Vanderbilt University

Department of

Biomedical Engineering

BME 273

Automated Maze System Development

Group 9 Samar Shah (BME) Tanvir Haque (BME) Siddartha Sanathanamurthy (EE)

Advisors: Dr. Herbert Y. Meltzer, Department of Psychiatry

Dr. Paul King, Biomedical Engineering

ABSTRACT One of the simplest tests for examining memory in animals is the rat maze. A group in

the Department of Psychiatry is interested in the effects of certain drugs on memory. By

using a process called microdialysis, the group is able to study drug distribution within

the animal's body. In order to obtain data pertinent to memory effect, the machine must

be attached to the rat continuously. The problem that arises with the experiment is the

burden that the dialysis machine presents. As the rat runs through the maze, it is up to the

researcher to ensure that tubes do not get tangled against maze walls, and that the rat

cannot sense the presence of the overhead machine. Thus, he must manually guide the

machine through the course of the maze. It is the objective our group to propose a design

for a fully independent module that facilitates the researchers' study. In order to perform

such a task, three objectives must be met: a means of sensing the rat's position, a means

of moving the dialysis machine, and a way to communicate the imaging system's position

information to the drive mechanism. Our design involved using a standard web cam to

locate the rat's position, a written LabVIEW script to calculate distance change, a lead

screw drive mechanism to translate the dialysis machine, and a microcontroller to

communicate between the latter two. Due to budget constraints, however, we could not

fulfill the original intentions of our design. As an alternative, we developed theoretical

models to test the principles of both our imaging system and our drive mechanism.

Although no tangible design will be developed, a better understanding of image

acquisition systems, processed information from microcontrollers, and mechanical

principles of linear actuators was obtained. With the development of the two theoretical

models, the perceived design was realized and will be used for educational purposes.

1

INTRODUCTION

Research in pharmaceutical drug development involves a battery of testing,

particularly in animals. In the case of studies pertaining to drug effects on memory

cognition, a common experiment involves the use of a lab rat within a maze. Food is

designated as the prize for each run, and thus the motivation behind every decision. By

making the rat run through the maze multiple times, the rat will base its decisions on his

memory, in hopes of achieving its ultimate goal: food. Dr. Herbert Meltzer's lab in the

Department of Psychiatry is using the method to study the effects of schizophrenic drugs

on the cognitive centers of the brain. His group is interested in analyzing the

neurochemical processes that accompany the concept of memory. In doing so, he hopes

to apply his findings to the biochemistry of schizophrenics, eventually producing drugs

that will help restore proper chemical ratios. To facilitate "study of drug distribution,"

the group uses a process called microdialysis, where neurochemical samples are

continuously collected from certain regions of the brain, and then analyzed for chemical

content1. Through this analysis, the researchers will know what types of

neurotransmitters are being affected by the introduction of the drug.

The challenges faced by the lab include the physical limitations imposed by the

apparatus of the

microdialysis machine,

shown in Figure 1. The

machine is roughly a

square foot in area, and

weighs 2 pounds. Two tubes are implanted within a rat's skull into the prefrontal cortex - Figure 1 Dialysis machine from lateral view

2

one delivering dialyzing fluid, the other removing the fluid and eventually leading to a

collecting duct. These tubes each measure a maximum of 36 inches in length, and both

are directly attached to a dialyzing unit. Because the acquisition of samples requires a

fixed connection during the task, the rat must be continually be attached to the machine

via the tubes, depicted in Figure 2, even as it runs through the maze. The maze itself is a

radial 8-arm maze, and can be seen in Figure 3. Each arm spans 20 inches, while the

central area is 11 inches in diameter. The depth of the maze is 18 inches. To maintain

the integrity of the experiment, it is up to the researcher to manually guide the machine

throughout the maze, to match the rat's path and

speed. Not surprisingly, these imposed limitations

causes problems for the researchers. First, the

tubes connecting the rat to the machine often

times get tangled, and caught on the corners of the

maze wall. Secondly, the researcher must be

extremely careful not move the machine within

the perception field of the rat – that is, it is

imperative that the rat not sense the presence of

the machine, as it can have serious psychological repercussions, and thus affect the purity

of the collected sample. Finally, it often proves cumbersome for the researcher to have to

occupy himself with the guidance of the machine. If the process was somehow

automated, the researcher would be free to do other things during the experiment.

Figure 2 Rat hooked up to a microdialysis machine

3

4

Our goal is thus to eliminate these problems posed by the experimental setup.

Our design should provide a self sustaining module that will facilitate the researcher's

study. As explicitly plotted in the process diagram, (Appendix 2), the entire procedure

should be replicated within our module, and also automated as an open loop system.

Thus, the rat can run through the maze without any assistance from the researcher, and

the entire experiment can be self sustaining.

