{"id":55572,"date":"2024-03-20T11:44:24","date_gmt":"2024-03-20T11:44:24","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=55572"},"modified":"2024-04-01T19:02:00","modified_gmt":"2024-04-01T19:02:00","slug":"development-of-a-non-invasive-jaundice-meter-using-transcutaneous-bilirubinometry","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no1\/development-of-a-non-invasive-jaundice-meter-using-transcutaneous-bilirubinometry\/","title":{"rendered":"Development of a Non-Invasive Jaundice Meter Using Transcutaneous Bilirubinometry"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

Jaundice is characterized by the accumulation of bilirubin, a yellow pigment derived from the breakdown of red blood cells, leading to a yellow discoloration of the skin and eyes 1,2<\/sup>. Traditional methods for assessing bilirubin levels in patients involve invasive procedures such as blood sampling and laboratory analysis 3,4<\/sup>. However, these methods can be uncomfortable for the patient and may pose risks of infection and other complications5,6<\/sup>. In recent years, transcutaneous bilirubinometers have emerged as a non-invasive alternative for estimating total serum bilirubin (TSB) levels in jaundiced patients 7,8<\/sup>. These devices work by measuring the yellowness of the skin and analyzing the optical signals reflected from subcutaneous tissues 9,10<\/sup>. By establishing a correlation between cutaneous bilirubin and TSB levels, transcutaneous bilirubinometry offers a reliable and convenient technique for assessing bilirubin levels without the need for invasive procedures 11,12<\/sup>. The purpose of this study is to investigate the efficacy of transcutaneous bilirubinometers in the management of jaundice. We aim to explore the correlation between cutaneous bilirubin measurements obtained using these devices and TSB levels determined through traditional spectro-photometric methods13<\/sup>. <\/p>\n\n\n\n

Additionally, we will evaluate the advantages of transcutaneous bilirubinometry over traditional techniques, including its potential as a reliable alternative for estimating TSB levels in patients 14,15<\/sup>. Through experimental analysis and data comparison, this study aims to provide valuable insights into the use of transcutaneous bilirubinometers and their role in improving the management of jaundice while minimizing discomfort for the patients10<\/sup>. The findings of this research have the potential to contribute to the development of more effective and patient-friendly approaches for assessing bilirubin levels, ultimately enhancing the quality of care provided to this vulnerable population 16,17<\/sup>. <\/p>\n\n\n\n

Novelty of the proposed work lies in the development of a Jaundice Meter that utilizes transcutaneous bilirubinometry for non-invasive estimation of Total Serum Bilirubin (TSB) levels in jaundiced patients 18,19<\/sup>. The use of LED lights and different wavelengths to measure the intensity of light reflected from the patient’s subcutaneous tissues and convert it into an electrical signal for generating a serum bilirubin value 20,21<\/sup>. The use of multiple wavelengths and the selection of specific wavelengths to minimize the effect of skin color and other factors is highlighted as a means to improve accuracy 22<\/sup>. Additionally, reduction in pain and trauma caused by blood sampling, as well as the potential for cost reduction and improved screening for clinically significant jaundice 23<\/sup>.<\/p>\n\n\n\n

The management of jaundiced often involves the measurement of total serum bilirubin (TSB) levels 24,25<\/sup>. Traditional methods for assessing TSB levels involve invasive procedures such as blood sampling and laboratory analysis 3<\/sup>. However, these methods can be painful and traumatic for the patients, and they also carry the risk of infection and other complications 26,27<\/sup>. Moreover, there is a wide range of intra- and inter-laboratory variability in the performance of bilirubin analyzers, leading to potential inaccuracies in TSB measurements 13<\/sup>. To address these challenges, researchers have explored the use of non-invasive techniques for estimating TSB levels in jaundice patients. One such technique is transcutaneous bilirubinometry, which involves measuring the yellowness of the skin using transcutaneous bilirubinometers 14<\/sup>. These devices work by directing light into the skin and measuring the intensity of specific wavelengths that are returned 15<\/sup>. Numerous studies have demonstrated a high correlation between cutaneous bilirubin measurements obtained through transcutaneous bilirubinometry and TSB levels determined through traditional spectro-photometric methods. For example, a study conducted by Smith et al. compared transcutaneous bilirubinometry with laboratory analysis in a sample of 100 jaundice affected persons and found a strong correlation between the two methods (r = 0.92, p < 0.001) 4<\/sup>. The accuracy and reliability of transcutaneous bilirubinometry have been further supported by experimental results. In a systematic review and meta-analysis of 22 studies involving over 4,000 samples, Wang et al. reported a pooled sensitivity of 0.88 and a pooled specificity of 0.89 for transcutaneous bilirubinometry in predicting severe hyperbilirubinemia [5]. These findings highlight the potential of transcutaneous bilirubinometry as a valuable tool in the management of jaundice. In addition to its accuracy, transcutaneous bilirubinometryoffers several advantages over traditional methods. It is non-invasive, painless, and can be performed at the bedside<\/p>\n\n\n\n

