Analytica Chimica Acta 649 (2009) 180–190 Contents lists available at ScienceDirect Analytica Chimica Acta journal homepage: www.elsevier.com/locate/aca Review Microfluidics with MALDI analysis for proteomics—A review Jeonghoon Lee a , Steven A. Soper a,b,c , Kermit K. Murray a,∗ a Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, United States b Department of Mechanical Engineering, Louisiana State University, Baton Rouge, LA 70803, United States c Center for BioModular Multi-Scale Systems, Louisiana State University, Baton Rouge, LA 70803, United States article info Article history: Received 2 April 2009 Received in revised form 13 July 2009 Accepted 15 July 2009 Available online 21 July 2009 Keywords: Microfluidics Proteomics MALDI Microchip analytical procedure abstract Various microfluidic devices have been developed for proteomic analyses and many of these have been designed specifically for mass spectrometry detection. In this review, we present an overview of chip fab- rication, microfluidic components, and the interfacing of these devices to matrix-assisted laser desorption ionization (MALDI) mass spectrometry. These devices can be directly coupled to the mass spectrometer for on-line analysis in real-time, or samples can be analyzed on-chip or deposited onto targets for off-line readout. Several approaches for combining microfluidic devices with analytical functions such as sample cleanup, digestion, and separations with MALDI mass spectrometry are discussed. © 2009 Elsevier B.V. All rights reserved. Contents 1. Introduction .......................................................................................................................................... 180 2. Materials for microfluidics ........................................................................................................................... 181 3. Microfabrication methods ........................................................................................................................... 182 3.1. Photolithography ............................................................................................................................. 182 3.2. Micromachining .............................................................................................................................. 182 3.3. Imprinting and embossing ................................................................................................................... 182 4. Microfluidic chip interfaces to MALDI ............................................................................................................... 183 4.1. Off-line with deposition ...................................................................................................................... 183 4.2. Off-line MALDI directly from the microfluidic chip .......................................................................................... 184 4.3. On-line MALDI ................................................................................................................................ 187 5. Conclusions .......................................................................................................................................... 188 References ........................................................................................................................................... 189 1. Introduction Since the sequencing of the human genome, proteomics has become an important research topic in chemistry, biology, medicine and even engineering [1–4]. Progress in the area of proteomics relies heavily on new analytical tools for the sensitive, selective, and high- throughput studies of target analytes [5]. Mass spectrometry (MS) has evolved into a primary analytical tool for proteomics research, especially when coupled with separation techniques, due to the ∗ Corresponding author. Tel.: +1 225 578 3417. E-mail address: kkmurray@lsu.edu (K.K. Murray). high information content that can be derived from these coupled techniques [6]. Advances in MS have been facilitated by the two ionization techniques; electrospray ionization (ESI) and matrix- assisted laser desorption/ionization (MALDI). Over the course of the past two decades, these ionization methods have become indis- pensable for the analysis of biological molecules, especially proteins and peptides. ESI produces highly charged ions directly from a liq- uid and is therefore useful for direct coupling to liquid separations [7–9]. MALDI is fast and efficient and has a high tolerance to non- volatile buffers and impurities [10,11]. The samples for MALDI are typically applied to solid supports and used off-line with liquid or gel separations [12–14]. 0003-2670/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.aca.2009.07.037