken to be opened

● Breakage often reveals sharp edges that can lacerate operators

● Same risk of needle punctures when drawing up fluid

● Glass shards can break off into solution

○ Must be filtered before administration

Review of Intellectual Property

● A vial designed to store medical samples while the vial itself is made of a durable

and somewhat flexible plastic. This addresses our primary concern of safety as no

glass would be broken. However, sterility is still a concern.

● A plastic ampoule layered with polymers that provide: gas, steam, and light barrier

property. Additionally, the ampoule prevents drug permeation while also

preventing absorption and adsorption. This materials from this ampoule may be of

great interest to address our sterility concerns.

Review of Related Design Work

● Facilitator mechanisms to guide ampoule breaking (VIBRAC and OPC)

● Alternative materials to glass (plastics and polymer coating)

● SafeBreaK, Snapit (glass ampoule breaking devices)

● Twist-Tip vials (unit-dose squeezable vials)

● Hisafe ampoules

● Pre-filled syringes

Critical Evaluation of Existing Solutions (Individual Work) • Based on current solutions described above

Current Cost of Not Having This Technology (Individual Work)

● Unsafe working environment

○ Lacerations (often go undocumented)

○ Needle prick injuries

● Glass shards that may be injected inside a patient

○ Risk associated with procedures

● Time saved in the operating room (e.g. filter needle not needed)

Consequences of Success (Individual Work)

● Reduce injuries to OR personnel

● Create a safer working environment within the OR

● Increased in the effectiveness / efficiency of the OR

● Increased safety for patient

Barriers to Implementing This Technology (Individual Work)

Technological challenges

• Materials already exist. It will mostly be design/fabrication

• Sterilization

Economic, Ethical, Social, Legal, and Regulatory Issues

Legal

• Reduced potential for workplace injury lawsuits

Regulatory

• May need some approval since it potentially comes into contact with drugs

• Sterilization approval?

Economic

• Easier/quicker operating room times can reduce costs for patients

Ethical

Social

Plan of Work

Pending - we have suggested to Dr. Gow an idea for our Capstone (will meet with him

on Thursday, 2/4/16 to discuss our idea in further detail)

• Our idea: A device which can cut open a vial or ampoule. We would want to

accomplish this while still meeting all of the goals set by Dr. Gow.

o We may become interested in meeting with M E students to synthesize a

viable model for our device.

• If Dr. Gow wants to remain on track with developing a vial or ampoule, we will

have to continue to develop some other ideas. This will require for us to conduct

extensive research regarding appropriate materials that we can use.

o Pursuing this idea would require us to meet with MSE students who have

a better grasp of appropriate materials that we could utilize in our design

Specific Design Goal

Design Overview

Materials and Methods

Materials

Methods

Deliverables

Phase I (necessary product)

Phase II (desired product)

Anticipated Decision Points and Problems

Evaluation Methods

Resources

Timeline

Replace with Gantt chart (theoretical vs. actual)

Date Due Activities

Week 1 (1/4) Timeline and Resource Request (1/8)

- Seattle Children’s Medical Observership Form (online)

- Determine dates for operating room visits (Dr. Gow)

- Follow up with Dr. Low - Background research

Week 2 (1/11) - Observing - Needs Finding - Patent research (current solutions)

Week 3 (1/18) Patent / Literature Search (1/20)

- Observing - Needs Finding - Benchmarking (current solutions) - Begin outline

Week 4 (1/25) - Observing - Needs Finding - Brainstorming / Ideation - Continue outline

Week 5 (2/1) Proposal Outline (2/3) - Brainstorming / Ideation - Prototyping - Experimentation - Begin proposal

Week 6 (2/8) - Ideation - Prototyping - Experimentation - Continue proposal

Week 7 (2/15) Proposal Rough Draft (2/17) - Ideation - Prototyping - Continue proposal

- Share proposal draft and ideas with clinical mentors / gain feedback

Week 8 (2/22) - Ideation - Prototyping - Continue proposal - Begin presentation

Week 9 (2/29) Proposal Rough Draft (3/4) - Ideation - Prototyping - Continue proposal - Continue presentation

Week 10 (3/7) Presentation (3/7) Presentation Critique (3/9) Final Written Proposal (3/11)

- Ideation - Prototyping - Finish proposal - Finish presentation

Finals Week

Key Personnel

Anyone who has helped us along the way.

References

References go here.

Creating a Reproducible, High-Throughput Method of Inflicting Traumatic Brain Injury in Fruit Flies

Kimberly Willis and Kaleb Smith

PI and Primary Mentor: Dr. Promislow

January 18, 2016

Device overview: We are creating a semi-automated, tunable device to create repeatable traumatic brain injury in fruit flies. This device is designed for optimizing throughput and durability while maintaining or improving the repeatability of the injury delivered. This device will be able

to have predicted and actual measurements for impact parameters.

Background and Significance Problem Statement

Traumatic brain injury (TBI) is a malady that damages the brain, and is caused

by a combination of force and rapid acceleration/deceleration. TBI poses a serious

health risk in the United States and the rest of the world. It is the number one cause of

brain damage in youth (1).

We seek to design and build a device that may repeatedly and consistently inflict

TBI in Drosophila melanogaster. Drosophila melanogaster (fruit flies) have not been as

extensively studied compared to other animals. Fruit flies may offer insight into the

underlying causes of TBI that are unfeasable in other animals due to their relatively

short lifespans and availability. The ability to generate homozygous genetic lines

relatively quickly may shed light on the genetic factors associated with TBI

susceptibility.

Current Methods and Devices

Presently, the device in use to create TBI in Drosophila, the High-Impact Trauma

(HIT) device, has a patent application in process (2). This device consists entirely of

parts obtainable at a typical hardware store. A spring is pulled from a horizontal to a

vertical position while holding a vial of the appropriate group of flies in order to create

potential energy in the spring. When released, the vial of flies accelerates toward and

impacts a pad that is placed so that the vial can rest on it when the spring is at its

equilibrium position and length. Force and velocity measurements have been estimated

but have not been experimentally determined while the device is in use. Flies were

contained within a relatively small space by filling approximately ¾ of the vial with a

cotton ball. Outside of this device, there are very few devices and methods of creating

traumatic brain injury of a concussive type in flies.

In larger and more complex animals, many methods of inflicting traumatic brain

injury have been used. One common method occurs when a weight is dropped from a

specific point onto the open or closed skull of a rodent or rabbit when the skull is

immobilized (3, 4). Another very common method that is used in a variety of

circumstances and procedures is a controlled cortical impact, typically using a

pneumatic piston that delivers a specific force over a surface area determined by the

piston tip used (5, 6, 7, 8). One method used to specifically study TBI effects on people

who are injured without contact (i.e. soldiers with brain injury due to a bomb detonation)

is the detonation of a specific type of paper bomb at a specific position and distance

from an animal’s skull (9).

Intellectual Property and Ongoing Design Work

As mentioned, the HIT device has a patent application in process. This

application has multiple facets by including not only the device needed to inflict trauma

on flies, but also to measure and determine the genetic and molecular mechanisms

underlying the effects of the injuries. The portion of the patent relevant to this project

relies mostly on the sections denoting the devices. Another device that has an

application for a patent in process uses a pneumatic piston to inflict injury on larger

animals such as rodents. The intellectual property owned regarding specifically devices

designed to inflict brain injury in fruit flies is yet to be claimed. Therefore, there is a

significant amount of freedom in the designs that we can use.

In addition to specifically devices used to injure flies, there is a fully robotic

method of photographing and handling Drosophila produced by a group at Stanford

(10). There have been many methods and devices used to create traumatic brain injury

in larger animals, and multiple devices to handle and experiment on fruit flies, but

devices produced and in production that fall into both categories seem to be lacking.

However, there is a wealth of patents that deal with the prevention, detection,

and treatment of TBI. The lack of TBI-inducing mechanisms is perhaps due to the

potentially unethical nature of creating devices to specifically induce bodily harm.

Critical evaluation of existing approaches and design work

The existing devices in the field of traumatic brain injury (TBI) typically are

applied to medium to large animals such as mice, rats, rabbits, and piglets. For this

reason, as well as the recent discovery of Drosophila as a reasonable model for TBI, no

patented devices that inflict TBI on flies are readily found. The precision of physical

impact used by piston devices on vertebrate animals such as rats, although successful

for that size of animals, cannot be readily transferrable to flies due two major reasons:

the flies are too small and mobile to be easily positioned and restrained, and the

difference in depression of the head of the fly for injury and for death is less than one

millimeter.

