776028

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DSTXXX10.1177/1932296818776028Journal of Diabetes Science and TechnologyPayne et al

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Journal of Diabetes Science and Technology

Capabilities of Next-Generation
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© 2018 Diabetes Technology Society
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DOI: 10.1177/1932296818776028
https://doi.org/10.1177/1932296818776028

Instant Occlusion Detection, and journals.sagepub.com/home/dst

Dual-Hormone Therapy

Forrest W. Payne, PhD1, Bradley Ledden, PhD1,

and Greg Lamps, MS, MBA1

Abstract
Insulin pumps allow patients to attain better blood glucose control with more lifestyle flexibility. Their size and cost,
however, limit their usefulness. Current CSII pumps are bulky, intrusive, and expensive. SFC Fluidics is addressing
these problems by developing a new type of wearable patch pump based on the patented electro-chemiosmotic (ECO)
microfluidic pumping technology. This nonmechanical pumping technology allows accurate and precise delivery of very
small amounts of insulin and/or other drugs, including concentrated insulin. The pump engine is small and can be made
inexpensively from injection molded parts, allowing its use in a disposable or semidisposable pod format. In addition,
a single ECO pump engine can be used to deliver two drugs through independent pathways. Other features of SFC
Fluidics’ pod include latching safety valves that prevent accidental overdosing of insulin due to pressure changes and an
instantaneous occlusion sensor that can immediately detect delivery failure at the first missed dose. These features allow
for the development of a series of patch pumps that will offer users the benefit of CSII therapy in a more discreet and
reliable patch pump form.

Keywords
insulin patch pump, occlusion detection, dual-hormone therapy, automated insulin delivery, artificial pancreas, concentrated
insulin

There is significant evidence that people with diabetes who

use continuous subcutaneous insulin infusion (CSII) have
better clinical outcomes compared to those who use multiple
daily injections (MDI),1,2 however, only about 30% of people
suffering from type 1 diabetes use this therapy. SFC Fluidics
has developed new technology that will enable a new genera-
tion of much smaller insulin pumps. SFC is using electrical,
rather than mechanical pumping, to create a range of innova-
tive products to serve the needs of all insulin-using people
with diabetes. The core electro-chemiosmotic (ECO) pump-
ing technology delivers excellent precision, which coupled
with a valve system and flow sensor, deliver a unique safety
factor. Together these three technologies form a “pump
engine” (Figure 1) that will be utilized for a simple patch Figure 1.  ePump and valves.
pump, an insulin-only automated insulin delivery (AID) sys-
tem, and a dual-hormone artificial pancreas (AP) system.
1
SFC Fluidics, Inc, Fayetteville, AR, USA

Technical Details of ECO Pumping Corresponding Author:

