We designed and prototyped an infusion pump for subcutaneous administration of immunoglobulin (IgG), an immunodeficiency treatment.  The device is an improvement on the technology which is currently available.  The prototype was fully functioning and was capable of administering customized medical therapy.  This project was completed as the final project submission in University of Pennsylvania's Medical Devices (BE 470) course.

Video #1 - Preparing Immunotherapy Infusion Demo

Video #2 - Executing Immunotherapy Infusion Demo

Video #3 - Concluding Immunotherapy Infusion Demo

Video #4 - Syringe Purge Demo

Problem Statement

Patients with compromised immune systems have what is called a primary immunodeficiency disorder (PID), where part of the immune system such as the immunoglobulin (Ig), or antibody population is missing or performing incorrectly. This makes them more susceptible to severe and recurrent infections because their body defense mechanism, the immune system, lacks a vital component (Bonagura). As of 2007, approximately “1 in 1,200 persons” is affected by PID in the United States (Boyle and Buckley). Patients who are unable to produce a sufficient amount of Ig require a treatment known as immunoglobulin replacement therapy. By taking into account the advantages and disadvantages of current treatments for PID, we propose a medical device that performs as an antibody pump and can provide more constant delivery of antibodies.

The current standard of care offers monthly injections, via IV infusions, or weekly subcutaneously-administered injections (Bonagura). The IV infusion is known as intravenous immunoglobulin (IVIG) therapy—it is administered approximately every 28 days and is “effective in preventing serious bacterial infections and improving the quality of life for treated patients” (Kobrynski). The other method is subcutaneous (SCIG) treatment, which is different because it is not administered through the vein and into the bloodstream, but rather under the skin in fatty tissue of the thighs, upper arm, or abdomen. Other differences include regularity of treatment reception, as SCIG must be delivered weekly. We will focus only on IVIG.

Patients with the immunodeficiency disorder are unable to produce the appropriate number of antibodies that a healthy individual has and so this treatment seeks to provide an external supply of antibodies on a regular basis. “Since [IgG] only replaces the missing end product but does not correct the patient’s defect in antibody production, [IgG] replacement is usually necessary for the patient’s lifetime” (Immunoglobulin Therapy & Other Medical Therapies for Antibody Deficiencies). This also creates a peak and trough pattern for antibody levels (a graphic representation is attached in the Figure 1). The peaks arise when treatment is given at the beginning of the 28-cycle and there is a trough in antibody levels towards the end of the cycle. Essentially, to prevent a patient from having a below-normal level of antibodies, doctors prescribe a large enough dose so that by the end of the month, patients will still have an antibody count that is greater than or equal to approximately 800 mg/dL, the healthy level for an adult (Immunoglobulins (IgG, IgA, and IgM), Serum).

Figure 1 - Increasing regularity of treatment decreases total amount of medication needed to maintain minimum, healthy antibody levels for patients with Primary Immunodeficiency Disorder. The areas under the curves decrease with greater regularity, which means less medication required, and therefore lower costs. 

This treatment has been the standard of care because patients are able to go about their daily normal lives, so long as they regularly receive infusion. However, the treatment also has several disadvantages. IVIG therapy is extremely wasteful. Patients must receive enough treatment such that the level of antibodies is sufficient until each treatment This treatment must also continue for an indefinite amount of time because it is not a curative process. The combination of these two issues make costs extremely high for patients; the cost ranges from “$164 to $314” (Immune Globulin Subcutaneous (Human), 20% Liquid). Moreover, not only are patients susceptible to lethargy when Ig levels are low but adverse effects of IgG infusions also include “headache, myalgia, fever, chills, low back pain, nausea and/or vomiting” (Duhem, Dicato and Ries). As a result, patients require separate medications, both before and after infusions to manage these side effects. The particular disadvantage we will focus on is reducing costs for patients by increasing regularity of treatment with the creation of a user-friendly infusion device.

The code for my project is attached here.

Device Specifications

This device is essentially an infusion pump for immunodeficiency therapies. Patients will receive medication through the pump. Patients typically know how much medication they should receive from a doctor’s prescription, so they can simply program that number through the keypad. This function will cause the motor to move the carriage a certain distance back from its “home base” position. During this time, the yellow LED will turn on to inform the patient that this function is running. Then the patient will load the 60 mL syringe which will contain the medication fluid. Once the patient initiates the infusion process and the motor begins pushing the syringe forward, he/she can perform various functions for important functions and information. For example, patients can navigate the keypad to determine how much more time is remaining in the infusion, or they can pause/cancel the infusion. When the infusion ends, the red LED turns on so that the user can be aware that the overall procedure has ended.

Specification Table

Specification	Value, Value Range, or Quality of Specification	Additional Comments (if needed)
Battery Life of motor	Indefinite	Powered through outlet
Battery Life of LCD, LEDs, Arduino	Indefinite	Powered through computer
Syringe Life	Replace after each infusion
Tubing Life	Replace after each infusion
Needle Life	Replace after each infusion
Age requirements	Safe/intended for all ages	Doctor prescription required, but operation should not be for children under
FDA Classification	Class II	Some harm to the user may occur because of motor, tubing, and needle; mandatory performance standards required so that users know that the medication works appropriately; other pumps are given Class II regulatory controls
Sterility	Syringe, tubing, needle must be sterile materials

Block Diagram

CAD Modeling

Feature and Benefit Table

Feature	Benefit
Red LED	Patient knows when infusion has completed
Yellow LED	Patient knows when carriage is moving to its appropriate place along rail
Green	Patient knows when…
LCD display	Informs patient about various features, such as how much medication to deliver, how much time is left over in the infusion, and allows patient to pause/cancel infusion
Servo Motor	This motor allows for constant delivery of medication because it can move a specified distance at a regular rate
Tubing	Wiring allows for simple transportation of medication from the syringe to the patient
Needle	Transportation from the syringe to the patient, as well
Arduino	Overall functionality and output device controls

Prototype Description

The device we have built is a user-friendly and easy to use apparatus at home. This allows for increased regularity of treatment so that patients incur lower costs for Primary Immunodeficiency Disorder therapies, which include antibody infusions. However, our device has much room for improvement. To begin with, we would want our device to mimic an insulin pump’s feature of checking blood insulin levels and provide dosages appropriately; if our device could record patient antibody levels, patients would receive more appropriate treatment, thereby further decreasing costs and keeping patients healthier. For example, immune systems may have to combat infections more actively during the winters when infections are more prevalent. As a result, the daily dosage can be higher if a patient needs it to be and lower when not necessary.

Other improvements include changing the power system so that wiring is not necessary. A battery-powered device would be more portable for the patient and allow for less restricted movement. Additionally, our pump has an open design as of now, but with more time, we would have placed it in a box so that the only parts of the apparatus visible would be the LCD display and the rail for syringe placement. Finally, we would improve the LCD functionality to include more information such as the antibody level, calendar for treatments, and pre-set settings for speeding up the infusion process and improving effectiveness of the device.



PREVIOUS TECHNOLOGIES

CONCERNS
There are a wide range of treatment doses.  

• how to accomodate all sizes
• http://emedicine.medscape.com/article/2157901-overview

Doctors may be comfortable with wastefulness

• Bloodwork does not directly identify the appropriate prescription level.  It is hard to tell what is abnormal performance and what is low levels of antibodies.