The first task would be to identify where

the rat is in the maze, and determine if it

had moved. If so, the device needs to

calculate the change in position. Finally,

the device will communicate this change in

position to a type of drive system, which

will then translate the dialysis machine to

match the rat's new position. The process is

then repeated, and constrained to a looped system. In order to perform such a task, three

things are needed: a means of sensing the rat's position, a means of moving the dialysis

machine, and finally, a way to communicate the imaging system's position information to

the drive mechanism.

METHODOLOGY

The methodology to obtain and process an image required that the camera was

calibrated to acquire clear and well resolved images. From there, the 16-bit image was

converted to an 8-bit image to make the processing more manageable and more robust.

The image was then filtered using color thresholding techniques. Lastly the image was

Figure 3 8-arm radial maze. For dimensions, see Appendix 1

pattern matched with a template to determine the center pixel value of the pattern we

were looking for, in our case a circle. This pixel value was then converted to a physical

coordinate value and outputted to the microcontroller.

The camera was calibrated based on the following image requirements:

resolution, pixel resolution, field of view, working distance, sensor size and depth of

field. The resolution, dependent upon the smallest feature size on the object that the

imaging system must distinguish, was determined to 1cm. This would be appropriate

because it would prevent small particles or patterns to interfere with the imaging system.

The field of view or the area of the object that the camera must acquire was determined to

be 20 inches by 20 inches. The working distance, or the distance from the camera lens to

object was determined to be 30 inches. The depth of field or the maximum object depth

that remains in focus was determined to be 6 inches, based on the rat’s height. Using

these variables, the lens focal length was determined by Equation 1:

Equation 1

and a spatial calibration process was applied to convert the pixel to a real-world unit

transformation while accounting for many errors inherent to the imaging setup2.

The Full Dynamic approach is used by NI Vision Assistant 8.0 software to

convert a 16-bit image to an 8-bit image. The minimum intensity value of the 16-bit

image is mapped to 0, and the maximum intensity value is mapped to 255. All other

values in the image are mapped between 0 and 255 using the equation shown below. This

mapping method is general purpose because it insures the display of the complete

dynamic range of the image3. Because the minimum and maximum pixel values in an

image are used to determine the full dynamic range of that image, the presence of noise

5

or defective pixels can affect the appearance of the image. IMAQ Vision uses the

technique summarized in Equation 2:

Equation 2

where z is the 8-bit pixel value, x is the 16-bit pixel value, y is the minimum intensity

value and v is the maximum intensity value.

Clustering thresholding technique was

used to filter the image. This technique sorts

the histogram of the image within a discrete

number of classes corresponding to the

number of phases perceived in an image4. The

gray values are determined along with a

barycenter is for each class. This process repeats, until it obtains a value that represents

the center of mass for each phase or class. This allows for the results to be obtained

regardless of the lighting conditions as well as the histogram values from the image.

From Figure 4 it can be seen that the clustering technique can be used to determine the

threshold pixel value (k) such that all gray-level values less than or equal to (k) belong to

one class 0 and the other gray level values belong to another class 1. The threshold value

is the pixel value (k) for which Equation 3 is true:

Figure 4: Image histogram where i represents gray level value, k represents the chosen threshold, h(i) – number of pixel values.

Equation 3

where μ1 is the mean of all pixel values that lie between 0 and (k), and μ2 is the mean of

all the pixel values that lie between k+1 and 255.

6

Pattern Matching was employed to detect and locate the center pixel value of a

specified pattern. Firstly, a template was created which represents the object for which

we were searching; in our case it was a dark circle. Pattern matching techniques include

normalized cross-correlation, pyramidal matching, scale- and rotation-invariant matching,

and image understanding. We focus our discussion on normalized cross-correlation

because it was the primary method used in pattern matching. Normalized cross-

correlation is based on a series of multiplication operations. MMX technologies are

employed by IMAQ Vision to find a template in an image5. Although the technology is

complex, the basic concept of correlation is as follows: Consider a sub-image w(x,y) of

the size K x L within an image f(x,y) of size M x N, where K ≤ M and L ≤ N. The

correlation between w(x,y) and f(x,y) at a point (i,j) is given by Equation 4:

Equation 4

where i= 0,1,…M-1 and j= 0,1…N-1, and the summation is taken over the region in the

image where w and f overlap.

From the above mentioned pattern matching technique, the center pixel value of

the pattern in determined by the IMAQ Vision program. This pixel value is then

converted to a physical coordinate value based on the calibration principles mentioned

above.

The crucial challenges associated with the design of the translational device was

to provide a means of movement that will be able to compete with the demands of the lab

rat, as well as the limitations of the experimental setup. The scope of the radial maze, as

stated above, includes 8 individual arms that measure 20 inches in length as well as a

7

central circular area 11 inches in diameter. Thus, the entire maze spans a total of 51

inches in diameter. Because the rat can travel the entire length of the maze at a minimum

time of 2 seconds, its top speed is roughly 2 feet per second. Keeping in mind the

limitations of the experimental setup, the length of the transmission tubing connecting the

rat to the dialysis machine could not exceed a length of 36" and still preserve the integrity

of the machine's collection mechanism6. The device should also protect the integrity of

the experimental setup in that it should introduce little to no experimental variables in the

psychological study. Factors affecting any of the cognitive senses, whether that is the

rat's visual perception of the overhead device or the tactile sensation of the moving

implanted tubing, can affect the rat's neurochemistry during the experiment.