Greg Lamps, MS, MBA, SFC Fluidics, Inc, 534 W Research Center Blvd,
Currently marketed insulin delivery pumps generally use a Ste 260, Fayetteville, AR 72701, USA.
mechanical motion to drive a piston or a shuttle through a Email: glamps@sfcfluidics.com
2 Journal of Diabetes Science and Technology 00(0)
Figure 2.  Schematic of ECO pump operation.
syringe to push the insulin into the patient. While this is a
well understood and straightforward method, it does have
drawbacks that limit its usefulness for delivering the small
doses required by people with type 1 diabetes. The limita-
tions of the current syringe pump technology include:3
•• precision limitations due to discrete motor movement
•• inaccurate dispenses caused by stiction of the plunger
•• strict design limitations due to the straight-line form
requirements
•• engineering constraints that prevent further miniatur-
ization of mechanical components
The heart of SFC Fluidics patch pump system, the patented
ePump® (an ECO pump), solves these problems. The ECO
pump is a nonmechanical pump that is highly accurate and
readily scales with delivery requirements, allowing for a
more discrete product.
Fundamentally, the ECO pump is two electrochemical half-
cells separated by a semipermeable membrane. Each half-cell
contains an electrode, is bound on one side by a flexible,
impermeable diaphragm and is filled with a nontoxic proprie-
tary solution that supports fully reversible aqueous electro-
chemical reactions. Initially, each half-cell contains the same
solution, and there is no movement in the pump. The applica-
tion of a small voltage (≤1.5 VDC) between the two electrodes
drives chemical reactions which change the osmotic pressure
between the two chambers. When this happens, ions and asso-
ciated solvent move from one half-cell to the other through the
semipermeable membrane to equilibrate the pressure. As the
fluid moves between chambers, the flexible diaphragms move
to accommodate the volume change in each cell. This dia-
phragm movement is used to pump insulin or other drug into
and out of a metering chamber that is adjacent to the flexible
diaphragm. After the correct fluid volume has been pumped,
the applied potential is reversed to drive the half-cells back to
equilibrium. The flow rate and total volume pumped are easily
controlled by controlling the rate and number of reactions that
take place using established electrochemical techniques and
simple electronics. The direction of the insulin flow is con-
trolled using SFC’s latching safety valves, described later in
this paper. A single stroke of this reciprocating displacement
pump can be infinitely varied to deliver any amount between 0
and 1 U of U100. Larger doses are delivered using multiple
strokes at a rate of 1U/min. This system is able to deliver nor-
mal, square-wave, dual-wave, or any other shape of bolus
dose. The 1U/stroke limit ensures that the pump isn’t damaged
during operation. A schematic diagram showing the operation
of the ECO pump is shown in Figure 2.
This type of system has several advantages over a mechan-
ical system. First, there is no discrete stepping mechanism
that limits the precision of doses that can be delivered. While
existing mechanical insulin patch pumps are very good at
delivering the small volumes required when using U100, they
typically are limited to 0.05 U dose step sizes. For U500, this
same minimum step size becomes a dose of 0.25U for exist-
ing systems. Increments of 0.05 U are fine for adults, but
smaller controlled dosing increments are needed for children
and are essential for migration to the use of more concen-
trated insulins. Other advantages stem from the construction
of the ECO pump itself. For example, the liquid working
material virtually eliminates engineering constraints on the
shape and size of the pump. Drugs that require smaller doses,
such as concentrated insulin, can be delivered using a smaller
pump. The design freedom in the shape of the pump allows
the pump to be tailored to fit into an organically shaped pod
with consideration of the other components. A third benefit of
this construction is that the pump can be made almost entirely
of injection molded parts and is amenable to high-speed,
automated manufacture and assembly, permitting its use in a
discreet, disposable pod/patch pump type application.
Another not-so-obvious advantage of this type of recipro-
cating pump with potentially huge significance for diabetic
therapy is that the diaphragms of both chambers move in con-
cert as fluid is moved across the semipermeable membrane. By
adding a second set of the latching safety valves, two different
Payne et al 3
hormones can be independently dosed through separate fluidic
pathways using a single pump engine. Each side of a dual-hor-
mone ECO pump will have the same accuracy and precision as
a single hormone ECO pump. This means that two hormones,
for example insulin and glucagon, can be delivered as neces-
sary in an AP system to either lower or raise blood sugar in
response to a continuous glucose monitor (CGM) reading.
Dual-hormone therapy has been shown to significantly reduce
the occurrence of hypoglycemia in studies using two CSII
pumps—one filled with insulin and the other with glucagon.4-13
Although these studies have shown benefits to dual hormone
therapy, the mental, physical, and financial burden of maintain-
ing two pump systems and a CGM is too much for many peo-
ple to manage, even with the prospect of reduced hypoglycemic
events and better-long term outcomes. SFC Fluidics will take
advantage of the dual-hormone delivery capacity of the ECO
pump in meeting patient needs for comfort and discretion. The
dual-hormone pod will be larger than the insulin-only AID
device by only the size of the glucagon reservoir; dramatically
reducing patient burden. SFC’s single-pod AP system will
make dual-hormone therapy a practical treatment option for
both children and adults with type 1 diabetes.
The latching safety valves are designed, as the name sug-
gests, with safety of the patient in mind. These mechanical
inlet and outlet valves are created as a set and interact with
each other during operation so that they can never both be
open at the same time. During the switching of the valves,
both valves must close momentarily before the other can
open. Once switched, the open valve physically holds the
other closed so that there is never an open path from the drug
reservoir to the patient. A failure of the pump or external pres-
sure change such as during an airplane flight will not cause an
overdosing of the insulin to the patient. The outlet valve to the
patient is always closed when the pump is not actively dis-
pensing insulin to the patient. When pumping is initiated,
both valves are closed and then the outlet valve is open. The