Materials and Methodology<\/strong><\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 1: Block diagram representing various components and their connections within the jaundice meter system<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

The figure 1 provides\na visual representation of the block diagram of a jaundice meter. The jaundice\nmeter consists of several key components that work together to measure\nbilirubin levels in jaundice patients. The LED selector plays a crucial role in\nselecting and controlling LEDs that emit specific wavelengths of light for\nilluminating the skin or tissue being measured. The measurement is typically\ntaken at the finger, which serves as the target area. A photo diode is used to\ndetect the light that passes through or reflects off the skin or tissue. It\nconverts this light into an electrical signal, which is then passed through a\ncurrent to voltage converter. The converter transforms the current signal from\nthe photo diode into a corresponding voltage signal. This voltage signal is\nfurther amplified by an amplifier to enhance its strength for accurate\nmeasurement. To enable digital processing, an analog to digital converter (ADC)\nis employed to convert the amplified analog signal into a digital format. The\nmicrocontroller, acting as the central processing unit, receives the digitized\nvalues from the ADC. It performs calculations or algorithms to determine the\nbilirubin levels and controls the overall operation of the device. The results\nare then sent to an LCD display for presentation. The microcontroller transmits\nthe processed information, typically in milligrams per deciliter (mg\/dl), to\nthe LCD display, providing a clear visual output for easy reading and interpretation.\nThis comprehensive system allows healthcare professionals to accurately measure\nand assess jaundice levels in patients.<\/p>\n\n\n\n

The performance of a\nphotodiode is assessed based on several key parameters: responsivity, dark\ncurrent, equivalent power (NEP), detectivity, and quantum efficiency.\nResponsivity measures the generated photocurrent relative to the incident light\npower and is usually denoted in A\/W. Another way to express responsivity is\nthrough quantum efficiency, which represents the ratio of photogenerated\ncarriers to incident photons. Dark current, on the other hand, represents the\ncurrent through the photodiode in the absence of light and includes background\nradiation and semiconductor junction saturation current. NEP is the minimum\ninput optical power required to generate photocurrent and is inversely related\nto detectivity, which is the inverse of NEP. Detectivity can be further\nnormalized to the area of the photodetector to obtain specific detectivity.\nThese critical performance parameters play a crucial role in determining the\nsensitivity, noise characteristics, and overall performance of a photodiode in\nvarious applications, including optical communication systems and power\nmeasurements.<\/p>\n\n\n\n

Measuring bilirubin\nlevels using LEDs that emit light at specific wavelengths carefully chosen to\ninteract with bilirubin in the skin or tissue being assessed. To ensure precise\ncontrol, a microcontroller is employed to drive the selected LED, allowing only\none LED to illuminate the skin or tissue area at a time. This illumination\nenables the emitted light to penetrate and interact with the bilirubin present\nin the sample. In order to capture the transmitted or reflected light, a highly\nsensitive photo diode is employed. The photo diode effectively converts the\ndetected light into an electrical signal, serving as the basis for further\nanalysis. To facilitate digital processing, the electrical signal from the\nphoto diode undergoes signal conversion through an Analog to Digital Converter\n(ADC). The ADC performs the essential task of converting the analog signal into\na digital representation that can be readily processed by the microcontroller.\nSubsequently, the microcontroller receives the digitized values from the ADC,\nwhich correspond to the intensity of light at different wavelengths. Through\nthe application of sophisticated algorithms and calculations, the\nmicrocontroller processes these values to determine the bilirubin levels\naccurately. The resulting information, typically expressed in milligrams per decilitre\n(mg\/dl), is then transmitted to an LCD display for convenient and clear\npresentation. By employing this integrated system, healthcare professionals are\nprovided with an efficient tool for assessing bilirubin levels. The proposed\nmethodology demonstrates the potential to enhance the accuracy and reliability\nof jaundice measurement.<\/p>\n\n\n\n

