A Novel Approach to Lactate Sensing: Use of a
Mouth guard Embedded Microfluidic Lactate
Sensor for Performance Evaluation
Submitted to: NCIIA BME Idea
Date: November 4, 2010
Tuo Fu Li
L. Wern Ong
Joseph Sun
Stephanie Wu
Christine Zhang
Department of Biomedical Engineering
Vanderbilt University
2301 Vanderbilt Place
Nashville, TN 37235
615-322-3521
Zhang, Wu 11.05.2010
Project Abstract
Blood lactate level is a common clinical measure of anaerobic metabolism. This tool is
invaluable to physicians assessing the extent of irreversible tissue damage in conditions as varied
as heart attack, muscle fatigue, Alzheimer’s, ischemic stroke, and septic shock. Changes in
lactate level during abnormal physiological processes hold immense potential as a clinical
indicator of disease state, progression, and outcome. Changes in lactate level during normal
physiological processes are also useful in sports physiology and performance evaluation, where
determination of lactate threshold or anaerobic threshold can maximize training efficiency.
Modeling lactate levels over time will reveal information that discrete sampling cannot.
Our project goal is to develop a lactate sensor that is:

Robust and versatile

Accessible to patients of various age, size, ethnicity, and gender

Enables continuous and accurate measurement of lactate levels
Introduction
Blood lactate level is a common clinical measure of anaerobic metabolism. This tool is
invaluable to physicians assessing the extent of irreversible tissue damage in conditions such as
heart attack, muscle fatigue, Alzheimer’s, ischemic stroke, and septic shock (Romero 2010).
Changes in lactate level during abnormal physiological processes hold immense potential as a
clinical indicator of disease state, progression, and outcome (Ellmerer 2009, Scott 2010, Simoes
2010). Changes in lactate level during normal physiological processes may are also useful in
sports physiology and performance evaluation, where determination of lactate threshold or
Zhang, Wu 11.05.2010
anaerobic threshold can maximize training efficiency (Scharhag 2010). Monitoring lactate levels
continuously over time will reveal information that discrete sampling cannot.
Recent studies indicate a significant correlation between saliva and blood lactate levels
(Kelsay et al 1972, Kesay et al1974, T Ohkuwa et al 1995, C Schabmueller et al 2006, Segura
1996, Takeda I et al. 2009)], and sensing using saliva lactate will facilitate the non-invasive
methodologies in lactate level monitoring. Saliva is easily sampled from subjects yet blood
lactate measurements remain ubiquitous in clinical settings. A non-invasive device capable of
continuously sampling saliva lactate levels will replace traditional invasive techniques. Our
design project addresses this non-invasive monitoring need with the research and development of
a mouth guard embedded micro-fluidic lactate sensor device capable of transmitting real time
lactate level data to users. Possible future models may also include multi analyte sensors to
provide physicians and users with a broad spectrum of information in addition to lactate levels.
History and Context
Many revisal and applications have been researched during the first phase of design.
Initially, our team began brainstorming from a seed topic, lactate sensing, suggested by our
mentor Dr. Franz Baudenbacher as a potentially useful clinical diagnosis and prognosis tool. In
addition, extensive research within the past two months has revealed the many limitations of
current sensing techniques and the niche market that a non-invasive continuous saliva lactate
sensor will occupy.
Initial design models focused on the possibility of a subcutaneous multi-analyte electrode
capable of interfacing with Medtronic’s continuous glucose monitoring system. The premise of
this design was to replace only the electrochemical electrode embedded into a subject’s
subcutaneous abdominal adipose tissue. Multiple “pockets” within the tip of the sensing
Zhang, Wu 11.05.2010
electrode would preferentially hold different analytes (glucose or lactate) and their respective
oxidases (Reghabi 2005). This layout would enable differential measurements of glucose and
lactate levels from one fluid sample. However, further investigation revealed subcutaneous
lactate levels are not significantly correlated with blood lactate levels and a ten-minute latency
period exists for changes in subcutaneous adipose tissue glucose levels with respect to blood
