Real Time Blood Testing Using Quantitative Phase Imaging

Abstract

We demonstrate a real-time blood testing system that can provide remote diagnosis with minimal human intervention in economically challenged areas. Our instrument combines novel advances in label-free optical imaging with parallel computing. Specifically, we use quantitative phase imaging for extracting red blood cell morphology with nanoscale sensitivity and NVIDIA’s CUDA programming language to perform real time cellular-level analysis. While the blood smear is translated through focus, our system is able to segment and analyze all the cells in the one megapixel field of view, at a rate of 40 frames/s. The variety of diagnostic parameters measured from each cell (e.g., surface area, sphericity, and minimum cylindrical diameter) are currently not available with current state of the art clinical instruments. In addition, we show that our instrument correctly recovers the red blood cell volume distribution, as evidenced by the excellent agreement with the cell counter results obtained on normal patients and those with microcytic and macrocytic anemia. The final data outputted by our instrument represent arrays of numbers associated with these morphological parameters and not images. Thus, the memory necessary to store these data is of the order of kilobytes, which allows for their remote transmission via, for example, the cellular network. We envision that such a system will dramatically increase access for blood testing and furthermore, may pave the way to digital hematology.

Considerations for point-of-care diagnostics: evaluation of acridine orange staining and postprocessing methods for a three-part leukocyte differential test

“…There are label-free techniques that require no contrast agents but rely on intrinsic properties where some are based on projections of the cells, such as lens-free shadow imaging, white light diffraction phase microscopy/quantitative phase imaging, and lensless incoherent holography. [26][27][28] Another approach uses fluorescence imaging since the optical system can be simplified and easily incorporated into low-cost imaging platforms such as cell phones and microcomputers, for example, 3-D printed compact devices attached to cell phones, plastic lenses developed via diamond turning, and small microfluidic-based blood cassettes that automatically combine the blood with the fluorescent dye without the need of additional reagents. 11,12,20 Overall, these systems have reported adequate results; however, further work needs to be done to optimize for POC leukocyte counting.…”

Network signatures of nuclear and cytoplasmic density alterations in a model of pre and postmetastatic colorectal cancer

“…22,23 Using a novel optical approach combining quantitative phase microscopy and PWS microscopy, we quantified nanoscale and microscale cellular density properties including nanoscale nuclear disorder strength, and at the micron scale: nuclear and cytoplasmic area, dry mass content, mean dry mass density, and shape metrics of the dry mass density histogram including the median, mode, min, max, skew, and kurtosis. Similar multiparameter approaches have been previously utilized to characterize phase distortions in tissue sections, 14 red blood cells, 24 phase fluctuations observed in waves transmitted through cells, 16 and in the context of monitoring the cell cycle through phase-derived parameters. 25 Our approach is the first to investigate the interdependence of these parameters.…”

Исследование Показателя Преломления Обезвоженных Клеток С Помощью Цифровой Голографической Микроскопии

“…Проведен статистический анализ полученных данных и оценена абсолютная погрешность метода для различных условий эксперимента. В последние годы цифровая голографическая микроскопия находит широкое применение в биологических исследованиях [1,2], а также в работах, связанных с медицинскими приложениями, в частности при диагностике целого ряда заболеваний [3,4]. В отличие от оптичес-кой микроскопии голографическая микроскопия позволяет получать количественные данные о фазовом запаздывании волнового фронта, прошедшего через клеточные структуры, что широко используется при наблюдении различных биологических процессов [5,6].…”