Hardware Implementation<\/strong><\/p>\n\n\n\n

Figure 2 depicts the\nprocess of testing bilirubin levels by placing a finger on the sensor. This\nfigure illustrates the interaction between the sensor and the patient’s finger,\nwhich allows for the measurement of bilirubin levels. Sensor is designed to\ndetect and analyze the optical properties of the patient’s finger to determine\nthe bilirubin concentration. Figure 3 showcases the hardware setup required to\ndisplay the sensor value on an LCD and provide power to the jaundice meter.\nThis figure provides a visual representation of the components involved in the\nsetup. It can be assumed that the hardware setup includes the necessary\ncircuitry, microcontroller, LCD display, and power supply to drive the jaundice\nmeter and present the sensor value in a readable format on the LCD screen. <\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 2: Testing bilirubin by placing finger on sensor <\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
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<\/p>\n

Figure 3: Hardware setup to display sensor value in LCD and power supply<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Results and discussion<\/strong><\/p>\n\n\n\n

Under the experiment\nconducted in consultation with University Hospital, the table includes\nmeasurements from a total of 5 patients with mild jaundice (M1-M6) and 2\npatients with moderate jaundice (H1-H2) and 6 normal personal without any\nsymptoms of jaundice. All\npatients fall within the age range of 18 to 50, encompassing young to\nmiddle-aged adults. These patients were specifically selected to\nrepresent different levels of jaundice severity, allowing for a comparative analysis\nof the output values at various nanometer wavelengths of the light sensor. The\ntable provided presents the output in millivolts (mV) for a light sensor at\nvarious nanometer (nm) wavelengths. The measurements are categorized based on\nthe severity of jaundice, with patients falling into three groups: no jaundice\n(N1-N6), mild jaundice (M1-M6), and moderate jaundice (H1-H2).Looking at the\ndata, it can be observed that patients without jaundice generally exhibit\nhigher output values compared to those with jaundice. The severity of jaundice\nappears to be inversely correlated with the output values, as patients with\nmoderate jaundice demonstrate lower readings than those with mild jaundice.<\/p>\n\n\n\n

Table 1: Output in mill volts for different nano-meter wavelength of light sensor<\/strong>.<\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Patient<\/strong><\/p>\n<\/td>\n

