System, method, and product for scanning of biological materials

• US 20050057676A1
• Filed: 10/27/2004
• Published: 03/17/2005
• Est. Priority Date: 03/15/2002
• Status: Active Grant

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Oleink-Ovod, Ksenia, Weiner, Nathan K., Miles, Christopher, Schultz, Eric, Bukys, Albert, Bradbury, David, DiPaolo, Roger, Odoy, Patrick J., Stura, David A., Regan, Thomas P., Jones, Mark, McKenzie, Eric Earl, Deweerd, Herman, Overbeck, James, Woolaver, Tim, Katz, Joel
• Granted Patent: US 7,871,812 B2
• Time in Patent Office: Days
• US Class Current: 348/331
• CPC Class Codes: G01N 2021/6471 Special filters, filter wheel
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates

Abstract

An embodiment of a scanning system is described including optical elements that direct an excitation beam at a probe array, detectors that receive reflected intensity data responsive to the excitation beam, where the reflected intensity data is responsive to a focusing distance between an optical element and the probe array, a transport frame that adjusts the focusing distance in a direction with respect to the probe array, an auto-focuser that determines a best plane of focus based upon characteristics of the reflected intensity data of at least two focusing distances where the detectors further receive pixel intensity values based upon detected emissions from a plurality of probe features disposed on the probe array at the best plane of focus, and an image generator that associates each of the pixel intensity values with at least one image pixel position of a probe array based upon one or more position correction values.

Claims

1. A scanning system, comprising:

one or more optical elements constructed and arranged to direct a excitation beam at a probe array;

one or more detectors constructed and arranged to receive reflected intensity data responsive to the excitation beam, wherein the reflected intensity data is responsive, at least in part, to a focusing distance between an optical element and the probe array;

a transport frame constructed and arranged to adjust the focusing distance in a first direction with respect to the probe array;

an auto-focuser constructed and arranged to determine a best plane of focus based, at least in part, upon one or more characteristics of the reflected intensity data as received at two or more focusing distances;

and wherein;

the one or more detectors are further constructed and arranged to receive a plurality of pixel intensity values based, at least in part, upon detected emissions from a plurality of probe features disposed on the probe array at the best plane of focus; and

the system further comprises an image generator constructed and arranged to associate each of the pixel intensity values with one or more image pixel positions of a probe array based, at least in part, upon one or more position correction values.

2-107. -107. (cancelled)

108. A holder for an array unit having a planar substrate and an array of chemical moieties on a surface of the substrate, the holder comprising:

a body with a retaining mechanism which releasably retains an array unit in a seated position, such that an array unit can be repeatedly inserted into and removed from the seated position in which it is retained in the holder;

a machine readable holder identifier which includes data on a characteristic of the holder or seated array.

109. A holder according to claim 108 wherein the holder identifier includes data on a spatial characteristic of the holder or seated array.

110. A holder according to claim 109 wherein the holder identifier includes data on a a position or dimension of an array unit seated in the holder.

111. A holder according to claim 110 wherein the holder identifier includes data on the position or dimension of the substrate of an array unit seated in the holder unit.

112. A holder according to claim 110 wherein the position or dimension data includes data on the x, y, or z positions or dimensions of the seated array unit, where x and y are the directions along the length and width of the substrate and z is the direction perpendicular to the substrate plane.

113. A holder according to claim 110 wherein the position or dimension data includes data on the z position of the seated array unit.

114. A holder according to claim 110 wherein the position data includes data on the angular orientation of the seated array unit.

115. A holder according to claim 110 wherein the holder identifier comprises a bar code.

116. A holder according to claim 110 wherein the holder additionally comprises a magnetic or solid state memory attached to the body and the identifier is carried by the memory.

117. A holder according to claim 110 additionally comprising a seated array unit.

118. A holder according to claim 117 wherein the seated array unit additionally includes an array unit identifier.

119. A holder according to claim 118 wherein the array unit identifier is a machine readable identifier.

120. A holder according to claim 119 wherein the array unit identifier comprises a bar code or is carried in a memory attached to the remainder of the array unit.

121. A holder according to claim 110 which has a maximum length and width each no greater than 50 cm, and a thickness no greater than 10 cm.

128. A holder according to claim 119 wherein the holder identifier comprises a bar code or is carried in a memory attached to the remainder of the holder.

122. A method of reading an array of chemical moieties on a substrate of an array unit, the method comprising:

seating the array unit in a holder, which holder carries a holder identifier;

mounting the holder with seated array unit into an array reader;

reading the holder identifier and retrieving data on a position or dimension of the seated array unit based on the read holder identifier; and

reading the array.