In order to propel the dialysis machine across the enclosed area of the maze, we

needed to choose a translational drive mechanism. Common mechanisms include a

pulley/belt drive system, a lead screw drive, hydraulics, and geared systems. Using a

QFD plot, we chose to use a lead screw device, as it is relatively cheap to make, it

requires low maintenance, and also is relatively easy to work with (Appendix 3). A

schematic of the lead screw device is pictured in Appendix 5. To encompass the entire

two dimensional area of the maze, the translational device would consist of two different

lead screw arms, one for the x direction, and one for the y direction. The Appendix

depicts a bird's-eye view of the device (Appendix 10). The arms will then be supported

by an aluminum scaffold, as depicted in the Appendix (Appendix 4).

As the lead screw device is motor driven, we had to look at two different

parameters – rotational speed and torque. The rotational speed is dependent on the

modeled speed of the mouse as well as the pitch of the threaded rod being rotated.

8

Assuming a speed of around 2 ft/s, and then using a small common pitch of 2 revolutions

per inch, the rotational speed needed is 2880 RPM. Torque is dependent on the force

required to drive the load. The Force is calculated by Equation 57:

FT = Fa + FF Equation 5

where FT is the total force, FA is the force of acceleration and FF is the frictional force.

The Force of acceleration is governed by Equation 27:

FA = W/g + a/12 Equation 6

where W is the weight of the load, and a is the acceleration in in/s. To arrive at an

approximate acceleration, the mouse's movements were modeled as a worst case

scenario. Assuming that the rat runs continuously from end to end, its position is

modeled as a sine function, and the rate acceleration was determined by differential

calculus. The maximum weight that needs to be driven comes out to be around 16

pounds, while the acceleration is around 21.16 in/s. The frictional force is determined by

the coefficient of friction of the nut/screw system (.15) times the normal force of the load

(16 pounds). The torque needed is then calculated via Equation 37:

T = FT * (1/(2π*e*p)) Equation 7

where e is equal to the efficiency of the threaded rod (.4) and p is the pitch of the screw

(2 inches / revolution). The calculated torque finally came to around 750 g-cm. The

motors that we selected provide a torque of 816 g-cm and a speed of 3000 rpm. With the

selected motors, the dialysis machine would be able to be translated across all areas of the

maze, as the lead-screw drive would span the entire 51 inches of the maze.

The purpose of the microcontroller is to take the change in position according to

an image change from the LabVIEW software and convert it into a current waveform that

9

can be used by the driver and mechanical arm system. Choosing a microcontroller for

this operation proved to be quite logical. Since there were two systems from which to

choose, the sensor system and image acquisition system, there ended up being two types

for microcontrollers to use, the Motorola 68HC11E and the National Instruments PCI-

7342, each with their advantages and disadvantages.

The use of the Motorola microcontroller was optimal with the sensor system. The

advantages were the low cost, around $200, the on-board Analog to Digital converter and

the external independence from a computer. The disadvantages were the less calculating

capabilities resulting in a slower resolution, and less input ports8.

The use of the National Instruments microcontroller was optimal with the image

acquisition system. The advantages were the four 8-bit input ports, the available

processing capabilities and the software compatibility with the LabVIEW software. The

disadvantages were the relatively high cost, and the dependence of a computer since it is

an internal PCI card9. After meeting with Dr. Karsai of the Vanderbilt School of

Engineering, the decision to use a more advanced microcontroller to control the image

system was made. Ultimately, the National Instruments PCI-7342 microcontroller was

chosen since the image acquisition system was picked10.

The way the calculation process of the microcontroller described earlier works in

a simple way. The LabVIEW software will output a physical coordinate based on the

position of the target in pixels. Since the feed is in real time, the microcontroller will

constantly be given this physical coordinate from each frame. This will be anywhere

from 5-30 frames a second. The microcontroller will then take this coordinates (Xn ,Yn)

and compare it with the coordinate given previous (Xn-1, Yn-1). The comparison taken

10

will be the difference between the two coordinates. In other words, the distance from the

first coordinate to the second coordinate will be taken. This number will be rounded for

significant digits and converted into a pulsed waveform.

There will be two outputs from the microcontroller. One output for the change in

x-coordinate and one output for the change in y-coordinate. The waveform will be

predetermined based on testing how far the motor will translate the mechanical arm in a

given rotation. However, since the output current of the microcontroller will only be a

few milliamps, a current driver will be needed to obtain the amps needed. The driver will

be connected from the microcontroller and will feed into the motors translating the arm

through the maze.