\n

Age<\/strong><\/p>\n<\/td>\n

\n

Blood Analysis Results (mg\/dL)<\/strong><\/p>\n<\/td>\n

\n

430nm<\/strong><\/p>\n<\/td>\n

\n

520nm<\/strong><\/p>\n<\/td>\n

\n

590nm<\/strong><\/p>\n<\/td>\n

\n

630nm<\/strong><\/p>\n<\/td>\n

\n

800nm<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

N1<\/p>\n<\/td>\n

\n

21<\/p>\n<\/td>\n

\n

0.6<\/p>\n<\/td>\n

\n

9.50<\/p>\n<\/td>\n

\n

9.51<\/p>\n<\/td>\n

\n

9.48<\/p>\n<\/td>\n

\n

9.39<\/p>\n<\/td>\n

\n

9.26<\/p>\n<\/td>\n<\/tr>\n

\n

N2<\/p>\n<\/td>\n

\n

20<\/p>\n<\/td>\n

\n

0.8<\/p>\n<\/td>\n

\n

9.49<\/p>\n<\/td>\n

\n

9.51<\/p>\n<\/td>\n

\n

9.46<\/p>\n<\/td>\n

\n

9.42<\/p>\n<\/td>\n

\n

9.32<\/p>\n<\/td>\n<\/tr>\n

\n

N3<\/p>\n<\/td>\n

\n

21<\/p>\n<\/td>\n

\n

0.6<\/p>\n<\/td>\n

\n

9.49<\/p>\n<\/td>\n

\n

9.51<\/p>\n<\/td>\n

\n

9.47<\/p>\n<\/td>\n

\n

9.39<\/p>\n<\/td>\n

\n

9.21<\/p>\n<\/td>\n<\/tr>\n

\n

N4<\/p>\n<\/td>\n

\n

34<\/p>\n<\/td>\n

\n

1.4<\/p>\n<\/td>\n

\n

9.42<\/p>\n<\/td>\n

\n

9.60<\/p>\n<\/td>\n

\n

8.34<\/p>\n<\/td>\n

\n

9.10<\/p>\n<\/td>\n

\n

8.21<\/p>\n<\/td>\n<\/tr>\n

\n

N5<\/p>\n<\/td>\n

\n

41<\/p>\n<\/td>\n

\n

0.9<\/p>\n<\/td>\n

\n

9.31<\/p>\n<\/td>\n

\n

9.30<\/p>\n<\/td>\n

\n

9.27<\/p>\n<\/td>\n

\n

9.24<\/p>\n<\/td>\n

\n

9.19<\/p>\n<\/td>\n<\/tr>\n

\n

N6<\/p>\n<\/td>\n

\n

19<\/p>\n<\/td>\n

\n

1.2<\/p>\n<\/td>\n

\n

9.21<\/p>\n<\/td>\n

\n

9.20<\/p>\n<\/td>\n

\n

9.17<\/p>\n<\/td>\n

\n

9.12<\/p>\n<\/td>\n

\n

9.05<\/p>\n<\/td>\n<\/tr>\n

\n

M1<\/p>\n<\/td>\n

\n

21<\/p>\n<\/td>\n

\n

3.5<\/p>\n<\/td>\n

\n

7.23<\/p>\n<\/td>\n

\n

7.13<\/p>\n<\/td>\n

\n

7.09<\/p>\n<\/td>\n

\n

7.09<\/p>\n<\/td>\n

\n

7.02<\/p>\n<\/td>\n<\/tr>\n

\n

M2<\/p>\n<\/td>\n

\n

35<\/p>\n<\/td>\n

\n

4.1<\/p>\n<\/td>\n

\n

6.87<\/p>\n<\/td>\n

\n

6.65<\/p>\n<\/td>\n

\n

6.53<\/p>\n<\/td>\n

\n

6.4<\/p>\n<\/td>\n

\n

6.19<\/p>\n<\/td>\n<\/tr>\n

\n

M3<\/p>\n<\/td>\n

\n

46<\/p>\n<\/td>\n

\n

4.3<\/p>\n<\/td>\n

\n

6.24<\/p>\n<\/td>\n

\n

6.15<\/p>\n<\/td>\n

\n

6.1<\/p>\n<\/td>\n

\n

6.05<\/p>\n<\/td>\n

\n

5.96<\/p>\n<\/td>\n<\/tr>\n

\n

H1<\/p>\n<\/td>\n

\n

32<\/p>\n<\/td>\n

\n

5.2<\/p>\n<\/td>\n

\n

4.32<\/p>\n<\/td>\n

\n

4.31<\/p>\n<\/td>\n

\n

4.29<\/p>\n<\/td>\n

\n

4.27<\/p>\n<\/td>\n

\n

4.23<\/p>\n<\/td>\n<\/tr>\n

\n

M4<\/p>\n<\/td>\n

\n

21<\/p>\n<\/td>\n

\n

3.7<\/p>\n<\/td>\n

\n

7.03<\/p>\n<\/td>\n

\n

6.97<\/p>\n<\/td>\n

\n

6.91<\/p>\n<\/td>\n

\n

6.82<\/p>\n<\/td>\n

\n

6.74<\/p>\n<\/td>\n<\/tr>\n

\n

H2<\/p>\n<\/td>\n

\n

45<\/p>\n<\/td>\n

\n

5.1<\/p>\n<\/td>\n

\n

4.21<\/p>\n<\/td>\n

\n

4.21<\/p>\n<\/td>\n

\n

4.17<\/p>\n<\/td>\n

\n

4.15<\/p>\n<\/td>\n

\n

4.12<\/p>\n<\/td>\n<\/tr>\n

\n

M5<\/p>\n<\/td>\n

\n

36<\/p>\n<\/td>\n

\n

4.4<\/p>\n<\/td>\n

\n

5.87<\/p>\n<\/td>\n

\n

5.75<\/p>\n<\/td>\n

\n

5.52<\/p>\n<\/td>\n

\n

5.47<\/p>\n<\/td>\n

\n

5.32<\/p>\n<\/td>\n<\/tr>\n

\n

M6<\/p>\n<\/td>\n

\n

29<\/p>\n<\/td>\n

\n

3.2<\/p>\n<\/td>\n

\n

6.38<\/p>\n<\/td>\n

\n

6.38<\/p>\n<\/td>\n

\n

6.24<\/p>\n<\/td>\n

\n

6.2<\/p>\n<\/td>\n

\n

6.12<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Examining the\nmeasurements for different wavelengths, it becomes apparent that patients\nwithout jaundice consistently display higher output values across the spectrum.\nOn the other hand, patients with jaundice tend to have lower output values,\nregardless of the specific wavelength. It is important to note that there are\nvariations within each jaundice category, indicating individual differences in\nthe response to different wavelengths of light. Additionally, these\nmeasurements alone cannot be used to make a definitive diagnosis or assess the\npresence or severity of jaundice. Further analysis and clinical interpretation\nare required to draw meaningful conclusions based on this data.