Blood analysis without pain for neonates

Blood analysis without pain for neonates

Abstract
Jaundice is a common and often harmless condition in neonates. However, especially pre-term neonates have an increased risk for developing jaundice related brain damage, which is the reason for close monitoring of the blood bilirubin concentration in these patients. The bilirubin concentration is determined from a blood sample obtained by a heel stick, often up to three times a day. Here is a method f detecting the Jaundice without pain to the neonates.

Introduction
In most countries, a blood sample from newborn babies is needed for screening tests. A heel lance is the standard way of taking blood, but it is a painful procedure with no optimal method of pain relief known. Jaundice is a common and often harmless condition in neonates. However, especially pre-term neonates have an increased risk for developing jaundice related brain damage, which is the reason for close monitoring of the blood bilirubin concentration (the indicator of jaundice) in these patients. The bilirubin concentration is determined from a blood sample obtained by a heel stick, often up to three times a day. Naturally, this is a very painful and harmful procedure for the child. In addition, this diagnosis creates an unwanted delay in the treatment of the patient, since it may last more than one hour.

peak of bilirubin around 455 nm allows for spectroscopic assessment of its presence in the blood vessels of the skin. Although bilirubin meters based on this principle have been developed since 1980, no device has been found accurate enough to completely replace the heel stick1. The focus of this study is therefore 1) to investigate the reasons for the inaccuracy of current bilirubin meters and 2) to develop a bilirubin meter that can replace the painful heel stick. Heel stick: A procedure in which a newborn baby's heel is pricked and then a small amount of the blood is collected, usually with a narrow-gauge ("capillary") glass tube or a filter paper Heel lance (HL) has been the conventional method of blood sampling in neonates for screening tests (phenylketonuria and hypothyroidism) or measurements of serum bilirubin or glucose. The heel stick was invented in 1923 by a Danish pediatrician named Paul Drucker.

At the AMC we investigate the possibility to measure the bilirubin concentration faster and non-invasively, by using optical spectroscopy. The absorption

Need for LCS

At the AMC we investigate the possibility to measure the bilirubin

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Blood analysis without pain for neonates

concentration faster and non-invasively, by using optical spectroscopy. The absorption peak of bilirubin around 455 nm allows for spectroscopic assessment of its presence in the blood vessels of the skin. Although bilirubin meters based on this principle have been developed since 1980, no device has been found accurate enough to completely replace the heel stick1. The focus of this study is therefore 1) to investigate the reasons for the inaccuracy of current bilirubin meters and 2) to develop a bilirubin meter that can replace the painful heel stick.

Low coherence spectroscopy (LCS)

Low Coherence Spectroscopy (LCS) enables quantitative, path-length resolved measurements of absorption in scattering media, by combining reflection spectroscopy with low coherence interferometry

Optical spectroscopic techniques possibly offer a faster and non-invasive alternative to laboratory blood analyses, because of the ability to measure absorption and scattering coefficients of tissue which are, in turn, related to physiological states in biological systems. Although spectroscopic techniques are available for this purpose, most of them only measure the presence of tissue chromophores qualitatively. The accuracy of quantitative spectroscopic measurements of tissue chromophore concentrations is limited by lack of knowledge about the path length the light has travelled in tissue. To overcome this limitation, we developed a new technique called Low Coherence Spectroscopy (LCS). In LCS, low coherence interferometry and absorption spectroscopy are combined for quantitative, path-length resolved measurements of absorption properties in the visible wavelength region (480 750 nm). Previous attempts to develop methods for quantitative spectroscopy involved spectroscopic optical coherence tomography (sOCT), which combines spectroscopy with high resolution imaging. To image at sufficiently high depths, sOCT requires wavelengths in the near-infrared (around 850 or 1300 nm). A disadvantage of this wavelength region is that it contains little spectral features of important tissue chromophores such as bilirubin and haemoglobin. In addition, spectral resolution is often sacrificed for high spatial resolution to produce high quality images. Therefore, the interest of most sOCT studies lies within contrast enhancement, instead of quantitative absorption spectroscopy. The only possibility to improve the accuracy of the existing bilirubinometers, is by confining the measurement volume to the inner lumen of a blood vessel. Current spectroscopic techniques are unable to do such a determination, since light scattering from the surrounding tissue always contributes to the measured value. Therefore, we developed a new spectroscopic technique low coherence spectroscopy (LCS) which, based on low coherence interferometry, allows for very careful control over the size and location of the