pump delivers the prescribed dose and then the valves close
again before the valve to the drug reservoir is open. The pump
then returns to equilibrium by drawing the same amount of
drug from the reservoir. In this way, failure of the pump can-
not cause an overdelivery of insulin to the patient.
The final piece of technology SFC has incorporated into the
pod, adding yet another layer of safety and reliability to the
device, is the instantaneous occlusion sensor. A main failure
point in continuous insulin infusion is silent occlusions.14-16
While this is primarily an infusion set/insertion issue, existing
occlusion sensors are unable to reliably detect the occlusion in
a timely manner. Too often, occlusions are “silent” and detected
when correction boluses are required to remedy a hyperglyce-
mic condition. A key benefit of SFC’s pod is the ability to con-
firm drug flow in real-time. Instantaneous confirmation of
individual basal dispenses may allow for detection of infusion
set faults or other occlusions within minutes. The flow confir-
mation sensor sits in line with the drug delivery path between
the valve and cannula tip and consists of a series of electrodes.
When a potential is applied, the fluid supports a very small
Figure 3.  Rendition of insulin delivery pod. The pod as designed
is 51 mm × 55 mm × 13 mm.
(nanoamperes) electrical current. This characteristic current
depends on fluid composition such as ionic strength and vis-
cosity. During pumping, the sensor confirms fluid flow by
measuring an increase in current due to convection augmenting
movement of charge carriers over diffusion alone. In addition
to being fast and accurate, SFC’s occlusion sensor is also quite
small with a sensing length of 1.5 mm and a diameter of 0.5
mm. The sensors are fabricated by mass manufacturable meth-
ods common in the electronics industry and can be made at a
size and cost suitable for disposable use. The power require-
ments are very low as well, requiring a few microamperes dur-
ing fluid flow but with the ability to be switched off completely
between dispenses. Finally, the processing power needed to
confirm flow is low as well, and easily within the capabilities
of a pod control system. Rapid detection of dispense failure is
key to diagnosing occlusions, whether from kinked cannulas or
other possible faults. Accurate occlusion detection holds the
promise of reducing time in hyperglycemia.
Figure 3 shows one potential design layout of the compo-
nents that would be used for the Bluetooth®-enabled, 3-day
use, fully disposable insulin-only CSII pod.
Performance Details
ECO pump and valves
During the development of the ECO pump technology, sev-
eral key aspects of the technology were proven before it
could be considered as a technology capable of delivering
life-saving drugs in a miniaturized embodiment. One of the
early questions was how this technology would be affected
by any backpressure in the system. Many nonmechanical
pumps are not capable of pumping reliably against backpres-
sure. Electroosmotic pumps that use surface charge of a
porous frit to generate fluid movement are significantly
affected by small changes in backpressure. Conversely, the
ECO pump has been shown to operate well against backpres-
sure and was able to generate enormous amounts of pressure
when pumping into a closed chamber. A well-fortified ECO
pump was used to generate a pressure of 23 atm (300 psi) in
a closed chamber (see Figure 4).17 This capability assures
reliable operation during subcutaneous delivery of drugs.
4 Journal of Diabetes Science and Technology 00(0)
Figure 4.  An ECO pump is used to generate 23 atm of pressure
in a closed chamber. The pump was operated at 20 mA reaction
current to generate the pressure. After a brief rest period, the
reactions were reversed at −20 mA to release the pressure.
Figure 5.  Shows the efficiency of an ECO pump remains
constant at temperatures ranging from 5-55°C while the flow rate
increases linearly with temperature.
In addition, the accuracy of the pump had to be character-
ized over a wide range of potential operating environments.
Unlike a motor driven pump, there is no mechanical dis-
placement that can be measured to determine how far a shut-
tle or plunger has moved. Instead of counting the number of
steps of a motor, ECO pump calibration is based on the num-
ber of reactions that take place inside the pump. While this is
an easy measurement to make, there are many factors that
can affect the result. It was shown that different solutions and
solvents and even different ionic concentrations affect the
amount of fluid that moves across the semipermeable mem-
brane per unit charge.18,19 It was also shown that for a given
solution, the pumping efficiency, measured as volume of
fluid delivered per number of reactions, was constant over
the broad temperature range applicable to drug delivery
(5-55°C), though the pump works faster at higher tempera-
tures (see Figure 5). The ECO pump can be tailored to work
at a certain efficiency and nominal flow rate while maintain-
ing dosing accuracy over a broad temperature range.
Figure 6.  Trumpet curve for 48-hour basal testing of ECO
pump and valves. 48-hour total error is 0%.
Figure 7.  Shows the trumpet curves from 48-hour dual
hormone AP dosing schedule onto dual IEC 60601-2-24
compliant test setups. The trumpet curves for insulin (black dots)
and glucagon (green dashes) were calculated separately.
Once these technical characteristics were understood,
the ECO pump technology was optimized for use in a wear-
able drug delivery device for delivery of insulin to people
who suffer from type 1 and type 2 diabetes. The flow rates
and energy requirements could be met with a pump with
chambers that were only 12.5 mm in diameter and 3 mm
high. Once this pump was designed and built, IEC testing
was begun.
The International Electrotechnical Commission (IEC) has
defined the standard for measuring and presenting the error
of dispenses for ambulatory drug infusion pumps in their
IEC 60601-2-24 document.20 In this procedure, a pump is
used to pump a dose of water onto a balance repeatedly, and
the measured change in mass is used to calculate the volume
of liquid that was dispensed. Pump accuracy and precision
are clearly presented in a “Trumpet Curve.” This chart con-
veniently displays the maximum amount that the pump over
or under dispensed over any specified time interval during
the testing. As the time interval is increased, the values
approach the overall average value, giving a trumpet shape.
The ECO pump and valves have been rigorously tested using
an IEC 60601-2-24 compliant test setup. The results of these
tests are shown in Figure 6. The figure shows the trumpet
curve for a basal delivery routine of 0.5 U/h dispensed as
0.05 U every 6 minutes over a total of 48 hours.
Payne et al 5

