Various biological fluids include components such as particulates that can be recovered or extracted therefrom an analyzed in order to determine if an individual possesses a particular condition or disease or precursor thereof.
Gout and Pseudogout
Monosodium urate monohydrate (MSU, leading to gout) and calcium pyrophosphate dihydrate (CPPD, leading to pseudogout) are the most frequently observed crystals types in the joint space. These crystals cause inflammation, pain and destruction in the joint. Gout affects 1-2% of the adult population and its incidence increases with age. Accurate diagnosis of the crystal type is imperative to pursuing correct treatment. A conclusive diagnosis requires the analysis of the synovial fluid aspirates for the presence of crystals.
Gout and pseudogout have very similar symptoms, such as acute and episodic attacks of joint warmth, pain, swelling, and stiffness, thus are often clinically confused with each other. However, the treatment of gout and pseudogout and different because the crystals accumulated are not the same. Therefore, accurate diagnosis is essential for effective treatment of the disease.
Microscopic polarized imaging (PLM), which is presently the clinical standard of identifying pathologic crystals in synovial aspirates of patients with gouty symptoms, has limited sensitivity, and is prone to the subjectivity of the different operators. Currently, false negative rate in gout is 30%, and false positives happen up to 20% of the time has been reported in the literature, lead to inappropriate long-term treatment and delay the treatment of the actual cause. There is a clear need for affordable, automated and portable technologies at the primary care setting for reducing the unacceptably high misdiagnosis rate of crystal species in joint spaces. A lower misdiagnosis would impact patients' quality of life as it translates to less suffering, less deterioration of joints and avoidance of incorrect treatments, introducing cost savings.
Raman spectroscopic analysis of synovial aspirates carries a diagnostic potential. McGill et al identified gout crystals in a synovial smear and a gouty tophus from a limited number of clinical samples using Raman analysis. Maugars et al observed CPPD crystals in cartilage, muscle, and tendon sections using Raman microscopy. Hawi et al have identified cholesterol crystals within cells resident in synovial aspirates. These studies utilized Raman spectroscopy in the microscopy mode which requires seeking for individual crystals visually on a large field of view. This strategy necessitates the utilization of research-grade Raman instruments with premium signal collection capability and, thus, limits the translation of the method to the clinical applications. Recently, sample preparation methods have been developed to congregate crystals at well-defined locations, enabling point-and-shoot Raman spectroscopy at clinically relevant crystal concentrations where the diagnostic performance of Raman analysis compared favorably over PLM in a limited number of clinical samples. Based on this premise, Raman spectroscopy based diagnosis of crystal species in synovial aspirates is beginning to gain feasibility.
Urinary Tract Stones
About 10% of the population develop stones in the urinary tract. Half of patients with kidney stones will have another attack within 5-10 years. If diagnosed correctly and timely, occurrence or recurrence of stones can be treated by diet and/or medications specific to the types of stones which are present. Kidney stone management market size is expected to increase from the current level of $420M to $500M by 2016.
The current paradigm of diagnosis and treatment of kidney stones has a number of unmet needs. First, the stone is not diagnosed until it has formed enough mass to be identified by the imaging studies such as CT scans. Second, the composition of the stone is not identified until and when the stone is removed or passed spontaneously. Third, in majority of modern day surgery, powerful energy sources are used to powder fragments of the stones so the patient could pass them and therefore the fragments of the stone may not be obtained for future analysis. Fourth, there are no available technologies to monitor the status of those patients with high risk of redeveloping stones, or to assess their responsiveness to treatment. Most physicians do not monitor high risk patients due to the absence of a practical diagnostic method that can be executed at the point of care.
Compositional analysis of urinary stones, performed after the confirmation of stone existence, is critical for both effective clinical treatment and recurrent prevention. Imaging modalities such as CT, X-rays and ultrasonography do not provide specific information on the type and composition of stones. Available techniques for stone compositional analysis (e.g. wet chemical analysis, infrared spectroscopy, x-ray diffraction, and scanning electron microscopy) are performed by specialty labs using bulky and expensive equipment. Instrument operation and data interpretation require expert operators. Further, there are indirect costs associated with shipping and handling samples and coordinating the test results post hoc. A technology that would enable compositional diagnosis at the point of care would eliminate such indirect costs and also reduce the number of patient visits.