glucose levels (Ellmerer 2009).
Despite these setbacks, continuous
lactate sensing remained the greatest priority.
The next model focused on the possibility of
machining a microfluidic lactate sensor for
saliva (Kelsey et al 1972). Thorough research
showed significant correlation between blood
and saliva lactate levels in a metabolic study
of seven young women. Multiple other studies
(Kelsay et al 1974, T Ohkuwa et al 1995, C
Schabmueller et al 2006, Takeda I et al. 2009)
also corroborate the relationship between
blood and saliva lactate levels. In order to
address concerns of stability, flow, and
Figure 1 – These figures show the level of lactate in the
blood (top graph) and saliva (bottom graph) over time. The
black dots correspond to sprinters, the white dots are for
long distance runners.
placement method, the current design seeks to
embed a microfluidic sensor hardwired to a microprocessor into a compact and versatile mouth
guard, capable of wirelessly transmitting data through Bluetooth technology.
Zhang, Wu 11.05.2010
The applications and settings in which this device can be used are diverse and exciting.
Sports teams may utilize continuous lactate level measurement techniques as a means to monitor
anaerobic threshold data and performance evaluation to plan more efficient and effective training
regimens. Normal lactate levels hover around 0.2 mmol/L (Ohkuwa). Figure 1 shows the
maximum lactate level
near 16 mmol/L in sprinters.
Abnormal lactate levels, at normal
conditions, are levels that go above 4.0 mmol/L, a condition known as lactate acidosis.
(Masharani) Knowledge of an individual’s anaerobic threshold will allow for intensive training
despite discomfort and cessation of training before lactate levels become deleterious. Studies
have shown that the lactate level, displayed in Figure 1, peaks in blood five minutes after
strenuous exercise and peaks in saliva 15 minutes after exercise (Ohkuwa). By setting an alert
for when lactate hits 50% of the maximum value, the athlete will be able to adjust his/her
performance to avoid premature fatigue. Another possibility is to incorporate a differentiator to
determine the rate at which lactate is increasing. In addition, increased knowledge of the
correlation or interaction between lactate levels and performance ability and muscle fatigue will
allow for better-coordinated and effective training regimens. There are over 400,000 student
athletes in the NCAA (Rosandich) and countless numbers of professional athletes for whom
having a reliable method of measuring lactate while performing would be beneficial.
There are also military applications to performance evaluation that can also utilize this
same data. A mouth guard embedded lactate sensor will provide a simple, versatile, and
continuous measure of lactate levels in many different scenarios for performance evaluation in
sports medicine or military applications in comparison to more costly, invasive methods
currently used in a clinical setting. The ability to use a monitoring device in the field is less
binding than clinical methods.
Zhang, Wu 11.05.2010
Our goal is to create a cheap but reliable device that can measure lactate levels during
activity in order to optimize exercise regimes and performance. We believe that there is a niche
market that can benefit from this type of device being on the market. Since it is a mouth guard,
athletes and solders will already be
accustomed to its use. We expect that our
device will easily outstrip bulkier, nonportable devices such as heart rate
monitors because of its low cost and ease
of use. Lactate concentration is a direct
product of muscle activity and is correlated
Figure 2 – This figure shows the lactate threshold plotted against
fatigue index. As the threshold increases, the amount of fatigue
decreases.
to fatigue level (Morris) and therefore tells much more information than pulse rate. Athletes do
not currently have a way to monitor lactate levels while on the playing field and the military does
not have an active lactate monitoring system. Since both groups do not have a way for instant
feedback in active performance, our device would fill a need while giving feedback about
physical fitness. Knowing when an athlete or solder is nearing the lactate threshold allows
trainers to produce workout regimes that go near the threshold, training the body to last longer
under near-fatigue conditions as well as notifying users of threshold levels. If each user were