Figure 8.  Carrier solution for three rapid acting insulin analogs show similar response during pumping of 1U equivalent volume.

Figure 9.  Graph of sensor response at different flow rates relevant for SFC pod. Signal amplitude is indicative of pumping speed.

In a separate experiment, an ECO pump was coupled with
two sets of latching safety valves, and two IEC 60601-2-24
compliant test apparatus were used to measure the ability of
the ECO pump to independently deliver doses using both
sides of the pump. After initial verification that the system
works, the dual-hormone pump prototype was used to repli-
cate the doses given to a patient in a published dual-hormone
AP trial study (Patient 303).21 One side of the pump dosed
the insulin protocol and the other delivered the required glu-
cagon. In the published dual-hormone study, an algorithm
was used to calculate a dose every 5 minutes using readings
from a CGM (sometimes the dose was 0 mg). The dispenses
ranged from 0-20 µL (0-2 U) of insulin and 0-6 µL (0-30 µg)
for glucagon. The total error for insulin was −2.8% over the
48-hour period. For glucagon the dosing error was +1.8%.
Each side of the two-sided ECO pump prototype demon-
strated precision comparable to that of the single-sided ECO
pump and existing insulin only pumps, as shown in the trum-
pet curves in Figure 7.
Occlusion Sensor Test Results
Commercially available rapid acting insulins give similar
response from the occlusion sensor due to their similar fluid
composition (Figure 8). The graphs in Figure 8 are of solutions
mixed based on formulations available from the package insert
for the three-predominant rapid acting insulin analogs on the
market. The graph for each solution shows four dispenses of 1
U (10 µL) given over a 5-minute time span. Apidra® carrier
solution is shown in green while Humalog® and Novolog®
are depicted with red and blue respectively. Each increase in
signal corresponds to a dispense of 1 U through the occlusion
sensor at a flow rate of 20 µL/min for 30 seconds. Data were
taken for each formulation separately and overlaid to create
the figure. For each dispense there is a rapid increase in the
current from the sensor when flow is initiated and a corre-
sponding quick decrease when flow is stopped.
The current measured by the sensor during pumping is
significantly higher than when the solution is at rest, with
signal amplitude indicative of flow rate (Figure 9). The data
in Figure 9 show current response at various rates from
5-20 µL/min, indicating the sensor can be used to identify
partial occlusions as well. In this figure, dispenses were
fixed to 30 seconds, so 10 µL/min and 5 µL/min dispenses
are equivalent to 0.5U and 0.25U, respectively. In case of a
partial occlusion the pump would dispense the correct
amount, but the low flow rate would occur over a long-time
period. By measuring both the flow rate as well as duration
of flow, the sensor can confirm dosage dispensed. The
occlusion sensor responds quickly to initiation of flow and
6 Journal of Diabetes Science and Technology 00(0)
can sense occlusion of volumes as small as 0.05 U of U100
rapid acting insulin, allowing confirmation of individual
basal dispenses.
Conclusion
SFC Fluidics’ microfluidic technologies represent a signifi-
cant step forward in the development of CSII treatment of
diabetes, allowing for safe, accurate continuous subcutane-
ous insulin injection in a reduced footprint for type 1 and
type 2 diabetes and greatly increasing the speed at which
occlusions are detected.
Abbreviations
AID, automated insulin delivery; AP, artificial pancreas; CGM, con-
tinuous glucose monitor; CSII, continuous subcutaneous insulin infu-
sion; ECO, electro-chemiosmotic; IEC, International Electrotechnical
Commission; MDI, multiple daily injections; U100, 100 units/ml insu-
lin; U, insulin unit; VDC, direct current voltage.
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest
with respect to the research, authorship, and/or publication of this
article: Forrest Payne, Bradley Ledden, and Greg Lamps are all full-
time employees of SFC Fluidics, Inc.
Funding
The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: Some
of this research was supported by the US Army Research Office and
the US Army Research Laboratory (Contract DAAD19-03-1-0053).
This material is based on work supported by the National Science
Foundation under Grant 0848253. Research reported in this publi-
cation was supported by the NIDDK of the National Institutes of
Health under Award R43DK110972.
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