SBIR Phase I: Tunable laser diode spectrometer for point-of-care testing

这个小型企业创新研究(SBIR)第一阶段项目将开发一种紧凑、可广泛调谐的高亮度激光二极管光谱仪，该光谱仪将成为能够跟踪重症监护病房患者关键血液代谢物的自动化护理点(POC)监护仪的核心。这种可调谐激光器基于2.4微米波长的激光二极管，该二极管使用Sb III-V半导体材料，并耦合到外腔。高亮度光源将对全血等光学吞吐量较低的混浊溶液中的光谱提供极大的帮助。可调谐激光光谱仪的亮度将显著高于传统的宽带光源。将目标分析物的光谱特征与其他生物分子的光谱特征区分开来所需的宽可调谐性首先将通过一系列具有交错发射波长的量子井来拓宽增益光谱，其次将通过制造使用弯曲波导几何结构的激光器件来抑制来自激光二极管小面的光反馈。内腔式温控声光可调滤光器将提供必要的波长稳定性和调谐范围，使仪器具有坚固耐用、紧凑、无移动部件的全固态设计。可调谐激光二极管将实现对小体积全血的直接光谱测量。该项目的更广泛的影响/商业潜力是显著提高患者护理水平。基于这种可调激光光谱仪的护理点监测仪将在床边自动测量关键的血液代谢物，并对代谢状态进行半连续监测。该监测仪将定期收集少量血液样本的吸收光谱，并通过动脉导管将血液重新注入患者体内，从而可以定期监测葡萄糖、尿素、肌酐和乳酸。定期监测血糖可以使用强化胰岛素治疗，这已被证明可以改善重症监护病房患者的结局。跟踪尿素和肌酐浓度提供了一种肾功能的测量方法，可用于早期识别急性肾功能衰竭。检测到升高的乳酸浓度可以作为不稳定患者代谢困难的一个指标。这种基于激光的可调谐护理点监视器可以在不增加成本的情况下提供比现在可用的更多信息。与标准的血液化学分析不同，光学测量不需要试剂，因此不需要增加成本来限制监测频率。由于测量结果不会导致失血，因此对于不能忍受频繁抽血的患者来说，使用它是安全的。

This Small Business Innovation Research (SBIR) Phase I project will develop a compact, widely-tunable, high-brightness laser diode spectrometer that will be the core of an automated point-of-care (POC) monitor capable of tracking key blood metabolites for patients in intensive care units. The tunable laser is based on a 2.4 micron wavelength laser diode that utilizes antimonide III-V semiconductor materials and is coupled to an external cavity. A high-brightness source will be a great aid for spectroscopy in turbid solutions with low optical throughput like whole blood. The tunable laser spectrometer will have significantly higher brightness than is available with conventional broad-band sources. The wide tunability required to differentiate the spectral signatures of the target analytes from those of other biomolecules will be achieved first by broadening the gain spectrum through a series of quantum wells with staggered emission wavelengths, and second, by fabricating laser devices using a curved-waveguide geometry to suppress optical feedback from the laser diode facets. An intracavity, temperature-controlled acousto-optic tunable filter will provide the necessary wavelength stability and tuning range, giving the instrument a rugged, compact, all-solid state design with no moving parts. The tunable laser diode will enable direct spectroscopic measurements in small volumes of whole blood.The broader impact/commercial potential of this project is to significantly enhance patient care. The point-of-care monitor based on this tunable laser spectrometer will provide automated measurement of key blood metabolites at the bedside and semi-continuous monitoring of metabolic status. The monitor will periodically collect absorption spectra of a small blood sample, and reinfuse the blood into the patient through an arterial catheter, allowing regular monitoring of glucose, urea, creatinine and lactate. Regular monitoring of glucose enables the use of intensive insulin therapy, which has been shown to improve the outcome of intensive care unit patients. Tracking urea and creatinine concentrations provides a measure of renal function that can be used for early identification of acute kidney failure. Detection of elevated lactate concentrations can be used as an indicator of metabolic distress for unstable patients. The tunable laser-based point-of-care monitor can provide more information than is available now without increasing costs. Unlike standard blood chemistry assays, optical measurements do not require reagents, so there is no incremental cost to limit the frequency of monitoring. Since the measurement results in no blood loss, it is safe to use in patients who would be intolerant of frequent blood draws.