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.

Melittin-induced alterations in morphology and deformability of human red blood cells using quantitative phase imaging techniques

“…Membrane fluctuation profiles showed that the mean membrane fluctuation levels decreased when the RBCs became spherocytes from the melittin treatment suggesting that melittin reduced the deformability of the RBCs. The measured values of the cell volume, surface area, sphericity, Hb concentration, dry mass, and mean fluctuation level of the control (0 nM) were in good agreement with previous results 30,[43][44][45][46] . The real-time measurements showed the characteristic time scale of the melittininduced changes and enabled us to study the Hb leakage process at high melittin concentrations.…”

White-light diffraction phase microscopy at doubled space-bandwidth product

“…QPI can investigate unlabeled specimens, by converting optical pathlength data into biologically-relevant information [2][3][4][5][6][7][8][9][10]. Since the optical phase delay introduced by the specimen depends on both its thickness and refractive index, which essentially represents density, QPI has been used in a variety of applications, including topography and volume try of red blood cells [11,12], cell membrane fluctuations [13,14], cell growth [15,16], intracellular mass transport [17][18][19], cancer diagnosis in biopsies [20][21][22].…”

Characterization of dormant and active human cancer cells by quantitative phase imaging

“…More broadly viewed, the quantitative, label-free, and ease-of-use advantages of this method may have important clinical applications (37)(38)(39)(40)(41)(42), including characterizing the heterogeneous cell populations in human osteosarcoma tumors. Combined with clinical biomarker staining, one can envision that the percentages of angiogenic and non-angiogenic cells could be quantified using QPI, providing potentially useful information to pathologists as they evaluate the neovascularization of tumors being studied.…”