Raman Spectroscopy pH Measurement in Cerebrospinal Fluid
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Solution Overview
Problem
Current methods lack a noninvasive and effective means to measure pH in cerebrospinal fluid (CSF) following spinal cord injury, which is crucial for understanding and managing the secondary injury processes that occur after trauma.
Innovation Solution
The use of Raman spectroscopy with a single NIR laser to collect elastically and in-elastically scattered light, allowing for the noninvasive in vivo measurement of pH in CSF, utilizing Principal Component Analysis (PCA) to account for chemical variations and calculate pH levels, while turbidity corrections are made as necessary.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If Raman spectroscopy is used to measure pH in CSF, then noninvasive measurement is achieved, but measurement precision is affected by tissue turbidity
Solution Approach 1:
The patent uses the ratio of inelastically scattered light to elastically scattered light as an intermediary measure. The elastically scattered light serves as a reference that is sensitive to turbidity, allowing the system to normalize the pH measurement against tissue optical properties. This intermediary ratio enables accurate pH measurement despite varying tissue conditions.
Solution Approach 2:
The patent changes the measurement parameter from absolute intensity to a ratio of intensities (inelastic to elastic scattering). This parameter transformation makes the measurement insensitive to turbidity variations while maintaining sensitivity to pH changes, as both scattering types are affected similarly by turbidity but differently by pH.
2Device complexity
If only inelastically scattered light is used for pH calculation, then measurement simplicity is improved, but reliability decreases due to turbidity effects
Solution Approach 1:
The elastically scattered light acts as an intermediary reference signal that carries information about tissue optical properties. By incorporating this reference into the calculation ratio, the system maintains simplicity in the measurement process while significantly improving reliability through automatic normalization of turbidity effects.
3Measurement precision
If elastically scattered light is collected along with inelastically scattered light, then turbidity corrections can be made, but device complexity increases
Solution Approach 1:
The patent designs the light collection system to simultaneously collect both elastically and inelastically scattered light using the same optical components. This multi-functional approach allows a single detection system to perform both pH measurement and turbidity correction functions, avoiding the need for separate measurement systems and reducing overall device complexity.
Data Source
AI summary
A system and method for determining the pH of tissue in vivo. A Raman spectrometer is used to collect Raman spectra from the target tissue. The Raman spectra are baseline subtracted and assessed to determine the concentration of HPO4−2 and H2PO4−1 for the purposes of calculating the pH. The approach was validate in vitro using PBS solutions of known pH. The approach was confirmed in vivo using rat and swine models by probing the immediate vicinity of a contusive spinal cord injury (SCI) in the first minutes and hours after injury. Using a dynamic analysis and the Henderson-Hasselbalch equation, the average of (N=12) noninvasive Raman-based pH measurements of CSF was 7.073±0.156 and at >95% confidence there is no statistically significant difference between the Raman-based and the physically sampled results.