The invention provides devices and methods for linked multimodal measurements of individual particles using a mass sensor and an additional sensor.

Disclosed herein are methods of high-throughput screening test agents for treating a disease. Also disclosed herein are methods of high-throughput screening diseases. Systems for high-throughput screening are also disclosed herein.

For analyzing a sample containing particles of at least two categories, such as a sample containing blood cells, a particle counter subject to a detection limit is coupled with an analyzer capable of discerning particle number ratios, such as a visual analyzer, and a processor. A first category of particles can be present beyond detection range limits while a second category of particles is present within respective detection range limits. The concentration of the second category of particles is determined by the particle counter. A ratio of counts of the first category to the second category is determined on the analyzer. The concentration of particles in the first category is calculated on the processor based on the ratio and the count or concentration of particles in the second category.

The disclosure provides a method of detecting heterogeneity of disease in a cancer patient comprising (a) performing a direct analysis comprising immunofluorescent staining and morphological characteristization of nucleated cells in a blood sample obtained from the patient to identify and enumerate circulating tumor cells (CTC); (b) isolating the CTCs from the sample; (c) individually characterizing genomic parameters to generate a genomic profile for each of the CTCs, and (d) determining heterogeneity of disease in the cancer patient based on the profile. In some embodiments, the cancer is prostate cancer. In some embodiments, the prostate cancer is hormone refractory.

Methods to detect contaminants in a solution and applications thereof are described. Generally, solutions are printed onto a substrate and then imaged via Raman spectroscopy, which can be utilized to detect signals derived from contaminants.

Electrode controlled hybridization is used to change local pH and selectively assemble oligonucleotide complexes on the surface of a microelectrode array. The oligonucleotide complexes have sticky ends that provide locations for subsequent oligonucleotide complexes to hybridize. The order in which specific oligonucleotide complexes are joined together encodes information. Controlled activation of individual electrodes in the microelectrode array creates negative voltages that reduces a buffer solution and raises the pH in proximity to the electrodes. At higher pH levels double-stranded oligonucleotides de-hybridize. Nicks between oligonucleotide complexes and oligonucleotides anchored to the microelectrode array are closed creating covalent attachments. De-hybridized single-stranded oligonucleotides are removed leaving only the oligonucleotides connected to microelectrode array. Thus, during a given round of synthesis, oligonucleotide complexes are added only to the locations on the microelectrode array where the electrodes are not activated.

A method for optically detecting biomarkers in a biosensor is disclosed, wherein the optical detection obtains spatially and spectrally resolved optical signals from a sample on a biosensor, and one or more of these spatially and spectrally resolved optical signals can be analyzed in parallel with image acquisition. The image analysis comprises reading data of the acquired images, correcting them to reduce inhomogeneities and noise, localizing particles in the images, characterizing each particle individually to obtain its position and characterization parameters, and classifying the particles based on their characterization parameters. Using the number of particles per class for all the acquired images of the sample, a statistical value is calculated per sample and each statistical value is correlated with an indication of the presence of a biomarker in the sample.

Disclosed are methods, systems, and articles of manufacture for performing a process on biological samples. An analysis of biological samples in multiple regions of interest in a microfluidic device and a timeline correlated with the analysis may be identified. One or more region-of-interest types for the multiple regions of interest may be determined; and multiple characteristics may be determined for the biological samples based at least in part upon the one or more region-of-interest types. Associated data that respectively correspond to the multiple regions of interest in a user interface for at least a portion of the biological samples in the user interface based at least in part upon the multiple identifiers and the timeline. A count of the biological samples in a region of interest may be determined based at least in part upon a class or type of data using a convolutional neural network (CNN).

Techniques for label-free determination of a value of at least one blood property are presented. The techniques may utilize a device that includes an optical objective including at least one lens, at least a first light source situated so as to provide light to a body part at a location that is off-center from a central axis of the objective, at least a first electronic detector situated to receive light gathered by the optical objective and generate image data, at least one electronic processor communicatively coupled to the first electronic detector, the at least one electronic processor configured to determine the value of the at least one blood property based at least in part on the image data, and an output interface communicatively coupled to the at least one electronic processor and configured to provide the value of the at least one blood property.

A system for analyzing biological specimens by spectral imaging includes a biosensor comprising at least one graphene layer on a substrate and a memory in communication with a processor. The biosensor is configured to acquire a biological specimen sample. The memory and the processor are configured to conduct Raman spectroscopy to obtain spectral data for the sample, transmit the spectral data to a hub for direct or indirect transmission to one or more servers, perform multivariate analysis on the spectral data, and deliver a report based on the multivariate analysis of the spectral data.