Improving Non-Invasive BloodAnalysis by Expanding the Medical Spectral Window Katherine Paseman
Goal: Detect Medical Problems by non-Invasively Measuring OpticalProperties of BloodOptical Blood Medical ExampleProperty Diagnostic Problem (Symptom)Fluorescence Zinc Protoporphyrin Iron Deficient (ZPP) Concentration Anemia, Lead PoisoningAbsorption Hemoglobin Anemia ConcentrationScattering Hematocrit Low- Blood loss, High - Dehydration
Beer-Lambert Law Optical approaches leverage the Beer-Lambert law which uses 3 variables to model light entering (Ii) and exiting (Io) a sample. Io = Ii 10 –2.303 ε(λ) c t /(64,500 g Hb/mole) t – Sample thickness – cm c – concentration of absorbent - g/liter (A typical value of c for whole blood is 150 g Hb/liter.) ε(λ) – extinction coefficient of absorbent, which is a function of the light’s wavelength. – Blood’s ε(λ) is very large for λ < 600 nm – This is why a flashlight shone through the hand only transmits red light.
Prior Work: Pulse Oximetry A Pulse Oximeter non- invasively determines Pulse and Blood Oxygenation using differential light absorption. A Photodiode measures light intensity of Red (660nm) & Infrared (940 nm) LEDs shone through a finger during systole/diastole. Blood Oxygenation is a function of the “Ratio of Ratios” of Light Intensities at these points. Webster, JG. Design of Pulse Oximeters
Prior Work: Masimo pt 1Most non-invasive blood λ Hb02 ε(λ) Hb ε(λ) nm cm-1/M cm-1/Msensors extend the pulseoximeter’s differential 610 1506 9443.6absorption trick. Like the 620 942 6509.6pulse oximeter, they 630 610 5148.8target the finger using 660 319.6 3226.56wavelengths above 600nm, the so called ”Medical 700 290 1794.28Spectral Window”, to 730 390 1102.2collect enough light. 805 844 730.28 905 1209.2 769.8 Source: Masimo [US7377794]
Prior Work: Masimo pt 2 Medical Spectral Window
Prior Work: Samsung pt 1Samsung’s work states “Three λ Hb02 ε(λ) Hb ε(λ) variables of R569,805, cm-1/M cm-1/M R569,940, and R569,975 were used for calibration and 569 44496 45072 prediction models.” producing this comment by 660 319.6 3226.56 one author: 805 844 730.28G Yoon <email@example.com> - “569nm is highly absorbing in 940 1214 693.44 tissue and, at the same time, 569nm intensity is small 975 1144 389.288 compared with that at longer wavelength. That is why you may not get good signal. We Samsung reported >8% error for used a custom-made LED array Hemoglobin [Jeong et. Al. 2002] and that has several chips of 569nm to increase intensity.” Hematocrit [Yoon et. al. 2005].
Prior Work: Samsung pt 2 569 nm lies outside the Medical Spectral Window Medical Spectral Window
Our Research: Target Thumb Webbingfor Absorption instead of Finger Our hypothesis: We can extend the medical spectral window by offsetting the increase in extinction coefficient at λ< 600 nm with a decrease in sample thickness [Sabrina Paseman 2008] did this by targeting the thumb webbing for fluorescence measurements. We do this for absorption. This allows us to get better absorption measurements by increasing the signal and so decreasing noise based error. It also allows us to detect additional sources of error.
The Apparatus We created an adjustable width clip that fits either the subject’s index finger or thumb webbing. One end of the clip holds the same 5-LED package used by Samsung and the other holds a fiber optic cable which connects to an Avantes AvaSpec-2048 spectrometer. The LEDs and spectrometer are controlled by an Arduino microcontroller. This allows us to double check the LED’s wavelength, determine LED intensity, see if there are any LED artifacts (emissions at wavelengths besides the primary wavelength), and observe any swamping or fluorescing effects.
