An Integrated Intelligent Insulin Pump

Zhi Xu', Sheng Liu 1, Zhiyin Gan', Bin Ma', Guojun Liu2, Xinxia Cai3, Honghai Zhang',
Zhigang Yang2
1. Division of MOEMS, Wuhan National Laboratory for Optoelectronics, Wuhan 430074, China
2. College of Mechanical Science and Engineering, Jilin University, Changchun, 130025, China
3. State Key Laboratory of Transducer Technology, Institute of Electronics, Chinese Academy of Sciences, Beijing,
100080, China
* Corresponding Author: Professor Sheng Liu, , 027-87542604

Abstract
As an evangel to diabetics, the invention of insulin
pump has drastically renovated the ways of treatment for
diabetes. Having been developing since 1970s, insulin
pump is an advanced product now. However, the insulin
pump in the market is still far from being satisfactory, as
pains were caused to patients out of the injection and
finger blood extraction. Even worse, if insulin is over
injected, the patient can have low blood sugar level that
could be life threatening to the patient. And the treatment is
expensive to the patients and it is estimated to be 10
RMB/hour due to the high cost of the current insulin
systems. It is desirable for regular patients to be provided
with a closed-loop, low cost glucose-insulin pump diabetes
treatment system, which is not yet available in the market.
This closed-loop system will make the glucose
measurement and insulin pumping be conducted
continuously so that a complete diabetic management can
be realized. A novel intelligent insulin pump with painless
and automatic injection coupled with the glucose metering
was introduced in the present study.
Keywords: insulin pump; painless injection; automatic
injection; micro-pump
1. Introduction
Diabetes, which is caused by the unbalance of incretion
and the kidney also can not bear the glucose in blood, is an
endocrinopathy with a diabetic from his birth to death. In
fact, the most terrible thing is not diabetes itself, but the
syndrome, via which the harm of diabetes is incarnated.
There are 12,000,000 people in total with high blood
pressure, 5,000,000 with cerebral hemorrhage, 6,000,000
with coronary heart disease and 450,000 with blindness
during the diabetics in China alone. As diabetes and the
syndrome are terrible to human's health, it is important to
look for the way of treatment and miracle drug for
diabetes.
Insulin has taken a most important place in the
treatment for the disease just from the discovery of insulin
and has been used for diabetes since 1921. The injection of
insulin via a common injector is the only way of treatment
in the past. However this method brings a great deal of
pain to patients.
During 1960s a concept of uninterrupted injection
appeared and replaced the traditional injection approach. In
1970s, the concept was advanced by simulating the
exudation of insulin from pancreas. Moreover, an insulin
pump was also proposed and developed in our study.
With the PZT insulin pump integrated with a silicon
micro needle array [1], an intelligent insulin pump was
invented. Painless injection; automatic injection has been
realized with this equipment.
The control of insulin dosage in the traditional pump
appears in our proposed pump, a RF module is added so
that a communication can be established. The RF module
can accept a signal, sent out by a glucose meter, which
denotes blood sugar. A MCU (micro-control unit) in the
pump will process the signal and provide a result to the
insulin pump. Then pump will adjust the insulin dosage
according to the result. With the RF module, the system is
an integrated, forming a closed-loop control system.
2 Design of Insulin Pump
The system includes a micro-pump, a drug reservoir, a
MCU, a RF module and a silicon needle array. Figure 1
shows the schematic structure.

1-4244-0620-X/06/$20.00 C 2006 IEEE. 2006 7th International Conference on Electronics Packaging Technology