Construction
Our LCS system consists of a standard open air Michelson interferometer with an oscillating mirror in the reference arm. The single mode light from a super continuum light source (SC430-4, Fianium Ltd., UK) with a spectral bandwidth of 430 2500 nm is spectrally filtered and in combination with the detector response (2001, New Focus, USA) reduced to a bandwidth of 480 750 nm. A 50:50 beam splitter splits the source light into a sample and a reference arm and a graded index multimode fibre is used to guide the reflected light from both arms to a photodiode and lock-in amplifier. The amplitude of the oscillating reference mirror produces a scanning window of 30 m, which is used to obtain a back scattered spectrum from the sample. This results in path length and spectral resolutions of 30 m and 6 nm, respectively. With a path length resolution of 30 m, the sample is translated with respect to the sample focus to select the path length in the sample. Focus tracking is applied by adjusting the length of the reference arm in correspondence to the sample displacement

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Blood analysis without pain for neonates

investigated tissue volume3. To validate our LCS measurements, the USB4000 was used repeatedly for measuring reference spectra2-5. Currently, LCS is the only spectroscopic technique that can be used for the measurement of blood values inside a single blood vessel, without any influence from the surrounding tissue. The first in vivo measurements with this technique are very promising LCS gives accurate, quantitative values of absorption and scattering coefficients in scattering media. LCS is a promising technique for the in vivo determination of tissue chromophores.

We redesigned the USB2000 -- the most popular spectrometer in the world -- to include an advanced detector and powerful high-speed electronics. The USB4000 features a 16-bit A/D, four triggering options, a darklevel correction during temperature changes, and a 22-pin connector with eight userprogrammable GPIOs. Whats more, the USB4000 interfaces to computers with Linux, Mac or Windows operating systems. The modular USB4000 is responsive from 2001100 nm and can be configured with various Ocean Optics optical bench accessories, light sources and sampling optics to create application-specific systems for thousands of absorbance, reflection and emission applications

Features
Low power consumption of only 250 mA @ 5 VDC 16 bit, 3MHz A/D Converter 5 triggering modes 2 programmable strobe signals for triggering other devices 22-pin connector for interfacing to external products Programmable for Standalone Operation CE Certification

Spectroscopic detection in LCS with the Ocean Optics USB4000

The relatively slow acquisition time of our LCS system limits the current clinical utility of the technique. Therefore, we investigated the possibility to replace the detecting photodiode in the LCS system by a spectrograph. The USB4000 proved to be very suitable for this purpose, resulting in an almost 4 times faster acquisition time5.

Outlook
Besides the above, we also used for the determination of neonatal skin in applications described the Ocean Optics probe of the optical properties the investigated patient

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Blood analysis without pain for neonates

population2. This information is of great value for both this research, and other studies involving optics and neonatal skin. For further improvement of the clinical utility of LCS, it is necessary to implement a spectrograph that has a higher acquisition rate than the USB4000. Since a spectrograph with the required specifications is not commercially available, such a spectrograph needs to be designed and developed. Furthermore, a fiber optic probe for clinical LCS measurements needs to be developed as well. The future development of LCS offers additional opportunities for clinical applications. The technique may not only be used for bilirubin concentration measurements, but also for the determination of other blood values, such as hemoglobin concentrations and oxygen saturation. Also for the determination of these blood values, a localized measurement in a single blood vessel implies a very valuable improvement compared to existing spectroscopic determinations. The expected

clinical utility of the technique is extensive, since it may be applied not only on neonates, but also on older children and adults. Furthermore, we found that LCS is also sensitive to the changes in tissue scattering that are related to the morphology and organization of cells6. The latter offers new opportunities for the diagnosis of cancer.

Bibliography http://www.photonicsonline.com http://www.google.com http://www.wikipedia.com http://www.oceanoptics.com http://journals.bmj.com/cgi/reprintform

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