RESULTS

Due to budget constraints imposed by the Department of Psychiatry, we could not

implement our design into a workable, final model. According to a correspondence with

Dr. Adam Prus, of the Department of Psychiatry, the decision to go forward with the

project ultimately came down to "the cost of the project vs. the number of experiments

that [the group] anticipate[s] this maze to be used for." Because "current methods of

combining microdialysis and behavior are far more rudimentary than what [we]

designed," the department held that "the current techniques [would] be sufficient." . For

the complete correspondence between our group and the department, please see

Appendix 14. In order to qualify the integrity of our design, we decided to develop

theoretical models to represent the basic principles of our design. The first would be a

model involving the workings of our image acquisition system. The second would

reproduce the operation of the lead screw device.

11

11

11

12

The image acquisition

program performed all the tasks

described above and thus

successfully tracks the movement

of the specified object in real

time. In order to examine our

script, we developed a test to

model the degree of contrast of

marking versus its background.

To represent the contrast between a marking and a white rat, the software was told to

locate a black circle against a white background as shown in Figure 5. The figure shows

a screen shot of the LabVIEW software program which is set to determine where the

circle is in the image. The tables to the left outputs the pixel values of the center of the

circle in a coordinate form. The X and Y axes start at the top right corner of the image.

Thus we have successfully demonstrated that the image acquisition program can track, in

real time, a previously specified pattern.

To test the theoretical principles of our lead screw mechanism, a scaled model of

our design was

constructed. The

parts used included a

3V DC motor

acquired from an

erector set, a 1 foot 8-

Figure 5: LabVIEW screen shot of image acquisition program set to determine the circle in the image and output the pixel value in the table towards the left in the screen-shot. LabVIEW Code in Appendix 18

Figure 6 Lead Screw theoretical model

32 threaded rod, an 8-32 nut, and various scaffolding parts from the aforementioned

erector set. Figure 6 shows the assembled device.

In running tests on the device, we found several design concerns that deserve

attention. The first regards the integrity of the rod itself. Slight bends or imperfections

may cause stoppage of the nut's carriage through the rod. These stoppages could prove to

be fatal to the arm's operation, and thus extra care should be given to ensure that the rod

is free of kinks. However, the prevalence of these imperfections decreases as the

thickness of the rod increases. Because we were working with such a small model of the

screw (diameter roughly equals 4 mm), the rod was more prone to developing flaws.

Secondly, we found that any debris on the surface of the rod would also hinder the nut's

movement. The rod should therefore be cleaned properly to avoid stoppage. We found

that a slight application of lubrication, such as WD-40, prevents many instances of

stoppage, however, does not eliminate stoppages completely (those caused by kinks).

Therefore it is imperative that the rod is well lubricated before use.

The total market for cognitively effective antipsychotic drugs (ADP) is about 12

billion dollars. Out of which about 3 billion dollars a year is spent on research

development. Bottom line profit for the industry is about 10% or about 1.2 billion dollars.

Current automated maze models cost from $30,000 to $50,000. Assuming that out of the

3 billion dollars spent on development, about 1% is spent on automated mazes, then

about 1,000 mazes are bought each year just for ADP development. This estimate is quite

conservative because institutional buyers are not included in the estimate and because

mazes used for other types of research and development are not included. Although we

do not have specific figures we could conservatively estimate at least 100 mazes sold to

13

institutional buyers a year. Thus, we set our market cap at 1,100 mazes sold per year and

a total market cost of about $55 million per year if buyers are willing to pay $50,000 per

maze. Our primary market would be commercial ADP developers, followed by

institutional buyers.

The total cost of our project is about $4,000

for just the parts and software; this does not include

development costs such as labor, training, repair and

other consulting costs. Table 1 shows the general

breakdown of costs based on four primary systems

including: scaffolding, mechanical arm,

microcontroller and the imaging software. Given the completed, prototyped, and tested

design for this system, it would take three engineering student fifty hours total to build

the complete system. At a wage rage of $15/hour, the total labor cost of building the first

automated maze system would be $750. Therefore the total development cost would be

$750. The specific cost breakdown for the components for each device is given in

Appendix 11.

Budget Support Scaffolding 99.70 Mechanical Arm (Including driver electronics) 1527.02 Microcontroller 895 Imaging Software 1,355.00 Grand Total 3876.72

Table 1: A general breakdown of costs based on the four primary systems

The cost of maintenance in the system would include re-calibrating the camera if

it becomes dismounted or loses focus due to excessively rugged use. Another cost could

be replacing the motors if they stop working. These costs would include travel expense

for an on-site visit, which would vary; and 3 hours of labor cost. The total cost of

maintenance would $45 not including travel costs.

The overhead cost for this device for sale to the manufacturer is $4,676.42, which

is the total cost (including labor) for the first production of the system. Marketing costs

14

would include talking with different companies and selling the system to them. This

would include traveling costs, advertisement costs and costs to upkeep a website. We

estimate these costs to be $2,000 not including travel. Distribution costs would include

shipping the product to the customer and travel costs to setup the system. We estimate

$1,000 towards distribution costs not including travel.