Figure 1. The structure of insulin pump
2.1 The micro-control unit
There are two work modes of pancreas. One is the
basic mode that pancreas secretes insulin uninterrupted
with little dose, the other is added mode that the insulin
dosage is added before each dinner. And a program has
been made to simulate the both modes. The daily dosage
which is needed for patient can be obtained from an
equation as follows:
Q(U)=[A(mg/dl)- 100] X 10 X B (kg) X 0.6 :1000:2;
Q is the daily dosage, A is the thickness of blood sugar, and
B is patient's weight. According to the equation above, a
program used to simulate has been embedded. Figure 2
shows the flowchart as follows:
start
model
choose
Figure 2. Flowchart of the simulant program.
With the figure above, an expert system is required in
the program. In addition, there are expert systems for
pregnant woman, child and patient with ketosis,
respectively. Patients can choose the relevant expert
system according to their own condition. For instance,
once the expert system for pregnant woman is chosen, the
weight, thickness of blood sugar and the pregnant periods
are required immediately. According to this information,
MCU will offer the needed insulin dosage. In addition, the
principles for injection are as followed: for patients whose
thickness of blood sugar is above 7.8 mmol/L, the basic
daily dosage is 0.6U for each kilogram everyday. From the
6th to 1 8th, 19th to 26th and 27th to 36th week, the basic
factors are replaced by 0.7U, 0.8U and 0.9U, respectively.
Then the basic factor is 1U until the childbirth. After the
child born out, it will go to the former factor 0.6U.
Age, weight and thickness of blood sugar are required
for children patients. The MCU will offer the needed
insulin dosage, too. And the principles for injection are as
followed: the basic dosage is 0.28U for each kilogram
everyday, the added dosage before dinner is 0. 105U for
each kilogram in an hour.
In the system for patients with ketosis, age weight and
thickness of blood sugar are also required. The principles
for injection are as followed: the basic dosage is 0. 1U for
each kilogram in an hour. The injection period is 3 hours.
The basic factor can be reduced to 0.05U for babies whose
ages are under 4 years old refers to the sensitivity to insulin.
However, it will take 0.1 5U for all patients whose
thicknesses are above 28mmol/L.
When the system works on the free inject model, RF
receiver obtains much significant information, such as time
and the concentration of blood sugar. MCU will count the
daily dosage in time and make the system work. All the
information will be stored in the EEPROM, which will be
provided to doctors later on.
2.2 PZT pump and micro-needles array
The PZT pump can deliver the precision insulin much
more accurately than the mechanical pump and the overall
size is much smaller than those mechanical pumps. If it is
drived by PWM (pulse width modulation), the precision of
dosage is small enough to deliver any solution.
With the Micro-Electro-Mechanical-Systems, a silicon
micro needle array has been designed and manufactured.
According to the anatomical features of the skin, a suitable
length in micro-needles array is 150-250um. In addition,
according to erythrocyte, the major component of blood is
about 20um in diameter. To avoid blocking the needle, the
inner diameter of needle is designed to be 30um [1]. The
packaging and assembly system is shown in Figure 3.
 continuously. Once the concentration is lower than
the normal value, the pump would be stopped
immediately by the remotely control from the
glucose-meter.
Repeat from process d) to h) twice, then three
experiments, signed with A, B and C, are completed.
Figure 5 shows the experiments A, B and C. As the rabbit
Figure 3. Packaging and assembly system is injected with glucose solution, it takes about 55 minutes
to resume for the rabbit without the assistance of insulin
3 Experimental Results pump. However, the period, with injecting the insulin
3.1 Fluidics tests pump to the rabbit, is obviously shorter than before. Here
Fluidics tests are performed using wide variety insulin pump injection is critical to make the change
concentrations of glucose solutions. The flow rate happen.
continuously decreases as the back pressure rises up. When
the piezoelectric membrane is working at resonant
frequency which is about 208Hz, drive voltage is 67.2 in
voltage; the pump will be at the high-point condition. The
flow rate can reach 40ul/s. The cut-off value of the voltage
is approximately 25V [1].
3.2 Animal tests
This test is performed using healthy rabbit and
glucose-meter and insulin pump (Figure 4). The principle
is as follows:
a) Make use of glucose-meter to obtain the
concentration of blood sugar. The normal value for
rabbit is approximately 6. immol/L.
b) Inject high concentration of glucose solution into
the rabbit's vein. The blood sugar value we detect
is 24.4mmol/L.
c) After the injection, track the concentration of
blood sugar with glucose-meter. In this case, the
rabbit can decrease the value to 6.3mmol/L by Figure 4. Experimental object and tools
itself in 55 minutes.
d) Monitor the concentration of blood sugar for 20
-+- experimentA
minutes while it is a normal one. _ experiment B
+ experiment C
e) Tie insulin pump and glucose-meter to the rabbit.
the rabbit secrete insulin itself
Prepare for injecting insulin. CE the minimum normal value
-- the maximum normal value
f) Inject the same glucose solution as process (b). 9 2

Track the concentration for the injected rabbit.

