Optical analysis of Lithium Carbonate: Towards the development of a Portable Lithium Blood Level analyzer for Bipolar Disorder Patients

Lithium medication is the gold standard of treatment in Bipolar Disorder patients, preventing and reducing mood swings and suicidality. However, despite its effectiveness, it is a potentially hazardous drug requiring regular monitoring of blood levels to ensure toxic levels are not reached. This paper describes the first steps towards developing a new portable device that can be used by Bipolar Disorder patients to facilitate the analysis of lithium blood levels at home. Solutions of lithium carbonate have been optically fingerprinted using a high-end spectrophotometer. Preliminary measurements indicate that while the visible to near infrared region of the absorption spectra fall heavily within the water band, measurements in the Ultraviolet region show a strong distinction between different lithium concentrations. The optical spectra of Lithium in the 220 nm to 230 nm region demonstrated the ability to differentiate between concentrations representing those found in patients

Development of non-invasive biochemical device for monitoring the Lithium level from saliva for bipolar disorder patients

This research aims at developing low cost portable proactive healthcare technologies to put more control into the hands of patients especially who have mental illness so that the earliest signs of health problems with medications can be detected and corrected. Monitoring prescription drugs such as lithium, clozapine etc is important for safe guarding the well-being of the bipolar sufferers. Therapeutically useful amounts of lithium (~ 0.6 to 1.2 mmol/L) are only slightly lower than toxic amounts (>1.5 mmol/L), so the concentration of lithium must be carefully monitored during treatment to avoid toxicity. A very sensitive analytical method was proposed for the spectrofluorimetric determination of lithium base on its reaction with 1,4- dihydroxyanthraquinone (Quinizarin). The fluorescence is measured at an excitation wavelength of 590 nm and emission wavelength of 620 nm. Saliva sample was tested using the proposed portable device in order to validate the feasibility of saliva as a sample to detect lithium ions. Calibration results presented that linear range of detection was 0.25 mM ~ 6.0 mM of Li+ in saliva with R2=0.99. The range of detection covers sufficiently the therapeutic range of lithium drugs

Methodology for rapid assessment of blood lithium levels in ultramicro volumes of blood plasma for applications in personal monitoring of patients with bipolar mood disorder

Bipolar disorder (BD) is a common mental health condition, characterized by extreme changes in mood, energy, and behavior. BD is often managed through mood-stabilizing medications, of which lithium formulations remain the most reliable and effective at reducing the risk of suicide. To achieve adequate and consistent efficacy, lithium concentrations need to be maintained within a narrow therapeutic range (0.4 to 1.2  mmol  /  L). Because of its narrow therapeutic index, long-term lithium therapy is associated with serious side effects and risks of toxicity. It is believed that the availability of a personal blood lithium analyzer would benefit patients who are on lithium treatment. We detail the results of a spectrophotometric method performed on ultramicro volumes to determine blood plasma lithium concentrations as compared with reference measurements of flame photometry, and validated in samples of unknown lithium content. Applying multiple linear regression, lithium concentrations could be determined in a rapid manner using full-range spectra or triwavelength data. Both techniques highly correlated with reference standards and could predict lithium levels accurately (R2  =  0.794214 and RMSEP  =  0.209584, and R2  =  0.863921 and RMSEP  =  0.167524, respectively). Therefore, this method can be a useful for rapid assessment of blood lithium in nonlaboratory settings i.e., general practices, hospital clinics, and community health centers by healthcare professionals and/or by patients. Future work will now focus on completion of a miniaturized and integrated system that will deliver a portable and personal lithium-monitoring device

A Method for Rapid, Reliable, and Low-Volume Measurement of Lithium in Blood for Use in Bipolar Disorder Treatment Management

GOAL: Lithium preparations are considered the most reliable mood stabilizers for patients with Bipolar Disorder (BD), and are the most effective at reducing the risk of suicide. However, maintaining blood lithium concentration within the narrow therapeutic range of 0.4-1.2 mEq is crucial but extremely difficult. The aim of this work is to develop a personal lithium blood level analyzer using a novel method of combined optical and electrical impedance spectroscopy to test micro volumes of spiked samples of human blood. RESULTS: Impedance measurements alone showed a limit of detection of less than 0.1 mEq within the therapeutic range, whereas optical measurements could verify the presence of lithium and provide a degree of lithium content. Optical specificity to lithium was further verified in qualitative assessment of lithium spiked blood samples with varying concentrations of sodium. Moreover, analysis of multiple linear regression yielded a prediction model of R2 = 0.322716 and RMSEP =0.223602 for optical measurements only using feature wavelengths, which were found to appear at minima 560 and 605 nm. Combined with impedance measurements, prediction of lithium concentration in samples with unknown lithium content was significantly increased to R2 = 0.876438, and RMSEP = 0.513554. CONCLUSION: The combination of optical and impedance modalities for determinations of blood lithium resulted in significant improvement to the sensitivity and accuracy of measurement. SIGNIFICANCE: Results are complementary of the proposed opto-impedance method, and future work will now focus on the technical development of an integrated and miniaturized system for measurement of lithium levels in blood with a high level of accuracy and sensitivity

