Parallel fluorescence detection of single biomolecules in microarrays by a diffractive-optical-designed 2 x 2 fan-out element

被引:44
作者
Blom, H [1 ]
Johansson, M
Hedman, AS
Lundberg, L
Hanning, A
Hård, S
Rigler, R
机构
[1] Royal Inst Technol, Dept Microelect & Informat Technol, Electrum 229, SE-16440 Kista, Sweden
[2] Chalmers, Dept Microelect, SE-41296 Gothenburg, Sweden
[3] ACREO AB, SE-16440 Kista, Sweden
[4] Karolinska Inst, Dept Med Biophys, SE-17177 Stockholm, Sweden
关键词
D O I
10.1364/AO.41.003336
中图分类号
O43 [光学];
学科分类号
070207 ; 0803 ;
摘要
We have developed a multifocal diffractive-optical fluorescence correlation spectroscopy system for parallel excitation and detection of single tetramethylrhodamine biomolecules in microarrays. Multifocal excitation was made possible through the use of a 2 X 2 fan-out diffractive-optical element with uniform intensity in all foci. Characterization of the 2 X 2 fan-out diffractive-optical element shows formation of almost perfect Gaussian foci of submicrometer lateral diameter, as analyzed by thermal motion of tetramethylrhodamine dye molecules in solution. Results of parallel excitation and detection in a high-density microarray of circular wells show single-biomolecule sensitivity in all four foci simultaneously. (C) 2002 Optical Society of America.
引用
收藏
页码:3336 / 3342
页数:7
相关论文
共 35 条
[1]   Fan-out diffractive optical elements designed for increased fabrication tolerances to linear relief depth errors [J].
Bengtsson, J ;
Johansson, M .
APPLIED OPTICS, 2002, 41 (02) :281-289
[2]  
BRINAC SJ, 1999, IEEE ENG MED BIOL, V18, P120
[3]   Probing ligand protein binding equilibria with fluorescence fluctuation spectroscopy [J].
Chen, Y ;
Müller, JD ;
Tetin, SY ;
Tyner, JD ;
Gratton, E .
BIOPHYSICAL JOURNAL, 2000, 79 (02) :1074-1084
[4]   Making and reading microarrays [J].
Cheung, VG ;
Morley, M ;
Aguilar, F ;
Massimi, A ;
Kucherlapati, R ;
Childs, G .
NATURE GENETICS, 1999, 21 (Suppl 1) :15-19
[5]   Conformational transitions monitored for single molecules in solution [J].
Edman, L ;
Mets, U ;
Rigler, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (13) :6710-6715
[6]   SORTING SINGLE MOLECULES - APPLICATION TO DIAGNOSTICS AND EVOLUTIONARY BIOTECHNOLOGY [J].
EIGEN, M ;
RIGLER, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (13) :5740-5747
[7]   FLUORESCENCE CORRELATION SPECTROSCOPY .1. CONCEPTUAL BASIS AND THEORY [J].
ELSON, EL ;
MAGDE, D .
BIOPOLYMERS, 1974, 13 (01) :1-27
[8]  
FARN MW, 1991, P SOC PHOTO-OPT INS, V1555, P34, DOI 10.1117/12.50619
[9]   DNA sequencing - Massively parallel genomics [J].
Fodor, SPA .
SCIENCE, 1997, 277 (5324) :393-&
[10]   Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors [J].
Gray, NS ;
Wodicka, L ;
Thunnissen, AMWH ;
Norman, TC ;
Kwon, SJ ;
Espinoza, FH ;
Morgan, DO ;
Barnes, G ;
LeClerc, S ;
Meijer, L ;
Kim, SH ;
Lockhart, DJ ;
Schultz, PG .
SCIENCE, 1998, 281 (5376) :533-538