Hình ảnh khối phổ với độ phân giải cao trong khối lượng và không gian

Springer Science and Business Media LLC - Tập 139 - Trang 759-783 - 2013
Andreas Römpp1, Bernhard Spengler2
1Institute of Inorganic and Analytical Chemistry, Justus-Liebig-University, Giessen, Germany
2Institute of Inorganic and Analytical Chemistry, Justus Liebig University, Giessen, Germany

Tóm tắt

Hình ảnh khối phổ (MS) kết nối thông tin phân tử và sự phân bố không gian của các chất phân tích trong một mẫu. Khác với hầu hết các kỹ thuật hóa học mô, hình ảnh khối phổ có thể phân biệt các biến đổi phân tử và không yêu cầu đánh dấu các hợp chất mục tiêu. Gần đây, chúng tôi đã giới thiệu phương pháp hình ảnh khối phổ đầu tiên cung cấp thông tin phân tử cụ thể cao (độ phân giải và độ chính xác cao về khối lượng) ở cấp độ tế bào (độ phân giải cao trong không gian). Phương pháp này dựa trên nguồn hình ảnh phân giải laser hấp thụ/bốc hơi (MALDI) làm việc ở áp suất khí quyển, được kết hợp với máy khối phổ bẫy quỹ đạo. Ở đây, chúng tôi trình bày một số ví dụ ứng dụng và chứng minh lợi ích của 'hình ảnh khối phổ với độ phân giải cao về khối lượng và không gian.' Các phospholipid, peptide và hợp chất dược phẩm đã được hình ảnh hóa trong một số mẫu mô với độ phân giải không gian từ 5–10 μm. Các protein được phân tích sau khi tiêu hóa trypsin tại chỗ với độ phân giải 50 μm. Các ứng dụng bổ sung bao gồm phân tích tế bào đơn lẻ và mô ung thư phổi ở người cũng như phép đo hình ảnh MALDI đầu tiên của mô với kích thước pixel 3 μm. Phân tích hình ảnh MS cho tất cả các thí nghiệm này cho thấy mối tương quan xuất sắc với đánh giá nhuộm mô học. Độ phân giải khối lượng cao (R = 30.000) và độ chính xác khối lượng (thường là 1 ppm) đã được chứng minh là điều cần thiết cho việc tạo ra hình ảnh cụ thể và xác định đáng tin cậy các chất phân tích trong các mẫu mô. Khả năng kết hợp phân tích khối lượng chất lượng cao cần thiết với độ phân giải không gian trong khoảng một tế bào là đặc điểm độc đáo của phương pháp của chúng tôi. Với điều đó, nó có tiềm năng bổ sung cho các giao thức hóa học mô cổ điển và cung cấp cái nhìn mới về các quá trình phân tử ở cấp độ tế bào.

Từ khóa

#khối phổ #hình ảnh khối phổ #độ phân giải cao #phospholipid #peptide #hợp chất dược phẩm #mô học

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