The rugged design and construction of the system will allow the use of this

system for at least five years. Some parts such as the motors or the lead screw may need

replacement due to normal wear and tear and frequency of use. With further development

the system will only become more robust and more stable. We estimate a minimum life

cycle of five years.

The projected market price for the product is $50,000 based on similar automated

maze system sold currently. Thus our product would be competitively priced at $45,000.

Unlike the systems currently available in the market, ours is completely customizable and

is easily convertible and thus can be used in various different types of experiments. Thus

we have a competitive advantage in terms of pricing, expandability and service. The total

cost of the system including parts, labor, marketing costs and distribution costs is

$7,676.42. This gives us a bottom line profit of about $37,000. Based on these estimates

we have a profit margin of about 20%. We believe that because of our competitive

advantage, we would be able to control at least 50% of the market share within two years.

This would mean that in two years we would sell about 500 mazes at the cost of $45,000.

A profit margin of 20% would give us a bottom line profit of $4.5 million within two

years.

15

One of the main goals of this design is to allow experiments to take place without

any interference or physical guidance of the experimenter. With this in mind, the safety

of the experimenter is ensured since there is minimal contact with the design.

Furthermore, another goal of the design is to avoid entanglements of the tube feeding,

which is connected to the rats head, around corners of the maze. Since the microdialysis

machine will theoretically be constantly above the rat and the rat will always be in one of

the corridors of the maze, there should be no entanglements due to the corners of the

maze. Thus, the safety of the rat from our design is guaranteed.

The benefits of the design are apparent because of the goals set up from the start.

The researchers will be able to conduct other experiments while the rat is progressing

through the maze. They will also be able to monitor the rat from a computer away from

the area of the maze ensuring the best cognitive responses of the rat with minimal

environmental changes. Furthermore, since the dialysis machine will constantly be over

the rat, the environment of the rat will be consistent leading to better cognitive results.

The FDA uses the regulations from the National Research Council in order to

determine proper animal and human considerations for this particular research12. The

regulations that apply to our design involve two different areas. The first one is the

treatment of the rat in the radial maze and the second is the microdialysis aspect. Our

physical design adheres to the FDA considerations of both areas. One of the techniques

used to encourage the rat's curiosity is food deprivation. Rates are food deprived to get

the appropriate response for a food reward. Animals are weighed daily and are not

allowed to have their weights fall below 85% of their free-feeding weight (the weight

before food deprivation). Furthermore, with this set up, the rat is the lowest level species

16

that can be used in this model. The maze is cleaned between sessions and is built using a

non-porous material. The cage where the rat's are housed is cleaned daily. The rats are

inspected daily by Vanderbilt's Department of Animal Care with veterinarians on call

24/7. Since the rats are social animals, they are housed in groups, except after the

microdialysis surgery in order to taper infections. Furthermore, the housing facility for

the rats are cleaned routinely and ventilated properly12.

For the microdialysis aspect of the project, the surgeries are conducted under

aseptic conditions in order to reduce infections. Additionally, the probes are sterilized to

further reduce infection. As a side note, microdialysis is only used on animals, so human

considerations of this aspect are not needed. If the rats need to be killed, an anesthetic

overdose, which is recommended by the FDA and the National Veterinary Council, is

used. The procedure allows the assessment of regional neurotransmitter release, which

currently cannot be conducted on humans. This procedure allows for the testing of

therapeutic drugs that are not yet approved for use with humans due to efficacy and

safety concerns12.

CONCLUSION

Overall, this research will allow for the correlation between neurotransmitter

release and memory performance and will allow for the testing of any

pharmacotherapeutics that may have relevance for treating cognitive impairment in

humans in diseases such as Alzteimer's and Schizophrenia. These are common methods

for evaluating potential drug therapies prior to being administered to humans.

The budget sent to the advisors of our senior design proved to be a sticking point for the

project. Due to departmental reconsiderations in the psychiatric department, the funding

17

to build our design was not given11. According to the advisor, before our design could be

realized, an assessment of microdialysis in an alternative behavioral model needed to be

completed. Additionally, since the experiment set up and the data obtained were rather

rudimentary, using a complicated system such as the image acquisition system to gather

this type of information was considered overkill. Additional suggestions of applications

of our design were offered, however, the budget limitations proved to be too much for the

psychiatric department to overcome. Ultimately, our design, though considered valuable

by the psychiatric department, was not approved.

Although the actual design was not constructed, two theoretical models were

developed in order to demonstrate the fundamental principles of the design. The first

model is a demonstration of the image acquisition system using the LabVIEW software.

The demonstration shows the capabilities of the LabVIEW software obtaining an image,

isolating the image, determining the pixel coordinate, and converting to a physical

coordinate. All of this will be accomplished in real-time. The second model is a

demonstration of the mechanical arm and motor system. This model will be 1/5 scaled to

the actual design size. The system is constructed from Erector set materials and two

Erector set motors. With this model, the platform can be translated along the X and Y

coordinates exactly the way it would if it were the actual design.

Though no tangible design will be developed, a better understanding of image

acquisition systems, processed information from microcontrollers, and mechanical

principles of linear actuators was obtained. With the development of the two theoretical

models, the perceived design was realized and used for its educational purposes.

RECOMMENDATIONS

18

The sensor system's advantages are the independence from a computer, the

relatively lower cost of the system, and the low processing requirements. Along each

arm of the 8-arm radial maze, 5 IR detectors would be used with 5 IR emitters. Detecting

the center of the maze proved to be challenging. Normal IR detectors would not be

sufficient in this area because of the numerous crossings in that area which would make

the position of the rat difficult to determine. In order to get a proper reading of the

center, piezo sensor strips would be implemented. There would be 8 piezo sensor strips

connected to each other making a circle 5-6" away from the center of the maze.

All of these sensors would be connected to filter circuits. This would eliminate

the unwanted objects from detection and only allow the physical body of the rat to be

detected. The signals from these filters would then be connected to an analog to digital

converter. This conversion is necessary so the microcontroller can use this information

for its computation. The signal is then connected to the microcontroller. The Motorola

68HC11E has an analog to digital converter on board8 . The microcontroller would have

a predetermined table set up with different coordinate combinations. Each combination

would take into consideration the sequential steps the microprocessor would need to take

in order to translate the mechanical arm system when each sensor is set off. Each step

would have an x-coordinate and y-coordinate associated with it. These would be fed into

the driver, amplified, and fed into the motors to drive the mechanical arm system10.

The sensor system would not be independent from the maze. Each sensor would

be physically connected to the maze. They would have to stay there permanently in order

for the table set up in the microcontroller to work. If a new maze were to be used, a new

19

sensor system as well as a new table for the microcontroller would both need to be set

up10.

After review of the lead-screw device, it may be reasonable to explore other

alternatives. Due to issues such as nut carriage stoppage, and load related speed-

dampening, the lead screw device may not be as reliable as perceived. These problems,

however, can be avoided with the use of more powerful motors. Nevertheless, if price is

not an issue regarding budgeting, it may prove worthwhile to invest in a belt drive

system, as it is less prone to stoppages, and provides superior accuracy in terms of

carriage placement. If one were to still venture into the lead screw realm, there is another

alternative that uses the same principles. A company called Roh'lix developed a

threadless linear actuator that converts rotary energy to linear motion. Instead of using a

threaded rod, the Roh'lix actuator uses a polished rod to run through. With the absence of

threads, the frequency of stoppages is dramatically reduced, as friction is minimized.

However, with the reduction of stoppage frequency comes a slight loss in accuracy as

well as resolution, as the device is prone to slippage. The Roh'lix device, however,

deserves consideration for a project on somewhat of a limited budget. While the lead

screw device will work for the designed application, it may be easier as well as more

convenient to set up an alternative mechanism.

References 1 Hodht C, Opezzo AW, Taira CA. Microdialysis in Drug Discovery. Current Drug

Discovery Technologies. 1:269-285 2004 2 "System Setup and Calibration." IMAQ Vision Concepts Manual. National Instruments 2005. 3 "Image Processing and Analysis." IMAQ Vision Concepts Manual. National Instruments 2005

20

4 "Thresholding." IMAQ Vision Concepts Manual. National Instruments 2005. 5 "Pattern Matching." IMAQ Vision Concepts Manual. National Instruments 2005. 6 Prus, Adam. Personal interview. 8 Dec 2005. 7 "Drive Mechanisms" Techno Isel H830 Catalog. Techno Isel.11-16. 2006

<http://www.techno-isel.com/Tic/H830/PDF/H830P011.pdf> 8 "Motorola 68HC11E." Family Data Sheet. 2005. Freescale Semiconductor. 20 Feb.

2006 <http://www.freescale.com>. 9 "NI PCI-7342." Datasheet. Nov 2005. National Instruments. 20 Feb. 2006

<http://www.ni.com>. 10 Karsai, Gabor. Personal interview. 11 Feb 2006. 11 Prus, Adam Ph. D. "Next Steps." E-mail to Samar Shah. 15 2006. 12 "Guide for the Care and Use of Laboratory Animals." 1996. National Research

Council. 10 Apr. 2006 <http://www.nap.edu/readingroom/books/labrats/chaps.html>.

13 "Rats and Mazes" Rat Behavior. 2004. 08 November 2005

<http://www.ratbehavior.org/RatsAndMazes.htm>

21

Appendix 1

Appendix

Maze Dimensions13

Depth = 18"

Appendix 2

Process Diagram

Operate Transport Store Idle

Identify Rat Position

Compare to Previous Location

Calculate Change in Position

Convert Image Space Coordinates to Physical Coordinates

Convert Physical Distance to Rotational Distance

Power Motor for set Revolutions

Translate Dialysis Machine

Appendix 3

QFD Plot

Lead Screw

Drive Belt

Hydraulics

Gear Rail

Quality Methods Weight

Precision + ++ ++ 5

High Speed + ++ ++ + 5

Low Cost ++ - - - 3

Low Maintenance + - 2

Durability + + + 3

Large-Scalability + + - 5

Appendix 4

Box Scaffolding

Appendix 5

Lead Screw Device

Appendix 6

Threaded Rod

The threaded rod will span the entire length of the maze (51") and will have a

pitch of 2 revolutions / inch. They have a bore diameter of 3/8".

Guide Rod The guide rod will counter act the motor's generated moment and provide a linear

guide for the translation of the block.

Coupling

The couplings will connect the motor to the threaded rod, so that the motor's

torque will be transferred to the screw. Couplings will also be used to transfer the

motor's rotational energy to the optical encoders.

Optical Encoders Optical Encoders will be used to count the number of revolutions that the motor

turns per command. The encoders will feed into the microcontroller so that position may

be monitored

Linear Bushing (not pictured)

Linear bushing acts as a friction minimizing guide for the block along the guide

rod.

Linear Block

The linear block is an end support for the guide rods used in the design.

Threaded Nut

The threaded nut will be welded onto the block so that the screws rotation will be

converted to linear motion

Crowned Roller Rail (not pictured) The rail will act as a counter balancing support as well as a friction reducing

guide for the mechanical arm dimension traversing the maze.

Roller Bearing (not pictured)

The roller bearing is the wheel that will run within the rail.

End Stop (not pictured)

The end stops will prevent the wheel from escaping the two ends of the railing

system

Machined Items

A total of 5 blocks will need to be machined due to the dimensions of the various

components needed. The schematics for each are shown below

Appendix 7

Block 1 – will support block 2 as well as dimensional arm

Block 2 – will support dialysis machine and camera

Appendix 8

Angle Bracket – 2 needed

Support Block – will be mounted with wheel to run with rail system

Appendix 9

Overall Schematic

Appendix 10

Transverse View13

Software for Image Acquisition From Labview Vendor Item Quantity Price Labview Software 1 $2,900 $2,900 Vision Development Module 1 $2,400 $2,400 Academic Discount (75%) 1 $3,975 $3,975 Total $1,325 Parts for Image Acquistion USB WebCam 1 $30 $30 Total $30 SUBTOTAL A $1,355 Microcontroller Costs From LabView Vendor Item Quantity Price NCI PCI 7342 1 $895 $895 Total $895 SUBTOTAL B $895 Mechanical Arm Parts From mscdirect.com ORDER # Item Quantity Price

01206986 6 ft Stainless Steel Threaded Rod (3/8" dia. 8 thread, 4 stop) 2 $70.38 $140.76

85273381 Gray Iron Nut 2 $23.21 $46.42 35538280 Precision Steel Ball Bushing Bearing 2 $41.09 $82.18 02730349 Stainless Steel Retaining Ring 4 $8.31 $33.24 60038288 5 ft Hollow Steel Rod 1" 2 $192.16 $384.32

Appendix 11

35523018 Linear Shaft Support Block 4 $34.10 $136.40 6 ft Crowned Roller Rail 1 $52.24 $52.24 Roller Bearing 1 $17.42 $17.42 End-Stop 2 $2.76 $5.52 Total $898.50 From Jameco 237403CE Motors 2 $25.95 $51.90 1323942CE Motor Driver 2 $149.95 $299.90 Total $351.80 From Automationdirect.com Optical Encoder 2 $81.50 $163.00 Total $163.00 From Rocom Coupling - 5 mm to 3/8" 2 $15.93 $31.86 Coupling - 6 mm to 3/8" 2 $15.93 $31.86 Total $63.72 Scaffolding Parts From Home Depot Item Quantity Price 6 ft Angle Bracket Aluminum Bar 2 $13.27 $26.54 6 ft Flat Bracket Aluminum Bar 4 $6.97 $27.88

Appendix 12

4 ft Angle Bracket Aluminum Bar 4 $7.17 $28.68 4 ft Flat Bracket Aluminum Bar 2 $5.57 $11.14 5/16" Hex Bolt 16 $0.13 $2.08 5/16" Washer Bag (25 count) 1 $1.80 $1.80 5/16" Nut Bag (25 count) 1 $1.58 $1.58 Total $99.70 Machining Costs Total approx $50 SUBTOTAL C $1,626.72 GRAND TOTAL $3,876.72