For the one device that currently has a patent application and is used for flies

specifically, the success of the device is limited to injuring the flies on a full-body level

with a moderate repeatability and what seems to be little predictive ability of the degree

of injury (2). The flies are injured by being thrown against the walls of the vial, and

therefore receive not only brain injury but also body injury of many varieties based on

position in the vial and orientation when the vial accelerates. In addition to the variability

in the injury that each fly receives, the force that causes the injuries can only be

estimated from calculating the approximate force based upon the spring’s approximate

initial position. This exploits the imprecision due to the approximate nature of a person

determining each trial what the spring being vertical means as well as the force being

calculated as an ideal situation rather than returning a specific value.

In our lab, the device being used is modeled off the the device undergoing a

patent application, and requires a compressed foam pad for the impact surface. Due to

the most repeatable method being when the spring is pulled up to vertical, the scientist

pulls the spring to approximately vertical, and then releases the spring with a vial of flies

stuck onto the end. This seems to be a fairly imprecise method of creating injury, and

this method does not allow for a reasonable level of repeatability for multiple starting

positions of the spring. The compressed foam on the device used in the lab may also be

degrading, and therefore changing the damping of the impact force from trial to trial, that

could be causing another degree of imprecision. Another note when observing the

device used now in the lab, high-speed cameras show that the vial has a rebounding

path in which the flies are subjected to the initial impact injury as well as two more due

to rebounding and a second (lower force) impact. The difference between the HIT

device undergoing a patent application and the device used in our lab is the ability to

hold multiple vials of flies, which leaves room for maximizing throughput.

The current cost or consequence of not having this technology

Due to the spring system used, tunable impact mechanism that fits the more

common standard lab vial is not available. This minimizes throughput on the injury that

the flies receive as well as decreasing the ability to tune the degree of injury that the

flies will receive with a significant amount of precision between trials. One major area for

improvement is allowing the system to have multiple “settings” for the severity of impact

while maintaining at least the current degree of precision. Our device would improve

upon this by having a motor increase the acceleration of the vial-holder as it goes

through angular free-fall, and having the motor be responsive to an input of desired

impact severity. The inability to accurately assess the injury received is another way that

the device could be improved, as this device has a significant rebounding after the initial

impact that causes variable lower-force impacts on the flies. Our device would negate

this issue by having a locking mechanism of the vial holder at the time of impact so that

no rebound impacts could occur. The system now also forces back-calculations and

estimates from a high-speed video camera to be used in order to determine the final

velocity. Having a sensing system of the force or acceleration, as will be present on our

proposed device, could allow for determination of what level of injury harms the fly on

each trial in addition to the ability to predict the final velocity based upon the torque

produced by the motor and the mass of the vials and vial holder as a function of initial

position.

Barriers to implementing the technology

o Technological challenges (might be better later in paper)

-automation may be difficult without more precise instrumentation than we have

access to, sampling rates may be limited based upon the components used.

o Economic, Ethical, Social, Legal and Regulatory Issues

We are killing fruit flies, there is not an ability to add on to the $50,000 fruit fly

sorter robot as we don’t have the funds to purchase it. We may need to give royalties

(once the Katzenberger group’s application goes through) for the initial device design.

Social issues may come up as we are looking at genetic profiling fruit flies, and the

ethics of disseminating genetic dispositions to aging and neurodegeneration may be

detrimental to the mental health of some in society.

Plan of Work

Specific design goal: -To create a tunable device that will be used to inflict traumatic brain injury in

Drosophila melanogaster with a 50% mortality rate.

-The device will feature a computer interface that displays force and velocity

readings.

-The device should hold multiple vials of fruit flies for higher throughput.

-The device should be able to carry out multiple strikes in a run.

-The components, for the most part, should not wear down with repeated strikes.

Materials, methods, and specific tasks:

-We will be using general hardware store appliances (metal rods, a drill press,

screws and other attachment methods) as well as a motor and a locking mechanism.

-We will be creating a sensing method in LabView to relate the motor setting to

the intended force applied to the flies, and then to determine and record the actual force

applied to the vials.

-We will be building a device that can hold multiple vials of flies and torques the

vial holding arm enough to create an injury on the flies.

Deliverables:

Phase One- Build the device prototype and incorporate sensors

-We will be physically building the device to torque (a) vial(s) of flies for a 50%

mortality rate on one strike using a programmable motor.

