Antiepilepsy drugs (AEDs) are the mainstay of treatment for persons with epilepsy (PWE)1,2. Optimizing the effectiveness of AEDs involves adjusting dosages and timing of dosages to minimize side effects and maximize seizure control. Utilizing AED serum concentrations can guide this process, but obtaining blood tests is presently impractical due to the associated inconvenience and costs, as well as the often long latency between side effects and/or seizures and when blood tests are obtained. However, as many as two out of three PWE suffer from recurrent seizures or AED-related side effects.

In either case, optimization of AED dosages is clinically important and often guided by measuring AED serum concentrations. AED serum concentrations are typically quantified by High Performance Liquid Chromatography (HPLC) in conjunction with UV and photodiode arrays3. However, these methods are lab-based and not point of care (POC) nor obtained at the moment of need (for example after a seizure or when side effects are occurring), because they rely on expensive equipment and skilled technicians4. Thus, there is a great need for simple, rapid, reliable and disposable tests for AED measurements that can be performed at the doctor’s office or by the patient or a family member.

Here, we propose to develop a micro-a-fluidic based disposable AED detection that can be performed anywhere and automated to handle 100 μL of blood obtained with a fingerprick, such as used for blood glucose monitoring. The proposed system will require a cell phone and an inexpensive micro-a-fluidic chip (<$2) for detection that can give results in approximately 15 minutes. A version of this device could be made with readouts that the patient or family member can see, to report to the physician or to implement actions that the physician provided them in advance.

Importance of the Project

Epilepsy is a medical condition that affects the brain and causes a person to have seizures. A seizure happens when nerve cells in the brain work abnormally, affecting consciousness or movement. Epilepsy affects 65 million people worldwide and 2.2 million people in the U.S., including about 60,000 people in Massachusetts. It is most common among the very young and the very old, although anyone can develop epilepsy at any age.

Experiencing seizures or their disabling side effects can severely limit patients’ educational achievements, employment prospects and participation in all of life’s experiences. Seizures can even be life-threatening. And, our device can save lives.

In U.S., there are several treatment centers for epilepsy; however, the current treatment procedure can be burdensome for epilepsy patients. Medications need to be taken every day, sometimes several times a day. Physicians often use blood tests to measure the levels of medications to be sure the dosage is just right—to prevent seizures without causing drug-related side effects. The problem is that people with epilepsy have to visit a laboratory or hospital for these blood tests. This is difficult, especially because many people with epilepsy are not allowed to drive. Additionally, the timing of blood tests is very important.

What is hoped to be accomplished?

Our project seeks to help patients and their doctors take control over when and where these blood tests are done. We are designing a device that patients can use to test their blood at home, which will help their doctors better manage their medications to prevent seizures, emergency room visits and side effects.

How will this therapy be of help?

Our platform will be the first POC test to measure blood levels of seizure drugs. We are designing an easy testing device that adult patients or parents of children with epilepsy can carry in a pocket or a purse. This test can be performed anywhere, anytime.

By translating enzyme-linked immunosorbent assay (ELISA) to localized surface plasmon resonance (LSPR) platform, the device contains very tiny sensors called nanoplasmonics—like the ones inspired by the tiny hand-held machines in the “Star Trek” movies.

Patients provide a very small drop of blood through a fingerprick, like in a glucose-meter. The device checks the blood sample and gives results in fewer than 10 minutes. Easy and safe.

When will it be available?

This platform aims to develop an inexpensive, disposable and easy to use AED quantification chips for POC testing. First we will develop the test prototype. We intend to make the microchip operation automatic once the sample is introduced to the chip.

What patient group may benefit from this new therapy?

The device gives results quickly, so when patients call their doctors or nurses for advice on how to manage their epilepsy, they can give these results to their doctor and get help immediately, when they need it.

Our device can improve the quality of life for anyone affected by epilepsy and can even help save lives in emergency settings, such as an ambulance ride or a hospital emergency room.

References:

1 “Epilepsy” Fact Sheets. World Health Organization. (October 2012).

2 Baker, G. A., Jacoby, A., Buck, D., Stalgis, C. & Monnet, D. Quality of life of people with epilepsy: a European study. Epilepsia 38, 353-362 (2005).

3 Bhatti, M. M., Hanson, G. D. & Schultz, L. Simultaneous determination of phenytoin, carbamazepine, and 10, 11-carbamazepine epoxide in human plasma by high-performance liquid chromatography with ultraviolet detection. Journal of pharmaceutical and biomedical analysis 16, 1233-1240 (1998).

4 Patsalos, P. N. et al. Antiepileptic drugs-best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia 49, 1239-1276 (2008).

Disposable Microfluidic Chip
Methods Used for AED Quantification

The standard method required expensive HPLC equipment and skilled technician. Whereas, cell phone ELISA can be applied in POC settings.