able to determine his/her threshold level using our device, this would save considerable costs
against performing a costly, individual exertion tests, saving hundreds of dollars per individual.
(http://orthosurg.ucsf.edu) We estimate that all NCAA athletes (400,000+) and members of
active military service in the United States currently serving in active combat zones (Afghanistan,
Iraq), numbering 243,740, would be able to benefit from our device. (siadapp.dmdc.osd.mil)
Zhang, Wu 11.05.2010
Team
Five biomedical engineers, Toby Li, Joseph Sun, Wern Ong, Christine Zhang, and
Stephanie Wu, compose this design team. Altogether, a broad spectrum of strengths, motivations,
and perspectives are represented. It is important that a collaborative team dynamic be put in
place to best harness the individual strengths in a synergistic manner. Toby Li is a double major
in Economics and Biomedical Engineering. His expertise in both fields provides a unique
perspective on the market potential and financial constraints of our design product. Joseph Sun, a
Biomedical Engineer, has extensive research experience in basic sciences and design of
microfluidic devices. His prior projects include development of a myocardial cell picocalorimeter, a topic that heavily overlaps with the design of our lactate sensor. Wern Ong, a
Biomedical Engineer, brings industry expertise to our design process. His prior internship with
Medtronic’s sensor division in San Francisco will prove invaluable to the accessibility of
industry experts and availability of physical resources. Stephanie Wu, a Biomedical Engineer
with a minor in Engineering Management, provides expert guidance through the proper
application and documentation procedures as well as regular assessments of the feasibility of our
design. Christine Zhang, a Biomedical Engineer and minor in Molecular and Cellular Biology,
gives in depth insight to the physiology and disease mechanisms encountered. Her research
experience encompasses both computational modeling in a neurophysiology lab and profiling of
Avian beta defensins in a Salmonella pathogenesis study published in BMC Microbiology.
Christine will also serve as team technology guru, responsible for building and maintaining the
group’s online presence.
Zhang, Wu 11.05.2010
Work Plan and Outcomes
The main purpose of this design project is to give the team a chance to pursue our own
various different interests while applying all the knowledge and skills we have learned in the past
three years. We seek to gain firsthand experience of building a device to meet a need we see in
the community. At the end of this project, we hope to contribute new knowledge to the scientific
community on the feasibility of continuous lactate level measurements in saliva as well as build
a prototype that may be used in athletic and battlefield settings. We intend to apply for the
BMEIdea stipend, BMEIdea grant and obtain IRB approval to develop and test our device on
human subjects. A patent may be filed if the device proves to be effective. Though the viability
of this tool is undoubted, too many factors remain undefined to predict commercial success of
this product.
Evaluation and Sustainability Plan
A robust and versatile lactate sensor is required for continuous monitoring in hospitals,
clinics, and athletic fields. Sensing must be accessible to patients of various age, size, ethnicity,
and gender and account for the differences that may arise due to these traits. Continuous
measurements are necessary to study fluctuations in lactate levels on a small time interval and to
extract patterns from fluctuations over a long time course. Our goal is to design and build a
prototype possessing all the above detailed features using saliva lactate levels. Success will be
achieved if and when our prototype is capable of reflecting physiological changes in real time.
Completing landmarks in the design and development will also provide a periodic measure of
success.
Zhang, Wu 11.05.2010
Due to the nature of exercise and military training, consistent use of the consumable
lactate sensor will mean most customers will become repeat consistent paying customers.
Sustained growth can also occur through expansion of the product into other markets,
specifically clinical diagnostics in the ICU and in cases of sepsis, and pediatric cardiac surgery.
Lactate levels are an indicator of outcome in pediatric cardiac surgery (Ranucci 2010).
