Diffraction tomography for accurate digital pathology on a portable microscope

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.