References:1.Lee, Katherine, et al (2010). UCSD Department of Bioengineering.2.Baker, Dale A (1995). "A Continuous, Implantable Lactate Sensor." 3.Cerovic, et al (2003). Intensive Care Medicine. 29.8 (2003): 1300-1305.

Design and Development of a Subcutaneous Oxygen Sensor for Eventual Adaptation for Lactate Measurement

Rick Chen, San Lou, Kenneth Ng, Ned Premyodhin, & Dale A. Baker Department of Bioengineering, University of California, San Diego

• Figures 4 and 5 show that the linear relationship between oxygen concentration and normalized sensor current remained constant over the course of two days for the 15 gauge sensor and 19 gauge sensor.

• The regression lines from Days 1 and 2 were compared using an F-test, with F = 0.21 and 0.19 for the 15 and 19 gauge sensors, respectively (Fcrit = 18.00 for P<0.01). This demonstrated that there was no significant change in the 19 gauge sensor’s current outputs with respect to days.

• As shown in Figure 6 and Table I, the transient response time for the 19 gauge sensor is faster by 0.833 minutes.

Background – Lactate-Modulated Oxygen Sensor• An oxygen sensor utilizes an immobilized lactate enzyme to produce a lactate-

modulated oxygen-derived current, as shown:(i)

(ii)• When lactate levels are high, the amount of O2 consumed by the enzyme is

proportionally higher (i). Less O2 molecules are available to react with the platinum electrode (ii), therefore producing a smaller current.

Design Functional Requirements1. Generate linear, continuous measurements2. Measure oxygen range: 1%-10% (7-70 mmHg oxygen)3. Time response of less than 5 minutes4. 19 gauge catheter size (0.025” outer diameter)

Design Solution• Similar to the 15 gauge sensor, the 19 gauge sensor utilizes a 3-electrode

system but with smaller-sized electrodes and a smaller catheter body and membrane.

Fabrication• Platinum-iridium and silver wires were welded to stainless steel (SS) lead

wires and epoxied into a glass bead, forming the 3-electrode system. pHEMA soaked in an ion solution formed the salt bridge between the platinum electrodes. The system was slipped through a silicone rubber catheter, and capped with more silicone rubber. The SS leads were epoxied to 4-pin connectors.

• A 24% mortality rate was observed for shock and trauma patients with heightened lactate levels that weren’t normalized within the first 24 hours upon admission.3 Blood lactate levels therefore provide significant prognostic value. Implantable, electrochemical oxygen sensors using the 3-electrode system complemented with an immobilized lactate-oxidase produce linear, continuous measurements of blood lactate levels over long periods of time, allowing for optimal monitoring and delivery of care.

• Currently-used designs are large (15 gauge) and have only adequate response times of 4-5 minutes.1 There exists a need for a smaller size (less invasive) sensor capable of making linear, continuous measurements without excessive drift and with a fast transient response (2-3 minutes) to accommodate for fluctuating lactate levels.

• Because the oxygen sensor lies at the basis of this system, improvement in performance is solely achieved by enhancing the oxygen sensor. The objective is to develop a 19 gauge oxygen sensor that can generate continuous, linear measurements in response to changes across a physiologically relevant range of O2 concentrations without excessive drift and with a faster response time compared to the 15 gauge sensor.

0% 2% 4% 6% 8% 10% 12%0

0.2

0.4

0.6

0.8

1

1.2

f(x) = 10.7736745491847 x − 0.0635190584170177R² = 0.990855041717659

f(x) = NaN x + NaNR² = 0f(x) = NaN x + NaNR² = 0 Figure 4: 15 Gauge Sensor

Day 1Linear (Day 1)Day 2

Oxygen Concentration

Nor

mal

ized

Curr

ent

0% 2% 4% 6% 8% 10% 12%0

0.2

0.4

0.6

0.8

1

1.2

f(x) = 10.9301549429793 x − 0.0749293454333713R² = 0.990492879704586

f(x) = NaN x + NaNR² = 0f(x) = NaN x + NaNR² = 0 Figure 5: 19 Gauge Sensor

Day 1Linear (Day 1)Day 2

Oxygen Concentration

Nor

mal

ized

Curr

ent

PROBLEM DEFINITION

Prototype Testing1. The eight oxygen sensors were soaked in a continuously-stirred oxygen

chamber containing phosphate buffer solution (pH 7.34) heated to 37oC. 2. Examining drift. Four different O2 concentrations (1%, 2%, 5%, 10%) were

sparged into the chamber in repeated sequences. One hour was allowed between each concentration change to let the chamber stabilize. The steady state current was plotted. The procedure was repeated to produce n = 3 data points per concentration for each day.

3. Examining response time. Two different O2 concentrations were sparged into two chambers. The sensors were allowed to reach steady state in one chamber and then instantaneously dipped into the other chamber. The current was continuously plotted. The procedure was repeated to produce n = 3 data series per sensor.

Analysis4. The 15 gauge sensor was used as a control.5. Examining drift: The regression lines between day 1 and day 2 for each

sensor were compared using a statistical F-test to test for a significant difference, indicative of significant drift. Since the sensors produced similar output, data for only one sensor for each gauge size was used for the results.

6. Examining response time: The times to reach steady state from the initial concentration to the step challenge were compared for each sensor. The current outputs for each sensor were normalized and plotted to visualize approximate time points corresponding to a steady state current.

DESIGN & FABRICATION

TESTING & ANALYSIS

RESULTS

Figure 2: Oxygen Testing Chamber

Figure 3: 19 Gauge Sensor & 15 Gauge Sensor

Figure 1: Diagram of Sensor Layout

References

Silicone Rubber Catheter Membrane

Reference Electrode

Salt Bridge

Working ElectrodeCounter Electrode

Silicone Rubber Fill

Glass Bead

Stainless Steel Wires

Sensor Time Response

15 Gauge 245 sec(4.08 min)

19 Gauge 195 sec(3.25 min)

Table I: Transient response time

0 50 100 150 200 250 3000

0.5

1

1.5

2Figure 6: Transient Response Time

19 gauge Sensor15 gauge Sensor

Time (sec)

Nor

mal

ized

Curr

ent

(𝑖 − 𝑖_𝑚𝑖

𝑛)/(𝑖_𝑚

𝑎𝑥−𝑖_𝑚𝑖

𝑛 )

O2

O2

O2

• Based on the results, the 19 gauge platform has proven to be a promising design for less invasive, fast-response measurement capable of operating without excessive, undesired drift.

• For future progress, the 19 gauge platform will be coupled with the lactate enzyme and confirmed for accuracy and functionality for lactate detection.

• Future fabrication procedures could incorporate platinization of electrodes to construct sensors capable of producing more stable currents.

DISCUSSION