Additionally, it has been found that independent of other factors, hyperlactemia is an indicator of
outcome and hospital mortality in critically ill patients in general (Nichol 2010). In that study,
the authors recommended that lactate be used to identify patients at higher risk of death.
According to the US Department of Health and Human Services, there were 4.4 million
individual patient admissions into the ICU in 2000 providing a large market to expand into. In
treating sepsis, lactate measurements are important as a lactate level greater than 2mmol is one of
the diagnostic criteria for sepsis (Halam 2008). Sepsis itself accounts for $16 billion dollars a
year of healthcare spending (Halam 2008). Currently, clinical lactate sensing is done with
expensive blood gas analyzers. Our device would be preferred due to its low cost, and portability.
Clinically, the importance of lactate sensing is just beginning to be realized and the introduction
of a low cost sensor could take advantage of this emerging trend.
References
1.
Martin Ellmerer et al. “Clinical Evaluation of Subcutaneous Lactate Measurement in Patients after Major
Cardiac Surgery.” International Journal of Endocrinology 2009 (390975), (03 Mar 2009).
2.
J Kelsay et al. “Pyruvate and Lactate in Human Blood and Saliva in Response to Different Carbohydrates.”
Journal of Nutrition 102 (5), 661 (1972).
3.
J Kelsay, K Behall, and W Clark. “Glucose, fructose, lactate and pyruvate in blood and lactate and pyruvate
in parotid saliva in response to sugars with and without other foods.” The American Journal of Clinical
Nutrition 27, 819-25 (Aug 1974).
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4.
Bahar Reghabi et al. Implantable apparatus for sensing multiple parameters. US Patent 2005/0148832 A1.
5.
Marcelo Romero et al. “Amperometric Biosensor for Direct Blood Lactate Detection.” Analytical
Chemistry 82 (13), 5568-72 (02 Jun 2010).
6.
C Schabmueller et al. “Micromachined sensor for lactate monitoring in saliva.” Biosensors and
Bioelectronics 21 (1), 1170-1776 (2006).
7.
Friederike Scharhag-Rosenbergera et al. “Exercise at given percentages of VO2max: Heterogeneous
metabolic responses between individuals.” Journal of Science and Medicine in Sport 13 (1), 74-9 (Jan
2010).
8.
Sean Scott et al. “Two-Hour Lactate Clearance Predicts Negative Outcome in Patients with
Cardiorespiratory Insufficiency.” Critical Care Research and Practice 2010 (917053), (23 May 2010).
9.
R Segura et al. “A new approach to the assessment of anaerobic metabolism: measurement of lactate in
saliva.” British Journal of Sports Medicine 30 (4), 305-9 (1996).
10. Herbert Simoes et al. “Methods to identify the anaerobic threshold for type-2 diabetic and non-diabetic
subjects.” Arquivos Brasileiros de Cardiologia 94 (1), 71-8 (Jan 2010).
11. Takeda I et al. “Understanding the human salivary metabolome.” NMR in Biomedicine 22 (6), 577-84 (Jul
2009).
12. Rosandich, Thomas. "Collegiate Sports Programs: A Comparative Analysis." page 474. Education, 2002
13. Morris, Martyn G et al. “Relationships between muscle fatigue characteristics and markers of endurance
performance.” Joursnal of Sports Science and Medicine 7, pages 431 – 436, 2008.
14. Masharani Umesh, "Chapter 27. Diabetes Mellitus & Hypoglycemia" (Chapter). McPhee SJ, Papadakis MA:
CURRENT Medical Diagnosis & Treatment 2011: http://www.accessmedicine.com/content.aspx?aID=15524.
15. Wilder, Doug. “The Clinical Utility of Lactic Acid Testing with ABGs in the Neonatal Setting: A Case
Study.” Respiratory Therapy the Journal of Pulmonary Technique Special Supplement (2008)
16. Nichol et al. ”Relative hyperlactatemia and hospital mortality in critically ill patients: a retrospective multicentre study.” Critical Care 2010, 14:R25
17. Ranucci, Marco Isgro, Giuseppe. “Central venous oxygen saturation and blood lactate levels during
cardiopulmonary bypass are associated with outcome after pediatric cardiac surgery.” Critical Care 2010,
14:R149
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18. Robson, W. “Sepsis: a need for prehospital intervention?” Emergency Medicine 2009:25:535-538
19. "ACTIVE DUTY MILITARY PERSONNEL STRENGTHS BY REGIONAL AREA AND BY
COUNTRY (309A)" Web. 11 Nov. 2010.
<http://siadapp.dmdc.osd.mil/personnel/MILITARY/history/hst0709.pdf>.
Appendix

Budget Template with Budget Justification

Gantt Chart

Tuo Fu Li Resume

L. Wern Ong Resume

Joseph Sun Resume

Stephanie Wu Resume

Christine Zhang Resume
Zhang, Wu 11.05.2010