Experiment 1: Approach A clamp is adjusted to fit the subject’s index finger. The subject removes their finger so that the spectrometer/LED distance can be measured with a micrometer. The thumb webbing is placed over the entire LED. The spectrometer auto-adjusts the integration time to a full scale reading and the data is collected. The subject removes their thumb webbing and places their index finger over the LED. The data is collected with the same integration time and plotted on the same axis for comparison.
Experiment 1: Data569 nm Subject 1 Thumb webbing Index Finger 54054.5 counts Integration Time: 404.05 ms Width: 0.7175 cm 4131.5 counts
Experiment 1: Findings General: Transmission increased 13 fold. Artifacts: Samsung’s LED chip has an artifact at around 875nm when the 569nm LED is lit. If Samsung’s device uses a photodiode to collect light, especially at low intensities, much of the collected light would come from the artifact rather than the 569nm peak. Race: This method limited the quality of the readings we could take from subjects with darker skin. Age: Young people have smaller thumb webbing than older people.
Experiment 2: Approach Hold LED underneath the thumb webbing and the spectrometer on the other side. Let the spectrometer auto-integrate and capture the graph. For data analysis, find the ratio between the ratios of the peak counts at 569nm and the integration time. Counts thumb webbing Integration timethumb webbing Absorption Amplification = Countsindex finger Integration timeindex finger
Experiment 2: Data Summary569 nmSubject Scopetw Integrationtw Scopeif Integrationif Ampli- (ADC (ms) (ADC (ms) fication Counts) Counts)1 32847.801 99.70 13640.500 3097.90 74.8252 60849.000 208.91 33273.000 1736.15 15.1983 55602.750 114.73 60534.000 3808.11 30.488 Subject1: 58 years old - light skinned Subject2: 52 years old - dark skinned Subject3: 16 years old - light skinned
Key Finding:“Artifact Amplification” Why does the artifact size increase? Blood is a low pass filter, attenuating small λ (high frequencies) more than large λ. LED Artifacts (usually) appear “above” (at a larger λ) the primary emission λ. If the LED’s primary λ is below 600 nm and the artifact is above, the artifact will appear differentially amplified. This amplification is a key consideration when designing with LEDs that have this characteristic.
Conclusions Transmission through thumb webbing is at least 13x better than through the finger, but the exact ratio varies from subject to subject. “Artifact Amplification” was confirmed by both experiments and will be a key design consideration going forward. Both phenomena would partially explain Samsung’s error numbers. Low readings from people with darker skin in the first experiment and smaller thumb webbing for younger subjects indicate that probe design will be a key issue going forward.
Further Research See if there is a statistically significant difference between the light absorption of systolic and diastolic blood at 569, 660, 805, 940 and 975 nm. Correlate more medical problems to absorption differentials and fluorescent phenomena. – See if there is a statistically significant difference between the fluorescence of systolic and diastolic blood excited at 425 nm. Collect data for more subjects with varying melanin contents and ages
References [Sabrina Paseman 2008] Paseman, Sabrina. The Ferrometer: A Device to Detect Iron Deficient Anemia via Non-Invasive Optical Measurement of Zinc Protoporphyrin. Issue brief no. SO499. Los Angeles: University of Southern California, 2008. PDF file. [US7377794] "Multiple Wavelength Sensor Interconnect” – p57 lists Masimo’s wavelengths [Yoon et. Al. 2005] Yoon, Gilwon, Ph.D, et al. "Development of a Compact Home Health Monitor for Telemedicine." TELEMEDICINE AND e-HEALTH 11.6 (2005): 660-67. PDF File. [Jeong et. Al. 2002] Jeong, Kye Jin, Su-Jin Kim, and Kun Kook Park. "Noninvasive Total Hemoglobin Measurement." Journal of Biomedical Optics 7.1 (2002): 45-50. PDF file. “Tabulated Molar Extinction Coefficient for Hemoglobin in Water” http://omlc.ogi.edu/spectra/hemoglobin/summary.html