While the glucose-meter detects a high
concentration, it will send a RF signal to remotely
control the insulin pump.
g) The insulin pump receives the signal from
glucose-meter, and then begins to work. During
the work period, the injecting means will update
once a new RF signal is received.
h) The glucose-meter monitors the concentration
time (min)
Figure 5. The experiment A, B and C
Figures 6 and 7 show the relationship between the
dosage and the concentration. The concentration, which
was monitored by the glucose-meter, is in the normal area,
the dosage decided by insulin pump is OU. The dosage will
increase as the concentration rises up. The dosage also will
decrease immediately as the concentration falls down. As [5] Barry, BW, "Novel Mechanisms and Devices to
the concentration resumes to normal value, the pump stops Enable Successful Transdermal Drug Delivery,"
injecting at once. European Journal of Pharma ceutical Sciences, 2001,
35 14:1-114.
30 experiment A [6] JW Kan, JW, Yang, ZG, , Tang, KH, Cheng,
E 25 experiment B
GM, "Pumping Performance of a New Piezoelectric
0 20 , D
experiment C
1_
-15 Pump for Drug Delivery" Journal of Biomedical
C:
c V Engineer., 2004; 21 (2), 297 301.
c= 00
D
I [7] Guo, Z, Sprecher, AF, Conrad, H, "Crack Initiation
0 1.t 20 30 40 50 and growth during low cycle fatigue of Pb-Sn solder
time (mOh) joints," Forty First IEEE ECTC Conference, Atlanta
Figure 6. Concentration got via glucose-meter (GA), 1991: 658-66. [A reference to a conference ... ]
[8] Gadre, AA, Kastantin, M., Li, S, and Reza Ghodssi,
--J -. experiment A
4 experiment B RZ, "An Integrated Biomems Fabrication
0
- experiment C Technology," Micromech. Microeng. 2001; 7:186-9.
0
E
.-
[9] Polla, DL, "BioMEMS Applications in Medicine,"
0
0
International Symposium On Micromechatronics And
Human Science, Kawasaki, Kanagawa (Japan), 2001:
1o 20 30 4(,0 50 60 13-15.
time (min) [10] Bhatia, SN, and Chen, CS, "Tissue Engineering at the
Figure 7. Dosage decided by the insulin pump Microscale," Biomedical Microdevices. 1999;
4. Conclusions 2:131-44.
The insulin pump consists of the piezoelectric pump, [11] Folch, A, and Toner, M, "Microengineering of
silicon needles array and RF module. It can be Cellular Interactions," Annu. Rev. Biomed. Eng. 2000;
conveniently operated from a remote control glucose-meter 2: 227-56.
through a secured RF communication. The application of [12] Polla, DL, "MEMS Technology for Biomedical
this insulin pump demonstrates the improved safety in the Applications," International Symposium on
system, convenience and painlessness to the patients. Micromechatronics and Human Science,
5. Acknowledgement Nagoya(Japan), 2001: 102-35.
The support from Ministry of Science and Technology [13] Gerstel, MS, Place, VA, "Drug Delivery Device," US
of the People's Republic of China with a contract with a Patent No. 3,964,482, 1976.
number of 2005AA404220 is highly appreciated. The [14] Emst, T, Emst, 0, "Micro-actuators and Their
authors wish to thank Dr. Yuhai Mei for helpful Technologies," Journal of Mechanics, 2000,
discussions. (10):431 45.
6. References [15] Fukuda, T, Menz, M, "Micro Mechanical Systems:
[1] Bin Ma and Sheng Liu, "A PZT Insulin Pump Principles and Technology," Journal of Elsevier
Integrated with a Silicon Micro Needle Array for Science B, 1998, V
Transdermal Drug Delivery" Fifty sixth IEEE ECTC [16] Spence, WJ, Corbett, WT, Dominguez, LR, "An
Conference, San Diego, 2006: 677-681. Electronically Ccontrolled Piezoelectric Insulin Pump
[2] Bronaugh, R.L., Maibach, H.I. "Percutaneous
, and Valves," IEEE Trans. Sonics Ultra Sonics. 1978,
Absorption: Drugs Cosmetics Mechanisms 25(3): 153.
Methodology," Marcel Dekker, New York, 1999. [17] H.T.V. Van Lintel, HTV, F.C.M. van de Pol and
[3] Touitou, E., "Drug Delivery Across The Skin," Bouwstra A., "A Piezoelectric Micro Pump Based on
Expert Opin. Biol.Ther. 2 (2002) 723- 733. Micromachining of Silicon", Sensors & Actuators A,
[4] Petersen K. "From Microsensors to Micro 1988(15):153-168
instruments," Sensors and Actuators, 1996,A56s Cl [18] Stemme, E, Stemme, G., "A Valve Less
-2, 143- 149. Diffuser/Nozzle-based Fluid Pumps," Sensors &
 Actuators A, 1993, (39):159-167
[19] Gong, Q, Zhou, Z, Yang, Y, Wang, X, "Design,
Optimization and Simulation Micro Electro Magnetic
Pump," Sensors & Actuators A, 2000,(83):200-207
[20] F.C.M. Van de Pol, H.T.G. Van Lintel, M. Elvenspoek,
J.H.J. Fluitman, "A Thermopneumatic Micropump
Based on Microengineering Techniques," Sensors &.
Actuators A, 1990, (21):198-202
[21] Kaushik, S, Hord, AH, Denson, DD, McAllister,
DV, Smitra, S, Allen, MG, and Prausnitz, M, "Lack of
Pain Associated with Microfabricated Microneedles,
" Anesth. Analg., 2001; 92:502-504,.
[22] Elias, PM, "The Stratum Corneum As An Organ of
Protection Old and New Concepts in Fritsch," P., G.
Schuler and H. Hintner, Editors. Current problems in
dermatology, New York: Switzerland, 1989:10-21.
[23] Elias, PM, "The Stratum Comeum As An Organ of
Protection: Old and New Concepts," Curr. Probl.
Dermatol. 1989; 18: 10-21.
[24] Williams, AC, Barry, BW, "Skin Absorption
Enhancers, " Crit. Rev. Ther. Drug Carr. Syst. 1992; 9:
305-53.
[25] Woias, P, "Micropumps:Summarizing The First Two
dDecades," Microfluidics and BioMEMS,
2001,(4560): 39-52