-We will be incorporating an accelerometer into the vial holder in order to

determine the force upon impact.

-We will be introducing a locking mechanism into the system so that there is only

one impact with no (or minimal) rebound.

Criteria:

-induce some torque that has at least a 5% mortality rate

-different accelerations based on different inputs to the motor

-rebound after the impact should be less than 5% of initial height

Phase Two-

- Test and modify the device, optimize sensors.

- The device will be calibrated to provide accurate force/velocity readings.

- The device will be tested for wear-down over multiple strikes.

Criteria: - Sensor validation using other force/velocity measurement techniques

- Force/velocity measurements do not differ significantly after cyclic use.

- Critical parts do not fatigue over time.

- The device will be tuned for one genetic line of fruit flies to induce 50%

mortality.

Anticipated decision points, problems, and planned workarounds-

-We will have to decide the exact materials we would like to use, what sort of

locking mechanism we would like to use, and the sensing components and interfaces

we would like to use. At each of these points, there is the possibility of choosing an

option that is not optimal, and will therefore be doing research to prevent this and will

have the ability to use different components relatively easily due to our device type

being made up of hardware-store type components.

Methods to evaluate product-

-We will run through durability tests to determine what component has the

quickest breakdown (ideally an easily replaceable part)

-We will have a force plate put on the existing device and on the device we build

to determine if there has been any precision gained with this new design.

-We will statistically compare the desired force input that controls the motor and

the actual force output at the strike plate.

-We will go through the vials in each position to make sure that there is no

statistically significant difference in mortality between the vials through multiple trials.

Resources:

-We will likely need machine shop access for metalwork.

-3D printer for specialty parts.

-Sensor-computer interfaces such as ADC’s and LabView.

-Circuitry components such as soldering equipment.

References: 1. Hannay HJ, Howieson DB, Loring DW, Fischer JS, & Lezak MD (2004). "Neuropathology for neuropsychologists". In Lezak MD, Howieson DB, Loring DW. Neuropsychological Assessment. Oxford [Oxfordshire]: Oxford University Press. pp. 158–62. 2. Katzenberger RJ, Loewen CA, Wassarman DR, Petersen AJ, Ganetzky B, & Wassarman DA (2013). A Drosophila model of closed head traumatic brain injury. PNAS 110 (44): E4152-E4159. 3. Wei XE, Zhang YZ, Li YH, et. al. (2012). Dynamics of Rabbit Brain Edema in Focal Lesion and Perilesion Area after Traumatic Brain Injury: A MRI Study. Journal of Neurotrama 29(14): 2413-2420. 4. Mychasiuk R, Hehar H, Ma I, et. al. (2015). Dietary intake alters behavioral recovery and gene expression profiles in the brain of juvenile rats that have experienced a concussion. Frontiers in Behavioral Neuroscience 9(17). 5. Bao TH, Miao W, Han JH, et. al. (2014). Spontaneous Running Wheel Improves Cognitive Functions of Mouse Associated with miRNA Expressional Alteration in Hippocampus Following Traumatic Brain Injury. Journal of Molecular Neuroscience 54(4): 622-629. 6. Namjoshi DR, Cheng WH, McInnes KA, et. al. (2014). Merging pathology with biomechanics using CHIMERA (Closed-Head Impact Model of Engineered Rotational Acceleration): a novel, surgery-free model of traumatic brain injury. Molecular Neurodegeneration 9(55). 7. Margulies SS, Kilbaugh R, Sullivan S, et. al. (2015). Establishing a Clinically Relevant Large Animal Model Platform for TBI Therapy Development: Using Cyclosporin A as a Case Study. Brain Pathology 25(3): 289-303. 8. Zhang Z, Saraswati M, Koehler RC, et. al. (2015). A New Rabbit Model of Pediatric Traumatic Brain Injury. Journal of Neurotrauma 32(17):1369-1379. 9. Zhang Y, Yang Y, Tang H, et. al. Hyperbaric Oxygen Therapy Ameliorates Local Brain Metabolism, Brain Edema and Inflammatory Response in a Blast-Induced Traumatic Brain Injury Model in Rabbits. Neurochemical Research 39(5): 950-960. 10. Savall J, Ho ETW, Huang C, Maxey JR, & Schnitzer MJ (2015). Dexterous robotic manipulation of alert adult Drosophila for high-content experimentation. Nature Methods 12(7): 657-660.