Lactate Sensor Design: A Novel Approach to Lactate Sensing
Submitted to: NCIIA BME Idea
Date: March 4, 2011
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
Lactate Sensing 3.4.2011
Project Abstract
There is great need in the market for a Type-II Diabetes prescreening device, and this lactate sensor is the perfect means for filling the void. Diabetes is a chronic and life-threatening illness that affects more than 170 million individuals worldwide with predictions at 300 million people by the year 2050. Not only can diabetes cause serious health problems, but there is not a prescreening device on the market that can accurately predict the onset of Type-II Diabetes. The current standard for diagnosing diabetes, the fasting blood glucose test, is only affective in diagnosing patients after the onset of diabetes in which prevention is no longer possible. However, this novel approach to lactate sensing utilizes the correlation between high lactate levels and the development of Type-II Diabetes, so that patients can accurately determine their risk of developing the disease and take steps to prevent it if necessary. This device will in no way replace tests used to diagnosis Type-II Diabetes, but instead add another level of screening and testing to current protocols so that patients can have earlier knowledge of diabetes indicators. This novel lactate sensor employs a hydrogel design that utilizes the directional change caused by swelling as well as a colorimetric assay to indicate specific lactate concentrations in the saliva that can then be correlated to the probability of developing diabetes. If the patients’ lactate levels indicate a sufficiently high probability of the developing the disease, then they can affect lifestyle changes before the onset of the disease, effectively preventing the disease before it can become a serious problem.
Our project goal is to develop a lactate sensor that is:
· Inexpensive, easy to use, hygienic, accurate, and disposable
· Able to utilize directional swelling as well as colorimetric assay to indicate lactate concentration in saliva
· A good tool for use as a Type II diabetes prescreening device
Introduction
High or increased blood lactate level is good predictor of Type II diabetes (Bakker, 2004). And recent studies have shown that high plasma lactate levels are linked to an increased risk of developing Type II diabetes (Crawford, 2010). According to the CDC and the WHO there is a great need for a tool or device that can be used to prescreen for Type II diabetes. Diabetes is a serious chronic illness that is characterized by high blood sugar that affects more than 170 million people worldwide. It is predicted that by the year 2025 over 300 million people will be affected by disease. This screening tool will become an invaluable asset to preventative efforts and public health initiatives. It will allow clinicians, physicians, and patients to quickly, easily, and accurately to asses patients with a high risk of developing the disease and allow them to take preventative measures such as a change in diet or exercise.
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 using saliva lactate levels will allow for a non-invasive method to evaluate and access high risk patients. Saliva is easily sampled from subjects yet blood lactate measurements remain ubiquitous in clinical settings. Our design project addresses the market need for a product that will accurately, easily, cheaply, and non invasively screen for diabetes without the need of blood samples. The development of a thermometer-like sensing device that utilizes colorimetric assays and directional swelling will allow patients to monitor their health and get proper testing if their risk is high. Possible future models include digital readouts of lactate concentration and the corresponding probability of Type II diabetes onset.
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 for prescreening diabetes sensors.
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 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, 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. Current design seeks to embed utilize hydrogel polymers that can transduce lactate concentration in the saliva to mechanical and chemical changes that can be detected and correlated to the probability of diabetes development.
The applications and settings in which this device can be used are diverse and exciting. Public health initiatives have called for widespread testing and screening of type II diabetes. This device will allow patients to be more aware of their probability of developing the disease so as to better protect their health and possibility prevent the development of the disease. Childhood obesity is also becoming more and more of an epidemic. This tool will allow for non invasive and more widespread testing of children. 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)
Our goal is to create a cheap but reliable device that can measure lactate levels during activity in order to optimize screening and preventative measures. We believe that there is a niche market that can benefit from this type of device being on the market. We expect that our device will easily outstrip bulkier, non-portable devices such as heart rate monitors because of its low cost and ease of use. Lactate concentration is correlated to diabetes (Morris).
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 pico-calorimeter, 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.
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 gain more knowledge and understanding of Type II diabetes as well as develop a new tool for use in Type II diabetes screening using lactate sensing. This device has the potential to change 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 other settings. 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.
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).
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).
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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 multi-centre 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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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
Lactate Sensing 3.4.2011