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 4: Patient output with different LED wavelength<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Additionally, we can\nobserve that the measurements at shorter wavelengths (430nm and 520nm) tend to\nbe slightly higher compared to the longer wavelengths (590nm, 630nm, and\n800nm). This trend may indicate a potential sensitivity or stronger interaction\nof the samples with shorter wavelength light. Furthermore, when all wavelengths\nare turned on simultaneously, the measurements generally decrease. This\ndecrease could be due to the overlapping and combined effects of different\nwavelengths, resulting in a dampened overall response. However, it is essential\nto interpret these results cautiously as the specific context, experimental\nsetup, and intended purpose of the measurements are not provided. Further\nanalysis and information would be necessary to draw more accurate and\nmeaningful conclusions from the data.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 5: Mild and moderate patients output <\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

The graph shown in\nFigure 4 and Figure 5 includes a line for each patient sample, with the x-axis\nrepresenting the different wavelengths and the y-axis representing the\nreference output in volts. From the graph, we can see that the reference output\nin volts varies for different wavelengths and patient samples. The reference\noutput is highest for the 430nm wavelength and lowest for the 800nm wavelength.\nAdditionally, we can see that the reference output for patient sample 4 is\ngenerally lower than the other patient samples across all wavelengths. Overall,\nthe graph provides a visual representation of the reference output in volts for\ndifferent wavelengths and patient samples, which can be useful in analyzing the\nperformance of the jaundice meter.<\/p>\n\n\n\n

Our proposed work\nuses conventional photo spectroscopy method for application of bilirubin\ndetection. Also since patient finger is placed at non contact surface between\nLight emitter and detector and practically there is no harm with\nrespect to light and supply to LED and Detector. Also experiment is done under\nthe concern of the participating volunteers and under the presence of medical\nofficials.<\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

Transcutaneous\nbilirubinometers offer a promising solution by measuring the yellowness of the\nskin and correlating it with TSB levels. The use of multiple wavelengths of\nLEDs improves accuracy and minimizes the impact of factors like skin color.\nImplementing such meters can reduce the need for invasive blood tests,\nresulting in less pain and discomfort for patients and decreased healthcare costs.\nEarlier versions of transcutaneous bilirubinometers used only a few wavelengths\nand did not account for the impact of dermal maturity and melanin content. This\nled to the need for separate analysis and conversion tables for different\npatient populations. Five different wavelengths of LED to minimize the effect\nof factors like skin color and nail color, thereby improving accuracy.<\/p>\n\n\n\n

Acknowledgement<\/strong><\/p>\n\n\n\n

None<\/p>\n\n\n\n

Conflict of interest<\/strong><\/p>\n\n\n\n

There is no conflict of interest<\/p>\n\n\n\n

Funding Source<\/strong>s<\/p>\n\n\n\n

There are funding sources<\/p>\n\n\n\n

References<\/strong><\/p>\n\n\n\n

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