US 12,070,748 B2
Smart well device, multimodal system, and method for multi-analyte monitoring and processing
Thomas W. Chen, Fort Collins, CO (US); Daniel S. Ball, Fort Collins, CO (US); and Caleb R. Begly, Colorado Springs, CO (US)
Assigned to Colorado State University Research Foundation, Fort Collins, CO (US)
Filed by Colorado State University Research Foundation, Fort Collins, CO (US)
Filed on Apr. 11, 2020, as Appl. No. 16/846,330.
Claims priority of provisional application 62/833,205, filed on Apr. 12, 2019.
Claims priority of provisional application 62/833,082, filed on Apr. 12, 2019.
Prior Publication US 2020/0324289 A1, Oct. 15, 2020
Int. Cl. B01L 3/00 (2006.01)
CPC B01L 3/502715 (2013.01) [B01L 3/5025 (2013.01); B01L 3/5085 (2013.01); B01L 2200/027 (2013.01); B01L 2300/0645 (2013.01); B01L 2300/0825 (2013.01); B01L 2300/0829 (2013.01)] 23 Claims
OG exemplary drawing
 
1. A well plate for measuring one or more of a first, second, third, and fourth analyte in a sample, the well plate comprising:
a base plate defining a bottom of the well plate;
a sidewall extending vertically from and surrounding the base plate;
a set of electrodes including at least a first, a second, and a third electrode located at the bottom of the well plate, wherein the first electrode comprises surface chemistry modification having glucose oxidase as a first coating to have a higher sensitivity to glucose than the second and third electrodes, wherein the second electrode comprises a second surface chemistry modification having lactose oxidase as a second coating to have a higher sensitivity to lactate than the first and third electrodes, and wherein the third electrode comprises a third surface chemistry modification having a solid-state-electrolyte as a third coating to have a higher sensitivity to oxygen than the first and second electrodes;
a set of conductive pins that electrically connect to the set of electrodes, including a first conductive pin that connects over a first conductive trace along the bottom of the well plate to the first electrode, a second conductive pin that connects over a second conductive trace along the bottom of the well plate to the second electrode, and a third conductive pin that connects over a third conductive trace along the bottom of the well plate to the third electrode; and
electrical circuitry operatively coupled to the set of conductive pins of the well plate, wherein the electrical circuitry is configured to measure the first electrode, the second electrode, and the third electrode to provide a measure of abnormal or normal cell metabolism.
 
6. A multimodal well plate for measuring an analyte in a sample, the assembly comprising:
a first well plate having:
a base plate defining a bottom of the first well plate;
a sidewall extending vertically from and surrounding the base plate;
a plurality of electrodes including at least a first, a second, and a third electrode located at the bottom of the first well plate, wherein the first electrode comprises surface chemistry modification having glucose oxidase as a first coating to have a higher sensitivity to glucose than the second and third electrodes, wherein the second electrode comprises a second surface chemistry modification having lactose oxidase as a second coating to have a higher sensitivity to lactate than the first and third electrodes, and wherein the third electrode comprises a third surface chemistry modification having a solid-state-electrolyte as a third coating to have a higher sensitivity to oxygen than the first and second electrodes,
a closure covering the first well plate, wherein at least a portion of the closure is transparent,
a set of conductive pins that electrically connect to the plurality of electrodes, including a first conductive pin that connects over a first conductive trace along the bottom of the first well plate to the first electrode, a second conductive pin that connects over a second conductive trace along the bottom of the first well plate to the second electrode, and a third conductive pin that connects over a third conductive trace along the bottom of the first well plate to the third electrode;
a circuit plate having an electrical circuit configured to operatively couple to the first well plate and measure at least one of a voltage or a current between at least two of the plurality of electrodes, the electrical circuit connected to the set of conductive traces, wherein the electrical circuit is configured to multiplex the measured voltage or current of the first electrode, the second electrode, and the third electrode; and
an optical instrument configured to take images inside the first well plate while the electrical circuit measures the voltage or current between the at least two of the plurality of the electrodes of the first well plate.
 
12. A well plate assembly for measuring one or more analytes in a sample, the assembly comprising:
a plurality of separate well plates, including a first well plate and a second well plate, wherein each of the plurality of separate well plates comprises:
a base plate defining a bottom of the respective well plate;
a sidewall extending vertically from and surrounding the base plate;
a set of electrodes including at least a first, a second, and a third electrode located at the bottom of the respective well plate, wherein the first electrode comprises surface chemistry modification having glucose oxidase as a first coating to have a higher sensitivity to glucose than the second and third electrodes, wherein the second electrode comprises a second surface chemistry modification having lactose oxidase as a second coating to have a higher sensitivity to lactate than the first and third electrodes, wherein the third electrode comprises a third surface chemistry modification having a solid-state-electrolyte as a third coating to have higher sensitivity to oxygen than the first and second electrodes;
a set of conductive pins that electrically connect to the set of electrodes, including a first conductive pin that connects over a first conductive trace along the bottom of the well plate to the first electrode, a second conductive pin that connects over a second conductive trace along the bottom of the well plate to the second electrode, and a third conductive pin that connects over a third conductive trace along the bottom of the well plate to the third electrode; and
electrical circuitry operatively coupled to the set of conductive pins of the respective well plate, wherein the electrical circuitry is configured to measure the first electrode, the second electrode, and the third electrode to provide a measure of abnormal or normal cell metabolism.
 
19. A multimodal well plate assembly for measuring an analyte in a sample, the assembly comprising:
a plurality of separate well plates, including a first well plate and a second well plate, wherein each of the plurality of separate well plates comprises:
a base plate defining a bottom of the respective well plate;
a sidewall extending vertically from and surrounding the base plate;
a set of electrodes including at least a first, a second, and a third electrode located at the bottom of the well plate, wherein the first electrode comprises surface chemistry modification having glucose oxidase as a first coating to have a higher sensitivity to glucose than the second and third electrodes, wherein the second electrode comprises a second surface chemistry modification having lactose oxidase as a second coating to have a higher sensitivity to lactate than the first and third electrodes, and wherein the third electrode comprises a third surface chemistry modification having a solid-state-electrolyte as a third coating to have higher sensitivity to oxygen than the first and second electrodes,
a closure covering the well plate, wherein at least a portion of the closure is transparent,
a set of conductive pins that electrically connect to the set of electrodes, including a first conductive pin that connects over a first conductive trace along the bottom of the well plate to the first electrode, a second conductive pin that connects over a second conductive trace along the bottom of the well plate to the second electrode, and a third conductive pin that connects over a third conductive trace along the bottom of the well plate to the third electrode, and
electrical circuitry operatively coupled to the set of conductive pins of the respective well plate, wherein the electrical circuitry is configured to measure the first electrode, the second electrode, and the third electrode to provide a measure of abnormal or normal cell metabolism;
a circuit plate having an electrical circuit configured to operatively couple to the well plate and measure at least one of a voltage or a current between at least two electrodes of the first well plate, the electrical circuit connected to the set of conductive traces; and
an optical instrument configured, via a controller, to take images inside the first well plate while the electrical circuit measures the voltage or current between the at least two electrodes of the first well plate.