On the merits of tetrapolar impedance spectroscopy for monitoring lithium concentration variations in human blood plasma

Bipolar disorder is characterized as a manic-depressive psychiatric syndrome with life-threatening risks to the patient. Diagnosed individuals undergo long-term lithium therapy which has proven to be effective for mood stabilization. Maintaining blood lithium concentration levels within a narrow therapeutic window between 0.6-1.5 mM is vital for the patient as slightly elevated concentrations of the order of 0.1 mM can be toxic. This paper aims to evaluate the merits of tetrapolar electrical impedance spectroscopy (TEIS) as an alternative method in monitoring blood Lithium levels. Measurements were performed using a custom-made tetrapolar probe in human blood plasma with Lithium concentrations covering the therapeutic range. The results indicate a limit of detection less than 0.1 mM and a response time of less than 5 s. Prediction of Lithium concentration levels using impedance values is in good agreement with conventional standard techniques to approximately 0.05 mM. This technique provides a basis for further development of instrumentation for point of care healthcare technologies

A novel electrochemical sensor for non-invasive monitoring of lithium levels in mood disorders

Lithium is the main drug for the treatment of mood disorders. Due to its narrow therapeutic window, Therapeutic Drug Monitoring (TDM) is a norm during therapy in order to avoid adverse effects. Consequently, patients are obliged to frequent check-ups in hospitals to determine their serum concentration and optimize accordingly the drug dose. Wearable sensors have attracted a growing interest in the research community in recent years owing to their promising impact in personalized healthcare. In particular, sweat diagnosis has seen an enormous expansion and is currently entering the market thanks to the large availability and simple collection of this fluid. In this paper a novel approach for non-invasive decentralized monitoring of lithium drug concentration through sweat analysis is proposed for the first time. An all-solid-state Ion- Selective Electrode (ISE) with a nanostructured Solid-Contact (SC) is used to detect lithium ions in sweat. The sensor offers near-Nernstian behaviour (57.6±2.1 mV/decade) in the concentration range of interest. In addition, it shows fast response (15-30 s), good reversibility and small potential drift over time. A wide pH stability window (pH 4-12) is also proved

Complexity index from a personalized wearable monitoring system for assessing remission in mental health

This study discusses a personalized wearable monitoring system, which provides information and communication technologies to patients with mental disorders and physicians managing such diseases. The system, hereinafter called the PSYCHE system, is mainly comprised of a comfortable t-shirt with embedded sensors, such as textile electrodes, to monitor electrocardiogram-heart rate variability (HRV) series, piezoresistive sensors for respiration activity, and triaxial accelerometers for activity recognition. Moreover, on the patient-side, the PSYCHE system uses a smartphone-based interactive platform for electronic mood agenda and clinical scale administration, whereas on the physician-side provides data visualization and support to clinical decision. The smartphone collects the physiological and behavioral data and sends the information out to a centralized server for further processing. In this study, we present experimental results gathered from ten bipolar patients, wearing the PSYCHE system, with severe symptoms who exhibited mood states among depression (DP), hypomania(HM), mixed state (MX), and euthymia (EU), i.e., the good affective balance. In analyzing more than 400 h of cardiovascular dynamics, we found that patients experiencing mood transitions from a pathological mood state (HM, DP, or MX - where depressive and hypomanic symptoms are simultaneously present) to EU can be characterized through a commonly used measure of entropy. In particular, the SampEn estimated on long-term HRV series increases according to the patients' clinical improvement. These results are in agreement with the current literature reporting on the complexity dynamics of physiological systems and provides a promising and viable support to clinical decision in order to improve the diagnosis and management of psychiatric disorders

Advances in Therapeutic Monitoring of Lithium in the Management of Bipolar Disorder

Since the mid-20th century, lithium continues to be prescribed as a first-line mood stabilizer for the management of bipolar disorder (BD). However, lithium has a very narrow therapeutic index, and it is crucial to carefully monitor lithium plasma levels as concentrations greater than 1.2 mmol/L are potentially toxic and can be fatal. The quantification of lithium in clinical laboratories is performed by atomic absorption spectrometry, flame emission photometry, or conventional ion-selective electrodes. All these techniques are cumbersome and require frequent blood tests with consequent discomfort which results in patients evading treatment. Furthermore, the current techniques for lithium monitoring require highly qualified personnel and expensive equipment; hence, it is crucial to develop low-cost and easy-to-use devices for decentralized monitoring of lithium. The current paper seeks to review the pertinent literature rigorously and critically with a focus on different lithium-monitoring techniques which could lead towards the development of automatic and point-of-care analytical devices for lithium determination