CoreView: fresh tissue biopsy assessment at the bedside using a millifluidic imaging chip.

Minimally invasive core needle biopsies for medical diagnoses have become increasingly common for many diseases. Although tissue cores can yield more diagnostic information than fine needle biopsies and cytologic evaluations, there is no rapid assessment at the point-of-care for intact tissue cores that is low-cost and non-destructive to the biopsy. We have developed a proof-of-concept 3D printed millifluidic histopathology lab-on-a-chip device to automatically handle, process, and image fresh core needle biopsies. This device, named CoreView, includes modules for biopsy removal from the acquisition tool, transport, staining and rinsing, imaging, segmentation, and multiplexed storage. Reliable removal from side-cutting needles and bidirectional fluid transport of core needle biopsies of five tissue types has been demonstrated with 0.5 mm positioning accuracy. Automation is aided by a MATLAB-based biopsy tracking algorithm that can detect the location of tissue and air bubbles in the channels of the millifluidic chip. With current and emerging optical imaging technologies, CoreView can be used for a rapid adequacy test at the point-of-care for tissue identification as well as glomeruli counting in renal core needle biopsies.

Microscopy with ultraviolet surface excitation for wide-area pathology of breast surgical margins.

Intraoperative assessment of breast surgical margins will be of value for reducing the rate of re-excision surgeries for lumpectomy patients. While frozen-section histology is used for intraoperative guidance of certain cancers, it provides limited sampling of the margin surface (typically <1 % of the margin) and is inferior to gold-standard histology, especially for fatty tissues that do not freeze well, such as breast specimens. Microscopy with ultraviolet surface excitation (MUSE) is a nondestructive superficial optical-sectioning technique that has the potential to enable rapid, high-resolution examination of excised margin surfaces. Here, a MUSE system is developed with fully automated sample translation to image fresh tissue surfaces over large areas and at multiple levels of defocus, at a rate of ∼5 min / cm2. Surface extraction is used to improve the comprehensiveness of surface imaging, and 3-D deconvolution is used to improve resolution and contrast. In addition, an improved fluorescent analog of conventional H&E staining is developed to label fresh tissues within ∼5 min for MUSE imaging. We compare the image quality of our MUSE system with both frozen-section and conventional H&E histology, demonstrating the feasibility to provide microscopic visualization of breast margin surfaces at speeds that are relevant for intraoperative use.

Fluorescence anisotropy near-field scanning optical microscopy (FANSOM): a new technique for nanoscale microviscometry.

A near-field scanning optical microscope system was implemented and adapted for nanoscale steady-state fluorescence anisotropy measurement. The system as implemented can resolve approximately 0.1 cP microviscosity variations with a resolution of 250 nm laterally in the near field, or approximately 10 microm when employed in a vertical scanning mode. The system was initially used to investigate the extent of microviscous vicinal water over surfaces of varying hydrophilicity. Water above a cleaved mica surface was found to have a decreased microviscosity, while water above a hydrophobic surface showed no change (detection limit approximately 0.1 cP at approximately 30 + nm from the surface).