123. A method according to claim 122 wherein the position or dimension data includes data on the x, y, or z positions or dimensions of the seated array unit, where x and y are the directions along the length and width of the substrate and z is the direction perpendicular to the substrate plane.

124. A method according to claim 122 wherein the position or dimension data includes data on the z position of the seated array unit.

125. A method according to claim 122 wherein the position data includes data on the angular orientation of the seated array unit.

126. A method according to claim 122 additionally comprising reading an array unit identifier carried by the array unit.

127. A holder according to claim 126 wherein the array unit identifier is machine read.

129. A method according to claim 122 wherein the reading of the array comprises scanning an interrogating light over the array.

130. A method according to claim 129 wherein the interrogating light is a spot scanned across the array in an x and y direction, where x and y are the directions along a length and width of the array.

131. A method according to claim 129 wherein a position or dimension of an area over which the interrogating light is scanned is based on data retrieved using the read holder identifier.

132. A method comprising forwarding data representing a result of a reading obtained by the method of claim 122.

133. A method according to claim 132 wherein the data is communicated to a remote location.

134. A method comprising receiving data representing a result of a reading obtained by the method of claim 122.

135. A method of reading an array of chemical moieties on a substrate of an array unit, the method comprising:

seating the array unit in a holder, which holder carries a holder identifier;

reading the holder identifier and retrieving a characteristic of the holder or seated array based on the read holder identifier; and

when the retrieved characteristic does not meet a predetermined condition, rejecting the seated array unit for reading or generating an operator alert.

136. A method according to claim 135 wherein the retrieved characteristic of the holder or seated array comprises a spatial characteristic.

137. An apparatus for reading an array of chemical moieties on a substrate of an array unit, the apparatus comprising:

a receptacle into which is mountable a holder carrying a seated array unit, which holder carries a holder identifier;

a reader system to read the holder identifier and data from different chemical moieties of the array; and

a processor which retrieves data on a characteristic of the holder or seated array based on the read holder identifier.

138. An apparatus according to claim 137 wherein the processor retrieves data on a spatial characteristic of the holder or seated array based on the holder identifier.

139. An apparatus according to claim 138 wherein the processor retrieves data on a spatial characteristic which comprises data on a position or dimension of an array unit seated in the holder.

140. An apparatus according to claim 139 wherein the reader system comprises a first identifier reader to read the holder identifier, and an array reader to read the data from different chemical moieties of the array.

141. An apparatus according to claim 139 wherein the processor retrieves data which includes data on the x, y, or z positions or dimensions of the seated array unit, where x and y are the directions along the length and width of the substrate and z is the direction perpendicular to the substrate plane.

142. An apparatus according to claim 139 wherein the reader system also reads an array unit identifier carried by a-seated array unit in the mounted holder.

143. An apparatus according to claim 140 additionally comprising a second identifier reader to read an array unit identifier carried by a seated array unit in the mounted holder.

144. An apparatus according to claim 139 wherein the reader system comprises a light system which provides and scans an interrogating light over the array.

145. An apparatus according to claim 144 wherein the light system provides a light spot which is scanned in an x and y direction across the array of the seated array unit in the mounted holder, where x and y are the directions along a length and width of the array.

146. An apparatus according to claim 144 wherein the processor controls a position or dimension of an area over which the interrogating light is scanned based on data retrieved using the read holder identifier.

147. An apparatus according to claim 137 wherein the processor retrieves data on a spatial characteristic of the holder and compares this with a predetermined condition in a memory and when the retrieved spatial characteristic does not meet the retrieved condition generates a user alert or inhibits reading of data from different chemical moieties of the array.

148. An apparatus according to claim 142 wherein:

the reader system comprises a light system which provides and scans an interrogating light over the array;

the processor controls a position or dimension of an area over which the interrogating light is scanned based on data retrieved using the read holder identifier; and

a position or dimension of the area over which the interrogating light is scanned is also based on data retrieved using the read array unit identifier.

149. An apparatus according to claim 139 wherein the array reader comprises a detector having a focal plane, wherein the position of the focal plane is adjusted relative to an array based on the data retrieved using the read holder identifier.

150. A computer program product for use with an apparatus of claim 139, comprising a computer readable storage medium having a computer program stored thereon for reading the holder identifier and retrieving data on the position or dimension of the seated array unit based on the read holder identifier.

151. A computer program product according to claim 150 wherein the program additionally reads an array identifier carried by a seated array unit in the mounted holder and retrieves data on the position or dimension of the array also based on the read array identifier.

152. A computer program product according to claim 151 wherein the program additionally controls a position or dimension of an area on the array of the seated array unit in the mounted holder, over which an interrogating light is scanned.