Appendix 13

Date: Wednesday, March 15, 2006 10:16 AM -0600 From: "Prus, Adam J" <adam.j.prus@Vanderbilt.Edu> To: "Shah, Samar Kulin" <samar.k.shah@vanderbilt.edu> Subject: RE: Next Steps I just received word from Dr. Meltzer about the final decision on the radial arm maze project. Everyone was very impressed with your designs and ideas, but in the end, it came down to the cost of the project vs. the number of experiments that we anticipate this maze to be used for. Current methods of combining microdialysis and behavior are far more rudimentary than what you designed, but for our own current goals, the current techniques will be sufficient. This is not to say that what you designed may not be of great interest to other laboratories, especially in the future, when these combined experiments become more common place. In other words, your work was by no means a worthless endeavor and I would urge you to hang on to your ideas and plans for a possible profitable implementation in the future. It was a joy to work with you and please let us know how we can help with any evaluations, etc., that you may need for completing this course. Regards, Adam Adam Prus, Ph.D. Research Fellow Department of Psychiatry Vanderbilt University 1601 23rd Ave. south, Suite 306 Nashville, TN 37212-8645 Email: adam.prus@vanderbilt.eduPhone: (615) 327-7241 Fax: (615) 327-7093 __________________________________________________ From: Shah, Samar Kulin [mailto:samar.k.shah@vanderbilt.edu] Sent: Tue 3/14/2006 9:54 PM

Appendix 14

To: Prus, Adam J; tanvir07@yahoo.com; Sanathanamurthy, Siddartha; s.shah@vanderbilt.edu; King, Paul H Subject: RE: Next Steps Hi Adam, We did not hear from you, so we are still wondering about the status of the project. We are approaching a time when its too late to develop the project and finish it in time. Thus we are currently working with our BME adviser to develop an alternative educational project. Please keep us posted, if the status of the project changes; but as of right now, we are devoting all our time in the development of the educational module. Samar Shah --On Thursday, March 02, 2006 11:15 AM -0600 "Prus, Adam J" <adam.j.prus@Vanderbilt.Edu> wrote: > __________________________________________________ > From: Shah, Samar Kulin [mailto:samar.k.shah@vanderbilt.edu] > Sent: Wed 3/1/2006 3:15 PM > To: Prus, Adam J; Shah, Samar Kulin; Haque, Tanvir Rezwan; > s.shah@vanderbilt.edu; Sanathanamurthy, Siddartha; Dai, Jin > Subject: Re: Next Steps > > > > Hi, > Hope you are doing well. I was wondering if you had a > chance to > discuss the project with Dr. Meltzer and if the project time line > was in adequate detail. We are waiting on your decision, and eager > to hear from you. > > Thanks, > > Samar > > --On Wednesday, February 15, 2006 8:47 AM -0600 "Prus, Adam J" > <adam.j.prus@Vanderbilt.Edu> wrote: >

Appendix 15

>> >> >> Jin and I had a meeting with Dr. Meltzer yesterday afternoon. >> Dr. Meltzer was very impressed by your project designs and ideas >> and plans to say so on any kind of evaluation forms he will fill >> out for your project. However, he did not see an urgency in >> beginning the construction of this work at the current time and >> would first like to see an assessment of microdialysis in an >> alternative behavioral model. While the project is affordable, >> it is a bit too expensive to invest in while other options may be >> available. The alternative model (novel object recognition >> test), I should point out, has not been as thoroughly evaluated >> as the radial arm maze and may not produce useful results. Upon >> determination of this, he would then give a final decision on >> going ahead with the project. >> >> What was not clearly known at this meeting was the amount of time >> it would take to complete your project. I think it would be >> helpful to have a time line (just estimate and not too much >> detail) on the construction of your assembly, assuming you had >> everything you needed to begin (i.e., don't worry about shipping >> time, for example). If you can provide this to me, preferably >> soon, then I will try to get a clear decision on the continuation >> of this project. >> >> Thanks, >> >> Adam >> >> >> Adam Prus, Ph.D. >> Research Fellow >> Department of Psychiatry >> Vanderbilt University >> 1601 23rd Ave. south, Suite 306 >> Nashville, TN 37212-8645 >> Email: adam.prus@vanderbilt.edu>> Phone: (615) 327-7241 >> Fax: (615) 327-7093 >> >> >> >> __________________________________________________ >> From: Shah, Samar Kulin [mailto:samar.k.shah@vanderbilt.edu] >> Sent: Mon 2/13/2006 3:54 PM

Appendix 16

>> To: Prus, Adam J; Haque, Tanvir Rezwan; s.shah@vanderbilt.edu>> Cc: Sanathanamurthy, Siddartha; Dai, Jin >> Subject: Project Outline >> >> >> >> Hi, >> This PDF contains all the information regarding the >> project. It >> outlines the image system, the microcontroller, the scaffolding >> and >> the mechanical arm. It also includes the costs breakdown of each >> part and the whole system. >> I have put in an order for the LabView Software, and I >> will let >> you know as soon as it becomes available. >> In the mean time, if you want a video of how the software >> works in >> real time or if you have any questions, please feel free to >> contact >> us. >> >> --------------------------------------- >> Shah, Samar Kulin >> Vanderbilt University >> Email: samar.k.shah@Vanderbilt.Edu> > > > --------------------------------------- > Shah, Samar Kulin > Vanderbilt University > Email: samar.k.shah@Vanderbilt.Edu>

Appendix 17

Labview Code

Appendix 18

Program Screen Shot

Appendix 19