Diffraction tomography for accurate digital pathology on a portable microscope

标题：在便携式显微镜上进行精确数字病理的衍射层析成像 摘要：全血细胞计数(CBC)和外周血涂片(PBS)分析最多 被要求进行无处不在的血液测试，以帮助了解患者的潜在病理状况。 目前，通常使用两种不同的仪器来进行这些测试，并且都需要 专门的实验室人员进行操作。因此，这些测试的范围仅限于集中式 医院中的实验室设施或具有所需基础设施的独立实验室。这种“受限”的访问方式 扩展到初级保健中心和医院的急诊室，患者在那里体验 更长的周转时间，症状的不确定性，以及测试和测试之间的多次随访 医生的预测。为了应对这些挑战，最近进行了几项努力，以开发一种 便携式CBC和PBS分析系统，基于光学高分辨率成像 显微镜。不幸的是，由于在大体积上进行高分辨率成像的挑战，这些 系统无法成功解决此问题。此外，CBC的参数，如平均细胞体积 (MCV)、平均细胞血红蛋白(MCH)和血红蛋白(Hb)不能从标准中获得 显微镜的强度图像。取而代之的是，需要一种3D“断层成像”系统来 准确地从PBS获得这些参数，但商业断层扫描系统很笨重， 价格昂贵，而且只能成像一小块样品。在本提案中，我们将使用3D 一种称为傅里叶层析成像(FPT)的显微成像技术 PBS和CBC参数，如MCV和MCH来自所产生的折射率和细胞 厚度测量。我们的FPT设置只需要在样本下面放置一个LED阵列 标准显微镜的平面，从而产生了紧凑、便携和通常低成本的仪器。 其额外的断层扫描信息也改进了血细胞形态的检测 镰状细胞性贫血或白血病等病症。在这笔第一阶段的赠款中，我们将开发世界上 第一台便携式断层扫描显微镜，并展示了其在自动化血液学(即CBC)中的应用 和PBS分析)，这将为我们新仪器的未来临床测试铺平道路 在第二阶段。

Title: Diffraction tomography for accurate digital pathology on a portable microscope Abstract: Complete blood cell count (CBC) and peripheral blood smear (PBS) analysis are the most ubiquitous blood tests ordered to help understand the underlying pathological condition of a patient. Currently, two separate instruments are typically used to conduct these tests, and both require dedicated lab personnel to operate. As a result of this, the reach of these tests is limited to centralized lab facilities in hospitals or independent labs with the required infrastructure. This ‘limited’ access extends to primary care centers as well as emergency rooms in the hospital, where patients experience longer turnaround times, uncertainty around their symptoms, and multiple follow-ups between tests and doctor’s prognosis. To address these challenges there have been several recent efforts to develop a portable system for CBC and PBS analysis, based on high-resolution imaging with an optical microscope. Unfortunately, due to the challenge of high-resolution imaging over a large volume, these systems cannot successfully address this problem. Also, parameters of CBC such as Mean Cell Volume (MCV), Mean Cellular Hemoglobin (MCH), and Hemoglobin (Hb) cannot be obtained from the standard intensity images of the microscope. Instead, a 3D “tomographic” imaging system is needed to accurately obtain these parameters from a PBS, but commercial tomographic systems are bulky, expensive, and can only image a small area of the sample. In this proposal, we will use a 3D microscopic imaging technique termed Fourier ptychographic tomography (FPT) to generate complete PBS and CBC parameters such as MCV and MCH from the resulting refractive index and the cell thickness measurements. Our FPT setup simply requires an LED array placed beneath the sample plane of a standard microscope, resulting in a compact, portable, and generally low-cost instrument. Its additional tomographic information also improves the detection of blood cell morphological conditions such as sickle cell anemia or Leukemia. In this Phase-1 grant, we will develop the world’s first portable tomographic microscope and demonstrate its utility for automated hematology (i.e., CBC and PBS analysis) at point-of-care, which will pave the way for future clinical tests of our new instrument in Phase II.