Provided herein are methods and systems for biochemical analysis, including compositions and methods for processing and analysis of small cell populations and biological samples (e.g., a robotically controlled chip-based nanodroplet platform). In particular aspects, the methods described herein can reduce total processing volumes from conventional volumes to nanoliter volumes within a single reactor vessel (e.g., within a single droplet reactor) while minimizing losses, such as due to sample evaporation.

Systems and methods for automated laser microdissection are disclosed including automatic slide detection, position detection of cutting and capture lasers, focus optimization for cutting and capture lasers, energy and duration optimization for cutting and capture lasers, inspection and second phase capture and/or ablation in a quality control station and tracking information for linking substrate carrier or output microdissected regions with input sample or slide.

Provided herein are methods and systems for biochemical analysis, including compositions and methods for processing and analysis of small cell populations and biological samples (e.g., a robotically controlled chip-based nanodroplet platform). In particular aspects, the methods described herein can reduce total processing volumes from conventional volumes to nanoliter volumes within a single reactor vessel (e.g., within a single droplet reactor) while minimizing losses, such as due to sample evaporation.

Systems and methods for automated laser microdissection are disclosed including automatic slide detection, position detection of cutting and capture lasers, focus optimization for cutting and capture lasers, energy and duration optimization for cutting and capture lasers, inspection and second phase capture and/or ablation in a quality control station and tracking information for linking substrate carrier or output microdissected regions with input sample or slide.

A carrier for holding a biological sample includes a substrate. The substrate is configured to engage a first sample chamber comprising a first opening characterized by a first opening diameter or a second sample chamber comprising a second opening characterized by a second opening diameter that is greater than the first opening diameter. The substrate includes an upper portion, a lower portion, and an intermediate portion disposed between the upper portion and the lower portion. The lower portion is disposed below the upper portion and comprises a bottom surface configured to receive a biological sample. The intermediate portion is characterized by a first substrate diameter and the lower portion is characterized by a second substrate diameter that is less than the first substrate diameter.

A carrier for holding a biological sample includes a substrate. The substrate is configured to engage a first sample chamber comprising a first opening characterized by a first opening diameter or a second sample chamber comprising a second opening characterized by a second opening diameter that is greater than the first opening diameter. The substrate includes an upper portion, a lower portion, and an intermediate portion disposed between the upper portion and the lower portion. The lower portion is disposed below the upper portion and comprises a bottom surface configured to receive a biological sample. The intermediate portion is characterized by a first substrate diameter and the lower portion is characterized by a second substrate diameter that is less than the first substrate diameter.

Laser Capture Microdissection devices and methods are provided. A Laser Capture Microdissection device contains a transmissive film and a transfer film. The transmissive film includes a first material configured to transmit laser energy. The transfer film includes a second material configured to absorb UV-laser energy. The transfer film contains an absorptive substance to absorb UV-laser energy and convert it into heat.

A method and system for detecting, manipulating and isolating circulating tumor cells found in organic fluids comprising a simplified laser assisted transfer process. A liquid specimen of the organic fluid containing an enriched population of tumor cells and a population of non-tumor cells is spread onto a donor substrate with an interlayer comprising a semi-transparent polymeric adhesive tape. A fluorescent staining of at least one of the cell populations present in the liquid specimen is required to identify-using optical and fluorescence microscopy, the location of the cells to be manipulated and/or isolated. The laser beam energy is absorbed by the polymeric adhesive tape giving place to the formation of a blister that mechanically interacts with the liquid specimen and such interaction can induce the expulsion of a portion of the liquid specimen comprising the selected tumor cells or non-tumor cells, which can be a single cell or a cell cluster, towards the receiving substrate.

Compositions and methods for the simulataneous capture and release using micropattern surfaces for tissue and cell microdissection. In one example, a patterned thermoplastic film has a first surface and a plurality of projections attached to and extending outwardly from the first surface. The projections form a pattern on the thermoplastic film.

Described herein are systems and methods for a microfluidic immunoassay for in situ mass spectrometry analysis of intracellular protein biomarkers in tissue. In some embodiments, the tissue may comprise human brain tissue. In some embodiments, the protein biomarkers may comprise A species comprising monomers and oligomers of A.sub.1-42, A.sub.1-40, A.sub.1-39, A.sub.2-43, or combinations thereof. In some embodiments, the systems and methods may comprise laser capture microdissection (LCM) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry.